Polyphenol interactions. Part 4. Model studies with caffeine and cyclodextrins

Abstract

Studies of the reversible complexation of a range of phenols and natural polyphenols in aqueous media with caffeine and related heterocycles, and with α- and β-cyclodextrin, using a range of physical methods (1H and 13C NMR spectroscopy, microcalorimetry, and X-ray crystallographic analysis) are reported. Values of the assciation constants (K) for the formation of 1:1 complexes between caffeine and a range of natural polyphenols hav been determined (K 15–138 dm3 mol–1). Amongst galloyl esters there is a dependence for strong binding on molecular size, conformational flexibility, and the ‘free’ galloyl ester group content of the polyphenol. With phenolic flavan-3-ols, association is enhanced by galloylation at C-3. The extent of precipitation of polyphenols by caffeine is related to the assciation constants (K), the molecular size of the polyphenol, and the initial concentration of both substrates. Polysaccharide cavity sequestration of polyphenols has been studied by means of the model substrates α- and β-cyclodextrin. Compared with that of the natural galloyl esters (K 76–340 dm3 mol–1) the binding of phenolic flavan-3-ols to β-cycloextrin is strong (K 210–6232 dm3 mol–1). Models are proposed for encapsulation within the cyclodextrin cavity. The results of these model studies are discussed in terms of the relative significance of hydrophobic effects and hydrogen bonding in polyphenol complexation. They provide a basis for the interpretation of the behaviour of polyphenols in their association with proteins, polysaccharides and other macromolecules.