Description of the specific solvent effect in the tautomeric systems, QM/MM modeling

Curcumin, derived from Curcuma longa plant has been shown to exhibit antioxidant, antiinflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer’s disease, and other chronic illnesses [1–3]. In the light of these promising propertiesseveral questions need to be answered in order to improve its systematic applicability. These pertain to the solubility and stability of curcumin, its optimum dose, pharmacokinetics, mechanism of action of curcumin for a given disease, bioavailability profile, and intricacies of prevention and cure of an identified disease [1]. Curcumin is a tautomeric compound, potentially existing as three main tautomeric forms, enolketo(EK), keto-keto (KK), enol-enol form (EE) and it is naturally that the tautomerism influences its activities [4]. There is substantial number of theoretical studies and experimental data[4-16], showing the strong predominance of the enol–keto form (EK) in solution. However under some structural and environment conditions the diketo form (KK) could be observed as well.[17.18]. One of the important factors for tautomeric systems is the influence of the solvent. Using UV-Vis spectroscopy, which is the only method that can register tautomers as individual species, has been proven by us that the addition of water to organic solvents leads to stabilization of the diketo tautomeric form (KK) [19]. We have done quantitative analysis, based on chemometric analysis of the absorption spectra of curcumin in water/ethanol binary solvent mixtures, which has provided the molar fractions of the tautomers and hence the Gibb’s free energies in ethanol and water. The enol–keto form is only presented in ethanol, while in pure water the diketo tautomer is dominating. Quite often the interaction tautomer-solvent is very specific and it is complicated to be described using conventional methods of the Quantum chemistry. The group ofProf. Chiara Cappelliis internationally recognized in the Computational Modeling of Complex Systems.Recently, they have developed new method (QM/MM)that can be used for description of the effect of the water and the effect of the ethanol on the position of the tautomeric equilibrium. Our expectations are this method to be very useful in the solvent effect description in other tautomeric system in future.