Stereochemical Preference of 2′-Deoxycytidine for Chiral Bis(diamido)-bridged Basket Resorcin[4]arenes

Bis(diamido)-bridged basket resorcin[4]arene (all-S)-1 and its (all-R)-1 enantiomer proved able to interact with 2'-deoxycytidine (2) and pyrimidine nucleoside analogs in dimethyl sulfoxide (DMSO) solution. In such a solvent, the resorcinarene hosts adopt a preferential 1,3-alternate-like conformation, with a larger cavity delimited by two syn 3,5-dimethoxyphenyl moieties, and two external pockets, each delimited by the other 3,5-dimethoxyphenyl group and its diamido arm (the wing). Complexation phenomena were investigated by nuclear magnetic resonance (NMR) methods, including H-1 NMR DOSY and 1D ROESY experiments, and molecular modeling. Heteroassociation constants of [(all-S)-12] and [(all-R)-12] diastereoisomeric complexes were obtained from diffusion data by single point measurements, and from nonlinear fitting of H-1 NMR chemical shifts. Selective proton relaxation rate measurements allowed us to significantly discriminate the two complexes by identifying two different interaction sites of the guest in the resorcin[4]arene host, depending on its configuration. Chirality 25:840-851, 2013. (c) 2013 Wiley Periodicals, Inc.