Quantum chemical investigation of beta-CD–catechin flavonoid encapsulation in solution through NMR analysis: an adequate controlled drug-delivery system

Abstract

The high water solubility of the flavonoid catechin makes it a promising candidate as a drug in the treatment of various diseases. Formation of the beta-CD–catechin inclusion complex has been proposed experimentally, and we feel that a comprehensive theoretical investigation of the interaction of beta-CD and catechin in aqueous medium is of relevance. We report a density functional theory–polarizable continuum model (DFT–PCM) study of molecular complexes encompassing 28 distinct modes of interaction involving 1 : 1, 1 : 2, 2 : 1, 3 : 1 and 4 : 1 forms of complexation. Through comparison between calculated (DFT–PCM–water) and experimental (in D₂O) ¹H NMR chemical shifts we identified the preferred mode of complexation in water solution. While the full-inclusion 1 : 1 complex, an instinctive guess, was proposed experimentally, we found that a 1 : 1 adsorption complex structure with interaction at the secondary rim of beta-CD, named M9, showed good agreement with ¹H NMR data (in D₂O). The global minimum full-inclusion structure (named M1) exhibited an extremely poor accordance with experimental ¹H NMR data. Structure M9 has a moderate interaction energy value, not as tightly bound as the full-inclusion structure, so the release (of catechin) to the medium can be adequately accomplished. Experimental ¹H NMR chemical shifts in solution provide valuable information for the analysis of DFT-PCM simulated NMR results, enabling the determination of the most probable complex molecular structure in solution. This is an alternative to the well-known lowest energy criterion to find the preferred structure among various plausible candidates.