engleski

Modeling the hydrophilicity and lipophilicity of wine polyphenols using descriptors derived from 3D structures

Due to importance of three-dimensional (3D) shape of molecules for passive diffusion through the biological membranes, our attempt was to develop a quantitative structure- property relationship (QSPR) models that relates hydrophilicity (Hy) and lipophilicity (log P) of 19 polyphenols present in wine, with descriptors derived from an optimized 3D molecular structures. The aim of this study was also to correlate the experimentally determined log P values for polyphenols (taken from web database, http://chem.sis.nlm.nih.gov/chemidplus/) and values that are calculated using four different programs: HyperChem (log PHyp), MLOGP, ALOGP, and CLOGP. The 3D structures of 19 polyphenols were optimized applying the HyperChem 8.0 (Hypercube Inc.) using AM1 method. Several physico-chemical parameters were calculated with HyperChem: the energy of the highest occupied (EHOMO) and lowest unoccupied molecular orbital (ELUMO), difference between EHOMO and ELUMO (GAP), the heat of formation (Hf), and hydration energy (EHYDR). Applying the Dragon program, different group of molecular descriptors have been calculated: geometrical, 3D-MoRSE, Randic molecular profiles, GETAWAY, RDF, WHIM, and BCUT descriptors. Selection of descriptors based on best-subset method and multiple regression analysis was performed using the program Statistica 7.0 (StatSoft, Inc.). The generated QSPR models were validated by leave-one-out cross-validation procedure using the CROMRsel (Rugjer Bošković Institute, Zagreb). The best model for hydrophilicity contains the two 3D- MoRSE descriptors: Mor13e and Mor13e. The best agreement with experimentally observed log P values was obtained with CLOGP values. However, the most appropriate model was achieved for the ALOGP using two variables: BELe1 (BCUT) and RTm (GETAWAY). Obtained models imply that lipophilicity and hydrophilicity of polyphenols is mainly influenced by the presence of different substitutions on the basic structure of phenolic acids and flavonoids.

polyphenols ; lipophilicity ; hydrophilicity ; QSPR

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