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Pagina personale di Erika FERRARI

Dipartimento di Scienze Chimiche e Geologiche
Dipartimento di Scienze Chimiche e Geologiche - Sede Dipartimento di Scienze Chimiche e Geologiche

Nardo, Luca; Maspero, Angelo; Penoni, Andrea; Palmisano, Giovanni; Ferrari, Erika; Saladini, Monica ( 2017 ) - Excited state dynamics of bis-dehydroxycurcumin tert-butyl ester, a diketo-shifted derivative of the photosensitizer curcumin - PLOS ONE - n. volume 12 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Bis-dehydroxycurcumin tert-butyl ester (K2T23) is a derivative of the natural spice curcumin. Curcumin is widely studied for its multiple therapeutic properties, including photosensitized cytotoxicity. However, the full exploitation of curcumin phototoxic potential is hindered by the extreme instability of its excited state, caused by very efficient non radiative decay by means of transfer of the enolic proton to the nearby keto oxygen. K2T23 is designed to exhibit a tautomeric equilibrium shifted toward the diketo conformers with respect to natural curcumin. This property should endow K2T23 with superior excited-state stability when excited in the UVB band, i.e., in correspondence of the diketo conformers absorption peaks, making this compound an interesting candidate for topical photodynamic therapy of, e.g., skin tumors or oral infections. In this work, the tautomeric equilibrium of K2T23 between the keto-enolic and diketo conformers is assessed in the ground state in several organic solvents by UV-visible absorption and by nuclear magnetic resonance. The same tautomeric equilibrium is also probed in the excited-state in the same environments by means of steady-state fluorescence and time-correlated single-photon counting measurements. These techniques are also exploited to elucidate the excited state dynamics and excited-state deactivation pathways of K2T23, which are compared to those determined for several other curcuminoids characterized in previous works of ours. The ability of K2T23 in photosensitizing the production of singlet oxygen is compared with that of curcumin.

Rubagotti, Sara; Croci, Stefania; Ferrari, Erika; Orteca,Giulia; Iori, Michele; Capponi, Pier C.; Versari, Annibale; Asti, Mattia ( 2017 ) - Uptake of Ga-curcumin derivatives in different cancer cell lines: toward the development of new potential 68Ga-labelled curcuminoids-based radiotracers for tumour imaging. - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 173 - pp. da 113 a 119 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Thanks to the ability to suppress the proliferation and to kill tumour cells, several studies have shown the anti-cancer effects of curcumin (CUR) and its derivatives, i.e. diacetylcurcumin (DAC) and bis-dehydroxycurcumin (bDHC). This study is focused onto the development of curcuminoid complexes with gallium-68 employed as potential new radio-labelled probes to detect neoplastic tissues through imaging techniques such as positron emission tomography. To this purpose, the uptake of three Ga-curcuminoid complexes, namely Ga(CUR)2+, Ga(DAC)2+, Ga(bDHC)2+, by various tumour cell lines was compared with the uptake of the same compounds by normal human lymphocytes by flow cytometry using the intrinsic fluorescence of the curcuminoids. Ga(CUR)2+, and particularly Ga(DAC)2+, showed a higher uptake by colorectal carcinoma (HT29) and lymphoma (K562) cell lines than lymphocytes, while the uptake of Ga(bDHC)2+ was higher in lymphocytes than in all the other cell lines. Based on the fluorescence data, Gallium-68 labelled complexes were then tested in HT29 cell line. 68Ga(DAC)2+ showed the highest uptake by HT29 cells (higher internalization with a lower externalization) and the highest affinity. The obtained results are promising and the findings foster further investigation on the development of curcumin-metal-based radiopharmaceuticals.

Rosa, Roberto; Tassi, Lorenzo; Orteca, G.; Saladini, Monica; Villa, Carla; Veronesi, Paolo; Leonelli, Cristina; Ferrari, Erika ( 2017 ) - Process Intensification by Experimental Design Application to Microwave-Assisted Extraction of Phenolic Compounds from Juglans regia L. - FOOD ANALYTICAL METHODS - n. volume 10 - pp. da 575 a 586 ISSN: 1936-9751 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Microwave-assisted extraction was applied to Juglans regia L. fresh male flowers and unripe walnut seeds to evaluate the total phenolic contents of the extracts as well as the percentage of water-soluble polyphenols. The research was planned using the Design of Experiments technique to investigate the role on the extraction efficiency of different parameters, such as temperature, time and number of microwave heating cycles, together with their possible interactions. Optimization was achieved by applying a Response Surface Methodology comprising a three-factor, two-level, full-factorial Face-Centred Central Composite Design. The two input variables with a significant effect on the recovery of phenols from fresh male flowers were the extraction temperature and the number of microwave cycles. In the case of unripe walnut seeds, a linear two-factor interaction model was selected, with significant interactions occurring between temperature and time, and time and number of microwave cycles. The best experimental conditions were as follows: 100 °C, 6 min, three microwave heating cycles and 22.7 ± 0.2 mg gallic acid equivalent (GAE)/g (total phenolic content, PC); energy consumption calculations suggested slightly different conditions: 60 °C, 30 min, three microwave heating cycles and 20.7 ± 0.3 mg GAE/g (TPC).

Ferrari, Erika; Benassi, Rois; Saladini, Monica; Orteca, Giulia; Gazova, Zuzana; Siposova, Katarina ( 2017 ) - In vitro study on potential pharmacological activity of curcumin analogues and their copper complexes - CHEMICAL BIOLOGY & DRUG DESIGN - n. volume 89 - pp. da 411 a 419 ISSN: 1747-0277 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcumin and its derivatives have attracted great interest in the prevention and treatment of Alzheimer's disease, thanks both to the ability to hinder the formation of amyloid-beta (Aβ) aggregates and the ability to bind Cu (II) ion. In this article, we explore the ability of curcumin derivatives of K2T series to affect amyloid Aβ1-40 aggregation. These derivatives were obtained by introducing the t-butyl ester group through a methylenic spacer on the central carbon atom of the β-diketo moiety of curcumin frame. The studied curcuminoids were demonstrated to inhibit Aβ1-40 fibrillization at substoichiometric concentrations with IC50 value near that of curcumin. In addition, the antioxidant properties and DNA interaction of their Cu(II) complexes is evaluated. The structure of Cu(II)-K2T31 complex is also proposed on the basis of DFT calculation.

Romagnoli, Chiara; Prati, Fabio; Benassi, Rois; Orteca, Giulia; Saladini, Monica; Ferrari, Erika ( 2017 ) - Synthesis, characterization and metal coordination of a potential β-lactamase inhibitor: 5-Methyl-2-phenoxymethyl-3-H-imidazole-4-carboxylic acid (PIMA) - ARABIAN JOURNAL OF CHEMISTRY - n. volume 10 - pp. da 1061 a 1069 ISSN: 1878-5352 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Among relevant metal ions in biological systems, zinc and iron play a key role as active partners of the catalytic machinery. In particular, the inhibition of metal enzymes that are involved in physiological and pathological processes has been deeply investigated for the rational design of selective and efficient drugs based on chelators. Since imidazole histidine residue is one of the most versatile sites in proteins, especially in enzymes acting in the presence of metal ions as cofactors, in this work the synthesis and characterization of a new imidazole derivative, namely 5-methyl-2-phenoxymethyl-3-H-imidazole-4-carboxylic acid (PIMA) is reported. PIMA was designed as metallo-β-lactamase inhibitor thanks to its similarity with penicillin V, a β-lactam antibiotic inactivated by metallo-β-lactamase, for which there are no commercially available inhibitors. The evaluation of PIMA coordinating ability toward iron, zinc, and gallium, these latter selected as a non-paramagnetic probe for iron, is performed by theoretical DFT calculations and in solution by experimental techniques, i.e. potentiometry, UV-vis and NMR spectroscopy. PIMA exhibits an efficient metal chelating ability; the prevailing species in physiological condition are ML3 for Fe3+ and Ga3+ and ML2 for Zn2+, in which chelation is due to deprotonated carboxylic oxygen and imidazole nitrogen in the N,O donor set. The demonstrated ability of PIMA to chelate zinc ion, combined with its structure similarity with penicillin V, supports further exploration of this imidazole-4-carboxylate as metallo-β-lactamase inhibitor.

Rosa, Roberto; Zerazion, Elisabetta; Ferrari, Erika; Veronesi, Paolo; Villa, Carla; Saladini, Monica; Ferrari, Anna Maria; Leonelli, Cristina ( 2016 ) - Microwave-assisted extraction of phytochemicals ( The 3rd Global Congress on Microwave Energy Applications - - 25 - 29 Luglio 2016) ( - 3GCMEA - Atti del 3rd Global Congress on Microwave Energy Applications ) [Abstract in Atti di convegno (274) - Abstract in Atti di Convegno]
Abstract

Several epidemiological studies highlighted the importance of a diet based on fruits and vegetables, for a significant reduction in the risk of several human health diseases [1]. Therefore, the extraction of the so-called dietary phytochemicals started gaining an extraordinary research interest from both academia and industries, to the detriment of their synthesis, particularly when the concepts and principles of Green Extraction [2] and Process Intensification [3] are considered, in order to pursue a sustainable development. Among the green extraction techniques, the application of microwave energy is surely to be considered one of the most appealing ones, mainly as a direct consequence of its unique heating mechanism. According to the nature of the plant matrix as well as of the phytochemical compounds of interest, microwaves can be applied in a plenty of variants. Aim of the present work is to display some of our recent results obtained by microwave assisted extraction (MAE) of phenolic compounds from Juglans regia L., Cinnamomum Zeylanicum and Curcuma longa L. [4], highlighting the advantages, when any, over more conventional extraction procedures as well as over the chemical synthesis of those molecules, also in terms of energy consumptions as well as environmental assessments of these different approaches.

Rosa, Roberto; Zerazion, Elisabetta; Ferrari, Erika; Veronesi, Paolo; Leonelli, Cristina; Saladini, Monica; Ferrari, Anna Maria ( 2016 ) - Cradle to the grave Life Cycle Assessment of microwave assisted vs. conventional extraction for the obtainment of highly pure curcumin ( GENP 2016, the International Congress on Green Extraction of Natural Products - - 31 Maggio – 1 Giugno 2016) ( - Atti dell' International Congress on Green Extraction of Natural Products ) [Abstract in Atti di convegno (274) - Abstract in Atti di Convegno]
Abstract

Microwave assisted extraction of natural compounds is widely recognized as one of the most promising green extraction techniques, even if comprehensive comparisons with more conventional procedures are surprisingly scarce, being on the other hand limited to mere considerations concerning extraction time and yield. In this work, “cradle to the grave” environmental assessments of microwave assisted compared to conventional Soxhlet-based extraction procedures will be presented, for the particular case of curcumin molecule, extracted from Curcuma longa L., in view of its important antioxidant, anti-inflammatory and anticancer properties. The Life Cycle Assessment (LCA) methodology was applied, since it allows evaluating the environmental consequences associated with all the stages of the extraction process, thus including the crop production of the Indian plant, the subsequent production of the dried rhizomes, their commercialization, their transport, all the energy consumptions needed, the necessary laboratory facilities and their maintenance, together with the chemicals needed and their disposal treatments. The study was then completed by also comparing the obtained results with those of a particular synthetic strategy of curcumin, in order to establish the most environmentally friendly production procedure of this fundamental phytochemical.

Nicolini, Valentina; Caselli, Monica; Ferrari, Erika; Menabue, Ledi; Lusvardi, Gigliola; Saladini, Monica; Malavasi, Gianluca ( 2016 ) - SiO2-CaO-P2O5 bioactive glasses: A promising curcuminoids delivery system - MATERIALS - n. volume 9 - pp. da 1 a 11 ISSN: 1996-1944 [Articolo in rivista (262) - Articolo su rivista]
Abstract

In this paper, we report the study of the loading and the release of curcuminoids by bioactive glasses (BG) and mesoporous bioactive glasses (MBG). Through a detailed spectroscopic study, it was possible to determine the amount and the type of molecules released in water and in simulated body fluid (SBF). In particular, curcumin and K2T21 show a good ability to be released in di-keto and keto-enolic form, depending from the pH. However, after 24 h, the amount of pristine curcumin release is very low with a consequent increment of degradation products derived by curcuminoids. The presence of -OH groups on curcuminoids is a fundamental pre-requisite in order to obtain a high loading and release in polar solution such as water and SBF. The substrate on which we loaded the drugs does not seem to affect significantly the loading and the release of the drugs. The environment, instead, affects the release: for all the drugs, the release in SBF, buffered at pH of 7.4, is slightly worse than the release in water (basic pH values).

Rubagotti, Sara; Croci, Stefania; Ferrari, Erika; Iori, Michele; Capponi, Pier C.; Lorenzini, Luca; Calzà, Laura; Versari, Annibale; Asti, Mattia ( 2016 ) - Affinity of nat/68ga-labelled curcumin and curcuminoid complexes for β-amyloid plaques: Towards the development of new metal-curcumin based radiotracers - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES - n. volume 17 - pp. da 1480 a 1493 ISSN: 1661-6596 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer’s disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide). Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of threenat/68Ga-labelled curcumin analogues, namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl-curcumin (DAC), was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of 68Ga(CUR)2+,68Ga(DAC)2+, and68Ga(bDHC)2+ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood-brain barrier. Like curcumin, allnat/68Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo.

Zerazion, Elisabetta; Rosa, Roberto; Ferrari, Erika; Veronesi, Paolo; Leonelli, Cristina; Saladini, Monica; Ferrari, Anna Maria ( 2016 ) - Phytochemical compounds or their synthetic counterparts? A detailed comparison of the quantitative environmental assessment for the synthesis and extraction of curcumin - GREEN CHEMISTRY - n. volume 18 - pp. da 1807 a 1818 ISSN: 1463-9262 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Natural compounds represent an extremely wide category to be exploited, in order to develop new pharmaceutical strategies. In this framework, the number of in vitro, in vivo and clinical trials investigating the therapeutic potential of curcumin is exponentially increasing, due to its antioxidant, anti-inflammatory and anticancer properties. The possibility to obtain this molecule by both chemical synthesis and extraction from natural sources makes the environmental assessments of these alternative production processes of paramount importance from a green chemistry perspective, with the aim, for both industries and academia, to pursue a more sustainable development. The present work reports detailed and quantitative environmental assessments of three different curcumin production strategies: synthesis, conventional Soxhlet-based extraction (CE) and microwave-assisted extraction (MAE). The chemical synthesis of curcumin, as recently optimized by the authors, has been firstly evaluated by using the EATOS software followed by a complete “cradle to the grave” study, realized by applying the Life Cycle Assessment (LCA) methodology. The life cycles of CE and MAE were then similarly assessed, considering also the cultivation of Curcuma longa L., the production of the dried rhizomes as well as their commercialization, in order to firstly investigate the widely claimed green character of MAE with respect to more conventional extraction procedures. Secondly, the results related to the two different extraction strategies were compared to those obtained by the chemical synthesis of curcumin, with the aim to determine its greenest preparation procedure among those investigated. This work represents the first example of an environmental assessment comparison between different production strategies of curcumin, thus smoothing the way towards the highly desirable establishment of environmentally friendly rankings, comprising all the existing alternatives to the chemical synthesis of a target chemical compound.

Zerazion, Elisabetta; Rosa, Roberto; Ferrari, Erika; Neri, Paolo; Ferrari, Anna Maria ( 2015 ) - Analisi comparativa LCA dell’estrazione diretta convenzionale ed innovativa di Curcumina ( CGCS 2015, Terzo Workshop del Gruppo Interdivisionale di Green Chemistry - Chimica Sostenibile - - 12 Giugno 2015.) ( - Atti del Terzo Workshop del Gruppo Interdivisionale di Green Chemistry - Chimica Sostenibile ) [Abstract in Atti di convegno (274) - Abstract in Atti di Convegno]
Abstract

In order to develop new pharmaceutical strategies, natural compounds represent an extremely wide category to exploit. In this landscape, the number of in vitro, in vivo and clinical trials investigating the therapeutic potential of curcumin is exponentially increasing, due to its antioxidant, anti-inflammatory and anti-cancer properties. The possibility to obtain this phytochemical both by chemical synthesis and by extraction from natural sources, makes the environmental assessments of these alternative productions of paramount importance in a green chemistry perspective to pursue an always more sustainable development for industrial and academic research. The present work reports detailed and quantitative environmental assessments of three different curcumin production strategies: synthesis, Soxhlet-based extraction and microwave-assisted extraction. The chemical synthesis of curcumin, as recently optimized by the authors, has been firstly evaluated by using the EATOS software followed by a complete “cradle to the grave” study, realized by applying the Life Cycle Assessment (LCA) methodology, to account for fundamental impact categories, different from the mere quantification of the loads associated to the chemicals employed. Two different extraction strategies were completely assessed and quantified by similar studies, considering also the cultivation of Curcuma longa L., the production of the dried rhizomes as well as their commercialization. Particularly a conventional Soxhlet-based extraction and a microwave-assisted extraction (MAE) procedure were considered, in order to firstly confirm the widely claimed green character of MAE with respect to more conventional extraction procedures. The results related to the two different extraction strategies were finally compared to those obtained in the chemical synthesis of curcumin. Moreover, in order to account for the therapeutic characteristics of curcumin, particularly its well known curative effect on cancer cachexia, a new indicator has been developed and implemented in the present LCA investigation. This work represents the first example of a comparison of productions strategies based on environmental assessments, thus smoothing the way towards a highly desirable establishment of environmentally friendly rankings, comprising all the existing alternatives to the chemical synthesis of a target chemical compound.

Pizzeghello, Diego; Cocco, Stefania; Francioso, Ornella; Ferrari, Erika; Cardinali, Alessandra; Nardi, Serenella; Agnelli, Alberto; Corti, Giuseppe ( 2015 ) - Snow vole (Chionomys nivalisMartins) affects the redistribution of soil organic matter and hormone-like activity in the alpine ecosystem: ecological implications - ECOLOGY AND EVOLUTION - n. volume 5 - pp. da 4542 a 4554 ISSN: 2045-7758 [Articolo in rivista (262) - Articolo su rivista]
Abstract

In alpine environments, colonies of snow vole (Chionomys nivalis Martins) cause strong pedoturbation, which may affect humification process and soil organic matter (SOM) cycling, with repercussions on the hormone-like activity of organics. We investigated the effect of snow vole pedoturbation on the chemical and spectroscopic features of soil organic fractions, and the potential hormone-like activity of humic and fulvic acids (HA, FA). The study site was located on the high-mountain environment of the Majella massif (central Italy). Pedoturbated and regular soils were morphologically described and characterized for pH and content of total organic carbon, total extractable carbon, HA, and FA. Both HA and FA were extracted and investigated using attenuated total reflectance/Fourier transform infrared (ATR/FTIR), nuclear magnetic resonance with high-resolution magic angle spinning (HRMAS-NMR), and H-1-C-13 heteronuclear single quantum coherence (HSQC). HA and FA were also tested for their auxin-like and gibberellin-like activities. Results provide evidences that bioturbated and regular soils contain a poorly decomposed SOM, but HA and FA with a well-defined molecular structure. The HA and FA from both bioturbated and regular soils show a hormone-like activity with a different allocation along the soil profile. In the regular soil, the highest auxin-like activity was shown by HA and FA from Oe1 horizon, while gibberellin-like activity was expressed by FA from Oe2 horizon. Burrowing activity determines a redistribution of organics throughout the profile with a relatively high auxin-like activity in the FA from straw tunnel wall (STW) and gibberellin-like activity in the HA from vole feces (VF). The relative high presence of carboxylic acids, amides, proteins, and amino acids in the FA from STW and the aromatic moieties in the HA from VF put evidences for their different behavior. The fact that snow vole activity has modified the chemical and biological properties of SOM in these soils otherwise considered governed only by low temperature has important ecological implications such as the preservation of soil fertility and vegetal biodiversity.

Gioacchini, Paola; Montecchio, Daniela; Ferrari, Erika; Ciavatta, Claudio; Masia, Andrea; George, Elisabeth; Tonon, Giustino ( 2015 ) - Litter quality changes during decomposition investigated by thermal analysis - IFOREST - n. volume 8 - pp. da 827 a 837 ISSN: 1971-7458 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The litter decomposition process depends on the litter chemical composition, especially the ratio between more labile compounds, cellulose, and the recalcitrant lignin and waxes. Their determination is crucial to predict the process, though lignin measurement presents some limitations due to drawbacks of the different methods. Thermal analysis has been successfully applied to several organic materials in order to obtain quali-quantitative information of the chemical structure of the sample. In this work TG-DTA was used in a short-term litter decomposition study of two broadleaf forest stands of contrasting ages, and the results were compared to those obtained with a chemical method (Klason’s method) commonly used to quantify cellulose and lignin. TG-DTA was applied to the litter and to the cell walls (CW) extracted from the litter, whose cellulose and lignin content was determined using the Klason’s method. When applied to litter, thermal analysis showed a weak correlation with the Klason’s method, though it allowed the detection of the dynamics of waxes, that increased during the decomposition and could influence the later stages of the process. Contrastingly, a good correlation between cellulose and lignin determined with the two methods was found when TG-DTA was applied to the CW. In this case TG-DTA, according to NMR data, also highlighted the changes in the CW chemical structure compared with that of the litters, in particular the loss of waxes and the decreased thermostability of aromatic components. Moreover, a new concept of quality of the decomposing litter, based on the balance between the energy stored in the litter and the energy needed to release it obtained by thermal analysis, was recently introduced. Samples of the old forest litter had an initial energetic balance more favorable than those collected in the young stand. At the end of the period, the decrease in litter quality was greater in the young than in the old forest samples, due to the combined effect of the higher degradation of thermolabile substances and the accumulation of more thermostable components. Thermal analysis seems to have a good potential in litter decomposition studies, as it can link structural and energetic changes during the process.

Zanardi, Chiara; Ferrari, Erika; Pigani, Laura; Arduini, Fabiana; Seeber, Renato ( 2015 ) - Development of an Electrochemical Sensor for NADH Determination Based on a Caffeic Acid Redox Mediator Supported on Carbon Black - CHEMOSENSORS - n. volume 3 - pp. da 118 a 128 ISSN: 2227-9040 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Screen-printed electrode (SPE) modified with carbon black nanoparticles (CB) has been tested as a new platform for the stable deposition of caffeic acid (CFA) on the electrode surface. The electrochemical performance from varying the amount of CFA/CB composite has been tested with respect to NADH determination. The electrocatalytic activity of CFA/CB has also been compared with that of SPEs modified by a single component of the coating, i.e., either CFA or CB. Finally, glycerol dehydrogenase, a typical NADH-dependent enzyme, was deposited on the CFA/CB coating in order to test the applicability of the sensor in glycerol determination.

Zerazion, Elisabetta; Rosa, Roberto; Ferrari, Erika; Leonelli, Cristina; Corradi, Anna; Ferrari, Anna Maria ( 2014 ) - Valutazione ambientale della sintesi della curcumina tramite parametri quantitativi di green metrics ( IX Convegno Nazionale AICIng - - 14-17 Settembre 2014) ( - Atti del IX Convegno Nazionale AICIng ) [Abstract in Atti di convegno (274) - Abstract in Atti di Convegno]
Abstract

La curcumina [(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] è un composto fenolico presente nei rizomi della pianta Curcuma longa L. Essa, così come numerosi suoi derivati, possiede interessanti proprietà antiossidanti, antiinfiammatorie e antitumorali [1]. Per questo motivo la sintesi chimica dei diversi curcuminoidi risulta fondamentale allo scopo di realizzare un accurato studio di tutte le possibili relazioni esistenti tra struttura e proprietà. Lo scopo di questo lavoro è quello di presentare una dettagliata valutazione ambientale del processo sintetico della curcumina così come messo a punto da alcuni degli autori [2]. Infatti, ultimamente accanto ai tradizionali parametri che accompagnano una sintesi chimica (come resa, tempo di reazione, etc.) sta acquisendo sempre maggiore importanza l’utilizzo dei cosiddetti parametri di green metrics, allo scopo di promuovere uno sviluppo sempre più sostenibile, permettendo al chimico organico di scegliere la strategia sintetica meno impattante sull’ambiente e sulla salute umana [3,4]. L’approccio seguito ha previsto l’utilizzo del software EATOS (Environmental Assessment Tool for Organic Synthesis [5,6]) e di uno studio tramite metodologia LCA (Life Cycle Assessment) [7]. Al contrario del software EATOS (che è limitato alla sola valutazione delle sostanze chimiche coinvolte nella sintesi e nel work-up) l’analisi LCA permette di prendere in considerazione numerose altre categorie potenzialmente impattanti quali i consumi energetici, quelli dovuti al trasporto delle materie prime, agli imballaggi delle sostanze utilizzate, e molti altri, permettendo di realizzare una valutazione dell’intero ciclo di vita del processo “dalla culla alla tomba”. I risultati ottenuti permetteranno anche un successivo paragone con il processo estrattivo, così come con le sintesi e le estrazioni che prevedano l’utilizzo di tecniche non convenzionali, come ad esempio il riscaldamento dielettrico a microonde.

Nicolini, Valentina; Malavasi, Gianluca; Ferrari, Erika; Benedetti, Francesco; Luches, Paola; Lusvardi, Gigliola; Castagnetti, Mattia; Valeri, Sergio; Saladini, Monica; Menabue, Ledi ( 2014 ) - Biovetri come potenziali drug delivery systems ed impianti con proprietà antiossidanti ( XII CONVEGNO NAZIONALE AIMAT - - 21-24 Settembre 2014) ( - Atti del XII Convegno Nazionale AIMAT ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

Fra i biomateriali (“materiali progettati per essere usati a contatto con tessuti viventi, organismi o microorganismi”, definizione IUPAC), i biovetri ricevono un interesse sempre maggiore. Tali materiali trovano infatti largo impiego in chirurgia odontoiatrica ed ortopedica, nella produzione di impianti dentali, protesi o riempitivi ossei. Attualmente l’interesse è rivolto soprattutto ai biovetri di seconda e terza generazione: biovetri che oltre a formare un legame chimico coi tessuti che li circondano, sono capaci di indurre una specifica risposta a livello molecolare nei tessuti stessi, come l’osteoinduzione. I biovetri possono essere prodotti con processi ad alte temperature (metodo per fusione) o a basse temperature con i metodi Sol-Gel, ottenendo in questo caso biovetri porosi o con il metodo EISA ottenendo biovetri mesoporosi. Attualmente presso il nostro laboratorio due sono le linee di ricerca sui biomateriali: i) sintesi di biovetri Sol-Gel (BGSG) ed EISA (MBGSG) e verifica della possibilità di impiegarli come drug delivery systems (DDS) di molecole con proprietà antitumorali, quali i curcuminoidi; ii) sintesi per fusione di biovetri a partire dal vetro 45S5, drogati con CeO2 al fine di verificare la Catalase e SOD mimic-like activity di tali sistemi. Sui vetri porosi e mesoporosi, caricati con curcumina ed un suo derivato (K2T21) sono stati effettuati test di rilascio statico e dinamico in SBF. I rilasci sono stati quantificati ed in entrambi i casi le concentrazioni raggiunte dai farmaci nell’organismo sono nell’ordine del micromolare, ovvero sufficienti per manifestare l’attività antitumorale. Per ciò che concerne la valutazione della Catalase mimic-like activity, sono stati condotti test con H2O2 ed è stato verificato che i biovetri ottenuti per fusione manifestano questa proprietà. Sono inoltre in atto misure di rilascio di cerio in acqua e soluzione di SBF.

Asti, Mattia; Ferrari, Erika; Croci, Stefania; Atti, Giulia; Rubagotti, Sara; Iori, Michele; Capponi, Pier C.; Zerbini, Alessandro; Saladini, Monica; Versari, Annibale ( 2014 ) - Synthesis and characterization of 68Ga-labeled curcumin and curcuminoid complexes as potential radiotracers for imaging of cancer and alzheimers disease - INORGANIC CHEMISTRY - n. volume 53 - pp. da 4922 a 4933 ISSN: 0020-1669 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcumin (CUR) and curcuminoids complexes labeled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer’s disease. Gallium-68 is a positron-emitting, generator-produced radionuclide, and its properties can be exploited in situ in medical facilities without a cyclotron. Moreover, CUR showed a higher uptake in tumor cells compared to normal cells, suggesting potential diagnostic applications in this field. In spite of this, no studies using labeled CUR have been performed in this direction, so far. Herein, 68Ga-labeled complexes with CUR and two curcuminoids, namely diacetyl-curcumin (DAC) and bis(dehydroxy)curcumin (bDHC), were synthesized and characterized by means of experimental and theoretical approaches. Moreover, a first evaluation of their affinity to synthetic β-amyloid fibrils and uptake by A549 lung cancer cells was performed to show the potential application of these new labeled curcuminoids in these diagnostic fields. The radiotracers were prepared by reacting 68Ga3+ obtained from a 68Ge/68Ga generator with 1 mg/mL curcuminoids solutions. Reaction parameters (precursor amount, reaction temperature, and pH) were optimized to obtain high and reproducible radiochemical yield and purity. Stoichiometry and formation of the curcuminoid complexes were investigated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, NMR, ultraviolet–visible, and fluorescence spectroscopy on the equivalent natGa-curcuminoids (nat = natural) complexes, and their structure was computed by theoretical density functional theory calculations. The analyses evidenced that CUR, DAC, and bDHC were predominantly in the keto–enol form and attested to Ga(L)2+ species formation. Identity of the 68Ga(L)2+ complexes was confirmed by coelution with the equivalent natGa(L)2+ complexes in ultrahigh-performance liquid chromatography analyses.68Ga(CUR)2+, 68Ga(DAC)2+, and 68Ga(bDHC)2+ were highly (87 ± 4, 90 ± 1%) and moderately (48 ± 2%), respectively, retained by synthetic β-amyloid fibrils in vitro. All the Ga-curcuminoid complexes showed an uptake in A549 lung cancer cells, at least equivalent to the respective free curcuminoids, confirming potential applications as cancer-detecting radiotracers.

Erika Ferrari;Rois Benassi;Stefania Sacchi;Francesca Pignedoli;Mattia Asti;Monica Saladini ( 2014 ) - Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 139 - pp. da 38 a 48 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga3 +, Cu2 +) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto–enol form. The formation of metal complexes is followed by both NMR and UV–vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga3 + and Cu2 + are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2]+ was found more stable than curcumin one. Good agreement is detected between calculated and experimental 1H and 13C NMR data. The calculated Osingle bondH bond dissociation energy (BDE) and the Osingle bondH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga3 + complexes display possible superoxide dismutase (SOD)-like activity.

Marianne Lilletvedt Tovsen; Ellen Bruzell; Erika Ferrari; Monica Saladini; Vivek S. Gaware; Már Másson; Solveig Kristensen; Hanne Hjorth Tønnesen ( 2014 ) - Antibacterial phototoxic effects of synthetic asymmetric and glycosylated curcuminoids in aqueous formulations Studies on curcumin and curcuminoids. LIV - JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY - n. volume 140 - pp. da 150 a 156 ISSN: 1011-1344 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The aim of this study was to evaluate the in vitro phototoxic potential of synthetic asymmetric and glycosylated curcuminoids on planktonic model bacteria by counting the colony forming units. The Gram-positive Enterococcus faecalis and the Gram-negative Escherichia coli were exposed to aqueous solutions of the curcuminoids (≤ 2.5 μM) in the presence or absence of selected pharmaceutical excipients (Pluronic® F127, PEG 400 and HPγCD) in combination with a low irradiation dose (5 J/cm2). All the asymmetric curcuminoids, but only one of the glycosylated curcuminoids demonstrated substantial phototoxic effect on Enterococcus faecalis (≥ 4.7 log reduction). Only two of the asymmetric curcuminoids showed a moderate to low phototoxic effect on the more persistent Escherichia coli. This study emphasized that aromatic hydroxyl substituents in the para-position are important to maintain the phototoxic potential of curcuminoids independent of molecular symmetry. Glycosylation of the aromatic substituents resulted in a substantial loss in phototoxicity towards planktonic bacteria, an apparent change in the non-radiative S1-decay process and a weaker interaction with Pluronic® F127 compared to the non-glycosylated curcuminoids. The selected excipients Pluronic® F127, PEG 400 and HPγCD strongly influenced the phototoxic potential of the unsymmetrical, non-glycosylated compounds.

Basile V; Belluti S; Ferrari E; Gozzoli C; Ganassi S; Quaglino D; Saladini M; Imbriano C. ( 2013 ) - bis-Dehydroxy-Curcumin Triggers Mitochondrial-Associated Cell Death in Human Colon Cancer Cells through ER-Stress Induced Autophagy. - PLOS ONE - n. volume 8 - pp. da 1 a 18 ISSN: 1932-6203 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Background: The activation of autophagy has been extensively described as a pro-survival strategy, which helps to keep cells alive following deprivation of nutrients/growth factors and other stressful cellular conditions. In addition to cytoprotective effects, autophagy can accompany cell death. Autophagic vacuoles can be observed before or during cell death, but the role of autophagy in the death process is still controversial. A complex interplay between autophagy and apoptosis has come to light, taking into account that numerous genes, such as p53 and Bcl-2 family members, are shared between these two pathways. Methodology/Principal Findings: In this study we showed a potent and irreversible cytotoxic activity of the stable Curcumin derivative bis-DeHydroxyCurcumin (bDHC) on human colon cancer cells, but not on human normal cells. Autophagy is elicited by bDHC before cell death as demonstrated by increased autophagosome formation -measured by electron microscopy, fluorescent LC3 puncta and LC3 lipidation- and autophagic flux -measured by interfering LC3-II turnover. The accumulation of poly-ubiquitinated proteins and ER-stress occurred upstream of autophagy induction and resulted in cell death. Cell cycle and Western blot analyses highlighted the activation of a mitochondrial-dependent apoptosis, which involves caspase 7, 8, 9 and Cytochrome C release. Using pharmacological inhibitions and RNAi experiments, we showed that ER-stress induced autophagy has a major role in triggering bDHC-cell death. Conclusion/Significance: Our findings describe the mechanism through which bDHC promotes tumor selective inhibition of proliferation, providing unequivocal evidence of the role of autophagy in contrasting the proliferation of colon cancer cells.

Erika Ferrari; Mattia Asti; Rois Benassi; Francesca Pignedoli; Monica Saladini ( 2013 ) - Metal binding ability of curcumin derivatives: a theoretical vs. experimental approach - DALTON TRANSACTIONS - n. volume 42 - pp. da 5304 a 5313 ISSN: 1477-9234 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Theoretical calculations employing DFT at the B3LYP/6-311G++** level are used to investigate the tautomeric equilibrium in curcumin derivatives. The solvent effect is evaluated using the CPCM continuum solvation method. The results are compared with experimental data obtained from the X-ray crystal structure of K2A23 and UV-vis data. The KE tautomer is more stable in a vacuum and in the solid state, while in water the DK tautomer reaches a population of 90%. In agreement with spectroscopic data, theoretical calculations predict a slight prevalence of the DK form in non-aqueous solvent systems. The ability to chelate metal ions [Fe3+, Ga3+ and Cu2+] is then explored by means of 1H, 13C NMR and UV-Vis spectroscopy. From the calculation of the overall stability constants of metal complexes and 1H NMR titrations with Ga3+, it is clear that the more stable species has a 1 : 2 M/L molar ratio. The curcuminoid coordinates the metal ion through the keto–enol function in the dissociated form; in addition 2D 1H 13C NMR experiments suggest the involvement of carboxylic oxygen in metal coordination it was found in the solid state for the complex [Ga(K2A33)2]PF6. The rate of the complexation reaction is strongly influenced by the type of substituent on the aromatic ring of the curcuminoid (K2A33 ≈ K2A23 ≫ K2A21). In addition DPPH assay evidences how antioxidant ability of curcumin derivatives is mainly due to the presence of a phenolic group and metal coordination by a keto–enolic moiety does not affect it, especially for K2A21.

Shruti Shruti; Antonio J. Salinas; Erika Ferrari; Gianluca Malavasi; Gigliola Lusvardi; Antonio L. Doadrio; Ledi Menabue; M. Vallet-Regi ( 2013 ) - Curcumin release from cerium, gallium and zinc containing mesoporous bioactive glasses - MICROPOROUS AND MESOPOROUS MATERIALS - n. volume 180 - pp. da 92 a 101 ISSN: 1387-1811 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcumin is the main component of turmeric which is being used since centuries due to medicinal ben- efits with no side effects. In this paper, 80%SiO2–15%CaO–5%P2O5 mesoporous bioactive glasses (MBGs) containing two different concentrations of Ce2O3, Ga2O3 (1.0% and 2.0%) and ZnO (2.0% and 4.0%) (in mol%) were synthesized by evaporation induced self-assembly (EISA) method to investigate their potential as drug delivery system (DDS) for curcumin. Impregnation method was applied for incorporat- ing curcumin into MBGs and in vitro release was performed in simulated body fluid (SBF) at 37 °C up to 72 h. The substituted MBGs exhibited mesostructure and textural properties good enough for drug deliv- ery. Highest gallium and cerium substituted MBGs incorporated drug more than unsubstituted MBG (B_MBG) due to high affinity of curcumin towards hard Lewis acids. However, during in vitro drug release, B_MBG and lowest cerium, gallium and zinc substituted MBGs showed curcumin release that is capable to exert pharmacological activities. On the other hand, strong interaction between curcumin and substituent caused reduction in drug release from the other set of MBGs with negligible release from 2.0%Ga2O3. Furthermore, MBGs loaded with curcumin showed quick in vitro response except 4.0%ZnO. Hence, lowest Ce, Ga and Zn substituted MBGs can be considered as drug release system for curcumin because they showed higher drug release with quick in vitro bioactivity and the added values of the substituents.

S Belluti;V Basile;P Benatti;E Ferrari;G Marverti;C Imbriano ( 2013 ) - Concurrent inhibition of enzymatic activity and NF-Y-mediated transcription of Topoisomerase-IIα by bis-DemethoxyCurcumin in cancer cells - CELL DEATH & DISEASE - n. volume 4 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Topoisomerase-IIa (TOP2A) enzyme is essential for cell viability due to its fundamental role in DNA metabolism and in chromatin organization during interphase and mitosis. TOP2A expression is finely regulated at the transcriptional level through the binding of the CCAAT-transcription factor NF-Y to its promoter. Overexpression and/or amplification of TOP2A have been observed in many types of cancers. For this reason, TOP2A is the target of the most widely successful drugs in cancer chemotherapy, such as TOP2A poisons, which stabilize TOP2A-DNA cleavage complexes and create DSBs, leading to chromosome damage and cell death. We previously reported that the Curcumin-derivative bis-DemethoxyCurcumin (bDMC) is an anti-proliferative agent that inhibits cell growth by concomitant G1/S and G2/M arrest. Here we showed that bDMC irreversibly induces DSBs in cancer cells, but not in normal cells, by targeting TOP2A activity and expression. TOP2A ablation by siRNA corroborates its contribution to apoptosis induced by bDMC. Short-term exposure to bDMC induces retention of TOP2A-DNA intermediates, while longer exposure inhibits TOP2A transcription by affecting expression and sub-cellular localization of NF-Y subunits. ChIP analysis highlighted reduced recruitment of NF-Y to TOP2A regulatory regions, concomitantly to histone deacetylation and decreased gene transcription. Our findings suggest that the dual activity of bDMC on TOP2A represents a novel therapeutic strategy to induce persistent apoptosis in cancer cells and identify NF-Y regulation as a promising approach in anti-cancer therapy.

Dal Ferro, Nicola; Berti, A.; Francioso, Ornella; Ferrari, Erika; Matthews, P.; Morari Francesco ( 2012 ) - Investigating the effects of wettability and pore size distribution on aggregate stability. The role of soil organic matter and its humic fraction. - EUROPEAN JOURNAL OF SOIL SCIENCE - n. volume 63 - pp. da 152 a 164 ISSN: 1351-0754 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Soil organic matter (SOM) is an important factor influencing aggregate stability. Interactions between SOM and soil structure are widely studied, although the subtle relationship between SOM content, pore size distribution and aggregate stability is not fully known. Here we investigate such a relationship by means of a long-term experiment established in 1962 in northeastern Italy, which considers different fertilizer practices (organic, mineral and mixed) applied to a continuous maize crop rotation. We measured wet stability of 1–2 mm aggregates subjected to different pretreatments. Both soil physical properties (such as pore size distribution and hydrophobicity) and chemical properties (soil organic and humic carbon content) affecting aggregate stability were considered. The chemical structure of humic substances was characterized by thermal and spectroscopic analyses (TG-DTA, DRIFT and 1H HR MAS NMR). The Pore-Cor network model was then applied to evaluate the contribution of hydrophobicity and porosity to aggregate wetting. Our study suggests that SOM and its humic fraction can affect aggregate wetting and consequently slaking by modifying the pore size distribution with a shift from micropores (5–30 μm) and mesopores (30–75 μm) to ultramicropores (0.1–5 μm); hydrophobicity was also increased as a result of different humic composition. Spectroscopic analysis showed that hydrophobic compounds were mostly associated with complex humic molecules. Models of fast wetting dynamics, however, suggest that the contribution that hydrophobicity makes to aggregate stability, especially to soils with large carbon inputs, may not be the most significant factor.

G. Malavasi; A. Rustignoli; O. Francioso; A. Piva; C. Salomoni; E. Ferrari ( 2012 ) - A chemical protocol for the evaluation of potential biogas production from biologically pre-treated agro-industrial wastes ( XL Congresso Nazionale della Divisione di Chimica Inorganica - - 9-13 settembre 2012) ( - Atti del XL Congresso Nazionale della Divisione di Chimica Inorganica ) (SCI DIvisione Chimica Inorganica Genova ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

To date, the types of pre-treatment of agro-industrial wastes use mostly physical and chemical (alkaline hydrolysis, acid hydrolysis, oxidative de-lignification and solvent extraction) methods, which have drawbacks both from the environmental point of view and the energy consumption. In this scenario, BIT4enERgy, an entrepreneurial idea supported by SPINNER2013, has developed an innovative biological pre-treatments based on selected strains of microrganisms capable to decompose the biomass recalcitrant (hemicellulose, lignin - Figure) aimed to biogas production in anaerobic digestion. BIT4enERgy, in partnership with Biotec sys srl, is promoting new concept of integration between feedstock biological pre-treatment and advanced anaerobic digestion processes able to convert efficiently agro-industrial wastes with the conversion of high amount of CO2 for biogas production without additional climate change gas emission, supporting a transition towards a low-carbon economy [1,2]. In the present study we show the results on chemical-physical features of agro-industrial wastes before and after biological pre-treatment by using elemental, thermal (TG-DSC) and spectroscopic (ATR/FT-IR) analyses. Particular attention was paid to lignin structural changes as a consequence of biological pre-treatment. Chemical data suggested that the biological pre-treatment allowed a reduction in mass of biomasses in shorter time, the energetic power of the biomasses rich in lignin was increased, the efficiency of their conversion in bio-methane was improved and finally a considerable reductions of greenhouse gas (GHG) balance was expected.

Nardo, Luca; Maspero, Angelo; Selva, Marco; Bondani, Maria; Palmisano Giovanni; Ferrari, Erika; Saladini, Monica ( 2012 ) - Excited-State Dynamics of bis-dehydroxycurcumin Carboxylic Acid, a Water-Soluble Derivative of the Photosensitizer Curcumin. - JOURNAL OF PHYSICAL CHEMISTRY. A, MOLECULES, SPECTROSCOPY, KINETICS, ENVIRONMENT, & GENERAL THEORY - n. volume 116 - pp. da 9321 a 9330 ISSN: 1089-5639 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Bis-dehydroxycurcumin carboxylic acid (K2A23) is a synthetic curcuminoid designed to exhibit enhanced water solubility and photosensitizing potential with respect to natural curcumin. In this work, the tendency of the compound to form intra- and intermolecular hydrogen bonds in the ground state is studied by UV−visible absorption and by nuclear magnetic resonance (NMR). The excited-state dynamics of the drug are probed in different environments by means of time-correlated single-photon counting measurements and related to its hydrogen bonding affinity in the excited state.

Selmi T; Martello A; Vignudelli T; Ferrari E; Grande A; Gemelli C; Salomoni P; Ferrari S; Zanocco-Marani T. ( 2012 ) - ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways. - CELL CYCLE - n. volume 11(10) - pp. da 1977 a 1987 ISSN: 1538-4101 [Articolo in rivista (262) - Articolo su rivista]
Abstract

RNA binding proteins belonging to the TIS11/TTP gene family regulate the stability of multiple targets. Their inactivation or deregulated expression has recently been related to cancer, and it has been suggested that they are capable of displaying tumor suppressor activities. Here we describe three new targets of ZFP36 (PIM-1, PIM-3 and XIAP) and show by different approaches that its ectopic expression is capable of impairing glioblastoma cell lines viability and invasiveness by interfering with different transduction pathways. Moreover, we provide evidence that compounds capable of inducing the expression of TIS11/TTP genes determine a comparable biological effect on the same cell contexts.

E. Ferrari; M. Asti; G. Malavasi; C. Imbriano; F. Pignedoli; M. Bonavia; D. Daquino; M. Saladini ( 2012 ) - Development of new metal-based phyto-radiopharmaceuticals: diagnostic agents derived from Cur(e)cumin ( XL Congresso Nazionale della Divisione di Chimica Inorganica - - 9-13 settembre 2012) ( - Atti del Congresso ) (Società Chimica Italiana Genova ITA ) - pp. da 50 a 50 ISBN: XXXXXXXXXX ISSN: - [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

Curcumin, a yellow pigment extracted from the Indian spice Curcuma longa, has been widely linked with suppression of angiogenesis, inflammation, cardiovascular diseases, tumorigenesis and A-binding activities in the context of therapies for Alzheimer’s disease [1,2]. Besides, Curcumin has shown interesting binding ability towards different metal ions such as Fe(III) and Ga(III) with the involvement of its keto-enolic moiety [3]. Metal complexation triggers an increased kinetic stability and bioavailability of Curcumin in physiological conditions, reducing one of its main drawbacks in therapeutic applications. Anyway biologically active curcuminoids have little been investigated as labelled radiopharmaceuticals for cancer diagnosis or therapy, and they represent a novelty in the field. In this presentation we show an overview of new classes of Curcumin-based ligands with bidentate and tridentate coordinating mode, we investigate their binding ability towards Rhenium and Gallium and report a complete thermodynamic and pharmaco-kinetic study on ligands and metal complexes with the aim of developing new radiopharmaceuticals.

Malavasi G.; Lusvardi G.; Menabue L.; Ferrari E.; Saladini M.; Aina V.; Martra G.; Bergandi L.; Ghigo D.; Valetti F. ( 2012 ) - Novel smart bio-nanomaterials: Bioactive glasses containing metal nano-particles conjugated with molecules of biological interest ( Conference Paper ) ( Nanotechnology 2012: Bio Sensors, Instruments, Medical, Environment and Energy - 2012 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2012 - - 18-21 June 2012) ( - Techical proceedings of the 2012 NSTI Nanotechnology Conference and EXPO, NSTI-Nanotech 2012 ) (CRC Press Taylor&Francis Group Boca Raton, FL USA ) - n. volume Vol. 3 - pp. da 114 a 117 ISBN: 9781466562769 ISSN: - [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

New smart materials based on phospho-silicate bioactive sol-gel glasses have been developed. To meet the ever-increasing demand for performing bio-materials, the surface features of the glasses have been tailored to achieve optimal behaviour in different applications (drug delivery, enzymes activity, chemo-signalling probe, stimuli-sensitive agents). In particular, the introduction on the glass surface of metal nanoparticles (NPs; Au and Cu are the metals) is very useful because the NPs can directly act, for example, as bactericides and imaging agents and can be used to immobilize, via a covalent linkage, an enzyme/protein and/or a drug on the glass surface. This can be achieved through the formation of self-assembled monolayers (SAMs), in order to obtain a stable bio-conjugate system. The systems prototyped in this way could be useful as materials bio-implantable into the human body. In the present contribution we report the development of smart bio-materials. In particular, it is demonstrated that bioactive glasses containing Au nanoparticles (AuNPs) can be selectively functionalized with small molecules carrying either amino or thiol groups by simply varying the temperature and pH of the functionalization batch. These results should allow the production, in a selective way, of different bonds exhibiting different strengths and, consequently, different release times in solution, with a wide range of possible applications. (For instance, weak Au-N bonds in the case of drug delivery, strong Au-S bonds for protein immobilization). Unlike other works, in which a preliminary silanization process has often been used, the introduction of AuNPs in the glass composition allows to exploit the easy SAMs formation process on the AuNPs dispersed in the bioactive glass matrix and, consequently, to immobilize an enzyme (soybean peroxidase, SBP). A thorough characterization of the materials, at different steps of the functionalization process, is also reported, together with in vitro activity tests of immobilized SBP, compared with merely adsorbed SBP, and cytotoxicity tests using human osteoblast (MG-63) cells. Overall, a new bio-conjugate material, able to maintain its activity over time and to decrease the oxidative stress when in contact with MG-63 cells, has been obtained. In the present work we have also prepared and characterized bioactive glasses containing CuNPs in order to prepare antibacterial biomaterials useful in the field of implantation surgery.

E. Ferrari; G. Foca; M. Vignali; L. Tassi; A. Ulrici ( 2011 ) - Adulteration of the anthocyanin content of red wines: perspectives for authentication by FT-NIR and 1H NMR spectroscopies - ANALYTICA CHIMICA ACTA - n. volume 701 - pp. da 139 a 151 ISSN: 0003-2670 [Articolo in rivista (262) - Articolo su rivista]
Abstract

In the Italian oenological industry, the regular practice used to naturally increase the colour of red wines consists in blending them with a wine very rich in anthocyanins, namely Rossissimo. In the Asian market, on the other hand, anthocyanins extracted by black rice are frequently used as correctors for wine colour. This practice does not produce negative effects on health; however, in many countries, it is considered as a food adulteration. The present study is therefore aimed to discriminate wines containing anthocyanins originated from black rice and grapevine by using reliable spectroscopic techniques requiring minimum sample preparation. Two series of samples have been prepared from five original wines, that were added with different amounts of Rossissimo or of black rice anthocyanins solution, until the desired Colour Index was reached. The samples have been analysed by FT-NIR and 1H NMR spectroscopies and the resulting spectra matrices were subjected to multivariate classification. Initially, PLS-DA was used as classification method, then also variable selection/classification methods were applied, i.e. iPLS-DA and WILMA-D. The classification with variable selection of NIR spectra permitted to classify the test set samples with an efficiency of about 70%. Probably these not excellent performances are due to the matrix effect, together with the lack of sensitivity of NIR with respect to minor compounds. On the contrary, very satisfactory results were obtained on NMR spectra in the aromatic region between 6.5÷9.5 ppm. The classification method based on wavelet-based variables selection, permitted to reach an efficiency in validation greater than 95%. Finally, 2D correlation analysis was applied to FT-NIR and 1H NMR matrices, in order to recognise the spectral zones bringing the same chemical information.

Ferrari, Erika; Saladini, Monica; Pignedoli, Francesca; Spagnolo, Ferdinando; Benassi, Rois ( 2011 ) - Solvent effect on keto-enol tautomerism in a new B-diketone: a comparison between experimental data and different theoretical approaches. - NEW JOURNAL OF CHEMISTRY - n. volume 35 - pp. da 2840 a 2847 ISSN: 1144-0546 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The novel -diketo compound (3-acetyl-4-oxopentanoic acid) OPAA is here synthesized, completely characterized in the solid state by means of X-ray crystallography and in solution by potentiometry and 1H and 13C NMR spectroscopy. In the solid state, OPAA exhibits the di-keto (DK) structure, while in solution a strongly solvent dependent tautomeric equilibrium is observed. Theoretical ab-initio calculations employing DFT at B3LYP/6-311G** level and different methods of theoretical model chemistry (CBS-4M, G3MP2, CBS-QB3) are used to extensively investigate the tautomeric equilibrium in comparison with experimental data. Solvent effects are evaluated using CPCM continuum solvation method; among all implied methods, CBS-4M is the one that better predicts experimental data and is able to qualitatively describe tautomeric equilibrium in solution, allowing thermodynamic calculation of pKa. Furthermore a supermolecular solvent approach is used to better analyze solvent-solute interactions in order to forecast chemical properties.

E. Ferrari; G. Lusvardi; V. Aina; G. Malavasi; F. Fantini; C. Morterra; F. Pignedoli; M. Saladini; L. Menabue ( 2011 ) - The role of coordination chemistry in the development of innovative Gallium-based bioceramics: the case of Curcumin - JOURNAL OF MATERIALS CHEMISTRY - n. volume 21 - pp. da 5027 a 5037 ISSN: 0959-9428 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcumin, an active ingredient in the traditional Ayurvedic herbal remedy [Curcuma longa L.], isnowadays also employed in western medicine for its pleiotropic activities, ranging from anticancer to itsfree radical scavenger ability. These features are related to curcumin’s function as a metal chelator,especially being selective for hard Lewis acids, such as Ga3+ which has interesting pharmacologicalactivities. We report the synthesis and characterization of a bioactive gel and mesoporous Ga-containing phospho-silicate glasses loaded with curcumin, in which, for the first time, coordinationchemistry was taken advantage of in designing novel drug delivery systems. In particular, it was foundthat: (i) there is a direct correlation between the external surface area and the amount of loadedcurcumin; (ii) the presence of Ga3+ species on the surface increases the quantity of drug moleculesuploaded and slows down their release in the biological medium (SBF), hinting at a coordination-likeinteraction between curcumin and the surface metal ions; (iii) curcumin molecules released in the SBFsolution stabilize Ga3+ ions, avoiding their precipitation.

G. Di Rocco; G. Battistuzzi; C. A. Bortolotti; M. Borsari; E. Ferrari; S. Monari; M. Sola ( 2011 ) - Cloning, Expression and Physico-Chemical Characterization of a New Di-Heme Cytochrome c from Shewanella baltica OS155. - JBIC - n. volume 16 - pp. da 461 a 471 ISSN: 0949-8257 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The 16 kDa di-heme cytochrome c from the bacterium Shewanella baltica OS155 (Sb-DHC) was cloned and expressed in E. coli and investigated through UV-Vis, MCD and 1H NMR spectroscopies and protein voltammetry. The model structure was obtained by means of comparative modeling using the X-ray structure of Rhodobacter sphaeroides di-heme cytochrome c (DHC) (with a 37% pairwise sequence identity) as a template. Sb-DHC folds into two distinct domains, each containing one heme center with a bis-His axial ligation. Both secondary and tertiary structures of the N-terminal domain resemble those of class I cytochrome c, displaying three -helices and a compact overall folding. The C-terminal domain is less helical, as the corresponding domain of R. sphaeroides DHC. The two heme groups are bridged by Tyr26 in correspondence of the shortest edge-to-edge distance, a feature which would facilitate fast internal electron transfer. The electronic properties of the two prosthetic centers are equivalent and sensitive to two acid-base equilibria with pKa values of approximately 2.4 and 5, likely corresponding to protonation and detachment of the axial His ligands from the heme iron and ionization of the heme propionate-7, respectively. Reduction potentials of -0.144 and -0.257 V (vs SHE), were determined for the C- and N-terminal heme group, respectively. An approach based on the extended Debye-Hückel equation was applied for the first time to a two-centered metalloprotein and found to reproduce successfully the ionic strength dependence of E°’.

R. Benassi; E. Ferrari; S. Lazzari; F. Pignedoli; F. Spagnolo; M. Saladini ( 2011 ) - How glucosylation triggers physical–chemical properties of curcumin: an experimental and theoretical study. - JOURNAL OF PHYSICAL ORGANIC CHEMISTRY - n. volume 24 - pp. da 299 a 310 ISSN: 0894-3230 [Articolo in rivista (262) - Articolo su rivista]
Abstract

In the present study, we investigate the structures of glucosylated curcumin derivatives with DFT at B3LYP/6-31G*level. A conformational analysis is performed in order to determine the conformational minimum (GS) and rotationaltransition state (TS) of curcumin derivatives and then their electronic features are evaluated. HOMO and LUMOfrontier orbitals and maps of electron density potential (MEPs) are plotted and compared. In order to correlate theirpredicted spectroscopic properties with IR, UV–vis and NMR experimental data we extended the theoretical study onelectronic properties to different solvents (H2O, MeOH, ACN, DMSO). The main finding is that the curcuminic coremaintains the same geometrical and electronic structures in all compounds miming the metal coordination capabilityshowed by curcumin. Therefore, wemay confirm that the presence of glucose does not affect the electronic propertiesof the derivatives.

G. Malavasi; G. Lusvardi; L. Menabue; E. Ferrari; M. Saladini; V. Aina; C. Monterra; E. Laurenti; L. Bergandi; D. Ghigo ( 2011 ) - Novel smart bio-materials: bioactive glasses containing metal nano-particles conjugated with molecules of biological interests ( XXXIX Congresso Nazionale di Chimica Inorganica - XXIV Congresso Nazionale della Società Chimica Italiana - - 11-15 Settembre 2011) ( - Atti del XXXIX Congresso Nazionale di Chimica Inorganica - XXIV Congresso Nazionale della Società Chimica Italiana ) (Società chimica Italiana Lecce ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

Novel smart bio-materials: bioactive glasses containing metal nano-particles conjugated with molecules of biological interests

E. Ferrari; O. Francioso; S. Nardi; M. Saladini; N. Dal Ferro; F. Morari ( 2011 ) - DRIFT and HR MAS NMR characterization of humic substances from a soil treated with different organic and mineral fertilizers. - JOURNAL OF MOLECULAR STRUCTURE - n. volume 998 - pp. da 216 a 224 ISSN: 0022-2860 [Articolo in rivista (262) - Articolo su rivista]
Abstract

In this study, using DRIFT and HR MAS NMR, we analyzed the humic substances isolated from a soil treated, over 40 years, with different organic, mineral and organic plus mineral treatments and cultivated with maize as the main crop. As expected, the structure of humic substances was very complex but by combining both techniques (DRIFT and HR MAS NMR) additional information was obtained on aromatic and aliphatic components, the most recalcitrant parts of these macromolecules. In so doing we wanted to investigate the relationship between HS structure and long-term management practices. An elevated content of lignin, aminoacids, peptides and proteins was observed mainly for farmyard manure treatments with respect to mineral or liquid manure amendments; this supports how the different management practices have greatly influenced the humification process of cultivated soils.

Erika Ferrari; Francesca Pignedoli; Carol Imbriano; Gaetano Marverti; Valentina Basile; Ettore Venturi; Monica Saladini ( 2011 ) - Newly synthesized curcumin derivatives: crosstalk between chemico-physical properties and biological activity. - JOURNAL OF MEDICINAL CHEMISTRY - n. volume 54 - pp. da 8066 a 8077 ISSN: 0022-2623 [Articolo in rivista (262) - Articolo su rivista]
Abstract

New curcumin analogues (ester and acid series) were synthesized with the aim to improve the chemical stability in physiological conditions and potential anticancer activity. Cytotoxicity against different tumorigenic cell lines (human ovarian carcinoma cells – 2008, A2780, C13* and A2780/CP - and human colon carcinoma cells - HCT116 and LoVo) was tested to evaluate cellular specificity and activity.Physico/chemical properties such as acidity, lipophilicity, kinetic stability and free radical scavenging activity were investigated to shed light on the structure-activity relationship and provide new attractive candidates for drug development. Most of ester derivatives show IC50 values lower than curcumin and exhibit selectivity against colon carcinoma cells. Especially they are extremely active after 24h exposure showing enhanced inhibitory effect on cell viability.The best performances of ester curcuminoids could be ascribed to their high lipophilicity that favors a greater and faster cellular uptake overcoming their apparently higher instability in physiological condition.

G. Tonon; S. Sohi; O. Francioso; E. Ferrari; D. Montecchio; P. Gioacchini; C. Ciavatta; P. Panzacchi; D. Powlson ( 2010 ) - Effect of soil pH on the chemical composition of organicmatter in physically separated soil fractions in twobroadleaf woodland sites at Rothamsted, UK - EUROPEAN JOURNAL OF SOIL SCIENCE - n. volume 61 - pp. da 970 a 979 ISSN: 1351-0754 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Although acid soils are common in forest ecosystems, and there is documented evidence of pH influencingtransformations of organic matter in soil, there are surprisingly few studies on the influence of soil pH onthe chemical structure of physically fractionated soil organic matter (SOM). The aim of this study was tocharacterize the influence of pH on the chemical and physical processes involved in SOM stabilization. Forestsoils of different pH (4.4 and 7.8) sampled from two long-term experiments at Rothamsted Research (UK)were physically fractionated. The free light fraction (FLF), the intra-aggregate light fraction and the fine siltand clay (S + C, <25 μm) were characterized using elemental, isotopic (δ13C), thermogravimetric, differentialthermal, diffuse reflectance infrared Fourier transform spectroscopy and high-resolution magic angle spinning1H nuclear magnetic resonance analyses. The quantitative distribution of carbon (C) between SOM fractionsdiffered between the two soils. Carbon contents in the light fractions from the acid soil were significantlygreater than in those of the alkaline soil. In contrast, in S + C fractions, C content was greater in the alkalinesoil. FLF from the acid soil was characterized by a greater C:N ratio, smaller δ13C and greater content ofthermo-labile compounds compared with FLF from the alkaline soil. In contrast, there was only a weak effectof soil pH on the chemical composition of the organic matter in S + C fractions. Irrespective of soil pH,these latter fractions contained mainly aliphatic compounds such as carbohydrates, carboxylic acid, amideand peptide derivates. This suggested that physical mechanisms, involving the interactions between SOM andmineral surfaces, are of greater importance than the presence of chemically recalcitrant species in protectingSOM associated with the finest soil fractions.

M. Caselli; E. Ferrari; C. Imbriano; F. Pignedoli; M. Saladini; G. Ponterini ( 2010 ) - Probing solute–solvent hydrogen bonding with fluorescent water-soluble curcuminoids - JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. A, CHEMISTRY - n. volume 210 - pp. da 115 a 124 ISSN: 1010-6030 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Glycosylated water-soluble curcuminoids (C1–C3, first scheme of this article) differing in the 3,3-ringsubstituents (–OH, –OCH3 and H) equilibrate between the di-keto and the keto–enol forms. The formerare well observable in the absorption spectra in water, but their emissions are always negligible. Theketo–enol forms of C1–C3 exhibit a broad range of fluorescence quantum yields in different solvents,organic and water: formation of solute–solvent hydrogen bonds through the 3,3-ring substituents maychange the radiationless S1-state decay constant by up to a factor 200. Such a fluorescence quenchingmechanism is extremely efficient in water and, for C1, in accepting organic media. On the contrary, noeffects traceable to intermolecular hydrogen bonds involving the central -dicarbonyl moiety have beenobserved. So, fluorescence of these curcuminoids may probe the hydrogen bonding ability, particularly asacceptor, of their microenvironments, including hydrophilic/hydrophobic domains in complex biologicalsystems. Interaction of C1 and C2 with bovine serum albumin results in emission enhancements inverseto the quantum yields of the curcuminoids in water. The observations support the idea that, although thecurcuminoid microenvironment within its complex with the protein is less polar and hydrogen bondingthan water itself, residual water/ligand hydrogen bonds are active in enhancing radiationless transitions.Finally, fluorescence confocal images of HCT116 cells treated with C1–C3 suggest the apparently smallstructural differences to affect, besides their fluorescence behaviour, their interactions and fate withinliving cells.

F. Fantini; E. Ferrari; G. Lusvardi; G. Malavasi; L. Menabue ( 2010 ) - Synthesis and characterization of Ga-containing silicate based sol-gel and mesoporous sol-gel bioactive glasses loaded with curcumin ( XXXVIII Congresso Nazionale di Chimica Inorganica - - 13-16 Settembre 2010) ( - Atti del XXXVIII Congresso Nazionale di Chimica Inorganica ) (Società chimica italiana Trieste ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

1.Introduction Silicate based bioactive glasses are synthesized with the aim to obtain materials usable as bone fillers for orthopedic and maxillo facial surgery1. The studied glasses are sol-gel and mesoporous sol-gel based on molar composition 15CaO-5P2O5-80SiO2 modified with Ga2O3; moreover, curcumin was loaded on these glasses. In fact, these materials may be also used as vehicles for the release of metal ions (Ga with anti-bacterial and anti-cancer properties2) and bio-molecules (curcumin, an anti-oxidant and anti-cancer agent3). 2.Results and Discussion Different techniques (UV-Vis, XRD, SEM, NMR, DTA, AE, ICP) are used to characterize glasses, the absorption and release of curcumin. The results showed that, due to higher external surface, sol-gel glasses adsorb more curcumin with respect to mesoporous; in this last case, another possibility of adsorption is by means of mesoporous, but its diameter is smaller than the dimension of curcumin molecules. The amount of curcumin uptaken is higher for Ga-containing glasses. All these materials, tested in water for 72 hours, show an initial (6 hours) fast and almost complete release of curcumin; afterwards the release is more slow. The amount of curcumin released from Ga-containing glasses is lower than the Ga-free ones. The amount of gallium present in solution is greater for the systems with curcumin, in this way Ga ions in solution could be act as antibacterial and antioxidant agents.

E. Ferrari; F. Pignedoli; S. Lazzari; C. Imbriano; G. Marverti; M. Saladini ( 2009 ) - Development of new metal-chelating multi target drus derived from Curcumin ( XXII Congresso Nazionale della società chimica italiana - - 5-10 Luglio 2009) ( - Atti del Congresso ) (Società chimica italiana Napoli ITA ) - pp. da 251 a 251 ISBN: / ISSN: - [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

With the aim to develop new anti-cancer approaches, which encompass therapies based on drug combinations, we are searching for innovative anti-tumor multi-targets treatments.1 In this research Curcumin represents our referring and starting point for the design of new derivatives. Curcumin, a natural occurring molecule, was shown to inhibit growth of several types of malignant cells and its biological activity was also related to its iron chelating ability.2 Recently curcumin proceeded onto clinical trials however its use is limited by a poor bioavailability. In order to improve curcumin water solubility and drug-delivery we have synthesized new derivatives which conjugate anti-proliferative effects with metal chelating capacity. They are able to reduce free iron level and to potentially deliver a chemotherapic metal ion such as Ga(III).

E. Ferrari; F. Pignedoli; C. Imbriano; M. Saladini ( 2009 ) - Development of new therapeutic Metal(III)-chelating agents derived from Curcumin ( Book of abstracts of "First International Conferece on Metal chelation in Biology and medicine" - - 11-14 Dicembre 2009) ( - First International Conferece on Metal chelation in Biology and medicine ) (/ Bath GBR ) - pp. da 79 a 79 ISBN: / ISSN: - [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

With the aim to develop new anti-cancer approaches, which encompass therapies based on drug combinations, we are searching for innovative anti-tumor multi-targets treatments.1 In this research Curcumin represents our referring and starting point for the design of new derivatives. Curcumin, a natural occurring molecule, was shown to inhibit growth of several types of malignant cells and its biological activity was also related to its iron chelating ability.2,3 Recently curcumin proceeded onto clinical trials however its use is limited by a poor stability and bioavailability. In order to improve these features, we have synthesized new derivatives which potentially conjugate anti-proliferative and anti-oxidant effects with metal chelating capacity, especially towards Fe(III) and Ga(III), reducing free iron level and potentially delivering a chemotherapic metal ion such as Ga(III). We have performed a complete characterization of the chelating ability of new ligands in vitro by means of potentiometry, UV-Vis spectroscopy and NMR spectrometry. Stability and cellular uptake together with cytotoxicity towards different cell lines were also investigated for all ligands and their Ga(III) complexes in order to shed light on their potential anti-cancer effects especially against human colon cancer cells, unravelling the molecular basis of their biological activity.

Erika Ferrari; Beatrice Arezzini; Marco Ferrali; Sandra Lazzari; Francesca Pignedoli; Ferdinando Spagnolo; Monica Saladini ( 2009 ) - Synthesis and characterization of glucosyl-curcuminoids as Fe3+ suppliers in the treatment of iron deficiency - BIOMETALS - n. volume 22 - pp. da 701 a 710 ISSN: 0966-0844 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The Fe3+ chelating ability of some curcumin glucosyl derivatives (Glc-H; Glc-OH; Glc-OCH3) is tested by means of UV and NMR study. The pK a values of the ligands and the overall stability constants of Fe3+ and Ga3+ complexes are evaluated from UV spectra. The only metal binding site of the ligand is the β-diketo moiety in the keto-enolic form; the glucosyl moiety does not interact with metal ion but it contributes to the stability of metal/ligand 1:2 complexes by means of hydrophilic interactions. These glucosyl derivatives are able to bind Fe3+ in a wide pH rage, forming complex species thermodynamically more stable than those of other ligands commonly used in the treatment of iron deficiency. In addition they demonstrate to have a poor affinity for competitive biological metal ions such as Ca2+. All ligands and their iron complexes have a good lypophilicity (log P > −0.7) suggesting an efficient gastrointestinal absorption in view of their possible use as iron supplements in oral therapy. The ligand molecules are also tested for their antioxidant properties in “ex vivo” biological system.

M. Saladini; S. Lazzari; F. Pignedoli; R. Rosa; F. Spagnolo; E. Ferrari ( 2009 ) - New Synthetic Glucosyl-Curcuminoids, and their 1Hand 13C NMR Characterization, from Curcuma longa L. - PLANT FOODS FOR HUMAN NUTRITION - n. volume 64 - pp. da 224 a 229 ISSN: 0921-9668 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Turmeric extracts, among which curcumin and bisdemethoxycurcumin, are by far known for their therapeutic activities. In this study we propose easy and low cost synthetic pathways in order to obtain glucosyl-curcuminoids, safe and water soluble potential drugs and dyes, which may be implied in different fields ranging from pharmacology to food chemistry. The complete 1H and 13C NMR characterization of naturally occurring curcumin, bis-demethoxycurcumin and new synthetic glucosyl-curcuminoids is reported.

G. Foca; E. Ferrari; M. Vignali; L. Tassi; A. Ulrici ( 2009 ) - Classification of NMR spectra collected on wines added with anthocyanins from grape and black rice ( 11th Scandinavian Symposium on Chemometrics - - 8-11 giugno) ( - atti del convegno ) (- - NOR ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

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V. Basile; E. Ferrari;S. Lazzari;S. Belluti;F. Pignedoli;C. Imbriano ( 2009 ) - Curcumin derivatives: molecular basis of their anti-cancer activity. - BIOCHEMICAL PHARMACOLOGY - n. volume 78 - pp. da 1305 a 1315 ISSN: 0006-2952 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Curcumin, a phenolic compound from the plant Curcuma longa L., has shown a wide-spectrum of chemopreventive, anti-oxidant and anti-tumor properties. Although its promising chemotherapeutic activity, preclinical and clinical studies highlight Curcumin limited therapeutic application due to its instability in physiological conditions. To improve its stability and activity, many derivatives have been synthesized and studied, among which bis-DemethoxyCurcumin (bDMC) and diAcetylCurcumin (DAC). In this report, we show that both bDMC and DAC are more stable than Curcumin in physiological medium. To explore the mechanism of their chemotherapeutic effect, we studied their role in proliferation in the HCT116 human colon cancer cells. We correlated kinetic stability and cellular uptake data to their biological effects. Both bDMC and DAC impair correct spindles formation and induce a p53- and p21(CIP1/WAF1)- independent mitotic arrest, which is more stable and long-lasting for bDMC. A subsequent p53/p21(CIP1/WAF1)- dependent inhibition of G1 to S transition is triggered by Curcumin and DAC as a consequence of the mitotic slippage, preventing postmitotic cells from re-entering the cell cycle. Conversely, the G1/S arrest induced by bDMC is a direct effect of the drug and concomitant to the mitotic block. Finally, we demonstrate that bDMC induces rapid DNA double-strand breaks, moving for its possible development in anti-cancer clinical applications.

Erika Ferrari; Sandra Lazzari; Gaetano Marverti; Francesca Pignedoli; Ferdinando Spagnolo; Monica Saladini ( 2009 ) - Synthesis, cytotoxic and combined cDDP activity of new stable curcumin derivatives - BIOORGANIC & MEDICINAL CHEMISTRY - n. volume 17 - pp. da 3043 a 3052 ISSN: 0968-0896 [Articolo in rivista (262) - Articolo su rivista]
Abstract

New curcumin derivatives are synthesized in order to improve chemical properties of curcumin. The aromatic ring glycosylation of curcumin provides more water-soluble compounds with a greater kinetic stability which is a fundamental feature for drug bioavailability. The glycosylation reaction is quite simple, low cost, with high yield and minimum waste. NMR data show that the ability of curcumin to coordinate metal ion, in particular Ga(III), is maintained in the synthesized products. Although the binding of glucose to curcumin reduces the cytotoxicity of the derivatives towards cisplatin (cDDP)-sensitive and -resistant human ovarian carcinoma cell lines, the compounds display a good selectivity since they are much less toxic against non-tumourigenic Vero cells. The combination of cDDP with the most active glycosyl-curcuminoid drug against both cDDP-sensitive and -resistant as well as against Vero cell lines is tested. The results show an improvement of cDDP efficacy with higher selectivity towards cancer cells than non-cancer cells. These studies indicate the need for developing new valid components of drug treatment protocols to cDDP-resistant cells as well.

V. Basile; E. Ferrari; S. Lazzari; S. Belluti; F. Pignedoli; C. Imbriano ( 2009 ) - Understanding the molecular mechanisms of Curcumin derivatives chemotherapic activity ( P8. “Mitosis and Cancer Symposium” - - 26-27 Febbraio 2009) ( - Atti del P8. “Mitosis and Cancer Symposium” ) (xx Amsterdam NLD ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

....

E. Ferrari; M Saladini; P. Gioacchini; O. Francioso; C. Ciavatta; S. Sohi; D. Powlson; G. Tonon ( 2009 ) - Structural investigation of organic matter in physical soil fractions from two broadleaf forests by High Resolution Magic Angle Spinning NMR ( International Symposium on Soil Organic Matter Dynamics: Land Use, Management and Global Change - - 6-9 Luglio 2009) ( - Atti del International Symposium on Soil Organic Matter Dynamics: Land Use, Management and Global Change ) (xx xx USA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

1H HR MAS NMR is a powerful technique that allows to examine the chemical and physical properties of heterogeneous and polydisperse macromolecular systems such as soil organic matter (SOM). SOM plays a major role in the fate, transport, and bioavailability of organic and inorganic components and its dynamics depends on its chemical composition as well as by physical protection mechanisms with the soil fractions. Soil pH seems to be a variable that affects the SOM decomposition progression by influencing microbial activity, hydrolysis and protonation processes. Protonation regulates many soil processes such as solubilisation and complexation which controls sorption and desorption of organic C on mineral surfaces. Despite its documented importance as factor influencing SOM transformation and despite the high frequency of acid soil in forest ecosystems the effect of pH on SOM dynamics has been studied rather little. In the present study 1H HR/MAS NMR is applied to SOM extracted from two forest soils differing mainly for soil pH: the acid site, called Gesscroft, and the calcareous site, called Broadbalk. The two soils were physically fractionated according to Sohi’s procedure. Only the SOM of three fractions for each site was investigated: free light fraction (FLF), light fraction (IALF) and fine silt and clay (S+C); in fact they represented together the 70-80% of the total SOM in our soils and the organic C content was above the threshold value of the 3%, needed to obtain good signal/noise ratios in NMR spectra. 2-D 1H-1H homo-correlation spectroscopy (COSY), 1H-13C heteronuclear single quantum coherence (HSQC) and 1-D experiments were assessed for both a qualitative and a quantitative analysis of the soil matter. For both sites the S/N (signal to noise) ratio is higher for FLF-SOM and IALF-SOM with respect to S+C-SOM fractions in agreement with the decrease in carbon content. Amino acid residues, peptides and carbohydrates are the prevalent species and 6 typical chemical shift regions can be identified for each sample. Although S+C-SOM fractions of both sites show a finely decomposed matter, which is confirmed by the presence of sharp peaks, in particular the decrease in aromatic content of Gesscroft extracts with respect to Broadbalk ones suggests that the effect of acid pH seems to be relevant for degradation processes.

E. Ferrari; S. Lazzari; F. Pignedoli; M. Saladini; O. Verna; A. Corradi; C. Leonelli; R. Rosa; P. Veronesi ( 2009 ) - Microwave assisted synthesis of new β-diketo derivatives ligands ( Zing, Microwave and Flow Chemistry Conference - - 28-31 Gennaio 2009) ( - Atti del Zing, Microwave and Flow Chemistry Conference ) (x xx ATG ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

The metal complexes of β-diketo derivatives and especially those of acetylacetone are well known and have been extensively studied. To improve the chelating ability of this molecule, we have introduced a further coordinative group. The designed compounds, which include a carboxylic group and the β-diketo moiety, are promising candidates as new metal ligands for pharmaceutical applications. Classical synthetic strategy for the obtainment of these adducts requires a two step procedure consisting first in the SN2 reaction of methylenic group and second deprotection of ester derivatives in order to set the carboxylic function free. Concerning the first step, traditional approach requires long reaction times and long work up procedures that lead to very poor product yields. Microwave (MW) irradiation at 2.45 GHz in closed vessels was exploited in this first synthetic step to take advantages from rapid heating rates thanks to the intrinsic volumetric and selectivity nature of MW heating. Results in terms of reaction times and yields as well as possible future developments, will be discussed.

R. Benassi ; E. Ferrari; S. Lazzari; F. Spagnolo; M. Saladini ( 2008 ) - Theoretical study on Curcumin: A comparison of calculated spectroscopic properties with NMR, UV–vis and IR experimental data - JOURNAL OF MOLECULAR STRUCTURE - n. volume 892 - pp. da 168 a 176 ISSN: 0022-2860 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The main target of this study is a high-level computational nalysis of Curcumin, employing DFT approach with two different sets of basis functions (B3LYP/6-31G* and B3LYP/6-311G**). Accurate quantum mechanical studies, both in vacuum and in methanol medium, are carried out with the aim to analyze the conformational equilibria, to find the most stable equilibrium structure and to define the nature of the molecular orbitals, fundamental to explain Curcumin binding characteristic. Our theoretical calculations, performed at B3LYP/6-31G* and B3LYP/6-311G** levels both in vacuum and in methanol medium,confirm that the keto-enolic forms are more stable than the di-keto one, whose extremely low population suggests that this structure should not influence Curcumin properties. Keto-enolic form C results the most stable, independently on calculation level and solvent (methanol) effect. HOMO and LUMO molecularorbitals are calculated for all the structures with the two sets of basis with very similar results. MEPs show that the negative charge is localized on the oxygen atoms, which, in the keto-enolic forms, point in the same direction enabling metal coordination.NMR, UV–vis and FT-IR experimental data are employed in the comparison with electronic and conformational properties of Curcumin resulting from theoretical calculations. The two different calculation levels (B3LYP/6-31G* and B3LYP/6-311G**) give very similar results.Good linear correlations between the experimental 1H and 13C NMR chemical shifts (dexp), in methanold4(MeOD) and DMSO-d6 (DMSO), and calculated magnetic isotropic shielding tensors (sigmacalc) are found (dexp = a *signacalc + b). A good prediction of UV–vis experimental maximum absorption (lambdamax) on the basisof conformer populations is obtained. A linear relation with a good correlation coefficient is observedplotting the FT-IR experimental wavenumbers vs. the calculated ones, allowing to predict FT-IR spectra.

Beatrice Arezzini; Marco Ferrali; Erika Ferrari; Chiara Frassineti; Sandra Lazzari; Gaetano Marverti; Ferdinando Spagnolo; Monica Saladini ( 2008 ) - Synthesis, chemical and biological studies on new Fe3þ-glycosilated b-diketo complexes for the treatment of iron deficiency - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY - n. volume 43 - pp. da 2549 a 2556 ISSN: 0223-5234 [Articolo in rivista (262) - Articolo su rivista]
Abstract

A simple synthetic pathway to obtain glycosilated b-diketo derivatives is proposed. These compounds show a good iron(III) affinity thereforewe may suggest the use of their Fe3þ-complexes as oral iron supplements in the treatment of anaemia. The glycosilated compounds (6-GlcH, 6-GlcOH and 6-GlcOCH3) are characterized by means of spectroscopic (UV, 1H and 13C NMR) and potentiometric techniques; they have a good water solubility, are kinetically stable in physiological condition (t1/2 > 100 h) and show a low cytotoxicity also in high concentrations (IC50 > 400 mM). They are able to bind Fe3þ ion in acid condition (pHw2) forming complex species thermodynamically more stable than those of other ligands commonly used in the treatment of iron deficiency. The iron complexes show also a good kinetic stability both in acidic and physiological pH and have a good lypophilicity (log P > 0.7) that suggests an efficient gastrointestinal absorption in view of their possible use in oral therapy. In addition they demonstrate a poor affinity for competitive biological metal ion such as Ca2þ, and in particular 6-GlcOCH3 is able to inhibit lipid peroxidation.

M. Saladini; E. Ferrari; S. Lazzari; F. Pignedoli; F. Spagnolo ( 2008 ) - Fe(III) containing complexes with beta-diketo derivatives for treatment of iron deficiency ( XXXV Congresso Nazionale della Divisione di Chimica Inorganica della Società Chimica Italiana - - 3-7 Settembre 2007) ( - Atti del XXXV Congresso Nazionale della Divisione di Chimica Inorganica della Società Chimica Italiana ) (xx Milano ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
Abstract

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R. Benassi; E. Ferrari; R. Grandi; S. Lazzari; M. Saladini ( 2007 ) - Synthesis and characterization of new beta-diketo derivatives with iron chelating ability - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 101 - pp. da 203 a 213 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

Here we report the synthesis, the characterization and a theoretical study on new glycosylated phenyl substituted beta-diketones; two classes of compounds are obtained according to the condensation reaction: central and side derivatives. Their iron(Ill) chelating ability is tested by means of UNT-visible (UV-vis), potentiometric and NMR techniques. The conformation of central derivatives does not allow any metal chelation, while side derivatives bind iron(111) through the P-dioxo moiety. The glycosyl moiety does not interact with metal ion but it helps to stabilize metal/ligand (1/3) complexes by means of hydrophylic interactions. The pK(a) of the ligands and the stability constants of their Fe(111) complexes are evaluated by means of UV-vis spectroscopy and potentiometry. A comparison with other iron-chelating agents, on the basis of lipophilicity and the pFe(III), is finally reported. (c) 2006 Elsevier Inc. All rights reserved.

O. FRANCIOSO; E. FERRARI; M. SALADINI; D. MONTECCHIO; P.GIOACCHINI; C. CIAVATTA ( 2007 ) - TG–DTA, DRIFT and NMR characterization of humic-like fractions from olive wastes and amended soil” (Elsevier BV:PO Box 211, 1000 AE Amsterdam Netherlands:011 31 20 4853757, 011 31 20 4853642, 011 31 20 4853641, EMAIL: nlinfo-f@elsevier.nl, INTERNET: http://www.elsevier.nl, Fax: 011 31 20 4853598 ) - JOURNAL OF HAZARDOUS MATERIALS - n. volume 149 - pp. da 408 a 417 ISSN: 0304-3894 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The purpose of the present study is to investigate, by means of thermogravimetric analysis (TG) and differential thermal analysis (DTA), diffuse reflectance infrared Fourier transform (DRIFT) and 2D nuclear magnetic resonance (NMR) spectroscopies, the structural features of the humic-like fraction (HLF) from olive pulp (OP), its effluents originated from the fermentation processes for hydrogen (EH2) and methane production (ECH4) and humic acid (HA) from soil amended with each of these materials. A considerable structural modification emerged between the HLF, in particular from the ECH4 effluent, which was characterised by a high content of polyphenolic and polypeptidic substances. The short-term amendment trial with OP and EH2 indicated that no chemical or structural changes in soil HA appeared. In contrast, the amendment with ECH4 substantially influenced the chemical and structural composition of soil HA. The structural interpretation performed by 2D NMR indicated the presence of aliphatic and aromatic protons while the sugar-like content and O–CH3 groups decreased with respect to the soil control HA. It emerges from this study that olive wastes contain stabilised humic-like material that may be recycled as an amendment in areas where olive trees are cultivated.

E.FERRARI; R.GRANDI; S.LAZZARI; G. MARVERTI; C. ROSSI; M. SALADINI ( 2007 ) - 1H, 13C, 195Pt NMR study on platinum(II) interaction with sulphur containing Amadori compounds - POLYHEDRON - n. volume 26 (15) - pp. da 4045 a 4052 ISSN: 0277-5387 [Articolo in rivista (262) - Articolo su rivista]
Abstract

AbstractThe NMR study on the interaction of Pt(II) with Amadori compounds is performed. The Amadori compounds are derived from the reaction of β-d-glucose with l-cystine leading to N,N′-di-(1-deoxy-β-fructos-1-yl)-l-cystine [FruCyscys], and with l-methionine leading to N-(1-deoxy-β-fructos-1-yl)-l-methionine [FruMet].The great instability of 2-(1,2,3,4,5-pentahydroxypentyl)-1,3-thiazolidine-4-carboxylic acid [GlcCys], formed by the condensation reaction of β-d-glucose and l-cysteine, prevents the formation of its Pt(II) complexes. Differently, FruMet well reacts with K2PtCl4 in 1:1 M/L molar ratio leading to the formation of [Pt(FruMet-N,S)Cl2], in which the Amadori compound coordinates the metal ion through nitrogen and sulphur atoms. FruMet originates also a solid trans complex [Pt(FruMet-N,S)2]Cl2. Its NMR solution study allowed to identify two isomers with respect to nitrogen and sulphur atoms: R,R and S,S.In [Pt2FruCyscysCl4] species, FruCyscys molecule links two Pt(II) ions giving rise to two pentaatomic N,S-chelate rings.

FERRARI, Erika; GRANDI, Romano; LAZZARI, Sandra; SALADINI, Monica ( 2007 ) - NMR study on Pt(II) interaction with Amadori compounds - INORGANICA CHIMICA ACTA - n. volume 360 - pp. da 3119 a 3122 ISSN: 0020-1693 [Articolo in rivista (262) - Articolo su rivista]
Abstract

AbstractHere we report the first evidence of Pt(II) interaction with Amadori compound [N-(1-deoxy-d-Fructos-1-yl)glycine (Fru-Hgly)]. The 1H and 195Pt NMR results show that complexation of Pt(II) by Fru-Hgly is strongly dependent on pH and reaction molar ratio. In 1/1 Pt/Fru-Hgly molar ratio, at acidic pH, the first coordination site is the carboxylic oxygen, while at physiological pH the anchoring group is the aminic one, in both cases the system slowly evolves towards an N,O chelating mode. In 1/2 Pt/Fru-Hgly molar ratio the only coordination site is nitrogen atom while the carboxylic oxygen is not involved in metal coordination.

P. Gioacchini; E. Ferrari; D. Montecchio; O. Francioso; M. Saladini; C. Ciavatta ( 2007 ) - Soil amendament with olive wastes-effects on mineral N, microbial biomass and humic acids structure ( P11. “International Symposium on Organic Matter Dynamics in Agro-Ecosystems” - - 16-19 Luglio 2007) ( - Atti del P11. “International Symposium on Organic Matter Dynamics in Agro-Ecosystems” ) (xx Poiters FRA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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E. Ferrari; C. Frassineti; S. Lazzari; G. Marverti; R. Grandi; M. Saladini ( 2006 ) - Glucosyl curcuminoid derivatives: Fe(III) and Ga(III) chelating agents with anti-cancer properties ( 1st European Chemistry Congress - - 27-31 Agosto 2006) ( - Atti del 1st European Chemistry Congress ) (xx Budapest HUN ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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E. Ferrari; C. Frassineti; S. Lazzari; G. Marverti; R. Grandi; M. Saladini ( 2006 ) - Glucosyl curcuminoid derivatives: Fe(III) and Ga(III) chelating agents with anti-cancer properties ( EUROBIC8 – 8th European Biological Inorganic Chemistry Conference - - 1-6 Luglio 2006) ( - Atti del EUROBIC8 – 8th European Biological Inorganic Chemistry Conference ) (xx Aveiro PRT ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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E. Ferrari; R. Grandi; S. Lazzari; M. Saladini ( 2005 ) - Hg(II)-coordination by sugar-acids: Role of the hydroxy groups - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 99 - pp. da 2381 a 2386 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

A solution study on the ability of some derivatised sugars [glucuronic acid (GluA), galacturonic acid (GalA) and glucosaminic acid (GlNA)] to complex the Hg(II) ion is reported. The stability constants of the complex species were determined by potentiometric measurements while H-1 NMR experiments allow to define the coordination sites of sugar molecules. GluA coordinates the metal ion through the carboxylic oxygen and the O-4 hydroxyl group and is found to form more stable complexes with respect to GalA in which metal ligation is from the carboxylic oxygen and the O-5 ring oxygen. GlNA forms stable complexes chelating Hg(II) ion through carboxylic oxygen and the a-amino group. The ternary 2,2´-bipyridine containing systems were also investigated by means of potentiometric studies. The ML2 complexes were also isolated in the solid state and characterised by IR spectroscopy.

E. Ferrari; R. Grandi; S. Lazzari; M. Saladini ( 2005 ) - New water soluble conjugated beta-diketones: potential iron-sequestering agents in treatment of Cooley’s anemia ( 8th FIGIPAS – Meeting in inorganic chemistry - - 6-9 Luglio 2005) ( - Atti del 8th FIGIPAS – Meeting in inorganic chemistry ) (xx Atene GRC ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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R. Benassi; E. Ferrari; R. Grandi; S. Lazzari; M. Saladini ( 2005 ) - New conjugated beta-diketones as iron chelators for clinical use ( 1st European Conference on Chemistry for life sciences - - 4-8 ottobre 2005) ( - Atti del 1st European Conference on Chemistry for life sciences ) (xx Rimini ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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B. Arezzini; M: Ferrali; E. Ferrari; R. Grandi; S. Monti; M. Saladini ( 2004 ) - Glycosyl-curcuminoids as potential new chelating agents in iron overload chelation therapy - EUROPEAN JOURNAL OF INORGANIC CHEMISTRY - n. volume 3 - pp. da 646 a 652 ISSN: 1434-1948 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The iron(III) chelating ability of some glycosyl derivatives of curcuminoids is tested by means of UV, potentiometric and NMR studies. The pK(a) of the ligands and the stability constants of their Fe3+ and Ga3+ complexes are evaluated by UV spectroscopy. The only metal binding site of the ligand is the beta-dioxo moiety; the glycosyl moiety does not interact with the metal ion at acidic pH values but it helps to stabilise metal/ligand (1:2) complexes by means of hydrophilic interactions. By comparing the pFe(3+) of our ligands with those reported for other chelating agents we suggest using these molecules as pro-drugs in iron overload treatment. Some of the more water-soluble derivatives are also tested for their antioxidant properties in vitro in biological systems and proved to act as free-radical scavengers inhibiting the iron redox cycle, ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

E. Ferrari; L. Menabue; M. Saladini ( 2004 ) - Characterization and metal affinity of Tirofiban, a pharmaceutical compound used in acute coronary syndromes - BIOMETALS - n. volume 17 - pp. da 145 a 155 ISSN: 0966-0844 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The crystal and molecular structure of Tirofiban [ N-(n-butanesulfonyl)-O-(4-(4-piperidinyl)-butyl)-(S)-tyrosine] is here reported. In the solid state the carboxylic group is in the anionic form while the piperidine molecule appear in the protonated form. By H NMR spectroscopy and potentiometric study three pK(a) are found: pKa(COOH) = 3.1(1), pKa(NHPIP) = 11.6(1) and pKa(NHSO2) = 13.8(1). The complexing ability of Tirofiban towards various metal ions (Cu(II), Ni(II), Co(II), Cd(II), Pb(II), Zn(II) and Ca(II)) is also determined by means of potentiometric studies. The prevailing species are [M(TirH)(2)](2+) where the ligand coordinates the metal ion through carboxylic group, while the piperidine nitrogen is still protonated. The great stability of these complexes may be due to the presence of hydrogen bond interactions, as well as the formation of stacking interactions involving the phenyl ring of the tyrosine residue.

E. Ferrari; M. Saladini ( 2004 ) - Iron(III) complexing ability of carbohydrate derivatives - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 98 - pp. da 1002 a 1008 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

A solution study on the coordinative ability of galactaric acid (GalAH(2)), D-glucosamine (GlcN) and D-glucosaminic acid (GlcNAH) toward Fe3+ ion is reported. UV spectroscopic study provides useful information to identify complex species formation and their stability constants are determined by means of potentiometric measurements. GalAH(2) behaves as chelating ligand through carboxylic oxygen and alpha-hydroxylic oxygen in the protonated or dissociated form depending on pH value. Two complex species [Fe(2)GalA(OH)(4)] and Na[FeGalAH(-2)](.)2H(2)O are also isolated in the solid state and characterised through IR spectroscopy. Glc-NAH also binds the Fe3+ ion through carboxylic and hydroxylic groups, while NH2 group is probably involved in metal coordiantion up to pH 4. GlcN demonstrates low ligating ability at acidic pH and does not prevent metal hydroxyde precipitation.

E. Ferrari; S. Lazzari; M. Saladini ( 2004 ) - The reaction of Pt(II) with glucosyl-sulphur-containing amino acids ( XXXII Congresso nazionale della divisione di Chimica Inorganica - - 20-24 Settembre 2004) ( - Atti del XXXII Congresso nazionale della divisione di Chimica Inorganica ) (XX Roma ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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E. Ferrari; R. Grandi; S. Monti; M. Saladini ( 2003 ) - New water soluble curcumin derivatives as iron(III) chelating agents ( 7th FIGIPS – Meeting in Inorganic Chemistry - - 11-14 Luglio 2003) ( - Atti del 7th FIGIPS – Meeting in Inorganic Chemistry ) (xx Lisbona PRT ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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M. Saladini; E. Ferrari; L. Menabue ( 2002 ) - Co-ordination of transition metal ions by galactaric acid: a potentiometric and spectroscopic study - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 92 - pp. da 121 a 127 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

A solution study on the ability of galactaric acid [GalaH(2), HOOC(CH)(4) COOH] in the complexation of biological metal ions such as Co(II) and Ni(II) and toxic metal ions such as Cd(II), Pb(II) and Hg(II), is reported. The stability constants of the complex species are determined by means of potentiometric measurements. Galactaric acid behaves as chelate ligand through carboxylic oxygen and alpha-hydroxy group towards Co(II) and Ni(II), while in the Pb(II) and Cd(II) containing system it co-ordinates the metal ion with carboxylic oxygen and two alcoholic hydroxy groups. The prevailing species at acidic or neutral pH is [MGala] which is also isolated in the solid state and characterized by means of IR spectroscopy. On increasing pH, the [MGalaH_(1)](-) species is also formed where the co-ordinated OH group undergoes deprotonation in all metal ion complexes except those with Hg(II), where the co-ordination of hydroxide ion is suggested as the precipitation of the metal hydroxide occurs at pH 7. (C) 2002 Elsevier Science Inc. All rights reserved.

M. SALADINI; MENABUE L; FERRARI E ( 2002 ) - Binding ability of sialic acid toward biological and toxic metal ions. NMR, potentiometric and spectrophotometric study. (Kluwer Academic Publishers:Journals Department, PO Box 322, 3300 AH Dordrecht Netherlands:011 31 78 6576050, EMAIL: frontoffice@wkap.nl, kluweronline@wkap.nl, INTERNET: http://www.kluwerlaw.com, Fax: 011 31 78 6576254 ) - JOURNAL OF INORGANIC BIOCHEMISTRY - n. volume 88 - pp. da 61 a 68 ISSN: 0162-0134 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The binary complexes of 5-amino-3,5-dideoxy-D-glycero-D-galactononulosic acid (NANA), commonly called N-Acetyl Neuraminic Acid, formed with biological metal ions such as Co(II) and Cu(II) and toxic metal ions such as Cd(II) and Pb(II) are investigated in aqueous solution by means of potentiometry, UV and NMR spectroscopy. The corresponding ternary systems with 2,2’-bipyridine are studied in aqueous solution by potentiometry and UV spectroscopy.NANA co-ordinates all metal ions, in both binary and ternary systems trough carboxylic group (protonated or deprotonated according to pH condition), pyranosidic ring oxygen and glycerol chain alcoholic hydroxy groups. The prevailing species in the pH range 2-7 are [M(NANA)2] type, their stability constants are greater than those of simple carboxylate complexes. Over pH 7 the species [M(NANA)2OH]- are also formed, but they don’t prevent the precipitation of metal hydroxides. This work provides information on the solution state chemistry of NANA in presence of bivalent metal ions; its great affinity for Cd(II) and Pb(II) toxic metals, near physiological condition, and the relatively high stability of the complex species found may account also for toxicity mechanism.

M. Borsari; E. Ferrari; R. Grandi; M. Saladini ( 2002 ) - Curcuminoids as potential new iron-chelating agents: spectroscopic, polarographic and potentiometric study on their Fe(III) complexing ability - INORGANICA CHIMICA ACTA - n. volume 328 - pp. da 61 a 68 ISSN: 0020-1693 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The pK(a) values of curcumin and diacetylcurcumin are, here doubtless, determined by means of spectroscopic and potentiometric measurements, and the enolic proton is the more acidic one. The interaction of Fe3+ with curcumin and diacetylcurcumin, in water/methanol 1:1 solution, leads to the fort-nation of the complex species [FeH2CU(OH)(2)] and [FeDCU(OH)(2)] (H2CU and DCU = curcumin or diacetylcurcumin monoanion, respectively) which prevails near pH 7. At more basic condition the prevailing species are [FeH2CU(OH)(3)](-) and [FeDCU(OH)(3)](-), which prevent metal hydroxide precipitation. H-1 NMR data state that the dissociated P-diketo moiety of the ligands is involved in metal chelation. The pK(a) value of the deprotonation reaction is strongly anticipated by the metal ion, as shown by UV spectral data. The stability constants, evaluated from potentiometric data, are near to that of desferrioxamine, which is, by now, the only iron-chelating agent for clinical use. (C) 2002 Elsevier Science B.V. All rights reserved.

E. Ferrari; R. Grandi; M. Saladini ( 2002 ) - Synthesis and characterization of new glycosyl-curcuminoids ligands with iron(III) chelating ability ( VII Convegno sulla chimica dei carboidrati - - 13-15 Giugno 2002) ( - Atti del VII Convegno sulla chimica dei carboidrati ) (xx Milano ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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E. Ferrari; L. Menabue; M. Saladini ( 2002 ) - Characterization and Metal affinity of tyrofiban®, a pharmaceutical compound used in acute coronary syndromes ( XXX Congresso nazionale della divisione di Chimica Inorganica - - 15-19 settembre 2002) ( - Atti del XXX Congresso nazionale della divisione di Chimica Inorganica ) (xx Modena ITA ) [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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E. Ferrari; R. Grandi; M. Saladini ( 2002 ) - Potential Iron(III)-chelating agents for treatment of Iron overload ( 35th International Conference on Coordination Chemistry ICCC35 - - 21-26 luglio 2002) ( - Atti del 35th International Conference on Coordination Chemistry ICCC35 ) (University of Heidelberg Heidelberg DEU ) - pp. da 391 a 391 ISBN: XXXXXXXXXX ISSN: - [Contributo in Atti di convegno (273) - Relazione in Atti di Convegno]
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M. Saladini; L. Menabue; E. Ferrari ( 2001 ) - Sugar complexes with metal(2+) ions: thermodynamic parameters of associations of Ca2+, Mg2+ and Zn2+ with galactaric acid - CARBOHYDRATE RESEARCH - n. volume 336 - pp. da 55 a 61 ISSN: 0008-6215 [Articolo in rivista (262) - Articolo su rivista]
Abstract

A solution study on the complex ability of galactaric acid (GalaH(2)) for complexation with Ca2+, Mg2+ and Zn2+ ions is reported. The stability constants of the complex species are determined by means of potentiometric measurements. From the dependence of stability constants on temperature, the DeltaH degrees and DeltaS degrees values are also determined. The formation of the complex species is an endothermic process and DeltaH degrees and DeltaS degrees values suggest a chelate coordination mode of galactaric acid involving carboxylic oxygen and a-hydroxylic group. The prevailing species at acidic or neutral pH is [MGala] (M = Ca2+, Mg2+, Zn2+) which is also isolated in the solid state and characterised by means of IR spectroscopy. On increasing pH, the [MGalaH -(1)](-) species is also formed, where the coordinated OH group undergoes deprotonation. (C) 2001 Elsevier Science Ltd. All rights reserved.

M. Saladini; L. Menabue; E. Ferrari; D. Iacopino ( 2001 ) - Amide group coordination to the Hg2+ ion. Potentiometric, 1H NMR and structural study on Hg2+-N-protected amino acid systems - JOURNAL OF THE CHEMICAL SOCIETY. DALTON TRANSACTIONS - n. volume non previsto - pp. da 1513 a 1519 ISSN: 1472-7773 [Articolo in rivista (262) - Articolo su rivista]
Abstract

The binary complexes of Hg2+ formed by N-carbonyl and N-sulfonyl amino acids, which are ligands containing peptide and sulfonamide groups respectively, are investigated in aqueous solution by H-1 NMR, UV spectroscopy and potentiometry. The corresponding ternary systems with 2,2'-bipyridine are studied in aqueous solution by potentiometry and in DMSO solutions by H-1-NMR. All the amino acids behave as simple carboxylate ligands at acid pH, while, around neutrality, N-p-tolylsulfonylglycine (tsglyH(2)), N-p-tolylsulfonyl-beta -alanine (ts-beta -alaH(2)) and N-2-nitrophenylsulfonylglycine (NO(2)psglyH(2)) switch to dianionic N,O-bidentate chelating ligands due to the involvement of the deprotonated amide nitrogen as an additional donor site. The Hg2+ ion is ineffective in promoting peptide nitrogen deprotonation in N-benzoylglycine (bzglyH). The binary and ternary species formed in aqueous solution and their stability constants are determined and compared with those of the homologous complexes of Pd2+, Cu2+, Cd2+ and Pb2+. The molecular structure of [Hg(bpy)(2)(NO2-psgly-N,O)].0.5H(2)O is determined by X-ray crystallography. It represents a rare example of Hg2+ N,O coordination by an amino acid molecule. In the complex Hg2+ shows a distorted octahedral environment with a N5O donor set. Four nitrogen atoms are derived from the two bpy ligands, while the oxygen and the fifth nitrogen are from the NO2-psgly dianion. New information on the solution and solid state chemistry of Hg2+ with ligands of biological interest is provided which may be of great relevance in understanding the mechanism of metal toxicity.