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 (1)H NMR DOSY and 1D ROESY experiments, and molecular modeling. Heteroassociation constants of [(all-S)-1·2] and [(all-R)-1·2] diastereoisomeric complexes were obtained from diffusion data by single point measurements, and from nonlinear fitting of 1H 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.