title: Biorelevant physicochemical profiling of (E)- and (Z)-resveratrol determined from isomeric mixtures.
abstract: Biorelevant, isomer-specific physicochemical parameters of resveratrol, a multifunctional component in red wines, with cardioprotective, anti-Alzheimer and several other pharmacologic activities were determined. The parameters include site-specific basicities, lipophilicities, solubilities and diffusion constants for the two geometric isomers. The protonation equilibria of (E)- and (Z)-resveratrol were monitored by1H NMR-pH titrations. Five closely related auxiliary compounds ((E)-pinostilbene, (Z)-pinostilbene, (E)-pterostilbene, (Z)-pterostilbene and resorcinol) were also studied. Combining the datasets, the group-specific protonation constants of resveratrol isomers were determined. The results show that (Z)-resveratrol is more basic at every protonation site than the (E)-isomer. Lipophilicities are quantified in terms of logP values and were determined by octanol/water partition experiments and quantitative NMR spectroscopy: (E)-resveratrol was found to be more lipophilic. Since the molecular geometries of the isomers differ, diffusion ordered NMR spectroscopy (DOSY) experiments were also carried out to quantify the diffusion capabilities of the isomers: (Z)-resveratrol of bent shape has a slightly higher diffusion coefficient than its extended (E) counterpart. A striking 10-fold difference of water solubility was found in favor of the (Z) isomer, due obviously to the reduced water-repellent character in the more compact molecule. This is so far the greatest recorded solubility difference between geometric isomers of any compounds.
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Budapest, H-1092, Hőgyes Endre u. 9, Hungary. Electronic address: orgovan.gabor@pharma.semmwelweis-univ.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Orgován
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Budapest, H-1092, Hőgyes Endre u. 9, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Gonda
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Budapest, H-1092, Hőgyes Endre u. 9, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
mesh_terms: D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D000442:Octanols / Q000737:chemistry; D000077185:Resveratrol; D012995:Solubility; D013267:Stilbenes / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000442:Octanols; D013267:Stilbenes; C522997:pinostilbene; D014867:Water; C107773:pterostilbene; D000077185:Resveratrol
keywords: Lipophilicity; Microspeciation; Pinostilbene; Pterostilbene; Resveratrol; Solubility; cis-Resveratrol