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Maria Cristina GAMBERINI

Ricercatore Universitario
Dipartimento Scienze della Vita sede ex Scienze Farmaceutiche Via Campi 103

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Pubblicazioni

2023 - Adsorption behaviour on silver nanocolloids at various concentrations of a bioactive therapeutic derivative of methylhydrazine: Experimental, DFT and molecular docking investigations [Articolo su rivista]
Al-Otaibi, J. S.; Sheena Mary, Y.; Shyma Mary, Y.; Kratky, M.; Vinsova, J.; Jalaja, K.; Gamberini, M. C.
abstract

A detailed theoretical and experimental study was implemented on a novel bioactive molecule 2-(3-bromobenzoyl)-N-methylhydrazine-1-carboxamide (BMC). Density Functional Theory (DFT), Time Dependent (TD)-DFT and Surface Enhanced Raman Scattering (SERS) studies were reported for the adsorption of BMC on silver hydrosols. SERS at various concentrations are discussed and there are orientation changes for BMC with concentration and BMC assumes a tilted orientation with the metal. The adsorption energy of BMC is −64.41 kcal/mol when adsorbed with Ag6, pointing to a chemisorption process. TD-DFT predicts a Ultraviolet (UV)-vis absorption of 595.11 when BMC adsorbed on Ag6, while that of BMC is 276.12 nm and the redshift, lowered intensity in UV spectra, caused by the aggregation of colloidal silver nano particles, was used to establish the adsorption of BMC on Ag6. Molecular docking is performed on BMC and BMC-Ag6 to find their ability to bind to target proteins, IP0I (human butyrylcholinesterase) and 4PQE (human acetylcholinesterase) and drug likeness properties are also assessed. The binding scores are high for BMC-Ag6 and hence the Ag6 will perform as a drug delivery vehicle.

2023 - Building an inclusive environment: exploring lecturers’ experience in inclusive and innovative academia [Working paper]
Negri, I.; Pistoresi, B.; Gamberini, M. C.; Mecugni, D.
abstract

As universities become more aware of diversity, with greater access to diagnoses of specific learning difficulties and increasing attention to multiculturalism, it is essential to adapt teaching methods to include everyone with their unique characteristics. However, despite Italian ministerial guidelines, many aspects of university inclusion, apart from examinations, are left to individual lecturers’ discretion. In order to understand their experiences, the research team carried out 18 semi-structured interviews with lecturers in the role of full professors, associate professors and assistant professors at the University of Modena and Reggio Emilia (UNIMORE). Non-probabilistic snowball sampling was used to recruit lecturers who had used or were currently using non-traditional teaching methods, with frontal teaching being considered the traditional method. The interviews were then analysed using Colaizzi’s descriptive phenomenological analysis to explore lecturers’ feelings and personal experiences (Colaizzi, 1978). This paper aims to raise awareness of the psychological and phenomenological aspects of applying innovative methodologies in higher education and to fill the existing research gap regarding the lack of qualitative research on the application of innovative and inclusive methodologies in higher education.

2023 - Concentration dependent SERS profile of p-tolyl 2-acetamido-3-(4-fluorophenyl)propanoate (AFP) in silver colloidal nanohydrosols: Experimental and DFT investigations [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Gamberini, M. C.
abstract

Based on Density Functional Theory (DFT) calculations and the Surface Enhanced Raman Scattering (SERS) technique, the adsorption properties of p-tolyl 2-acetamido-3-(4-fluorophenyl)propanoate (AFP) on silver surface were examined. The title compound, AFP showed balanced inhibition of acetyl- and butyrylcholinesterase along with mild cytotoxicity of HepG2 cells according to the previous study. After adsorption on silver surface, the structural properties of AFP exhibit a small modification, indicating an interaction between the AFP and Ag6 cluster. Experimental research on AFP and SERS spectra at various concentrations was conducted. Raman frequencies for AFP and AFP adsorbed on silver were computed. FMOs for AFP and AFP adsorbed on the silver surface were conducted. After AFP was adsorbed on the silver, the energy gap was dramatically lowered. The greater bioactivity of AFP is caused by the lowering energy gap, which denotes the electron delocalization. According to SERS spectrum analysis, AFP was adsorbed on silver with a tilted orientation. As a result, the current study has been used as a model system to comprehend how silver nanoprticles (NP) interact with AFP. Silver nanoparticles are successfully used for the treatment of different diseases alone or in association with other active components and the incorporation of AFP with silver nanocolloids will act as a nanodrug delivery system.

2023 - DFT, TD-DFT and SERS analysis of a bioactive benzohydrazide's adsorption in silver hydrosols at various concentrations [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Gamberini, M. C.
abstract

SERS was used to analyze the surface adsorption of a benzohydrazide derivative on silver nanoparticles. Density functional theory (DFT) calculations were used to determine the vibrational assignments in the surface-enhanced Raman scattering (SERS) spectra of (E)-4-methyl-Nˈ-[4-(trifluoromethyl)benzylidene]benzohydrazide (TFB) at various concentrations. TFB mostly adsorbs through C=O group and rings with silver. On the silver surface, however, the adsorption takes place through the ring's π-electrons. As concentration of silver hydrosol changes, changes in orientation of TFB occur. TFB is adsorbed with a binding affinity of −131.74 kcal mol−1, suggesting a chemisorption process according to theoretical analysis. The time dependent-DFT analysis gives an adsorption of 310 nm for TFB while with silver complex there is a peak to higher values as a doublet at 520 and 688 nm with lowering of intensity as expected. The changes of thermodynamical parameters during adsorption are all are negative suggesting the adsorption process is spontaneous and exothermic.

2023 - Experimental and DFT investigations of SERS Profile of a Bioactive Hydroxybenzamide Derivative [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Gamberini, M. C.
abstract

Surface enhanced Raman scattering (SERS) experiments were used to evaluate the adsorption and orientation of 5-bromo-N-[4-bromo-3-(trifluoromethyl)phenyl]-2-hydroxybenzamide (BTB) adsorbed on silver colloid and the results were compared to normal Raman spectra of BTB. Density functional theory (DFT) analysis was used to theoretically validate the observed spectra of BTB. BTB and BTB-Ag6 molecular structures were optimized at first. The BTB molecule is adsorbed with the Ag6 with energy of −10.67 eV through atoms, O9, F22 and Br17 atoms. The charge transfer interaction between Ag6 clusters and BTB, which lead to BTB adsorption on Ag6 metal clusters, is confirmed by the Frontier Molecular Orbitals (FMOs) study. The BTB chemisorbed on silver with a tilted orientation, as confirmed by SERS spectral analysis and the accompanying results were theoretically justified.

2023 - Innovative and inclusive academia: faculty development and practices evaluation. [Abstract in Atti di Convegno]
Addabbo, Tindara; Lotti, Antonella; Strozzi, Chiara; Pistoresi, Barbara; Tasselli, Chiara; Negri, Isabella; Mecugni, Daniela; Gamberini, Maria Cristina
abstract

2023 - Insights into the Adsorption Nature of a Bioactive Anticancer Derivative of Benzenesulfonate on Silver Colloids at Various Concentrations: Experimental and DFT Investigations [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y.; Kratky, M.; Vinsova, J.; Gamberini, M. C.
abstract

Density functional theory was used in the present study to report and validate the 4-chloro-2-[(3,5-dichlorophenyl)carbamoyl]phenylbenzenesulfonate’s (CPB) IR, Raman and SERS spectra. The molecular systems, CPB and CPB-Ag6 were initially optimized. Frontier molecular orbital study demonstrates that in CPB-Ag6 complex, charge transfer (CT) interaction occurs between Ag and molecule. CT interaction in the examined systems was further verified by the MEP surface. The CPB is chemisorbed on Ag6 with affinity and a tilted orientation through lone pair electrons of atoms, according to Raman and SERS spectral analyses. Additionally, there was good correlation between the theoretical and observed results. The current study thus lays the path for designing robust SERS active substrates that will be useful for creating biosensors related to the CPB molecule.

2023 - New Lidocaine-Based Pharmaceutical Cocrystals: Preparation, Characterization, and Influence of the Racemic vs. Enantiopure Coformer on the Physico-Chemical Properties [Articolo su rivista]
Ma, P.; Toussaint, B.; Roberti, E. A.; Scornet, N.; Santos Silva, A.; Castillo Henríquez, L.; Cadasse, M.; Négrier, P.; Massip, S.; Dufat, H.; Hammad, K.; Baraldi, C.; Gamberini, M. C.; Richard, C.; Veesler, S.; Espeau, P.; Lee, T.; Corvis, Y.
abstract

This study describes the preparation, characterization, and influence of the enantiopure vs. racemic coformer on the physico-chemical properties of a pharmaceutical cocrystal. For that purpose, two new 1:1 cocrystals, namely lidocaine:dl-menthol and lidocaine:d-menthol, were prepared. The menthol racemate-based cocrystal was evaluated by means of X-ray diffraction, infrared spectroscopy, Raman, thermal analysis, and solubility experiments. The results were exhaustively compared with the first menthol-based pharmaceutical cocrystal, i.e., lidocaine:l-menthol, discovered in our group 12 years ago. Furthermore, the stable lidocaine/dl-menthol phase diagram has been screened, thoroughly evaluated, and compared to the enantiopure phase diagram. Thus, it has been proven that the racemic vs. enantiopure coformer leads to increased solubility and improved dissolution of lidocaine due to the low stable form induced by menthol molecular disorder in the lidocaine:dl-menthol cocrystal. To date, the 1:1 lidocaine:dl-menthol cocrystal is the third menthol-based pharmaceutical cocrystal, after the 1:1 lidocaine:l-menthol and the 1:2 lopinavir:l-menthol cocrystals reported in 2010 and 2022, respectively. Overall, this study shows promising potential for designing new materials with both improved characteristics and functional properties in the fields of pharmaceutical sciences and crystal engineering.

2023 - SERS spectra of a bioactive carboximidamide derivative at different concentrations: Experimental and DFT investigations [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Gawad, J.; Gamberini, M. C.
abstract

In the current study (Z)-2-(2-oxoindolin-3-ylidene)hydrazine-1-carboximidamide hydrochloride's (OHC) Infrared (IR), Raman and surface-enhanced Raman scattering (SERS) spectra at various concentrations were presented experimentally and using density functional theory (DFT) simulations. Ag6, OHC and OHC-Ag6 systems’ structures were initially optimized. The OHC-Ag6 complex exhibits charge transfer interaction (CTI) between Ag and the OHC, according to frontier orbital molecular (FMO) analysis. The CTI under investigation was confirmed by molecular electrostatic potential (MEP) analysis. The molecule is chemisorbed on Ag6 in a tilted manner through the lone pair of atoms, according to SERS investigation. With changes in concentration, the interaction of OHC with metal also changes, resulting in orientation changes. Additionally, there was a strong correlation between theoretical findings and experimental values. Therefore, the current discovery opens the door for engineering robust SERS active substrates useful for creating OHC-related biosensors.

2023 - SERS spectroscopy for the therapeutic N-butyl-2-isonicotinoylhydrazine-1-carboxamide in silver nanocolloids at different concentrations: Experimental and DFT investigations [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Krátký, M.; Vinsova, J.; Gamberini, M. C.
abstract

SERS at different concentrations and vibrational spectroscopic studies of N-butyl-2-isonicotinoylhydrazine-1-carboxamide (INC) are reported. DFT calculations based on silver cluster model and TD-DFT calculations support experimental observations. Raman band enhancements that are only present in some of the SERS spectra further point to the contribution of charge transfer interactions to the overall enhancements INC's Raman modes. The presence of the inactive nR bands in the SERS spectrum is due to the presence of Ag and these show the chemisorption nature of INC with the silver surface in an inclined orientation according to selection rules. The method created in this study can accurately quantify INC and might be applied to medications with structural relevance.(c) 2023 Elsevier B.V. All rights reserved.

2023 - TD-DFT, DFT, docking, MD simulations, and concentration-dependent SERS investigations of a bioactive trifluoromethyl derivative having human acetylcholinesterase and butyrylcholinesterase in silver colloids [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Mahmood, T.; Gamberini, M. C.; Rajendran Nair, D. S.
abstract

Context: Various concentrations of (E)-4-methoxy-N′-(2-(trifluoromethyl)benzylidene) benzohydrazide (EMT) adsorbed on colloidal silver nanoparticles were studied using SERS and results were compared to the normal Raman spectrum. DFT calculations were used to validate experimental findings. Theoretically, the structures of the EMT and EMT-Ag6 systems were optimized. The UV-Vis spectral analysis’s red shift and lower intensity behavior show that EMT has chemisorbed onto Ag nanoparticles. Charge transfer (CT) from Ag to EMT is highlighted by FMO analysis. The CT interaction in EMT and EMT-Ag6 was further verified by MEP and Mulliken charge analyses. The EMT was adsorbed on Ag nanoparticles with tilted orientation and orientation changes with colloidal concentration, according to SERS spectrum analysis. Docking EMT with 4PQE and 5DYW binding affinities are found to be −9.7 and −8.1 kcal/mol. MD simulations give the competence of 5DYW-EMT and 4PQE-EMT in their intended binding interactions and their ability to establish enduring associations with the protein of interest. Methods: DFT was used to optimize the molecular structures of EMT and EMT-Ag6 using B3LYP/6-311++G* (LANL2DZ basis set for Ag). A molecular dynamics simulation study was conducted on the 4PQE-EMT and 5DYW-EMT systems using the Desmond software for 100 ns.

2023 - The concentration dependent SERS studies of a bioactive 4-chlorobenzylidene derivative: Experimental and DFT investigations [Articolo su rivista]
Sheena Mary, Y.; Shyma Mary, Y.; Kratky, M.; Vinsova, J.; Gawad, J.; Gamberini, M. C.
abstract

In this work, the vibrational spectroscopy of the compound (E)-4-(tert-butyl)-Nˈ-(4-chlorobenzylidene)benzyhydrazide (TCB), which was studied in conjunction with theoretical calculations, is applied for Surface Enhanced Raman Scattering (SERS) studies. The assignments of the vibrational modes were completed with Density Functional Theory (DFT)/B3LYP/6-311++G*. The information gathered is utilized to determine the chemical and electrical characteristics in addition to wavenumber measurements. The TCB molecule's chemisorbed status on colloidal nanoparticles is confirmed by acquired red shift and decreased intensity behavior in the UV–VIS spectrum analysis. Additionally, the SERS spectra at varied concentrations and the chemisorption of the molecule with metal cluster were recorded and examined. Additionally, a silver cluster-based theoretical SERS model is put forth. The findings presented here will help in the construction of more dependable SERS sensors by thoroughly describing the concentration-dependent profile of analyte orientation.

2022 - Concentration dependent SERS study of a bioactive methylsulfonyl derivative [Articolo su rivista]
Al-Otaibi, J. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Gamberini, M. C.
abstract

Concentration dependent surface enhanced Raman scattering (SERS) studies of biologically active methylsulfonyl derivative (BMSP) are reported. Out of various concentrations, SERS at 10-3 M gives maximum enhancement. The experimental results are supported by theoretical investigations. BMSP exhibited selective micro molar activity against Staphylococcus aureus. The interaction of charge transfer between Ag and S atoms is confirmed by the enhanced bond length values. Reduction in ionization potential suggests that the BMSP-Ag6 system has stronger electron donating characteristics than BMSP. The electrophilicity index of the adsorbed system containing BMSP and silver cluster represent biological activity and the adsorption process is chemisorption. Presence of CH3 modes in the SERS spectrum suggest that the molecule adopts a tilted orientation, and that para-substituted phenyl ring is more slanted than poly-substituted phenyl ring. Presence of ring stretches, bending modes for all concentrations suggest that the BMSP molecule may tilt, resulting in an interaction with the metal surface and there is an orientation change for the molecule with respect to the metal surface as concentration changes.

2022 - Quantification of cortisol and its metabolites in human urine by LC-MSn: applications in clinical diagnosis and anti-doping control [Articolo su rivista]
Arioli, F.; Gamberini, M. C.; Pavlovic, R.; Di Cesare, F.; Draghi, S.; Bussei, G.; Mungiguerra, F.; Casati, A.; Fidani, M.
abstract

The objective of the current research was to develop a liquid chromatography-MSn (LC-MSn) methodology for the determination of free cortisol and its 15 endogenous metabolites (6β-hydroxycortisol, 20α-dihydrocortisol, 20α-dihydrocortisone, 20-β-dihydrocortisol, 20β-dihydrocortisone, prednisolone, cortisone, α-cortolone, β-cortolone, allotetrahydrocortisol, 5α-dihydrocortisol, tetrahydrocortisol, allotetrahydrocortisone, 5β-dihydrocortisol, tetrahydrocortisone) in human urine. Due to its optimal performance, a linear ion trap operating in ESI negative ion mode was chosen for the spectrometric analysis, performing MS3 and MS4 experiments. The method was validated for limit of detection (LOD) and limit of quantification (LOQ) (0.01 ng mL−1 and 0.05 ng mL−1, for all compounds, respectively), intra- and inter-day precision (CV = 1.4–9.2% and CV = 3.6–10.4%, respectively), intra- and inter-day accuracy (95–110%), extraction recovery (65–95%), linearity (R2 > 0.995), and matrix effect that was absent for all molecules. Additionally, for each compound, the percentage of glucuronated conjugates was estimated. The method was successfully applied to the urine (2 mL) of 50 healthy subjects (25 males, 25 females). It was also successfully employed on urine samples of two patients with Cushing syndrome and one with Addison’s disease. This analytical approach could be more appropriate than commonly used determination of urinary free cortisol collected in 24-h urine. The possibility of considering the differences and relationship between cortisol and its metabolites allows analytical problems related to quantitative analysis of cortisol alone to be overcome. Furthermore, the developed method has been demonstrated as efficient for antidoping control regarding the potential abuse of corticosteroids, which could interfere with the cortisol metabolism, due to negative feedback on the hypothalamus-hypophysis-adrenal axis. Lastly, this method was found to be suitable for the follow-up of prednisolone that was particularly important considering its pseudo-endogenous origin and correlation with cortisol metabolism. Graphical abstract: [Figure not available: see fulltext.]

2022 - Spectroscopic investigations, concentration dependent SERS, and molecular docking studies of a hydroxybenzylidene derivative [Articolo su rivista]
Kumar, V. S.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Baraldi, C.; Roxy, M. S.; Gamberini, M. C.
abstract

Spectroscopic analysis, density functional theory (DFT) studies and surface enhanced Raman scattering (SERS) of (E)-N’-(5-chloro-2-hydroxybenzylidene)-4-trifluoromethyl) benzohydrazide (CHTB) have been studied on different silver colloids in order to know the particular chemical species responsible for the spectra. Very significant shifts are observed for Raman and SERS wavenumbers. Observed changes in the υ-ring modes may be due to surface interaction of the π-electrons and the presence of this suggested that RingII is more tilted in both cases than RingI and the molecule assumes a tilted orientation for the concentration 10−3 M. Orientation changes are seen in concentration dependent SERS spectra. The molecular electrostatic potential has also been constructed to determine the electron rich and poor site of CHTB. The molecular docking studies indicate that the binding affinity and hydrogen bond interactions with the receptors may be supporting evidence for further studies in designing other pharmaceutical applications of CHTB. Communicated by Ramaswamy H. Sarma.

2021 - Concentration and solvent dependent SERS, DFT, MD simulations and molecular docking studies of a thioxothiazolidine derivative with antimicrobial properties [Articolo su rivista]
Mary, Y. S.; Mary, Y. S.; Armakovic, S.; Armakovic, S. J.; Kratky, M.; Vinsova, J.; Baraldi, C.; Gamberini, M. C.
abstract

Spectroscopic analysis, DFT studies and surface enhanced Raman scattering of antimicrobial bioactive (Z)-2-[5-(5-bromo-2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetic acid (BPTA) have been studied on different silver sols. Very large changes are observed for Raman and SERS bands. Observed variations in the ring modes may be due to surface π-electron interactions and presence of this indicated that molecule is inclined with respect to the metal surface. Changes in orientation are seen in SERS spectra depending on concentration. The molecular docking results show that binding affinity and interactions with the receptors may be supporting evidence for further studies in design further BPTA pharmaceutical applications. Reactivity properties are obtained from DFT and MD simulations. The quantum-mechanical level of theory has been applied to obtain information about the MEP and ALIE surfaces. These calculations give sensitivity of BPTA towards autoxidation mechanism. An influence of water has been studied computationally, via the MD simulations and RDF analysis. This level of theory was also used to identify possible excipient substance for this molecule.

2021 - Concentration dependent SERS, DFT and molecular docking studies of a ureido derivative with antitubercular properties [Articolo su rivista]
Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Baraldi, C.; Gamberini, M. C.
abstract

Spectroscopic analysis, density functional theory (DFT) studies and surface enhanced Raman scattering (SERS) of antimycobactetial 4-[3-(4-acetylphenyl)ureido]-2-hydroxybenzoic acid (AUHB) have been studied on different silver sols. For Raman and SERS wavenumbers, very large changes are observed. Observed variations in the modes of ring may be due to surface π-electron interactions and presence of this indicated that poly substituted ring is more inclined than para substituted phenyl ring and assumes a inclined position for concentration 10−3 M. Changes in orientation are seen in SERS spectra depending on concentration. In order to find electron-rich and poor sites of AUHB, molecular electrostatic potential was also constructed. The molecular docking results show that binding affinity and interactions with the receptor DprE1 may be supporting evidence for further studies in design further AUHB pharmaceutical applications. Based on antitubercular activity of 4-aminosalicylic acid (PAS) and urea derivatives we designed, synthesized and investigated mutual PAS-urea derivatives as potential antimycobacterial agents.

2021 - DFT, molecular docking and SERS (concentration and solvent dependant) investigations of a methylisoxazole derivative with potential antimicrobial activity [Articolo su rivista]
Sheena Mary, Y.; Shyma Mary, Y.; Kratky, M.; Vinsova, J.; Baraldi, C.; Gamberini, M. C.
abstract

Spectroscopic analysis, DFT studies and surface enhanced Raman scattering of antimicrobial bioactive 4-[(2‑hydroxy-3,5-diiodobenzylidene)amino]-N-(5-methylisoxazole-3-yl)benzenesulfonamide (HDMB) have been studied. Changes in intensity and enhancement variations are observed for Raman and SERS bands. Changes observed in the ring mode vibrations may be due to surface π-electron interactions which means molecule is orientated in a tilted position with respect to metal surface. Changes in orientation are seen in SERS spectra depending on concentration. The molecular docking results show that binding affinity and interactions with the receptors may be supporting evidence for further studies in design further HDMB pharmaceutical applications. Reactivity properties are obtained from DFT analysis.

2021 - DFT, SERS-concentration and solvent dependent and docking studies of a bioactive benzenesulfonamide derivative [Articolo su rivista]
Sheena Mary, Y.; Shyma Mary, Y.; Kratky, M.; Vinsova, J.; Baraldi, C.; Gamberini, M. C.
abstract

Spectroscopic analysis, DFT studies and surface enhanced Raman scattering (SERS) of antimicrobial bioactive 4-[(5-tert-butyl)2-hydroxybenzylidene]amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (THPB) have been studied on different silver sols. Intensity and hence enhancement variations are observed for Raman and SERS bands. Observed changes in the ring modes may be due to surface π-electron interactions and presence of this indicated that molecule is inclined with respect to the metal surface. Changes in orientation are seen in SERS spectra depending on concentration. The molecular docking results show that binding affinity and interactions with the receptors may be supporting evidence for further studies in design further THPB pharmaceutical applications. Reactivity properties are obtained from DFT analysis.

2021 - Spectroscopic investigations, concentration dependent SERS, and molecular docking studies of a benzoic acid derivative [Articolo su rivista]
Gamberini, M. C.; Mary, Y. S.; Mary, Y. S.; Kratky, M.; Vinsova, J.; Baraldi, C.
abstract

Spectroscopic analysis, density functional theory (DFT) studies and surface enhanced Raman scattering of 4-((3-bromo-5-chloro-2-hydroxybenzylidene)amino)benzoic acid (BCHB) have been studied on different silver colloids concentrations in order to know the particular chemical species responsible for the spectra. For Raman and surface enhanced Raman scattering (SERS) wavenumbers, changes are observed. Observed variations in the modes of ring may be due to interaction of the π-electrons and presence of this indicated that RingII is more inclined than RingI and the BCHB assumes inclined orientation for concentration 10-3 M. Changes in orientation are seen in SERS spectra depending on concentration. In order to determine the electron-rich and poor sites of BCHB, the molecular electrostatic potential was also constructed. The molecular docking studies show that the bindings and interactions with the receptors may be supporting evidence for further studies in design further BCHB pharmaceutical applications.

2020 - DFT and MD simulations and molecular docking of co-crystals of octafluoro-1,4-diiodobutane with phenazine and acridine [Articolo su rivista]
Mary, Y. S.; Mary, Y. S.; Chandramohan, V.; Kumar, N.; Van Alsenoy, C.; Gamberini, M. C.
abstract

Co-crystals are of immense applications in crystal engineering and pharmaceutical chemistry. Co-crystals of octafluoro-1,4-diiodobutane with phenazine (PHEF) and acridine (ACRF) are investigated by DFT and MD simulations. It was characterized using quantum mechanical calculations for geometry and spectroscopic properties. Frontier orbital energies are used to predict the energy properties and model the possible charge transfer between the co-crystal constituents. The frontier molecular orbital analysis indicates chemical reactivity and bioactivity of the co-crystals. The MEP surface reveals the various reactive surfaces in the co-crystal system, which is very important in deciding various biological activities. The UV-Vis spectra show the possible electronic transitions of the molecules. Simulated electronic spectra using the TDDFT method with CAM-B3LYP functional was used to investigate the suitability of the co-crystals to be used in DSSC. Moreover, docking analysis proves that co-crystals can act as potential inhibitors and paves the way for developing effective drugs. Further MD simulations could identify the molecules binding energy and stability.

2020 - Investigating Novel Syntheses of a Series of Unique Hybrid PLGA-Chitosan Polymers for Potential Therapeutic Delivery Applications [Articolo su rivista]
Duskey, Jason Thomas; Baraldi, Cecilia; Gamberini, Maria Cristina; Ottonelli, Ilaria; Da Ros, Federica; Tosi, Giovanni; Forni, Flavio; Vandelli, Maria Angela; Ruozi, Barbara
abstract

Discovering new materials to aid in the therapeutic delivery of drugs is in high demand. PLGA, a FDA approved polymer, is well known in the literature to form films or nanoparticles that can load, protect, and deliver drug molecules; however, its incompatibility with certain drugs (due to hydrophilicity or charge repulsion interactions) limits its use. Combining PLGA or other polymers such as polycaprolactone with other safe and positively-charged molecules, such as chitosan, has been sought after to make hybrid systems that are more flexible in terms of loading ability, but often the reactions for polymer coupling use harsh conditions, films, unpurified products, or create a single unoptimized product. In this work, we aimed to investigate possible innovative improvements regarding two synthetic procedures. Two methods were attempted and analytically compared using nuclear magnetic resonance (NMR), fourier-transform infrared spectroscopy (FT-IR), and dynamic scanning calorimetry (DSC) to furnish pure, homogenous, and tunable PLGA-chitosan hybrid polymers. These were fully characterized by analytical methods. A series of hybrids was produced that could be used to increase the suitability of PLGA with previously non-compatible drug molecules

2020 - Phoenicians Preferred Red Pigments: Chemical Compositions of Make-Up Powders Found in Archaeological Sites from Sicily [Articolo su rivista]
Baraldi, C.; Toti, M. P.; Van Elslande, E.; Walter, P.; Gamberini, M. C.
abstract

Little is known concerning Phoenician and Punic cosmetics, and pertinent studies and analyses on archaeological finds are particularly scanty. The present study has taken into account 22 archaeological red and pink Punic make-up samples collected in several Sicilian museums. The samples were analyzed by infrared spectroscopy, Raman microscopy, and surface-enhanced Raman spectroscopy (SERS). The analyses revealed an interesting and unusual variability in the use of raw materials, ranging from the mineral to the organic world. Not only traditional dye-based pigments were identified, but also rare ones never reported previously for this use. We show also an occurrence unusual in antiquity of a lead chromate block presumably intended to be ground just before its use in cosmetics.

2020 - Repositioning natural products in drug discovery [Articolo su rivista]
Rastelli, G.; Pellati, F.; Pinzi, L.; Gamberini, M. C.
abstract

No abstract available

2019 - Characterisation of fibrous ferrierite in the rhyolitic tuffs at Lovelock, Nevada, USA [Articolo su rivista]
Zoboli, A.; Di Giuseppe, D.; Baraldi, C.; Gamberini, M. C.; Malferrari, D.; Urso, G.; Lassinantti Gualtieri, M.; Bailey, M.; Gualtieri, A. F.
abstract

Ferrierite is the name for a series of zeolite-group of minerals which includes three species with the same ferrierite framework (FER) crystal structure but different extra-framework cations. Recent studies have shown that ferrierite can exhibit a fibrous-asbestiform crystal habit and may possess the same properties as carcinogenic fibrous erionite. Characterisation of the ferrierite in and around a mine location will be helpful in assessing the potential for toxic outcomes of exposure in the mine and any local population.The zeolite-rich tuff deposit of Lovelock, Nevada, USA is the largest occurrence of diagenetic ferrierite-Mg. A previous survey reported that ferrierite hosted in these rocks displays a fibrous morphology. However, these observations concerned a limited number of samples and until now there has been little evidence of widespread occurrence of fibrous ferrierite in the Lovelock deposit.The main goal of this study was to perform a mineralogical and morphometric characterisation of the tuff deposit at Lovelock and evaluate the distribution of fibrous ferrierite in the outcrop. For this purpose, a multi-analytical approach including powder X-ray diffraction, scanning and transmission microscopies, micro-Raman spectroscopy, thermal analyses, and surface-area determination was applied.The results prove fibrous ferrierite is widespread and intermixed with mordenite and orthoclase, although there are variations in the spatial distribution in the bedrock. The crystal habit of the ferrierite ranges from prismatic to asbestiform (elongated, thin and slightly flexible) and fibres are aggregated in bundles. According to the WHO counting criteria, most of the ferrierite fibres can be classified as breathable. While waiting for confirmatory in vitro and in vivo tests to assess the actual toxicity/pathogenicity potential of this mineral fibre, it is recommended to adopt a precautionary approach for mining operations in this area to reduce the risk of exposure.

2019 - Investigation of the pigment use in the Tomb of the Reliefs and other tombs in the Etruscan Banditaccia Necropolis [Articolo su rivista]
Alfeld, Matthias; Baraldi, Cecilia; Gamberini, Maria Cristina; Walter, Philippe
abstract

The pigment use in the Tomb of the Reliefs (4th century BC) and four other tombs (7th-4th century BC) in the Etruscan Banditaccia Necropolis near Cerveteri, Italy, has been investigated. We made use of XRF and Raman spot analysis, XRF imaging, IR luminescence and photography supported by Dstretch contrast enhancement. We identified the use of haematite, goethite, calcite, carbon black, manganese oxide, Tyrian purple and Egyptian blue, with the last three only found under the central burial place of the Tomb of the Reliefs. The tuff in which these tombs were cut proved to be a significant challenge for XRF analysis as the signals of Ca, Mn and Fe vary strongly due to the heterogeneity of the stone, so that it is difficult to distinguish between signals from the tuff and the pigments. Finally, we show that lightweight instruments transported in check-in luggage may not answer all questions on pigment use, but do provide additional insights.

2018 - Antibacterial and Antifungal Efficacy of Partially Partitioned Fractions of Spondias mombin (Linn) Extracts (Root, Leaf and Stem Bark) against Clinical and Environmental Isolates [Articolo su rivista]
Oludare Temitope, Osuntokun; Idowu, To; Gamberini, Maria Cristina
abstract

The purpose this research work is to determine the antibacterial and antifungal assay of partitioned fractions of S. mombin (Linn) extracts against clinical and environmental isolates. The root, leaf and stem-bark of S. mombin were harvested and air-dried. The dried S. mombin was milled into powdered form using manual grinder. Powdered S. mombin (1 kg) each of the different S. mombin parts was extracted with 3 L of 70% (v/v) ethanol, ethyl acetate and distilled water for 72 h at room temperature. The SMRE and SMREA were used to code for root part; SMLE and SMLEA for the leaf part; and SMSBE and SMSBEA for the stem-bark part, each was fractionated on column chromatography with silica as the stationary phase using n-hexane, ethyl acetate and ethanol as the eluting solvent to obtain n-hexane, ethyl acetate and ethanol fractions. Antimicrobial and antifungal screened was observed using agar well diffusion test. The result obtained showed that in partially purified ethyl acetate leaf extracts, Fraction (F1 SMLEAH) showed significant inhibitory effect (p ≤ 0.05) on all the test bacteria, except Klebsiella pneumoniae and Salmonella typhi at concentrations of 20.0-2.5 mg/ml, Fraction (F2 SMLEAEA) was not effective against Salmonella cholleraesuis, B. substilis, Citrobacter koseri and Salmonella typhi. Fraction (F3 SMLEAE) showed little or no inhibitory effect on most of the bacteria at all the concentration used. It can be deduced that in partially purified ethanolic leaf extracts, Fraction (F1 SMLEH) showed inhibitory effect on Burkholderia cepacia. All the organisms were not susceptible to all the fractions except F1 which had diameter of zones of growth inhibition ranging between 4.0-1.0 mm at 5 mg/ml-0.625 mg/ml on Mycobacterium abscessus. Partially purified ethanolic stem bark extracts, antifungal activity of the partially purified ethanolic extracts of S. mombin, Fractions (F1 SMLEH, F2 SMLEEA) and F3 SMLEE), significant antifungal activity (p ≤ 0.05) was observed at 20.0 mg/ml with most test fungi. Trichoderma horizionum was not susceptible to all the three fractions, while Aspergillus niger and Syncephala strumracemosum were susceptible to only fraction (F2 SMLEEA). Fractions (F1 SMSBEH, F2 SMSBEEA), F3 SMSBEE) on the test as the eluting solvent. Significant inhibitory effect (p ≤ 0.05) was observed in all the fractions at 20 mg/ml against most of the test bacteria. While, zones of growth inhibition of the various fractions varied with the test bacteria with the highest diameter zone of 8.0 mm recorded in fraction F1 against Salmonella typhi. Fractions (F2 SMSBEEA and F3 SMSBEE) possessed significant inhibitory effect (p ≤ 0.05) at 20.0-5.0 mg/ml on the test fungi, except Candida kruise and Rhizopus stonifer. The plant part by solvent interactive effect was significant (p<0.05), suggesting that the MICs and MBCs of test bacteria were observed at 0.3125 and 0.1562 mg/ml and MICs and MFCs test fungal were observed at 0.3125 and 0.1562 mg/ml respectively, The various plants differ significantly according to extraction solvent, These findings demonstrate the possible effectiveness of the S. mombin plant, especially its stem bark extracts, in treating microbial infections.

2018 - Bio-guided Isolation, Purification and Chemical Characterization of Epigallocatechin; Epicatechin, Stigmasterol, Phytosterol from of Ethyl Acetate Stem Bark Fraction of Spondias mombin (Linn.) [Articolo su rivista]
Osuntokun, Oludare Temitope; Idowu, T O; Gamberini, Maria Cristina
abstract

Spondias mombin (Linn.) is a widely cultivated edible plant used in folkloric medicine for the treatment of severe infection and health disorders. This research work was carried out to isolation, purification and chemical characterization the bioactive constituents of the ethyl acetate stem bark fraction of Spondias mombin (Linn.), a medicinally important plant of the Anacardiaceae family. This study revealed the presence of flavonoid and steroids, which have been found to be important hormone regulators which possess antimicrobial, anti-inflammatory, antioxidant properties. The chemical investigation resulted in the isolation of (C15H14O6.) 5, 7, 3', 4'-pentahydroxy flavanol (Epicatechin), (C15H14O7.) Epigallocatechin (C29H48O.), Stigmasterol phytosterol. It is here reported isolated from Spondias mombin for the first time, this makes the Spondias mombin very important medicinal plant in Nigeria and west Africa. EGC and EC arts as a strong inhibitor of HIV replication in cultured peripheral blood cells and inhibition of HIV-1 reverse transcriptase in vitro. EGC binds directly to CD4 molecules with consequent inhibition of Gp 120 binding and inactivate viruses in-vitro by deformation of phospholipids. Stigmasterol phytosterol have been shown to lower/reduce blood cholesterol and this lowering may reduce the risk of coronary heart disease. The structure was elucidated using two dimensional NMR spectroscopy, NMR (1H, 13 C) spectroscopy in combination with Infra-red (IR) and Mass spectrometer (MS) spectra data.

2018 - EVALUATION OF QUANTITATIVE ELEMENTAL COMPOSITIONS AND ANTIOXIDANT POTENTIALS OF SPONDIAS MOMBIN EXTRACTS (LINN), A PRECURSOR AGAINST INFECTIOUS DISEASES [Articolo su rivista]
Oludare Temitope, Osuntokun; Baraldi, Cecilia; Gamberini, Maria Cristina
abstract

The purpose of this research work is to investigate the elemental composition and antioxidant potentials of Spondias mombin (leaf, root and stem bark) at concentration of 10, 20 and 5mg/ml. using different conventional laboratory methods, also to determine the antioxidant potentials of Spondias mombin. The element present are Sodium (Na), Calcium (Ca), Magnesium (Mg), Zinc (Zn), Iron (Fe), Lead (Pb), Copper(Cu), Manganese (Mn), Potasium (K) and Phosphorus (P).it was observed that all elements were present at appreciable quantity. It was observed that the highest and lowest quantity were found in Zinc (20.34) and Cu (1.22) for the leaf extract, Potasium (24.98) and (2.14) for stem bark, Calcium (29.35) and Pb (2.91) for the root extract. Pb has minimal quantity in all parts of Spondias mombin extract. P value< 0.0001, Significantly different standard deviations. The antioxidant composition are FRAP, DPPH, Fe2+,ABTS, H2O2 and superoxide. The percentage composition of FRAP, DPPH, Fe2+,ABTS, SO and H2O2, superoxide phenol and flavonoid were elucidated, it was observed that ABTS has the highest composition in the stem bark and superoxide (SO) has the lowest content in the aqueous root extract of Spondias mombin.it can be deduced that Spondias mombin is a very important medicinal plant which should not go into extinction, its uses, efficacy and importance should not be over emphasis for the fact that it is rich in both elemental and antioxidants potential, therefore, its cultivation and day to day usage of Spondias mombin should be therefore be encouraged.

2018 - Investigation of the pigment use in the Tomba dei Rilievi and other tombs in the Etruscan Banditaccia Necropolis. PIGMENTGEBRAUCH IM GRAB DER RELIEFS UND ANDEREN GRÄBERN DER ETRUSKISCHEN BANDITACCIA NEKROPOLE [Abstract in Atti di Convegno]
Alfeld, M.; Baraldi, C.; Gamberini, M. C.; Walter, P.
abstract

The use of pigments in antiquity, by Romans, Greeks and Egyptians, has been subject to a number of scientific studies. That of contemporary cultures, such as the Etruscans, have been described only in a small number of publications. We investigated the pigment use in five tombs of the Banditaccia Necropolis, near Cerveteri in central Italy: Tomba dei Rilievi (4th century BC), Tomba Mengarelli (7th century BC), Tumolo Policromo (4th century BC), Tomba delle Onde Marine (4th-3rd century BC) and an yet untitled recently excavated tomb (4th century BC (preliminary)). All were carved from the soft tuff bedrock. A special focus was put on the Tomba dei Rilievi (Tomb of the Reliefs. It is for up to 45 bodies with 13 loculus (burial niches) the largest of the investigated tombs and the only one decorated with painted stucco reliefs.

2017 - Cyclodextrin-based nanosponges for the targeted delivery of the anti-restenotic agent DB103: A novel opportunity for the local therapy of vessels wall subjected to percutaneous intervention [Articolo su rivista]
Coviello, Vito; Sartini, Stefania; Quattrini, Luca; Baraldi, Cecilia; Gamberini, Maria Cristina; La Motta, Concettina
abstract

Nano-sized colloidal carriers represent innovative drug delivery systems, as they allow a targeted and prolonged release of poorly water-soluble drugs, improving their bioavailability and modifying their pharmacokinetic parameters. In this work we describe cyclodextrin-based nanosponges, obtained through polimerization of β-cyclodextrin with diphenyl carbonate as the cross-linking agent, loaded with a novel multi-effective heterocyclic compound, DB103, able to regulate key cellular events involved in the remodelling of vessels wall. Fabrication and drug-loading procedures, as well as physical-chemical characterization and drug-release profile of the novel colloidal system are reported. Results achieved demonstrate the ability of nanosponges to enclose efficiently the target drug and release it slowly and continuously, thus suggesting the exploitability of the novel system for the local therapy of vessels wall subjected to percutaneous intervention.

2015 - A Raman investigation of ancient Colliria [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Pietro; Deviese, Tibaut; Baraldi, Cecilia; Tinti, Anna
abstract

In January 1884, in Atestino territory (PD-Este, northern of Italy), was discovered in Morlungo district, where is present the southern necropolis aged in pre-Roman and Roman period (Ateste), a tomb dated to the second half of the I sec d.C (Tomb civic IX) whose furnishings exhibition being a doctor-surgeon-apothecary (Simonetta Bonomi - "Medici in Este romana. 3. La tomba del medico” Aquileia nostra”, 55, 1984, p. 78-108.). Among the various finds is present a bronze box (capsula), several medicinal preparations in the solid state form were also found inside. They were collyria (from the greek = κολλύριον small pills solid elongated), not necessarily used in ophthalmologic practice (Celse V 28 G; Hippocrates, Mul. I 51). In bibliography, rare are the articles published regarding the discovery of these findings, but even more rare are articles on collyria chemical analysis. In this study, 17 collyria / fragments of collyria exposed in Este National Museum and other six fragments from the tomb of a physician and stored in warehouses, using non-invasive and non-destructive techniques were analyzed in-situ. Raman microscopy, FT-IR spectroscopy and X-ray Fluorescence techniques were chosen for the analysis using portable equipments. In this study we report the preliminary composition data of these remains. The analyzes performed, chemical charaterized several components already identified to the specific literature on these findings: calcite, indrocerussite, litharge, cuprite, tenorite, azzurite, realgar, pararealgar, orpiment. Moreover in this work some components, not analyzed in collyria forms yet, were also identified: pyrite and alumina. In the next future could be interesting study the remains with micro-invasive techniques, this in order to better investigate the organic component present and complete the knowledge of these rare and interesting archaeological finds, on which many questions still remain open and unanswered.

2015 - An approach to the identification of ambers from different archaeological sites (Part 2) [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Pietro; Deviese, Thibaut; Baraldi, Cecilia; Tinti, Anna; Pacciarelli, Marco
abstract

Chemical studies on resinous materials in archaeological remains are generally aimed at identifying the origin of the materials present, at studying the production and manufacturing techniques, and at improving techniques for their conservation and restoration. This is particularly true for ambers remains. This paper presents some significant results for a systematic characterisation of the chemical composition of ambers of different provenance. The study has been carried out by using spectroscopic techniques, Raman and FT-IR with the aim ofcreating or extend FT-IR, Raman, FT-Raman libraries of geological and archaeological ambers. The data could be used as references in provenance studies of archaeological amber finds. Based on this knowledge, archaeological resinous materials, recoveredin a various sites, dating back from the VI century BC to the second centuryAD, have been analysed and the relevant results discussed. Comparisons of analytical detailed results enable the recent and ancient history of the materials to be traced. It is shown that provenance can be ascertained, in addition to the classical Beck’s method of FT-IR spectra (based on the special shape of the infrared spectrum in the 1500- 1000 cm-1 region), also by using Raman spectra and XRF data. The alteration of Museum preserved samples are taken into consideration for a description of the rapid changes of the spectra recorded.

2015 - An approach to the identification of ambers from different archaeological sites (P1) [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Pietro; Deviese, Thibaut; Baraldi, Cecilia; Tinti, Anna; Pacciarelli, Marco
abstract

Chemical studies on resinous materials in archaeological remains are generally aimed at identifying the origin of the materials present, at studying the production and manufacturing techniques, and at improving techniques for their conservation and restoration. This is particularly true for ambers remains. This paper presents some significant results for a systematic characterisation of the chemical composition of ambers of different provenance. The study has been carried out by using spectroscopic techniques, Raman and FT-IR with the aim of creating or extend FT-IR, Raman, FT-Raman libraries of geological and archaeological ambers. The data could be used as references in provenance studies of archaeological amber finds. Based on this knowledge, archaeological resinous materials, recovered in a various sites, dating back from the ninth century BC to the second century AD, have been analysed and the relevant results discussed. Comparisons of analytical detailed results enable the recent and ancient history of the materials to be traced. It is shown that provenance can be ascertained, in addition to the classical Beck’s method of FT-IR spectra (based on the special shape of the infrared spectrum in the 1500- 1000 cm-1 region), also by using Raman spectra and XRF data. The alteration of Museum preserved samples are taken into consideration for a description of the rapid changes of the spectra recorded.

2015 - Experimental and theoretical SERS spectra: the case of Ampicillin [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Cecilia; Tinti, Anna; Ottani, Stefano
abstract

Surface enhanced Raman scattering (SERS) spectroscopy is a powerful tool for the study of structure, symmetry and orientation of molecules adsorbed on metal surfaces. It is a highly sensitive technique useful to detect species present at a trace level concentrations and to gather information concerning metal-adsorbate interactions. The study of drug molecules adsorbed on metallic substrate is becoming critical in future applications like drug delivery, bio-active surfaces, bio and chemical nano-sensors, etc. Moreover, the study of interaction of drug molecules with metals in solution can provide useful information on the biological activity of such molecules. Ampicillin or 6-[D(-)α-aminophenylacetamido] penicillanic acid is a well-known penicillin class antibiotic with betalactamic structure, which is getting new attention for drug resistance problems. In the past we have studied the existing polymorphic and solvate forms by different analytical techniques and by comparing experimental and theoretical data (C. Baraldi, A. Tinti, S. Ottani, M.C. Gamberini, J. Pharm. Biomed. Analysis 100 (2014) 329-340). In this work, ampicillin SERS spectrum at 10-4 M concentration was studied and discussed. The adsorption geometry of the ampicillin molecule on colloidal silver surface was deduced from the SERS selection rules. In addition, Density Functional Theory (DFT) computations on a couple of Ag atoms or AgCl interacting with different ampicillin groups were performed, to obtain theoretical spectra for the interpretation of the SERS experiments. Interactions with Ag colloidal surfaces have been approximated by placing an Ag2 cluster in positions close to electron donor groups of the ampicillin molecule (i.e. the carboxylic group (zwitterion), the sulfur atom (zwitterion), the aromatic ring (zwitterion), the -NH2 group (anion) and the tautomeric -COOH/-NH2 group). For the ampicillin the aug-cc-pVDZ (aug-cc-pV(D+d)Z for Sulfur atom) basis set was used, whereas the Ag atoms were modeled by the lanl2dz basis set. Calculations were performed with an implicit solvent model (CPCM). Computations led to stable optimized geometries with the exception of -NH3+/Ag2 (viz. the ampicillin in zwitterionic form) since such a group has a marked electrophilic character. Interpretation of the theoretical frequency spectra was performed by the Potential Energy Distribution (PED) analysis of the fundamental vibrations modes. According to the theoretical results, SERS experiments demonstrated that ampicillin was adsorbed in tilted orientation on silver colloid; the interaction mainly takes place by means of the benzenic ring and the aminic group.

2015 - The ampicillin experimental and theoretical SERS spectra [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Cecilia; Tinti, Anna; Ottani, Stefano
abstract

Surface enhanced Raman scattering (SERS) spectroscopy is a powerful tool for the study of structure, symmetry and orientation of molecules adsorbed on metal surfaces. It is a highly sensitive technique useful to detect species present at a trace level concentrations and to gather information concerning metal–adsorbate interactions. The study of drug molecules adsorbed on metallic substrate is becoming critical in future applications like drug delivery, bio-active surfaces, bio and chemical nano-sensors, etc. Moreover, the study of interaction of drug molecules with metals in solution can provide useful information on the biological activity of such molecules. Ampicillin or 6-[D(-)α-aminophenylacetamido] penicillanic acid is a wellknown penicillin class antibiotic with betalactamic structure, which is getting new attention for drug resistance problems. In the past we have studied the existing polymorphic and solvate forms by different analytical techniques and by comparing experimental and theoretical data [1]. In this work, ampicillin SERS spectrum at 10-4 M concentration was studied and discussed. The adsorption geometry of the ampicillin molecule on colloidal silver surface was deduced from the SERS selection rules. In addition, Density Functional Theory (DFT) computations on a couple of Ag atoms or AgCl interacting with different ampicillin groups were performed, to obtain theoretical spectra for the interpretation of the SERS experiments. Interactions with Ag colloidal surfaces have been approximated by placing an Ag2 cluster in positions close to electron donor groups of the ampicillin molecule (i.e. the carboxylic group (zwitterion), the sulfur atom (zwitterion), the aromatic ring (zwitterion), the –NH2 group (anion) and the tautomeric –COOH/–NH2 group). For the ampicillin the aug-cc-pVDZ (aug-cc-pV(D+d)Z for Sulfur atom) basis set was used, whereas the Ag atoms were modeled by the lanl2dz basis set. Calculations were performed with an implicit solvent model (CPCM). Computations led to stable optimized geometries with the exception of –NH3+/Ag2 (viz. the ampicillin in zwitterionic form) since such a group has a marked electrophilic character. Interpretation of the theoretical frequency spectra was performed by the Potential Energy Distribution (PED) analysis of the fundamental vibrations modes. According to the theoretical results, SERS experiments demonstrated that ampicillin was adsorbed in tilted orientation on silver colloid; the interaction mainly takes place by means of the benzenic ring and the aminic group.

2014 - A study of some illuminated Armenian manuscripts [Abstract in Atti di Convegno]
Keheyan, Yeghis; Baraldi, Pietro; Zannini, Paolo; Eliazan, Gayane; Baraldi, Cecilia; Gamberini, Maria Cristina; Nunziante, Stella
abstract

Due to its early Christianization, Armenia has preserved a huge patrimony of religious figures in paintings, statues, icons and illuminated codices. Most of the latter are still conserved in Matenadaran Library in Yerevan and their chronology is widely represented from the Middle Ages to XIX century. Armenian manuscripts embrace also various humanities, such as history, philosophy, law, medicine and mathematics. A rich historiographic literature is also present. Therefore it was attractive to carry out an attempt to discover materials and techniques used in the past to prepare the manuscripts and to assemble the codices. Inks and gilding were also considered. Specific materials of Armenian culture will be emphasized. The samples were taken by some of us at the Matenadaran Library of Yerevan (Armenia) and some additional materials, such as Armenian bole and cochineal powder, were found in Yerevan too. The samples were taken with a lancet on deteriorated portions of some papers and parchments pertaining to Armenian codices. Only small fragments were used, since the spectroscopic techniques used need amount down to some micrograms. This is due to their high spatial resolution, enabling also the overlapping layers of pigments and preparation to be studied and their molecular identity to be ascertained in a non-destructive non –invasive way: the same samples could be subjected to other analyses with other techniques. The use of so small samples enabled the use of high performance instrumentation in the Centre of Great Instruments in Modena (CIGS) and to carry out additional experiments with silver nano-particles for Sers technique (surface enhanced Raman spectroscopy). Fourier-Transform infrared (FTIR) spectra were recorded using an Alpha FT-IR spectrometer (Bruker) equipped with the Diffuse Reflection Infrared Fourier Transform ( DRIFT) module in the spectral range 7500 – 375 cm-1 at a resolution of 2 cm-1 cumulating at least 200 scans. The use of SEM-EDX technique was important for characterization of papers and inks. Py/GS/MS was fundamental for organic binding media characterization. The methods of study were the application of atomic (XRF X-ray fluorescence spectroscopy), molecular (FT-IR and microRaman), SEM-EDX and pyrolisis GS/MS spectroscopic techniques to the samples in such a way to obtain the information useful for the understanding of the materials and art techniques applied. Particularly, the analysis of the different inks used in different times and the decoration with gilding on bole with a proper binder was taken into consideration. Experimental Results. Many materials were seen to be used through centuries in Armenian illumination. As already pointed out by Orna and co-workers [1, 2] many materials were identified and the execution techniques were clarified. According to recent investigation [3] other results on new materials and specific products coming from the territory have appeared based on Raman microscopy. A rich polychromy was often present and rare materials are shown to have been employed, such as the green antlerite, a basic copper sulfate mineral present in Caucasus and South of Iran. Lazurite, vermilion, azurite, orpiment, white lead, red lead, indigo, litharge, massicot, carbon were identified. Gilding was applied on an assisa. The Armenian bole is shown to be composed of white Kaolinite and Hematite. Forthcoming information is the application of Raman Sers technique for the identification of the materials and techniques used in Armenian illumination through times. The Armenian Cochineal (from Porphyrophora hamelii Brandt) is composed of carminic acid, that is highly fluorescent in Raman microscopy, unless Sers is used on a sample. With the application of simple atomic and molecular spectroscopy techniques available in many laboratories it was shown to be possible to obtain fundamental information on the specificity of Armenian illuminati

2014 - Characterization of polymorphic ampicillin forms [Articolo su rivista]
Baraldi, Cecilia; Tinti, A; Ottani, S; Gamberini, Maria Cristina
abstract

In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a β-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred.

2013 - Experimental and theoretical study of polymorphic and solvate ampicillin forms [Abstract in Atti di Convegno]
Baraldi, Cecilia; L., Galavotti; A., Tinti; S., Ottani; Gamberini, Maria Cristina
abstract

In literature, many active pharmaceutical ingredients (APIs) are known to crystallize in different crystalline packings (polymorphs) or with solvent molecules as an integral part of their structures (pseudopolymorphs). In a pharmaceutical dosage form, the active ingredient solid-state phase identity or conversion could dramatically alter the final pharmaceutical properties. In particular, the solid state administrated drug can influence important properties like bioavailability. In this study four α- aminobenzylpenicillin forms were crystallized and the molecular vibrations of the various ampicillin forms were investigated by ATR/FT-IR, micro-Raman and SERS (surface enhanced Raman spectroscopy) spectroscopies (firstly reported). The HSRM (hot stage Raman microscopy) was also able to follow the transition from the trihydrate ampicillin to the amorphous monohydrate. The same technique allowed of controlling the solid-solid convertion from trihydrate to anhydrous forms. DSC, TGA, XRPD data were also afforded. For the first time, the Raman spectra of the four ampicillin forms are reported. Finally, for assisting experimental assignment bands quantum mechanical calculations were also performed and the density functional theory (DFT) predictions were used.

2013 - Experimental and theoretical study of polymorphic and solvate ampicillin forms [Abstract in Atti di Convegno]
Baraldi, Cecilia; L., Galavotti; A., Tinti; S., Ottani; Gamberini, Maria Cristina
abstract

In literature, many active pharmaceutical ingredients (APIs) are known to crystallize in different crystalline packings (polymorphs) or with solvent molecules as an integral part of their structures (pseudopolymorphs). In a pharmaceutical dosage form, the active ingredient solid-state phase identity or conversion could dramatically alter the final pharmaceutical properties. In particular, the solid state administrated drug can influence important properties like bioavailability. In this study four α-aminobenzylpenicillin [1-3] forms were crystallized [4,5] and the molecular vibrations of the various ampicillin forms were investigated by ATR/FT-IR [2,3], micro-Raman and SERS (surface enhanced Raman spectroscopy) [4] spectroscopies (firstly reported). The HSRM (hot stage Raman microscopy) was also able to follow the transition from the trihydrate ampicillin to the amorphous monohydrate. DSC, TGA, XRPD data were also afforded [1,4,5]. For the first time, the Raman spectra of the four ampicillin forms are reported. Finally, for assisting experimental assignment bands quantum mechanical calculations were also performed and the density functional theory (DFT) predictions were used [6,7]. References: [1] E. Shefter et al., J. Pharm. Sci. 62/5 (1973) 791. [2] M. N. J. James et al. Nature 220 (1968), 168. [3] E. Ivashkiv, In: Analytical Profiles of Drug Substances, vol. 2., (1973) Academic Press, New York, K. Florey, (Ed.). [4] K. W. B. Austin et al., Nature 208 (1965) 999. [5] Parker et al., 1976, USP 3933796. [6] A. D. Becke, J. Chem. Phys. 98 (1993) 5648–5652. [7] W. T. Yang, R. G. Parr, Phys. Rev. B 37 (1988) 785–789.

2013 - IR, Raman and SERS spectra of propantheline bromide [Articolo su rivista]
Baraldi, Cecilia; Freguglia, Giada; A., Tinti; M., Sparta; A. N., Alexandrova; Gamberini, Maria Cristina
abstract

The two known propantheline bromide polymorphs (form I and form II) were studied and characterized by a multianalytical approach. In the present work, the identification of propantheline bromide polymorphic forms through vibrational IR spectroscopies are presented and for the first time Raman microscopy and hot stage Raman microscopy (HSRM) studies are reported. Finally, quantum mechanical calculations were performed. For assisting the assignment of the experimental picks, the two IR spectra of the most and least stable representatives of a set of 56 conformers are calculated and studied. DSC thermograms data, are also reported. The surface enhanced Raman scattering (SERS) spectrum was also recorded in a silver colloid; it could be inferred that propantheline bromide is adsorbed on silver colloid through the oxygen atom with the molecular plane perpendicular to the metal surface.

2013 - Phoenicians preferred red pigments: micro-Raman investigation on some cosmetics found in Sicily archaeological sites [Abstract in Atti di Convegno]
Baraldi, Cecilia; Giada, Freguglia; Elsa Van, Elslande; Pamela, Toti; Baraldi, Pietro; Gamberini, Maria Cristina; Claudia, Pelosi
abstract

This research was undertaken in the aim of identifying and getting deeper knoowledge into materials and pigments used in cosmestics concerning the contest of the phoenician settlements in Sicilian territory. In fact, about the typologies of cosmetics in use among the Phoenicians, little is known. On this subject, generally references come from bibliographic latin sources: in antiquity, women preferred to paint white their face, red lips and cheeks, yellowish eyes and black to sorround their look (Pliny the Elder, Naturalis Historia; Ovidius, De medicamine faciei feminae). An interesting aspect of this research is that just one paper is known on Punic cosmetics.[1] In the Museo Archeologico Regionale “Antonino Salinas” (Palermo, Sicily) an important collection of unguentaries coming from the town of Selinunte is preserved. Some of them, finely crafted, come from the sanctuary of Demetra Malophoros, some unguentaries come from the acropolis and some more from the necropolis (dating from the 6th to the 5th century b. C). The sacred area, excavated by Cavallari (1818) and Salinas (1903-1905), have provided a great amount of archaeological materials. In the area where once the acropolis rose, the remains show a mixed village, Phoenician and Greek. In this study, the findings from Salinas were considered, as well as some others from the Museum Conte Agostino Pepoli (Trapani), from the Museum Baglio Anselmi (Marsala) and from the museum of Mozia. The number of glass and fictile unguentaries, pyxis and alabastra examined were large: 142 items from Salinas, 210 from Mozia, 14 from Pepoli and 117 from Baglio Anselmi. This research has completed the one carried out on 210 samples from the Museum of Whitaker Foundation from Mozia, a merely phoenician –punic settlement.[2,3] The samples were analyzed by spectroscopic techniques. The IR spectra were acquired with a spectrophotometer VERTEX 70 (Bruker) FT-IR, equipped with a detector deuterium triglycine sulphate (DTGS). The setting parameters were: resolution 4 cm-1, spectral range 4000-600 cm-1, number of scans 32. ATR spectra were recorded using an Elmer Golden-Gate accessory. The micro-Raman spectrometer used in this case was a Labram Model from the Jobin Yvon-Horiba with a spatial resolution of 1 µm and with quick detection ability as a result of the CCD detector 1024x256 pixels cooled to -70°C by the Peltier effect. The spectral resolution was 1 cm-1. The exciting wavelength was the 632.8 nm red line of a He-Ne laser. Generally the samples were presented as inorganic powders of different colors: white, black, blue and red. Though the samples came from different museums, they were considered togheter, since they belonged all to the Phoenician culture and coming from Trapani archaeological sites. The white samples were of two types. The first one was mainly composed of gypsum and anhydrite mixtures (e.g. Inv No 1680, 1663, 1753); the other type (e.g. pyxes Inv N° 1393, 1451) was composed of fully carbonated cerussite, gypsum and litharge. The second kind of cosmetic corresponded to the most famous Greek cosmetic, called psymition, used by women to white the skin. The first type suggested that, for the same use, alternative materials, cheaper and most readily available, could be employed in the past. The black powders, usually used to outline the eyes, were mostly given by carbon obtained from vegetable combustion (e.g. Inv. N° 1566, 2314, 4313) or, sometimes, from bone combustion (animal charcoal) as for the samples Inv. N° 3140, 1761. A single blue powder (Inv N° 42259) was consisted by the famous Egyptian blue (CaCuSi4O10). The love for the red color by Phoenician is evident from the great number of powders of this color, probably used to give color to the cheeks or lips. A wide variety of red minerals was found. In many cases the presence of hematite (e.g. Inv N° 2309, 2689, 4269) was detected. A large number of pink and r

2013 - Presence of endogenous prednisolone in human urine [Articolo su rivista]
Fidani, Marco; Gamberini, Maria Cristina; Pompa, Giuseppe; Mungiguerra, Francesca; Casati, Alessio; Arioli, Francesco
abstract

The possibility of an endogenous presence of the glucocorticoid prednisolone has already been demonstrated in bovine and horse urine, with the aim of clarifying its origin in this matrix, which is used by official agencies for the control of illicit treatments. From this point of view, the endogenous nature of prednisolone could be a major topic in doping control of both amateur and professional human athletes. A study was therefore made on 34 human volunteers (13 males and 21 females; aged 22–62) to detect the presence of prednisolone in their urine by HPLC–MS3. One of the volunteers underwent vernal allergy treatment with betamethasone for two subsequent years. An investigation was carried out with the aim of verifying if the suppression, and the circadian rhythm, of cortisol urinary levels could also apply to prednisolone. The results of the study show that prednisolone was present in the urine of all 34 volunteers, with a concentration very close to 100-times lower that of cortisol, with no dependence on gender. The same ratio (1/100) was observed in the prednisolone and cortisol levels detected during the 24 h together with the suppression of prednisolone by betamethasone treatment. These data demonstrate the endogenous nature of low concentrations of prednisolone in human urine, and motivate further studies about the biosynthetic pathways of this corticosteroid and its relationship with stress in humans, as already described in cows.

2013 - Structural, electronic, thermodynamical and charge transfer properties of Chloramphenicol Palmitate using vibrational spectroscopy and DFT calculations [Articolo su rivista]
Rashmi, Mishra; Anubha, Srivastava; Anamika, Sharma; Poonam, Tandon; Baraldi, Cecilia; Gamberini, Maria Cristina
abstract

The global problem of advancing bacterial resistance to newer drugs has led to renewed interest in the use of Chloramphenicol Palmitate (C27H42Cl2N2O6) [Palmitic acid alpha ester with D-threo-(-),2-dichloro-N-(beta-hydroxy-alpha-(hydroxymethyl)-p-nitrophenethyl)acetamide also known as Detereopal]. The characterization of the three polymorphic forms of Chloramphenicol Palmitate (CPP) was done spectroscopically by employing FT-IR and FT-Raman techniques. The equilibrium geometry, various bonding features, and harmonic wavenumbers have been investigated for most stable form A with the help of DFT calculations and a good correlation was found between experimental data and theoretical values. Electronic properties have been analyzed employing TD-DFT for both gaseous and solvent phase. The theoretical calculation of thermodynamical properties along with NBO analysis has also been performed to have a deep insight into the molecule for further applications.

2012 - Ampicillina: studio vibrazionale mediante FT-IR, micro-Raman e SERS di forme solvate e polimorfe [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; A., Tinti; Baraldi, Pietro
abstract

Dalla letteratura è noto che numerosi principi attivi farmaceutici (APIs) tendono a cristallizzare in differenti impaccamenti cristallini (polimorfi) oppure comprendendo molecole di solvente come parte della struttura cristallina (pseudopolimorfi). All’interno di una formulazione farmaceutica, l’identità o la possibilità di conversione del’API potrebbe alterare le caratteristiche e l’efficacia della forma farmaceutica, in particolare portando a differente biodisponibilità.L’ampicillina o α-aminobenzylpenicillina o 6-[D (-)-α aminophenylacetamido] penicillanic acid esiste come forma anidra (attestate 2 forme polimorfe) ed in altre forme idrate, in particolare triidrata e monoidrata. All’interno delle diverse formulazioni farmaceutiche in commercio, come polveri per uso iniettabile o orale, oppure come compresse o capsule, l’ampicillina è presente come forma triidrata, talora come anidra o come sale sodico.Dalla letteratura è noto che numerosi principi attivi farmaceutici (APIs) tendono a cristallizzare in differenti impaccamenti cristallini (polimorfi) oppure comprendendo molecole di solvente come parte della struttura cristallina (pseudopolimorfi). All’interno di una formulazione farmaceutica, l’identità o la possibilità di conversione del’API potrebbe alterare le caratteristiche e l’efficacia della forma farmaceutica, in particolare portando a differente biodisponibilità.L’ampicillina o α-aminobenzylpenicillina o 6-[D (-)-α aminophenylacetamido] penicillanic acid esiste come forma anidra (attestate 2 forme polimorfe) ed in altre forme idrate, in particolare triidrata e monoidrata [1-3]. All’interno delle diverse formulazioni farmaceutiche in commercio, come polveri per uso iniettabile o orale, oppure come compresse o capsule, l’ampicillina è presente come forma triidrata, talora come anidra o come sale sodico.Il presente studio ha compreso la cristallizzazione e la caratterizzazione delle varie forme polimorfe e solvate dell’ampicillina. La forma triidrata, la monoidrata (detta forma A) e la forma anidra γ (o forma B) sono state ottenute con tecniche riportate in letteratura [4]. Per la forma δ, meno nota e studiata (sono riportati XRPD e IR) si è seguito il metodo di cristallizzazione riportato da Parker et al. [5]. Tali metodi di cristallizzazione (forme A, B, δ) hanno portato ad un prodotto finale di colore giallo chiaro, che potrebbe indicare decomposizione dei campioni [1]. In questo lavoro viene riportato come le due forme anidre siano state cristallizzate da riscaldamento in un capillare sigillato: a seconda della velocità diriscaldamento si sono ottenute la forma y (riscaldamento lento) e δ (riscaldamento rapido) senza alcun cambiamento di colore della polvere (cristalli bianchi). Le forme ottenute allo stato solido sono poi state caratterizzate mediante differenti tecniche analitiche (FT-IR, XRPD e DSC) ed i dati sperimentali sono stati confrontati con la bibliografia [1,4,5]. Inoltre, le differenti forme sono state studiate anche mediante la microscopia Raman (laser 632 nm). Per la prima volta in questo studio viene riportato uno studio SERS della molecola di ampicillina, utilizzando una soluzione colloidale di nanoparticelle d’argento secondo Lee e Meisel [6]. L'uso della Hot Stage Raman Microscopy (HSRM) ha permesso di seguire il passaggio dalla forma triidrata ad ampicillina monoidrata amorfa. Inoltre, con la stessa tecnica si sono potute studiare le trasformazioni solido-solido dal triidrato alle due forme anidre.Bibliografia[1] E. Shefter et al., J. Pharm. Sci. 1973, 62/5 791.[2] M.N.J. James et al. Nature 1968, 220 168.[3] E. Ivashkiv, In: Analytical Profiles of Drug Substances, vol. 2., Academic Press, New York, K. Florey, (Ed.), 1973.[4] K.W.B. Austin et al., Nature 1965, 208, 999.[5] Parker et al., 1976, USP 3933796.[6] P.C. Lee and D. Meisel J. Phys. Chem. 1982, 86, 3391.

2012 - Analisi micro-Raman di polveri cosmetiche greche e puniche [Abstract in Atti di Convegno]
Freguglia, Giada; Baraldi, Cecilia; Gamberini, Maria Cristina; E., Van Elslande; Baraldi, Pietro
abstract

Presso il Museo Archeologico Regionale “Antonino Salinas” di Palermo è conservato un importante nucleo di balsamari provenienti da Selinunte. Taluni, di pregevole manifattura, provengono dal Santuario di Demetra Malophoros. Altri unguentari e balsamari provengono dall’acropoli, altri ancora dalle necropoli. Appartengono ad un periodo compreso tra la metà del VI e la metà del V secolo a. C. L’area sacra, messa in luce durante gli scavi effettuati da Cavallari nel 1818 e da Salinas nel 1903-1905, ha portato alla luce una quantità immensa di materiali archeologici. Nell'area dove prima sorgeva l'acropoli i resti presentano un abitato misto, punico e greco. Al fine di questo studio sono stati inoltre presi in esame anche altri campioni, conservati nei saloni espositivi e in magazzino, provenienti dall’isola di Mozia, insediamento prettamente fenicio-punico.Gli insediamenti da cui provengono i contenitori, Selinunte e Mozia, offrono una gamma di valenze culturali assai variegata che sta a confermare il loro carattere di insediamenti nati da e per lo scambio. Le analisi condotte nel presente lavoro fanno seguito a quelle relative ad un importante gruppo di contenitori cosmetici di età Punica, coevi a quelli qui studiati, conservati presso il Museo della Fondazione Withaker sull’isola di Mozia [1,2].Il nucleo di balsamari fittili e vitrei, pissidi e alabastra considerati è stato ispezionato e si sono raccolte polveri di vari colori.La microscopia Raman ha permesso di identificare e caratterizzare i residui. Campioni bianchi hanno rivelato essere composti prevalentemente da miscele di gesso e anidrite (n inv. 1680, 1663, 1753). Le pissidi n. 1393 e 1451 presentavano residui bianchi composti da cerussite completamente carbonatata, gesso e litargirio. Si tratta del cosmetico greco per eccellenza, denominato psymition, utilizzato dalle donne per conferire pallore all’incarnato.Polveri rosa contenute in balsamari figurati di origine greca hanno mostrato come componenti ematite, quarzo, calcite, anatasio e goetite oppure, nel caso dell’askos zoomorfo n. 610, calcite, ossido di piombo, ematite, carbone e residuo organico. Il contenitore in vetro policromo n. 34228 presentava un abbondante residuo rosso composto da magnetite, quarzo, silicati ed ematite. Una conchiglia del genere Pecten (n. 34396) mostrava residui rossi composti da ematite, magnetite, lepidocrocite, goetite e tracce di cinabro (HgS). Un’interessante polvere rossa, (HgS miscelato con anatasio) è stata rinvenuta all’interno dell’ alabstron n. 7317/7 proveniente dalla necropoli di Marsala (tomba n.34). Risultati simili si sono ottenuti nell’ambito delle precedenti indagini su Mozia relative a contenitori della stessa tipologia. Il rinvenimento di questi pigmenti in associazione ad alasbatra è interessante in quanto la letteratura generalmente indica l’uso dedicato di questi particolari contenitori ad unguenti e profumi. Le analisi del contenuto azzurro della coppetta fittile n. 42259 hanno rilevato la presenza del celebre blu egiziano (CaCuSi4O10).Bibliografia[1] G. Freguglia, C. Baraldi, M.C. Gamberini, P. Toti, P. Baraldi,; PRIN07- Colors and balms in antiquity: from the chemical study to the knowledge of technologies in cosmetics, painting and medicine. Aboca, Sansepolcro (Arezzo, Italy), 2-3th December 2010, p. 50-51[2] C. Baraldi, G. Freguglia, M.C. Gamberini, P. Baraldi, RAA2011 Parma 5-8th September 2011, pp. 103-104;

2012 - Chemico-physical investigation of tenofovir loaded polymeric nanoparticles [Articolo su rivista]
Belletti, Daniela; Tosi, Giovanni; Forni, Flavio; Gamberini, Maria Cristina; Baraldi, Cecilia; Vandelli, Maria Angela; Ruozi, Barbara
abstract

Tenofovir (PMPA), an acyclic nucleoside phosphonate analog, is one of the most important drugs used for the HIV treatment. Unfortunately, several adverse reactions are related to its i.v. administration owing to the saturation of an anionic renal transporter. In order to improve the drug administration, the PMPA was embedded into a new type of nanocarriers based on poly-(d,l-lactide-co-glycolide) (PLGA) and/or chitosan (CH). The strategies for the preparation of nanoparticles (Nps) with a more efficient drug loading respect to the one reported in the literature for PMPA nanoencapsulation were investigated. CH was added in the first inner emulsion or in the external phase during the second emulsion of water/oil/water (W/O/W) Nps. The addition of CH in the first inner emulsion was the most promising technique. The Nps have a Z-average of 230 nm, a Z-potential of −3 mV and an EE% of 15 that was 2.5–3 times higher than that obtained with PLGA Nps or CH Nps. In vitro release studies showed a limited control on drug release in phosphate buffer (pH 7.4) while an initial burst effect followed by a slow drug release was observed in acidic receiving phase (pH 4.6). These results suggest the PLGA/CH Nps should be an effective and attractive anti-HIV drug carrier to study the cellular uptake and drug delivery on target cells such as macrophages.

2012 - Intermolecular charge transfer and vibrational analysis of hydrogen bonding in acetazolamide. [Articolo su rivista]
Deepika, Chaturvedi; Vineet, Gupta; Poonam, Tandon; Anamika, Sharma; Baraldi, Cecilia; Gamberini, Maria Cristina
abstract

In the present work the structural and spectral characteristics of acetazolamide have been studied by methods of infrared, Raman spectroscopy and quantum chemistry. Electrostatic potential surface, optimized geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by density functional theory (DFT) employing B3LYP with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. Based on these results, we have discussed the correlation between the vibrational modes and the structure of the dimers of acetazolamide. The calculated vibrational spectra of three dimers of acetazolamide have been compared with observed spectra, and the assignment of observed bands was carried out using potential energy distribution. The observed spectra agree well with the values computed from the DFT. A comparison of observed and calculated vibrational spectra clearly shows the effect of hydrogen bonding. The frequency shifts observed for the different dimers are in accord with the hydrogen bonding in acetazolamide. Natural bond orbital (NBO) analyses reflect the charge transfer interaction in the individual hydrogen bond units and the stability of different dimers of acetazolamide.

2011 - A multi-analytical approach for the characterization of powders from the Pompeii archaeological site [Articolo su rivista]
C., Canevali; P., Gentile; M., Orlandi; F., Modugno; J. J., Lucejko; M. P., Colombini; L., Brambilla; S., Goidanich; C., Riedo; O., Chiantore; Baraldi, Pietro; Baraldi, Cecilia; Gamberini, Maria Cristina
abstract

Nine black powders found in Pompeii housesin three different types of bronze vessels (cylindricaltheca atramentaria, unguentaries, and aryballoi) werecharacterized in order to assess a correspondence betweenthe composition and the type of vessel and,possibly, to verify if these powders were inks or not.For the compositional characterization, a multi-analyticalapproach was adopted, which involved the use ofscanning electron microscopy–energy dispersive X-ray,Fourier-transformed infrared spectroscopy, Raman, X-raydiffraction, electron paramagnetic resonance spectroscopy,thermogravimetric analysis, gas chromatographycoupled with mass spectrometry (GC/MS), and pyrolysis GC/MS. Powders contained in cylindrical theca atramentariaform a homogeneous group, and their organic andinorganic compositions suggest that they were writinginks, while powders contained in unguentaries andaryballoi could have had several different uses, includingwriting inks and cosmetics. Furthermore, the compositionprofile of the powders found in cylindrical cases showsthat, at 79AD, in Pompeii, carbon-based inks were stillused for writing, and iron gall inks had not beenintroduced yet.

2011 - A round robin exercise in archaeometry: analysis of a blind sample reproducing a seventeenth century pharmaceutical ointment [Articolo su rivista]
M. P., Colombini; F., Modugno; Gamberini, Maria Cristina; M., Rocchi; Baraldi, Cecilia; T., Deviese; R., Stacey; M., Orlandi; F., Saliu; C., Riedo; O., Chiantore; G., Sciutto; E., Catelli; L., Brambilla; L., Toniolo; C., Miliani; P., Rocchi; J., Bleton; U., Baumer; P., Dietemann; G., Pojana; S., Marras
abstract

Chemical analysis of ancient residues of pharmaceuticalor cosmetic preparations such as balms orointments is made problematic by the high complexity ofthese mixtures, composed of organic and inorganic materials.Consequently, a multi-analytical approach and specialcaution in the interpretation of the results are necessary. Inorder to contribute to the improvement of analyticalstrategies for the characterization of complex residues andto reconstruct ancient medical practices, a replica of a pharmaceutical formulation of the seventeenth century wasprepared in the laboratory according to a historicallydocumented recipe. In a round robin exercise, a portion ofthe preparation was analysed as a blind sample by 11laboratories using various analytical techniques. Theseincluded spectroscopic, chromatographic and mass spectrometricmethods. None of the laboratories was able tocompletely reconstruct the complex formulation, but eachof them gave partial positive results. The round robin exercise has demonstrated that the application of a multianalyticalapproach can permit a complete and reliablereconstruction of the composition. Finally, on the basis ofthe results, an analytical protocol for the study of residuesof ancient medical and pharmaceutical preparations hasbeen outlined.

2011 - Characterization of fresh and aged natural ingredients raw materials used in historical ointments by molecular spectroscopic techniques: IR, Raman and Fluorescence [Articolo su rivista]
L., Brambilla; C., Riedo; Baraldi, Cecilia; A., Nevin; Gamberini, Maria Cristina; C., D’Andrea; O., Chiantore; S., Goidanich; L., Toniolo
abstract

Natural organic materials used to prepare pharmaceuticalmixtures including ointments and balsams havebeen characterized by a combined non-destructive spectroscopicanalytical approach. Three classes of materialswhich include vegetable oils (olive, almond and palm tree),gums (Arabic and Tragacanth) and beeswax are consideredin this study according to their widespread use reported inancient recipes. Micro-FTIR, micro-Raman and fluorescencespectroscopies have been applied to fresh and mildlythermally aged samples. Vibrational characterization ofthese organic compounds is reported together with tabulated frequencies, highlighting all spectral features and changes inspectra which occur following artificial aging. Synchronousfluorescence spectroscopy has been shown to be particularlyuseful for the assessment of changes in oils after aging;spectral difference between Tragacanth and Arabic gum couldbe due to variations in origin and processing of raw materials.Analysis of these materials using non-destructive spectroscopictechniques provided important analytical informationwhich could be used to guide further study.

2011 - Combined technique analysis on Punic cosmetic powders [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; Baraldi, Pietro
abstract

The Whitaker Museum in Mozia (Sicily) conserves some funerary vessels coming from the isle’s archaic necropolis. Greek, Phoenician and Etruscan amphorae, a rich collection of jars of Birgi necropolis and also materials coming from Mozia Tofet and houses are exposed. Also jewels and weapons, amulets, scarabs and objects with original inscriptions engraved are found, as well as cosmetic and surgical instruments and fragments of inscribed stones coming from the Lilibaeum necropolis. From the collection of the Mozia Museum 77 samples from an interesting variety of containers including Unguentaria, Balsamaria, Alabastra, pyxes and shell valves were taken. The powders found in this cosmetic vessels have been analyzed by using FT-IR, micro-Raman, SERS (Surface Enhanced Raman Spectroscopy) and XRF techniques and the results are reported in this work. The analyses carried out have shown the presence of a variety of compounds.The white powders, that are the more frequent ones, present in lead pyxes, were identified by micro-Raman as made of Cerussite PbCO3 coming from a complete carbonatation of hydrocerussite PbCO3*Pb(OH)2. This is compatible with the high chronology of the samples: instead, hydrocerussite has been identified in Pompeii samples. Its presence, confirmed by XRF measurements, can be a clear indication of cosmetic use, since it is well known that its use in mural painting is not advisable. At the time, cerussa (lead white) was employed as a foundation. Other white powders are mainly composed of calcite or aragonite: the first could come from the soil where the ancient founds were situated, the second one could derive from ground sea shells. Among white samples, but not only, TiO2 is frequently attested. Its presence should amount to the cosmetic use of ground rocks or could come from the Mozia soil, for example if ophiolites are available in the region.Litharge, an oxide present in many containers, could derive from the alteration of cerussa, or from a proper addition, whether the yellow colour had a special meaning for the population of the site. As to the yellow pigments a yellow ochre based on goethite was found together with lepidocrocite.Among the red pigments, beloved by Phoenician people, there are cinnabar and hematite: the latter can be found as a natural compound or as a thermodegradation product from goethite. The presence of red lead chromates crocoite and phoenicocroite, two rare minerals, in a particularly precious unguentary is a singular discovery.In one sample a trace of blue material was seen, that gave the spectrum of indigotine, a dye extracted in the past from many plants and used for dyeing tissues and in cosmesis.Among black materials carbon is one of the most frequently attested, alongside MnO2 (pyrolusite) and magnetite.Three samples analyzed exhibited red organic compounds, all fluorescent with normal Raman technique. By appliying a SERS technique it has been possible to record spectra relative to these red dyes, but till now, with a comparison of reference materials, it was only possible to exclude the common red such as madder, purple and kermes. Other comparisons are outstanding.In comparison with other sites, such as Pompeii, Herculaneum and Oplontis, this cosmetic powders showed a wider range of materials.

2011 - Spectral analysis of pharmaceutical formulations prepared according to ancient recipes in comparison with old museum remains [Articolo su rivista]
Gamberini, Maria Cristina; Baraldi, Cecilia; Freguglia, Giada; Baraldi, Pietro
abstract

A study of the composition of the remains ofancient ointments from museums was undertaken to enableunderstanding of the preparation techniques. Comparison ofancient recipes from different historical periods andspectroscopic characteristics of inorganic and/or organicremains recovered in museum vessels enabled preparationof ancient pharmaceutical–cosmetic formulations. FarmacopeaAugustana by Occo was one the most importantbooks studied for the 14 formulations prepared in thelaboratory. Three formulations are discussed in detail andraw materials and new preparations were proposed forozone ageing. The most important micro Raman results arediscussed. The spectra of the raw materials lipids, beeswax,and resins are discussed; beeswax and pig suet (axŭngia)Raman spectra were found to be similar, but different fromthose of the aged oils. SERS was applied to ancientointments and galbanum and the Raman spectra arereported and discussed for the first time.

2010 - Auctoribus curae fuere lapides mortariorum quoque nec medicinalium tantum aut ad pigmenta pertinentium (Pliny 36, 43). Our authors are interested in stones, for making mortars, and not only in officinal mortars or those uded for colors. [Relazione in Atti di Convegno]
Baraldi, Pietro; Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina
abstract

A very important phase for reconstructing ancient technology and human activities is the analisys of artifacts. It can supply a lot of information, but sometimes the data obtained are not understandable. On the other hand an amount of written information is available since the classical antiquity. Some of the authors are considered not to be scientist and therefore their data are neither used nor interpreted. Beyond published texts some unpublished manuscripts are known that could be very interesting. Other documents include ancient translations from other languages, such as the Greek papyrii, and the Arabian documents from Spain, documents regarding trade and history of countries, icones in ancient paintings, tools used for paintings and other activities. In more recent time it is to recall, the "secreti", the books for treating diseases, where the subjects not only concern madicine, but include preparation of pigments, dyes, lakes, cosmetics, alloys inks...Their contents can be very old, some being composed much before Christ and re-written many times, and translated and sometimes erroneusly read. The transcription, understanding and interpretationof these recipes can help in understanding: the ancient paintings, decorations, alloys, textiles and cosmetics; the presence of some compounds as a consequence of past treatments and restorations; the survival of some compounds not necessary for the formulate, but added for somo forgotten reasons, such as folklore, superstition, faith, magic; the degradation of somo parts of artworks due to time and environment.These items have been followed in examining and unpublished miscellanea from the Biblioteca Estense Universitaria in Modena.

2010 - Color traces and their identification in paintings, cosmetics, writings [Abstract in Atti di Convegno]
Baraldi, Pietro; Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; Ansaloni, Ivano
abstract

During the last years of research carried out on the basis of a financial support by MIUR, many samples have been encountered of different nature, colour, origin and physical state. In examining containers present in the Italian Archaeological depositories and Museums, we have found or we were adviced of interesting coloured materials and we were asked to identify them.The identification is sometimes rich of information about the ancient technology for preparing elaborated formulates, such as cosmetics, drugs, ointments, perfumes, pigments, lakes, dyes. Thereby, their analysis enables important passages of the production to be understood and some literary sourced to be interpreted. In examining some materials present on bones due to particular rituals of the first centuries after Christ in Aemilia, a particular identification of manganese based materials was encountered. The presence of manganese oxides can be related to the geology of the Aemilian territory. However, similar compounds are present in Etruscan tiles decorated with Egyptian blue and other pigments in Marzabotto. This fact supply information on the commerce of Egyptian blue far before Roman Empire times and the passage of manganese oxide treatment for painting to subsequent cicilizations.The necessity for ancient populations to paint testimonies of past religious or military chiefs lead to a search for materials coming from far centuries, such as Baltic amber, Egyptian blue, indigo… In places with an always more ancient chronology, such as Verucchio Aemilia, these materials are found in large amounts. It is not clear whether indigo was extracted from Isatis tinctoria or an Indigofera.Traces of saffron and indigotine on fictile antefissae in Cuma testifies the use of re-painting the artefacts every while, as a sign of respect for the temples. Ancient colored lipsticks contain pink ingredients, that may be purpurissum, but could be also the cheaper purpurissum puteolanum, as revealed by SERS analysis of Pompeiian samples.Residuals of precious materials are found also in small containers of the Roman ages. Smal traces of gold an a black preparation identify the knowledge of a gilding technique on alabaster, whit the black assisa applied on small spots. The ensemble of materials and their use enable an amount of knowledge to be supposed in ancient populations in order to make their life more comfortable and elegant.

2010 - COSMETIC AND PHARMACEUTICAL FORMULATIONS: FROM PAST TO PRESENT [Relazione in Atti di Convegno]
Gamberini, Maria Cristina; Freguglia, Giada; Baraldi, Cecilia; Baraldi, Pietro
abstract

The interest devoted to the scientific treatment of analytical data obtained from ancient founds preserved in Italian and foreign institutions and Museums is nowadays relevant. However, till now the study of the composition and the understanding of the preparation technologies of ancient founds is scanty and fragmentary. Now, the progress of instrumental techniques enables the material composition to be cleared in details and to advance a possible re-proposition of the handiworks. On the basis of analytical data, the possibility to establish the nature of raw materials and the formulations, becomes even more concrete.In the framework of the PRIN project the unit of Modena has thrown the basis for the study of ancient cosmetic, medical and pictorial founds, in particular: 1)Identification and sampling of ancient remains in national and international Museums and of handiworks not purely cosmetic or medical.2)Spectroscopic studies (FT-IR, micro-Raman and XRF) for the characterisation of inorganic and/or organic remains recovered in unguentaries and in containers of ancient workshops.3)Identification and study of the ancient published and unpublished bibliographic sources: translation from Latin and vernacular followed by an interpretation of the function of raw materials. 4)Identification in the actual market of the materials used in antiquity.5)Preparation or acquirement of raw materials not available on the market.6)Reproduction in a modern perspective of ancient formulations on the basis of the ancient sources. The first step faced was the acquirement of ancient founds, that is the sampling on the spot of samples to be studied. Therefore, samples were taken at the Museum Aboca (Sansepolcro, Arezzo). At the Aboca Museum about 68 pots were inspected and 30 exhibited a fair amount of residue of which 9 were the object of the study.After sampling, the materials were analysed by Micro-Raman and FT-IR in order to have a first screening of them, that is to determine whether they were of organic or inorganic origin and which compounds were present. In this way we got a first idea of what the materials were. Thanks to the spectroscopic analyses and to the labels on the containers, we proceeded into the research of ancient similar formulations. Therefore, it was necessary to examine the recipe books starting from the classical age till to the beginning of scientific chemistry and pharmacology in order to critically compare the materials found, to understand their nature, their possible alteration undergone with time, the novelties in comparison with preceding versions, the technological acquirements of an age in comparison with the others. From the study of the inscriptions reported on the containers and the interpretations carried out, the period of actualisation of the formulation was hypothesised. The study of the same formulation in subsequent times has shown the evolution and the adaptation to the age.Many ancient books and manuscripts reporting recipes concerning the subject in the period between 1597 and 1872 have been considered, the most interesting of these was Farmacopea Augustana by Occo, 1597. For each source, the desired recipes were searched for and then, if necessary, translated and interpreted. In fact, some texts are in Latin or vernacular (Farmacopea Augustana by Occo), French (Abrégé de Matière médicale et de Thérapeutique by C. Binz) or Spanish (Farmacopea Hispanica), and the translation must be careful, since the meaning of the terms at the time was searched 1-7.The next step was to study the raw materials used in the recipes, that is to verify the persistence of the ingredients today and their availability in commerce. The ointments to be prepared were chosen as a function of the remains found in the containers, but mainly on the basis of the results of the spectroscopic analyses. Those reproduced in the laboratory were many, sometimes the preparations have been ma

2010 - MULTI ANALITYCAL APPROACH TO AGED COMPLEX MATRICES [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; Baraldi, Pietro; M. P., Colombini
abstract

Since a decade our research group deals with the analysis of ancient cosmetics and drugs, starting from the Roman founds. At present some founds from pharmacies of Italy (Genua, Sansepolcro) and Spain (Majorca) amounting to the XVII century and Egyptian ointments of the II millennium b.C. from the Turin Museum are under study.The analysis protocol provides firstly non-destructive analyses and then the more expensive and destructive analyses, such as gas-chromatography-mass spectrometry (GC-MS) methods. We report the results of the vibrational spectroscopy techniques, such as Raman microscopy (laser 632 nm), FT-Raman spectroscopy (laser 1064 nm) and FT-IR/ATR with a golden gate accessory, were identified as the most suitable techniques for a first approach to the analysis of the ancient samples. Raman microscopy is the most suitable technique in order to identify minor inorganic components and contaminants at the micrometric scale inside these complex matrices. This technique can easily identify compounds like lead oxide, vermillion, rare minerals, (etc.) that could give interesting informations about the provenance of the raw materials and the original composition of the formulate. In this study are reported some data about the composition of some ancient Egyptian samples. It can be observed that Titanite is present, a mineral possibly coming from mines in Southern Egypt.Concerning to organic materials, their possibility of identification, is very different from that of inorganic ones. Some compounds were rapidly degraded, some others persisted till to present day, often unchanged (e.g. wax). Historical samples give a chemical variability like the natural products, in addiction there are the ageing and the degradation process that make very difficult to recognize the raw material originally present. For understanding the possible changes undergone by materials in ageing, a specific database of spectra must be available.Some thirty raw materials were chosen among oils (e.g. olive, almond, and palm oil), gums (e.g. gum arabic, gum tragacanth), animal fats and waxes commonly employed in the ancient preparations. On the basis of the examination and critical interpretation of ancient literature sources (pharmacopoeias) fifteen samples based on pharmaceutical and cosmetic recipes were prepared as a reference samples. The raw materials and thereference formulations were artificially aged by using heating (in a oven at 60°C for 1 month), photo-oxidation (with ozone for 20 hours) and enzymatic degradation (by means of a pool of cellulase, lipase and laccase).Concerning the raw materials, only few showed fluorescence in Raman microscopy, but this decreases sharply with the artificial ageing process. This fact could be due to the loss of fluorophores.The artificial ageing produces different alterations according to the type of ageing. Among the first results we reported the analysis of Pompeii sample already identified as palm oil by GC-MS2. The comparison with our database showed correspondence with palm oil enzymatically degraded. This indicates that this database is interesting in recognising the organic materials into archaeological holders.

2010 - Multianalytical approach to aged complex matrices [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; Baraldi, Pietro
abstract

Since a decade our research group deals with the analysis of ancient cosmetics and drugs, starting from the Roman founds. At present some founds from pharmacies of Italy (Genua, Sansepolcro) and Spain (Majorca) amounting to the XVII century and Egyptian ointments of the II millennium b.C. from the Turin Museum are under study. The analysis protocol provides firstly non-destructive analyses and then the more expensive and destructive analyses, such as gas-chromatography-mass spectrometry (GC-MS) methods. These measurements involve other research groups of our project supported by a national Fund (PRIN: Colours and ointments in antiquity). We report the results of the vibrational spectroscopy techniques, such as Raman microscopy (laser 632 nm), FT-Raman spectroscopy (laser 1064 nm) and FT-IR/ATR with a golden gate accessory, were identified as the most suitable techniques for a first approach to the analysis of the ancient samples. Raman microscopy is the most suitable technique in order to identify minor inorganic components and contaminants at the micrometric scale inside these complex matrices. This technique can easily identify compounds like lead oxide, vermillion, rare minerals, (etc.) that could give interesting informations about the provenance of the raw materials and the original composition of the formulate. Concerning the organic materials, their possibility of identification, is very different from that of inorganic ones. Some compounds were rapidly degraded, some others persisted till to present day, often unchanged (e.g. wax). Historical samples give a chemical variability like the natural products, in addiction there are the ageing and the degradation process that make very difficult to recognize the raw material originally present. For understanding the possible changes undergone by materials in ageing, a specific database of spectra must be available.Some thirty raw materials were chosen among oils (e.g. olive, almond, and palm oil), gums (e.g. gum arabic, gum tragacanth), animal fats and waxes commonly employed in the ancient preparations. On the basis of the examination and critical interpretation of ancient literature sources (pharmacopoeias) fifteen samples based on pharmaceutical and cosmetic recipes were prepared as a reference samples. The raw materials and the reference formulations were artificially aged by using heating (in a oven at 60°C for 1 month), photo-oxidation (with ozone for 20 hours) and enzymatic degradation (by means of a pool of cellulase, lipase and laccase).Concerning the raw materials, only few showed fluorescence in Raman microscopy, but this decreases sharply with the artificial ageing process. This fact could be due to the loss of fluorophores. The artificial ageing produces different alterations according to the type of ageing. Among the first results we reported the analysis of Pompeii sample already identified as palm oil by GC-MS2. The comparison with our database showed correspondence with palm oil enzymatically degraded. This indicates that this database is interesting in recognising the organic materials associated to archaeological founds.

2010 - MultyAnalytical Approach to Aged complex Matrices [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; Baraldi, Pietro; M. P., Colombini
abstract

Since a decade our research group deals with the analysis of ancient cosmetics and drugs, starting from the Roman founds. At present some founds from pharmacies of Italy (Genua, Sansepolcro) and Spain (Majorca) amounting to the XVII century and Egyptian ointments of the II millennium b.C. from the Turin Museum are under study.The analysis protocol provides firstly non-destructive analyses and then the more expensive and destructive analyses, such as gas-chromatography-mass spectrometry (GC-MS) methods. These measurements involve other research groups of our project supported by a national Fund (PRIN: Colours and ointments in antiquity). We report the results of the vibrational spectroscopy techniques, such as Raman microscopy (laser 632 nm), FT-Raman spectroscopy (laser 1064 nm) and FT-IR/ATR with a golden gate accessory, were identified as the most suitable techniques for a first approach to the analysis of the ancient samples. Raman microscopy is the most suitable technique in order to identify minor inorganic components and contaminants at the micrometric scale inside these complex matrices4. This technique can easily identify compounds like lead oxide, vermillion, rare minerals, (etc.) that could give interesting informations about the provenance of the raw materials and the original composition of the formulate. In Tab.1 are reported some data about the composition of some ancient Egyptian samples. It can be observed that Titanite is present, a mineral possibly coming from mines in Southern Egypt. Concerning to organic materials, their possibility of identification, is very different from that of inorganic ones. Some compounds were rapidly degraded, some others persisted till to present day, often unchanged (e.g. wax). Historical samples give a chemical variability like the natural products, in addiction there are the ageing and the degradation process that make very difficult to recognize the raw material originally present. For understanding the possible changes undergone by materials in ageing, a specific database of spectra must be available.Some thirty raw materials were chosen among oils (e.g. olive, almond, and palm oil), gums (e.g. gum arabic, gum tragacanth), animal fats and waxes commonly employed in the ancient preparations. On the basis of the examination and critical interpretation of ancient literature sources (pharmacopoeias) fifteen samples based on pharmaceutical and cosmetic recipes were prepared as a reference samples. The raw materials and the reference formulations were artificially aged by using heating (in a oven at 60°C for 1 month), photo-oxidation (with ozone for 20 hours) and enzymatic degradation (by means of a pool of cellulase, lipase and laccase).Concerning the raw materials, only few showed fluorescence in Raman microscopy, but this decreases sharply with the artificial ageing process. This fact could be due to the loss of fluorophores. The artificial ageing produces different alterations according to the type of ageing. Among the first results we reported the analysis of Pompeii sample already identified as palm oil by GC-MS2. The comparison with our database showed correspondence with palm oil enzymatically degraded. This indicates that this database is interesting in recognising the organic materials into archaeological holders.

2010 - RAMAN TECHNIQUES APPLIED TO ANCIENT COSMETIC AND PHARMACEUTICAL PREPARATIONS [Relazione in Atti di Convegno]
Baraldi, Cecilia; Gamberini, Maria Cristina; Freguglia, Giada; Baraldi, Pietro
abstract

Complementary spectroscopic techniques, such as FT-IR and Micro-Raman spectroscopies are valuable means for maximizing the amount of information provided by complex matrices like the remains in archaeological containers. The difficulty in analyzing archaeological samples is due to their composition which generally involves a mixture of different inorganic and organic materials, some times degraded by the environmental conditions. We report the results of the vibrational spectroscopy techniques, such as Raman microscopy (laser 632 nm), FT-Raman spectroscopy (laser 1064 nm) and FT-IR/ATR with a golden gate accessory, of a first approach to the analysis of the ancient samples. The analytical results showed the importance of micro-Raman Spectroscopy in discriminating between inorganic and organic materials, thereby underlining the complexity of pharmaceutical and cosmetic matrices.Raman microscopy is the most suitable technique in order to identify minor inorganic components and contaminants at the micrometric scale inside these complex matrices. On the basis of the FT-IR and micro-Raman spectra, it was possible to identify some specific old cosmetic materials and some binders used in cosmetic preparations. In particular, Raman microscopy was able to identify the presence of constituents at the trace levels or compounds having vibrations at low wavenumbers within the sample examined, that it is not possible with normal FT-IR technique. This technique can easily identify compounds like lead oxide, red lead, cinnabar, rare minerals, (etc.) that could give interesting information about the original composition of the formulate and the provenance of the raw materials.Concerning the organic materials, their possibility of identification is very different from that of inorganic ones. Some compounds were rapidly degraded, some others persisted till to present day, often unchanged (e.g. wax). Historical samples are subjected to ageing and degradation process that make difficult to recognize the raw material originally present. For understanding the possible changes undergone by materials during ageing, a specific database of spectra must be available.In the project PRIN 2007 “Colours and balms in antiquity” some thirty raw materials were chosen among oils (e.g. olive, almond, and palm oil), gums (e.g. gumarabic), animal fats and waxes, commonly employed in the ancient preparations. The raw materials and the reference formulations prepared in the laboratory, were artificially aged. The reference Raman spectra have supplied an interesting database.The use of Surface-Enhanced Raman Spectroscopy (SERS) enabled to increase Raman signal and to decrease the background fluorescence for some samples. This techniques exhibits new perspectives for the study of organic and inorganic compounds in the field of cultural heritage.

2010 - Spectroscopic Characterization Of Ancient Matrices [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; Baraldi, Pietro; M. P., Colombini; O., Chiantore
abstract

Since a decade our research group deals with the analysis of ancient cosmetics and drugs, starting from the Roman founds 1-3. Actually, this kind of study involves other research groups supported by a national Fund (PRIN: Colours and ointments in antiquity). Firstly the analysis protocol provides non-destructive analyses and then the more expensive and destructive analyses, such as gas-chromatography-mass spectrometry (GC-MS) methods. The samples analyzed in this study were collected from the Egyptian Museum of Turin, Italy. The discovery of the studied archaeological finds was made by Ernesto Schiaparelli (1906 until 1913) and the archaeological founds were dated from the late III millenium b.C. to early II millenium b.C. The sites of finding were in Assiut (at about 400 Km from Cairo on the bank of the Nile) and Gebelein (south of Assiut), near the southern border with Nubia. In the sarcophagus usually it is possible to find weapons, like bows and arrows, textiles and also ointments. Here the results of the vibrational spectroscopy techniques, such as Raman microscopy (laser 632 nm), FT-Raman spectroscopy (laser 1064 nm) and FT-IR/ATR with a golden gate accessory are reported. These techniques are identified as the most suitable ones for the first approach to ancient samples analysis. Raman microscopy is in fact the most suitable technique in order to identify minor inorganic components and contaminants at the micrometric scale inside these complex matrices4. This technique can easily identify compounds like lead oxide, vermillion, rare minerals, (etc.) that could give interesting informations about the provenance of the raw materials and the original composition of the formulate. In the present study some data are reported concerning the composition of five ancient Egyptian samples. It can be observed that Titanite is present, a mineral possibly coming from mines in Southern Egypt5.Concerning to organic materials, their possibility of identification, is very different from that of inorganic ones. Some compounds were rapidly degraded, some others persisted till to present day, often unchanged (e.g. wax). Historical samples give a chemical variability due to the natural products, in addiction, ageing and degradation processes make very difficult to recognize raw materials originally present. For understanding the possible changes undergone by materials in ageing, a specific database of spectra must be available. Some thirty raw materials were chosen among oils, gums, animal fats and waxes commonly employed in the ancient preparations. The reference materials were in laboratory artificially aged by heating, photo-oxidation and enzymatic degradation. Some artificial materials aged produced different alterations according to the type of ageing. The comparison to one remain sample and our database spectrum showed a correspondence with the enzymatically degraded palm oil spectrum. This indicates the importance of this database in recognising the organic materials into archaeological holders.

2010 - Studio di preparati farmaceutici del XVIII-XIX secolo tramite GC/MS e HPLC-DAD [Relazione in Atti di Convegno]
M., Rocchi; E., Ribechini; I., Degano; F., Modugno; Gamberini, Maria Cristina; Baraldi, Cecilia; M. P., Colombini
abstract

Il presente lavoro è volto allo studio e alla conoscenza chimica delle sostanze organiche naturali impiegate nella realizzazione di antichi preparati farmaceutici. Questa ricerca è stata svolta nell'ambito del progetto nazionale PRIN07 dal titolo "Colori e balsami nell'antichità: dallo studio chimico alla conoscenza delle tecnologie in cosmesi, pittura e medicina". In questa sede verranno mostrati i risultati ottenuti dallo studio di preparati antichi provenienti dal Museo di Aboca di S. Sepolcro (AR), della Real Cartuja de Valdemossa (Palma di Maiorca) e del Museo di S. Agostino (Palazzo Tursi, GE). A causa della complessità della composizione chinica delle matrici sono state scelte per l'analisi della componente organica tecniche cromatografiche e in particolare la gas cromatografia accoppiata alla spettrometria di massa (GC/MS) e la cromatografia liquida ad alta pressione con rivelatore a serie di diodi (HPLC-DAD). Queste tecniche permettono la separazione e l'identificazione delle singole specie chimiche presenti e tra queste il riconoscimento di markers bio-molecolari. La combinazione dei dati ricavati dalle analisi di sostanze naturali sottoposte a invecchiamento, di unguenti riformulati seguendo ricettari e documenti d'epoca hanno permesso la caratterizzazione delle sostanze prese in esame e a migliorare la conoscenza della farmacopea antica. La presenza di diverse classi di composti, in particolare di acidi grassi mono- e poliinsaturi a catena corta e a catena lunga, diacidi, idrossiacidi, alcol a catena lunga, n-alcani a catena lunga e acidi diterpenoidi hanno evidenziato tre diversi tipi di sostanze: cera d'api, olio vegetale e resina di pino.

2010 - STUDY AND PREPARATION OF ANCIENT COSMETIC AND PHARMACEUTICAL FORMULATIONS IN A PRESENT PRESPECTIVE [Abstract in Atti di Convegno]
Freguglia, Giada; Baraldi, Cecilia; Gamberini, Maria Cristina; Baraldi, Pietro
abstract

The study of ancient cosmetic and pharmaceutical formulations involved the examination of several recipe books starting from the classical age till to the beginning of scientific chemistry and pharmacology. The study of the same formulation in subsequent times has shown the evolution and the adaptation to the age. Many ancient books and manuscripts reporting recipes concerning the subject in the period between 1597 and 1872 have been considered. Study of the ancient remains found inside unguentaries and of the raw materials used in the recipes has been necessary. Not all the raw materials could be bought, some needed to be prepared in the laboratory, such as the rose-water and the turnip juice, two ingredients used in the preparation of many ointments.The ointments to be prepared were chosen as a function of the remains found in the containers, but mainly on the basis of the analytical results coming out from ancient remains analysis. Those reproduced in the laboratory were many, sometimes the preparations have been made in double or triple, according to the sources of different historical periods. The total number of the ointments reproduced was fourteen.

2010 - STUDY OF ANCIENT PHOENICIAN REMAINS [Abstract in Atti di Convegno]
Freguglia, Giada; Baraldi, Cecilia; Gamberini, Maria Cristina; P., Toti; Baraldi, Pietro
abstract

The Mozia Museum conserves some funerary vessels coming from the isle’s archaic necropolis, commercial Greek, Phoenician and Etruscan amphorae, a rich collection of black varnish jars with red images of Birgi necropolis and also materials coming from Mozia Tofet and houses. Also jewels and weapons, amulets, scarabs and objects with original captions engraved are found, as well as cosmetic and surgical instruments and fragments of inscribed stones coming from the Lilibeo necropolis. From the collection of the Mozia Museum about 200 samples from the Unguentaria and Balsamaria were taken, some having large amount of residue, others a very small one. A preliminary spectroscopic analysis was carried out on these samples by using Micro-Raman and SERS techniques and the results of a first series are reported in this study. The preliminary analyses carried out with the Raman techniques have shown the presence of a variety of compounds.The white powders, among the more abundant ones, present in lead pyxes, were made of Cerussite PbCO3 coming from a complete carbonatation of hydrocerussite PbCO3*Pb(OH)2. This is compatible with the high chronology of the samples: instead, hydrocerussite has been identified in Pompeii samples. Its presence can be a clear indicator of cosmesis, since it is well known that its use in mural painting is not advisable. At the time, cerussa (lead white) was employed as a foundation. Other white substances are calcite and aragonite: the first could come from the ground where the unguentaria were found, the second one could derive from ground sea shells.Litharge, an oxide present in many containers, could derive from the alteration of cerussa, or from a proper addition, whether the yellow colour had a special meaning for the population of the site.The container NI 3149 had a gray powder composed of Carbon mixed with calcium phosphate. This could have been a bone-black or could come from cinerary urn.Among the red pigments found there are cinnabar and hematite: the latter can be found as a natural compound or as a thermodegradation product from goethite. The presence of red lead chromates crocoite and phoenicocroite, two rare minerals, in a particularly precious unguentary is a singular discovery.With the SERS technique it has been possible to record spectra relative to red dyes. However, these spectra do not correpond to compounds coming from madder, purple and kermes. Other comparisons are outstanding. In comparison with other sites, such as Pompeii, Herculaneum and Oplontis, this cosmetic powders exhibit a wider range of materials.

2010 - Vibrational Study of Propantheline Bromide Polymorphism [Abstract in Atti di Convegno]
Baraldi, Cecilia; Freguglia, Giada; Gamberini, Maria Cristina; A., Tinti
abstract

Propantheline or 2-Propanaminium, N-methyl-N-(1-methylethyl)-N-[2-[(9H-xanthen-9-ylcarbonyl)oxy]ethyl]- bromide is a quaternary ammonium synthetic derivate with modulation activity on vagal tone. It is one of the most parasympatholytic active agent with peripheral activity similar to atropine. It reduces the hypersecretion and the ipermotility of the gastro-intestinal apparatus and it has spasmolitic properties. The presence of two known Propanteline bromide polymorphs is reported in literature1,2: the stable form I and the metastable form II. Through multi-analytical approach used by our group in other pholimorphic studies, in the present communication we report the study and characterization of the studied two forms. For the first time micro-Raman spectroscopy and Hot-Stage Raman microscopy (HSRM) studies of Propantheline polymorphs are reported. Raman techniques were useful tools for distinguish and monitor the conversion of polymorphs cause of changing temperature. The spectroscopic reported data, together with those form previous reports, complete the Propantheline bromide polymorphs knowledge. DSC thermograms and X-Ray powder diffraction data, were also collected. Furthermore XRPD patterns of I and II forms were in agreement with Kountourellis data. Some attributions of significant IR and Raman bands were firstly reported. In summary, the IR spectra permitted to identify I and II polymorphs through their typical bands at 1729, 1250-1235, 1171-1157, 1038, 758-746, 713, 630 cm-1 and 1727-1739, 1260, 1166, 1032, 753-744, 709 cm-1, respectively. The polymorphs characterization through Raman spectroscopy permitted to identify specific bands for form I (1267-1255, 1222, 520, 417-402-380, 294, 255 cm-1) and form II (in particular at 1229, 669, 537-530, 397, 295-282 and 185 cm-1).According to L. Borka results1,6, in this study a conversion of II into I form was observed. The conversion occurred above 100°C with a successive fusion of I form. A further heating caused a decomposition phenomenon. The used temperature program started form 35° until 200°C with an heating rate of 2°C/min. To confirm DSC results of form II, Hot-stage measurements were carried out with the same DSC temperature program (2°C/min; 35-200°C temperature range). By this technique, the same results recovered with DSC thermal curves were noticed: a conversion of II into I form was observed and the successively fusion phenomenon was noticed. At 35°C until 80°C, the micro-Raman spectra correspond to form II, while at 90°C and at 160°C the transformation into I and its melting event were occurred, respectively.Moreover, the thermodynamic and spectroscopic behaviour of ground form I was investigated. Propantheline form I was ground at different times (1, 5, 10, 15, 20 minutes) and FT-IR/ATR and DSC measurements were carried out. In addition, a certain amount of recrystallized Propantheline bromide (form I, II) was placed into a compressing machine to obtain Propantheline bromide tablets using different compression forces (2, 4, 8, 10, 12, 16 and 28 KN). Using Raman microscopy, surfaces and inside tablets studies were carried out for verifying the polymorphic transformations. Polymorphic transformations were not been induced.

2009 - As beautiful as the woman in Ancient Rome : an overview of the Raman studies on cosmetic powders from Pompeii [Abstract in Atti di Convegno]
E., Van Elslande; Gamberini, Maria Cristina; Baraldi, Cecilia; P., Walter
abstract

White for the face, black for the eyes and red for the lips and the cheeks, there are the principal colours used by the women of the ancient Mediterranean world to makeup themselves, as confirmed by the description of the habits given by Ovid1 or Tertullian2. But what about the materials used? A multi-analytical approach for the study of cosmetics samples from the ancient Greek and Roman worlds enlighted us about the diversity of materials used3,4.We propose here to focus on Raman and SERS results obtained on pompeian samples to show the complexity of the formulation of roman cosmetic powders.

2009 - Evaluation of equine urine reactivity towards phase II metabolites of 17-hydroxy steroids by liquid chromatography/tandem mass spectrometry [Articolo su rivista]
M., Fidani; Gamberini, Maria Cristina; E., Pasello; Palazzoli, Federica; P., De Iuliis; M., Montana; F., Arioli
abstract

Proper storage conditions of biological samples are fundamental to avoid microbiological contamination that can cause chemical modifications of the target analytes. A simple liquid chromatography/ tandem mass spectrometry (LC/MS/MS) method through direct injection of diluted samples, without prior extraction, was used to evaluate the stability of phase II metabolites of boldenone and testosterone (glucuronides and sulphates) in intentionally poorly stored equine urine samples. We also considered the stability of some deuterated conjugated steroids generally used as internal standards, such as deuterated testosterone and epitestosterone glucuronides, and deuterated boldenone and testosterone sulphates. The urines were kept for 1 day at room temperature, to mimic poor storage conditions, then spiked with the above steroids and kept at different temperatures (-18°C, 4°C, room temperature). It has been possible to confirm the instability of glucuronide compounds when added to poorly stored equine urine samples. In particular, both 17b- and 17a-glucuronide steroids were exposed to hydrolysis leading to non-conjugated steroids. Only 17b-hydroxy steroids were exposed to oxidation to their keto derivatives whereas the 17a-hydroxy steroids were highly stable. The sulphate compounds were completely stable. The deuterated compounds underwent the same behaviour as the unlabelled compounds. The transformations were observed in urine samples kept at room temperature and at a temperature of 4°C (at a slower rate). No modifications were observed in frozen urine samples. In the light of the latter results, the immediate freezing at -18°C of the collected samples and their instant analysis after thawing is the proposed procedure for preventing the transformations that occur in urine, usually due to microbiological contamination.

2009 - Vibrational study of acetazolamide polymorphism [Articolo su rivista]
Baraldi, Cecilia; Gamberini, Maria Cristina; A., Tinti; Palazzoli, Federica; Ferioli, Valeria
abstract

In this paper, an acetazolamide vibrational study has been conducted to identify its two known polymorphic forms (A and B). Other techniques, such as Hot-stage and X-ray powder diffraction, have been also reported. Moreover, the thermodynamic and spectroscopic behaviour of ground form A has been investigated.In this study, acetazolamide form A was ground at different times (1, 5, 10, 15, 20 min) and FT-IR/ATR and DSC measurements have been carried out. The grinding process, decreasing the particle sizes, has been induced a polymorphic transformation of A to B form.To determine the B in A percentages, calibration curves have been performed by FT-Raman measurements.

2008 - Development of a liquid chromatography–tandem mass spectrometry method for an euthanasic veterinarian drug: Tanax® [Articolo su rivista]
M., Fidani; Gamberini, Maria Cristina; E., Pasello; Palazzoli, Federica; T., Dimasi; M., Montana
abstract

A development of a rapid and sensitive LC–MS/MS method for the simultaneous detection of active ingredients of the euthanasic veterinarian drug Tanax® mixture is described.The method proposed, with a retention time of few minutes (6 min) was developed for an equine serum sample with solid-phase extraction (S.P.E). This S.P.E. procedure has been revealed useful for the determination of very low concentrations of Tanax® analytes (0.05–1 ng/ml).The method was validated in terms of specificity/selectivity, sensitivity, recovery and precision.

2008 - MicroRaman and infrared spectroscopic characterization of ancient cosmetics [Articolo su rivista]
Gamberini, Maria Cristina; Baraldi, Cecilia; Palazzoli, Federica; E., Ribechini; Baraldi, Pietro
abstract

By FT-IR and microRaman spectrometry a large number of black to gray powders have been analysed. The studied remains were found inside Pompeiian unguentaries situated in depository of ‘‘Casa Bacco’’. By the analytical results it has been possible to understand the different nature and composition of the materials employed in preparation of ancient cosmetic powders. Dark black powders were essentially composed of amorphous carbon probably due to the carbonisation of vegetal or animal tissues. By using different starting materials or by adding different powders to the black carbon other hues could be also obtained. Particularly, this study enabled to gain a complete and unambiguous composition characterization of these old cosmetics.

2007 - A Raman study of white cosmetics from the classic world [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Cecilia; Palazzoli, Federica; P., Walther; Baraldi, Pietro
abstract

Some samples coming from different regions of the ancient Mediterranean World have been studied by Raman microscopy. The powders were apparently white cosmetics used in female contexts. A detailed analysis of their FT-IR and Raman spectra revealed that many compounds were present.Fluorite, apatite, sodium nitrate; pyrolusite, lead white, quartz, indigo, black cuprite, gypsum, goethite, have been identified. The presence of so many different and coloured compounds can help in the description of the preparation method used at the time by the artisans and to understand the changes intervened due to chemical alterations and degradation in the course of time. Perhaps different technologies to obtain white cosmetics were used, depending on local availability of materials and social levels of buyers. Traces of binders are sometimes detectable by infrared spectroscopy.

2007 - Black eyeliners in ancient Rome: the case of Pompeii [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Baraldi, Cecilia; Palazzoli, Federica; E., Ribechini; Baraldi, Pietro; P., Walter
abstract

Many of the ancient black eye paints, the kohls, consisted of galena, stibine or antimony sulfide, cerussite and in addition laurionite and phosgenite as reported by other authors. The Roman civilization made of their own this type of Egyptian cosmetic, moreover the literature reports also the use of the simplest and cheapest fuligo (black smoke) used to mark the eyebrows and the contour of the eyelashes. A large number of black-to-grey powders found inside Pompeiian unguentaries have been analysed by infrared spectrometry and Raman microscopy. The analyses show that deep black powders are essentially amorphous carbon that can derive from the carbonisation of vegetal or, frequently, animal tissues. In fact, carbon is found to be associated with apatite, whose presence could be attributed to the carbonisation of animal bones in a controlled atmosphere. Concerning the gray powders it is also to underline the rare occurrence of some particular materials that have been detected in painting materials (“Casa dei Casti Amanti” and the “Officina pigmentaria”); among them it is to recall jarosite, a yellow basic iron sulphate already identified in Egyptian paintings.Other interesting findings are anglesite and epsomite, not ascribable to the existence on the site of minerals of this kind: they can be interpreted as degradation products of other materials, such as magnesite, dolomite and cerussa, in the presence of sulfur dioxide from the surges or from the modern acid rains.The rare occurrence of minium could be bound to the use as a pinkish material for fards or to a degradation due to heating of cerussa during the violent surges of the 79 a.C. The presence of the iron classes of compounds (hematite, goethite, lepidocrocite and magnetite) could derive in some cases from a proper addition of an ochre, in order to obtain a special nuance of fard. The occurrence of aragonite and dolomite is parallel to the analogous findings among the painting materials, whereas cerussite comes from a carbonatation of hydrocerussite, the proper component of cerussa, the preeminent ancient white cosmetic used as foundation cream.

2007 - Relationship between quantum-chemical descriptors of proton dissociation and experimental acidity contants of variously hydroxylated coumarins. Identification of the biologically active species for xanthine oxidase inhibition [Articolo su rivista]
Ferrari, Anna Maria; Sgobba, Miriam; Gamberini, Maria Cristina; Rastelli, Giulio
abstract

Quantum-chemical descriptors related to proton dissociation constants of a set of coumarins hydroxylated in various positions have been computed and related to the experimental pKa values. An excellent correlation was found between the computed deprotonation energies of hydroxycoumarins in water and their experimental pKa values, and the results were used to predict the pKa of other hydroxycoumarins. Then, predicted and experimental pKa values were used as a basis for interpreting and discussing the variation of xanthine oxidase inhibitory activities within a subset of coumarins, with the aim of identifying the molecular species most relevant for enzyme inhibition.

2007 - Vibrational study of tamoxifen citrate polymorphism [Articolo su rivista]
Gamberini, Maria Cristina; Baraldi, Cecilia; A., Tinti; Palazzoli, Federica; Ferioli, Valeria
abstract

The trans isomer of (Z)-2-[p-(1,2-diphenyl-butenyl)phenoxy]-N,N-dimethyletylamine (tamoxifen) is well known for its endocrine activity as an antiestrogenic agent. Its citrate salt, a widely used pharmaceutical agent, appears in three main polymorphic forms, two of which are well known (I and II) and another form not yet well evidenced.A vibrational study has been conducted for identifying the two known polymorphic forms of tamoxifen citrate (I and II) and for characterising the other form (form III) examined in this study.Other techniques for the characterization of the different polymorphs, such as XRDP, have been used

2006 - Analisi del contenuto di alcuni Unguentari Pompeiani [Articolo su rivista]
Baraldi, Pietro; C., Fagnano; Baraldi, Cecilia; Gamberini, Maria Cristina
abstract

Una ricerca svolta sul contenuto di un gruppo di balsamari di Pompei ha portato ad evidenziare una serie di composti organici di varia natura. Mediante tecniche di spettroscopia infrarossa, microRaman e di gascromatografia applicata alla spettrometria di massa si sono identificati vari componenti noti e alcuni finora incogniti. I composti inorganici identificati possono fornire indicazioni sulla provenienza di materiali o preferenze locali per prodotti disponibili, le sostanze organiche, le tecnologie di preparazione del cosmetico. In generale, dall'esame dei dati qui riportati, risulta una cosmesi di tipo economico, rispetto a siti contemporanei posti in zone limitrofe. Non mancano però alcune singolarità, come l'impiego dell' huntite e della jarosite, materiali di probabile provenienza egiziana.

2006 - Gli unguentari pompeiani e il loro contenuto -prima parte [Articolo su rivista]
Baraldi, Cecilia; Gamberini, Maria Cristina; Baraldi, Pietro; Mp, Colombini; E., Ribechini
abstract

Il gruppo di studio sulla cosmesi antica e moderna, costituito da ricercatori delle Università di Modena e Reggio Emilia e di Pisa, ha analizzato il contenuto di un gruppo di balsamari di area Campana. Mediante tecniche di spettroscopia infrarossa, microscopia Raman e di gascromatografia abbinata alla spettrometria di massa è stato possibile identificare componenti di varia natura tra i quali alcuni finora sconosciuti in questo campo. Una serie di composti inorganicipresenti fanno pensare alle preferenze delle matrone romane, altri alle vie commerciali diapprovvigionamento, altri ancora alle tecnologie per l’elaborazione del cosmetico. In generale, è possibile rilevare l’impiego di materiali di varia origine, di larga diffusione e di talora complessa preparazione. Non mancano però alcune singolarità,che si riferiscono all’uso di prodotti e tonalità particolari, di probabile provenienza extraitalica.

2006 - Gli unguentari pompeiani e il loro contenuto -seconda parte [Articolo su rivista]
Baraldi, Cecilia; Gamberini, Maria Cristina; Baraldi, Pietro; Mp, Colombini; E., Ribechini
abstract

Il gruppo di studio sulla cosmesi antica e moderna, costituito da ricercatori delle Università di Modena e Reggio Emilia e di Pisa, ha analizzato il contenuto di un gruppo di balsamari di area Campana. Mediante tecniche di spettroscopia infrarossa, microscopia Raman e di gascromatografia abbinata alla spettrometria di massa è stato possibile identificare componenti di varia natura tra i quali alcuni finora sconosciuti in questo campo. Una serie di composti inorganici presenti fanno pensare alle preferenze delle matrone romane, altri alle vie commerciali di approvvigionamento, altri ancora alle tecnologie per l’elaborazione del cosmetico. In generale, è possibile rilevare l’impiego di materiali di varia origine, di larga diffusione e di talora complessa preparazione. Non mancano però alcune singolarità, che si riferiscono all’uso di prodotti e tonalità particolari, di probabile provenienza extraitalica.

2006 - Solid state characterization of chloramphenicol palmitate. Raman spectroscopy applied to pharmaceutical polymorphs [Articolo su rivista]
Gamberini, Maria Cristina; Baraldi, Cecilia; A., Tinti; Rustichelli, Cecilia; Ferioli, Valeria; Gamberini, Gianfranco
abstract

A pharmaceutical active compound, chloramphenicol palmitate, appears in three polymorphic forms, that can be observed at room temperature.The stable form A (biologically inactive modification), the meta-stable form B (active modification) and unstable form C were found to have distinct Raman spectra, with bands attributable to the different polymorphs.The use of hot-stage Raman microscopy (the direct coupling of Raman microscopy and hot-stage) is demonstrated for the drug substance chloramphenicol palmitate form C. All modifications of form C were produced and identified by hot-stage Raman microscopy. A close correlation of thermal and spectroscopic information was achieved by this combination of techniques.As reported in several pharmacopoeias, the content of form A should be less than 10%; therefore, a mixture of 10% (w/w) A in B was prepared, and the presence of the characteristic bands of form A after subtraction of the pure B was revealed. Moreover, mixtures between 2 and 12% (w/w) A in B were investigated and the intensity ratio (as peak area) I413–435/I1035–1158 as a function of A percentage has been demonstrated to show a linear trend. Other methods for the characterization of polymorphs were used: Fourier transform infrared spectroscopy (FT-IR), Diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).

2005 - Direct HPLC enantioseparation of Cetirizine Hydrochloride on polysaccharide-based chiral stationary phases [Abstract in Atti di Convegno]
Rustichelli, Cecilia; Gamberini, Maria Cristina; Baraldi, Cecilia; Ferioli, Valeria; Gamberini, Gianfranco
abstract

Cetirizine hydrochloride is a non-sedating H1-receptor antagonist used in patients whit urticaria and allergic rhinitis. It is frequently administrated as racemate; although recent data demonstrate that the antihistaminergic activity of the racemate is primarily due to the levo-enantiomer, while dextrocetirizine failed to demonstrate any significant activity. Moreover levocetirizine exhibits a more pharmacokinetic behaviour due to a lower volume of distribution and a slower renal clearance; therefore cetirizine has been recently marked as levo- enantiomer (Xyzal) in Europe. In order to study the simultaneous determination of (+)- and (-)- cetirizine hydrochloride we have developed direct separation methods by HPLC on polysaccharide-based chiral stationary phases. Satisfactory results were achieved on a Chiralcel OD-R column under gradient elution whit a mobile phase of acetonitrile and perchlorate buffer (0.3M; pH 3.30); these conditions allowed the complete enantioseparations (Rs= 1.65) of the analyte in times suitable for routine analyses. Complete separations in short analysis time (Rs= 1.61) were performed on a Chiralcel OD column under isocratic normal phases conditions (85% n-hexane and 15% ethanol, containing 0.15% trifluoroacetic acid). These conditions were applied to the determination of the stability of cetirizine hydrochloride in methanolic solutions and our studies revealed the formation of an achiral and a chiral degradation product. The developed procedures could be of interest for routine analyses and stereoselective investigations.

2005 - Raman Spectroscopy applied to polymorphism of Tamoxifene Citrate [Abstract in Atti di Convegno]
Gamberini, Maria Cristina; Rustichelli, Cecilia; Baraldi, Cecilia; Ferioli, Valeria; Gamberini, Gianfranco
abstract

Different strategies for a systematic study of polymorphism can be applied: XRPD, DSC, FT-IR and Raman spectroscopy. Unlike X-ray diffraction Raman microscopy, a non-destructive and non-invasive technique, can be applied to pure solids or dosage forms without any sample preparation. The ability of Raman spectroscopy to discriminate between polymorphs has been demonstrated: different crystal structures usually show intensity and frequenciey changes in the Raman spectrum particularly in the rather crowded area from ~ 500 to ~ 1700 cm-1, known as “fingerprint region” which contains the majority of the bands used to identify a particular material. The use of Raman microscopy has been demonstrated for Tamoxifen Citrate: its trans isomer is in fact well known for its endocrine activity as an antiestrogenic agent. Tamoxifen citrate exists in two polymorphic form A and B, Which were found to have a distinct micro Raman spectrum whith bands attributable to the different forms. Another possible form was found and its Raman spectrum is different from the others. Other methods for the characterization of the three forms were used: XRDP, DSC, ATR/FTIR. Because of its non-invasive character, by focusing the micro Raman laser in to a capillary tube the convertion at room temperature of a suspension in ethanol of form A to B has been observed. Finally, the sensitivity to polymorphism of Raman spectroscopy, which makes it an ideal candidate for studies of crystal forms of Pharmaceutical compounds, could be analysed.

2004 - Enantioselective analyses of antihistaminic drugs by high performance liquid chromatography [Articolo su rivista]
Rustichelli, Cecilia; Gamberini, Maria Cristina; V., Ferioli; Gamberini, Gianfranco
abstract

High-performance liquid chromatographic methods have been developed for stereoselective separations of terfenadine and its active metabolite fexofenadine.Satisfactory enantioseparations of racemic terfenadine were achieved on a Chiralcel column by normal phase elution. Analysis of racemic fexofenadine, as such, took a very long time and achieved poor enantioselectivity on this column; nevertheless, the analyte when derivatised with diazomethane was well resolved.Racemic fexofenadine was also derivatised using a chiral agent: R-(+)-1-phenylethylisocyanate and subjected to achiral LC on a reversed-phase analytical column. Complete enantioseparations were achieved in short analysis times; excess reagent eluted before the diastereoisomeric pair and did not interfere.

2004 - Ricerca sul contenuto dei Balsamari di Oplontis [Articolo su rivista]
Baraldi, Pietro; Baraldi, Cecilia; C., Fagnano; Ferioli, Valeria; Gamberini, Maria Cristina
abstract

Sono stati presi in considerazione i balsamari rinvenuti al momento dello scavo della villa B di Oplontis. Mediante moderne tecniche di analisicome la gascromatografia abbinata alla spettrometria di massa e la spettroscopia infrarossa sono stati identificati sia i componenti inorganici che organici. Il contenuto dei balsamari è risultato prevalentemente di origine organica e permette di ipotizzare dai residui individuati la presenza originaria di grassi e di essenze di provenienza anche extraeuropea. Questo permette da una parte di comprovare una abilità locale per l'estrazione per l'estrazione e la lavorazione di prodotti cosmetici e dall'altra l'esistenza di vie commerciali dall'Estremo Oriente nel I sec. d.C. Alcune delle presenze accertate sono indicative dell'elevato livello di vita degli abitanti della domus.

2003 - Detachment of titanium and fluorohydroxyapatite particles in unloaded endosseous implants [Articolo su rivista]
Martini, D.; Fini, M.; Franchi, M.; De Pasquale, V.; Bacchelli, B.; Gamberini, M.; Tinti, A.; Taddei, P.; Giavaresi, G.; Ottani, V.; Raspanti, M.; Guizzardi, S.; Ruggeri, A.
abstract

The shape, surface composition and morphology of orthopaedic and endosseous dental titanium implants are key factors to achieve post-surgical and long-term mechanical stability and enhance implant osteointegration. In this study a comparison was made between 12 titanium screws, plasma-spray-coated with titanium powders (TPS), and 12 screws with an additional coating of fluorohydroxyapatite (FHA-Ti). Screws were implanted in the femoral and tibial diaphyses of two mongrel sheep and removed with peri-implant tissues 12 weeks after surgery. The vibrational spectroscopic, ultrastructural and morphological analyses showed good osteointegration for both types of implants in host cortical bone. The portion of the FHA-Ti implants in contact with the medullary canal showed a wider area of newly formed peri-implant bone than that of the TPS implants. Morphological and EDAX analyses demonstrated the presence of small titanium debris in the bone medullary spaces near the TPS surface, presumably due to the friction between the host bone and the implant during insertion. Few traces of titanium were detected around FHA-Ti implants, even if smaller FHA debris were present. The present findings suggest that the FHA coating may act as a barrier against the detachment of titanium debris stored in the medullary spaces near the implant surface. © 2002 Elsevier Science Ltd. All rights reserved.

2002 - Binding of 1-benzopyran-4-one derivatives to aldose reductase: A free energy perturbation study [Articolo su rivista]
Rastelli, Giulio; Costantino, Luca; Gamberini, Maria Cristina; A., Del Corso; U., Mura; Jm, Petrash; Am, Ferrari; S., Pacchioni
abstract

The relative binding affinities to human aldose reductase (ALR2) of three new 7-hydroxy-2-benzyl-4H-1-benzopyran-4-one inhibitors were predicted by free energy perturbation (FEP) simulations. Molecular substitutions were specifically designed to investigate the role of hydrogen bonding at the active site of ALR2. Starting from the lead inhibitor 7-hydroxy-2-(4'-hydroxy-benzyl)-4H-1-benzopyran-4-one, the 4'-hydroxyl was mutated to methyl and to trifluoromethyl, and an hydroxyl at position 8 was additionally introduced. Once synthesized and tested as inhibitors of ALR2, the compounds displayed variations of K-i that were in qualitative to quantitative agreement with the calculated relative free energies of binding. The results, discussed in terms of balance between free energies of solvation and free energies of binding to ALR2, elucidate the importance of hydrogen bonding with Thr113 and with Trp111 and cofactor, and provide a rationale to the observed differences in binding affinities. (C) 2002 Elsevier Science Ltd. All rights reserved.

2002 - Discovery of new inhibitors of aldose reductase from molecular docking and database screening [Articolo su rivista]
Rastelli, Giulio; Am, Ferrari; Costantino, Luca; Gamberini, Maria Cristina
abstract

Aldose reductase (ALR2) is a target enzyme for the treatment of diabetic complications. Owing to the limited number of currently available drugs for the treatment of diabetic complications, the discovery of new inhibitors of ALR2 that can potentially be optimized as drugs appears highly desirable. In this study, a molecular docking analysis of the structures of more than 127,006 organic compounds contained in the National Cancer Institute database was performed to find and score molecules that are complementary to ALR2. Besides retrieving several carboxylic acid derivatives, which are known to generally inhibit aldose reductase, docking proposed other families of putative inhibitors such as sulfonic acids, nitro-derivatives, sulfonamides and carbonyl derivatives. Twenty-five compounds, chosen as the highest-scoring representatives of each of these families, were tested as aldose reductase inhibitors. Five of them were found to inhibit aldose reductase in the micromolar range. For these active compounds, selectivity with respect to the closely-related aldehyde reductase was determined by measuring the corresponding inhibitory activities. The structures of the complexes between the new lead inhibitors and aldose reductase, here refined with molecular mechanics and molecular dynamics calculations. suggest that new pharmacophoric groups can bind aldose reductase very efficiently. In the case of the family of the nitro-derivative-inhibitors. a class of particularly interesting compounds, a round of optimizations was performed with the synthesis and biological evaluation of a series of derivatives aimed at testing the proposed binding mode and at improving interaction with active site residues. Starting from a hit compound having an IC50 of 42 muM, the most potent compound synthesized showed a 10-fold increase in inhibitory activity and 10-fold selectivity with respect to ALR1, and structure-activity relationships of the designed compounds were in agreement with the proposed mode of binding at the active site.

2002 - Mappatura e indagine sui reperti cosmetici rinvenuti a Pompei [Abstract in Atti di Convegno]
Ferioli, Valeria; Baraldi, Pietro; C., Fagnano; Gamberini, Maria Cristina; Baraldi, Cecilia
abstract

La città di Pompei rappresenta un unicum per qualità e quantità di reperti archeologici anche di tipo cosmetico. Da un’indagine condotta in archivio in collaborazione con il Laboratorio della Soprintendenza Archeologica di Pompei è emersa la presenza di un numero elevato di unguentari, balsamari e alabastra. Purtroppo le pratiche di reperimento e conservazione dei tempi passati ha eliminato il contenuto di gran parte dei contenitori considerati. In poco più di un centinaio di essi rispetto ad un totale di oltre un migliaio sono state rinvenute quantità più o meno cospicue del contenuto. Di questi è stato considerato un gruppo che presentava materiale polverulento colorato. A differenza dei balsamari di Oplontis, quelli di Pompei sono apparsi tutti di natura molto differente. Un gran numero conteneva polvere di un colore o nero vellutato o bianco candido e solo in alcuni casi si è rilevato un colore differente. Per l’identificazione della natura dei cosmetici sono state impiegate la spettroscopia FT-IR associata alla microscopia Raman e la gascromatografia abbinata alla spettrometria di massa GC-MS. Gli spettri infrarossi e Raman hanno consentito di accertare che i prodotti neri sono costituiti da carbone di probabile origine vegetale, un tipo di kohl facilmente reperibile, quelli bianchi da gesso diidrato, talora mescolato con calcite, il giallo da goethite. Non sono mancate identificazioni insolite, come ad es. cerussite, aragonite, anglesite, sulla cui origine sono possibili varie ipotesi. L’analisi degli estratti metanolici mediante GC-MS in molti casi non ha mostrato la presenza di componenti organici. Questo può indicare che venivano impiegati prevalentemente prodotti inorganici, ma anche che nei balsamari i cosmetici erano conservati allo stato di polvere e che solo al momento dell’uso una piccola quantità veniva mescolata con un legante che ne consentisse l’applicazione. La natura del contenuto dei balsamari fa propendere per un campionario di prodotti ristretto e di tipo popolare, rispetto a quelli corrispondenti di Oplontis. L’analisi della distribuzione statistica dei balsamari, anche non aventi contenuto, è risultato di interesse in quanto può, in qualche rispetto, essere collegato all’evento finale della città nel 79 d.C. e al valore e al significato attribuito ai balsamari in epoca Romana. La ricerca è stata condotta sul finanziamento CNRC00BEAC_002 Si ringrazia la Soprintendenza Archeologica di Pompei per aver reso possibile la Ricerca.

2002 - Nitrophenyl derivatives as Aldose Reductase inhibitors [Articolo su rivista]
Costantino, Luca; A. M., Ferrari; Gamberini, Maria Cristina; Rastelli, Giulio
abstract

Nitrophenyl derivatives were recently discovered as a new class of ALR2 inhibitors by means of docking and database screening of the National Cancer Institute database of organic molecules. The nitro group was predicted to bind to the Tyr48 and His110 active site residues of the enzyme, the site where acidic ALR2 inhibitors such as carboxylic acids bind in their anionic form. Given the novelty of these compounds, we decided to expand their structure-activity relationships by synthesizing and testing a series of derivatives and the corresponding compounds having a carboxylic group instead of the nitro moiety; the results obtained were rationalized by means of docking and molecular dynamics simulations. On the whole there is an agreement between inhibitory data and the results of molecular modeling experiments, supporting the hypothesized binding mode of these compounds.

2002 - Study of flavonoids/beta-cyclodextrins inclusion complexes by NMR, FT-IR, DSC, X-ray investigation [Articolo su rivista]
R., Ficarra; S., Tommasini; D., Raneri; M. L., Calabro; M. R., Di Bella; Rustichelli, Cecilia; Gamberini, Maria Cristina; P., Ficarra
abstract

Flavonoids are natural substances with a lot of biological activities, including the antioxidant one. Their use in pharmaceutical field is, however, limited by their aqueous insolubility. As the formation of the inclusion complexes can improve their solubility in water, the flavonoids hesperetin, hesperidin, naringenin and naringin have been complexed with beta-cyclodextrin (beta-CD) by the coprecipitation method and studied in solution and in solid state by NMR, FT-IR, differential scanning calorimetry and X-ray techniques, The effects of complexation on the chemical shifts of the internal and external protons of beta-CD in the presence of each flavonoid were observed. (C) 2002 Elsevier Science B.V. All rights reserved.

2000 - Pharmacological approaches to the treatment of diabetic complications [Articolo su rivista]
Costantino, Luca; Rastelli, Giulio; Gamberini, Maria Cristina; D., Barlocco
abstract

Diabetes is often accompanied by several long-term complications such as neuropathy, nephropathy, retinopathy, cataract and angiopathy; their occurrence has been linked to the modification of the physiological levels of glycaemia. Several interrelated metabolic pathways have been implicated in the toxic effects of glucose; the polyol pathways was one of the first considered. However, while in diabetic animal models the inhibitors of aldose reductase (ALR2, the first enzyme of this pathway) seem to be active, 16 years of clinical trials, based mainly on neuropathy, have been inconclusive; only one drug currently being marketed. Newer potent and selective aldose reductase inhibitors have been discovered in the last few years, but the lack of commercial success has probably led to the very rapid decrease in the number of patents relating to newer aldose reductase inhibitors. Inhibition of the second enzyme of this pathway, sorbitol dehydrogenase (SDH), has been shown to be detrimental. Other approaches for the prevention and the delay of progression of diabetic complications seem to be more promising, namely, the inhibition of the formation of advanced glycated end products (AGEs) or protein kinase C (PKC) β2 inhibition; compounds acting on these two pathways have proved effective in retarding the development of diabetic complications in animal models and some products are in clinical trials at the moment. Renewed attention has been paid to vascular involvement in the pathogenesis of diabetic neuropathy; the biological activity of C-peptide and the role of endothelin-1 (ET-1) in diabetic vascular disease are emerging as a new research area for the treatment of diabetic complications.

2000 - Solid-state study of polymorphic drugs: carbamazepine [Articolo su rivista]
Rustichelli, Cecilia; Gamberini, Gianfranco; Ferioli, Valeria; Gamberini, Maria Cristina; R., Ficarra; S., Tommasini
abstract

Polymorphs of a compound have solid crystalline phases with different internal crystal lattices; in pharmaceuticals,differences due to polymorphism and pseudopolymorphism can affect bioavailability and effective clinical use. Theaim of this work was to obtain the different polymorphic modifications of the anticonvulsant drug, carbamazepine,and to characterise them by means of typical structure-sensitive analytical techniques, such as FT-IR spectroscopy,XRPD and DSC. Further investigations were also performed by Hot Stage FT-IR thermomicroscopy, whichpermitted the visible and spectroscopic characterisation of the polymorphic forms during heating. Our results confirmthe existence of three different polymorphic forms for anhydrous carbamazepine: Form III, the commercial one,Form I, obtained by heating Form III and Form II, crystallised from ethanolic solution. Substantial differences weredetected among the polymorphs with regard to solid-state properties. Moreover, Hot Stage FT-IR thermomicroscopyproved its analytical potential to characterise the drug’s polymorphism.

2000 - Study of β-blockers/β-cyclodextrins inclusion complex by NMR, DSC, X-ray and SEM investigation [Articolo su rivista]
R., Ficarra; P., Ficarra; MR DI, Bella; D., Raneri; S., Tommasini; Ml, Calabro'; Gamberini, Maria Cristina; Rustichelli, Cecilia
abstract

...

1999 - Isoxazolo-[3,4-d]-pyridazin-7-(6H)-one as a potential substrate for new aldose reductase inhibitors [Articolo su rivista]
Costantino, Luca; Rastelli, Giulio; Gamberini, Maria Cristina; Mp, Giovannoni; V., DAL PIAZ; P., Vianello; D., Barlocco
abstract

The isoxazolo-[3,4-d]-pyridazin-7-(6H)-one (2) and its corresponding open derivatives 5-acetyl-4-amino-(4-nitro)-6-substituted-3(2H)pyridazinones (3, 4) were used as simplified substrates for the synthesis of new aldose reductase inhibitors with respect to the previously reported 5, 6-dihydrobenzo[h]cinnolin-3(2H)one-2 acetic acids (1). Moreover, a few derivatives lacking the 5-acetyl group were prepared. Several compounds derived from 2 displayed inhibitory properties comparable to those of Sorbinil. In this class the presence at position 6 of a phenyl carrying an electron-withdrawing substituent proved to be beneficial, independently from its position on the ring (5g,j-l). Acetic acid derivatives were more effective than propionic and butyric analogues. On the contrary, all the monocyclic compounds (6-8) were either inactive or only weakly active. The 3-methyl-4-(p-chlorophenyl)isoxazolo-[3,4-d]-pyridazin-7-(6H )-one acetic acid (5g), which proved to be the most potent derivative, was also investigated in molecular modeling studies, to assess possible similarities in its interaction with the enzyme, with respect to the model 1

1999 - Properties of the racemic species of verapamil hydrochloride and gallopamil hydrochloride [Articolo su rivista]
Rustichelli, Cecilia; Gamberini, Maria Cristina; Ferioli, Valeria; Gamberini, Gianfranco
abstract

It is well known that the stereoselective actions associated with the enantiomeric constituents of a racemic drug candiffer markedly in their pharmacodynamic or pharmacokinetic properties. Nevertheless, molecular chirality manifestsitself in the solid, that is, crystalline state. The aim of this work was to characterize the solid-state properties ofverapamil HCl and gallopamil HCl, two well-known chiral calcium channel antagonists. The characterization of thesolid state for the single enantiomers and equimolecular mixtures for both the calcium antagonists was performed bysolid-state techniques such as Fourier transform infrared (FT-IR spectroscopy), X-ray powder diffractometry (XRD)and differential scanning calorimetry (DSC). The FT-IR spectra and XRD of the single enantiomers are differentfrom those of the corresponding equimolecular mixture owing to their different crystalline structure. The thermalbehavior of the racemates and pure enantiomers were examined by DSC, and the resultant experimental andtheoretical binary phase diagrams are discussed. Spectroscopic solid-state techniques, such as FT-IR and XRD, areuseful in combination with thermal analysis for characterizing the racemic species of chiral drugs. The data obtainedprove that the equimolecular mixtures of both verapamil hydrochloride and gallopamil hydrochloride exist as racemiccompounds. Determination of the enantiomeric purity of the enantiomers and racemic compounds of both thecalcium antagonists analyzed was performed by DSC.

1999 - Solid-state study of polymorphic drugs: carbamazepine [Abstract in Atti di Convegno]
Rustichelli, Cecilia; G., Gamberini; V., Ferioli; Gamberini, Maria Cristina; R., Ficarra; S., Tommasini
abstract

Aim of this work was to obtain the different polymorphic modifications of anhydrous carbamazepine and to characterise them by means of typical structure-sensitive analytical techniques, such as Ft-IR, DRIFT, XRPD and DSC.

1999 - Structure of beta-blockers/beta cyclodextrin inclusion complex by NMR, X-Ray and DSC investigation [Abstract in Atti di Convegno]
P., Ficarra; S., Tommasini; M. R., Di Bella; D., Raneri; R., Ficarra; M. L., Calabrò; Gamberini, Maria Cristina; Rustichelli, Cecilia
abstract

The inclusion complexes between two beta-blockers, atenolol and celiprolol, and the beta-cyclodextrin has been investigated in solution and in the solid state using X-Ray, DSC and NMR.

1999 - 1-Benzopyran-4-one antioxidants as aldose reductase inhibitors [Articolo su rivista]
Costantino, Luca; Rastelli, Giulio; Gamberini, Maria Cristina; Ja, Vinson; P., Bose; Iannone, Anna; M., Staffieri; L., Antolini; A., DEL CORSO; U., Mura; A., Albasini
abstract

Starting from the inhibitory activity of the flavonoid Quercetin, a series of 4H-1-benzopyran-4-one derivatives was synthesized and tested for inhibition of aldose reductase, an enzyme involved in the appearance of diabetic complications. Some of the compounds obtained display inhibitory activity similar to that of Sorbinil but are more selective than Quercetin and Sorbinil with respect to the closely related enzyme, aldehyde reductase, and also possess antioxidant activity. Remarkably, these compounds possess higher pK(a) values than carboxylic acids, a characteristic which could make the pharmacokinetics of these compounds very interesting. Molecular modeling investigations on the structures of inhibitors bound at the active site of aldose reductase were performed in order to suggest how these new inhibitors might bind to the enzyme and also to interpret structure-activity relationships.