The cucurbit[7]uril effect on reference substances for NMR in deuterium oxide solution

Sodium 4,4-dimetyl-4-silapentane-1-sulfonate (DSS) and sodium 3-(trimethylsilyl)propionate-2,2,3,3-d(4) (TSP) are widely used as internal reference substances for NMR studies. Macrocyclic molecule cucurubit[7]uril (CB[7]) may form complexes with DSS or TSP and affect DSS or TSP. However, the details have not been reported to date. In this study, the effect of CB[7] on DSS or TSP and its causes are studied in deuterium oxide solution using NMR measurements, isothermal titration calorimetry, and molecular modeling calculations. The DSS or TSP proton signals exhibit a chemical shift change in the presence of CB[7], caused by formation of the 1 : 1 inclusion complex, where the trimethylsilyl group of DSS or TSP is encapsulated into the cavity of CB[7]. Detailed steric structures of these complexes were determined using molecular modeling calculations based on the NMR results. The results show that not only the hydrophobic effect but also the ion-dipole interaction formed by sodium ions plays a concerted role in the inclusion complexation of DSS or TSP with CB[7]. These findings suggest that DSS or TSP should be used as external standards when examining the exact H-1 NMR chemical shift change derived from CB[7] and a guest molecule upon investigating complexation with CB[7].