Long-Lived States Provide Insights from NMR into the β-Cyclodextrin Drug Assemblies

In the last two decades, extending spin memory in NMR has been used for several purposes. Long-lived states (LLS) or singlet states are one of the first spin memory enhancement techniques used. LLS have the potential to extract structural information and intra- and intermolecular interactions of complex systems other than studying slow phenomenon. The motional regime of β-cyclodextrin (β-CD) drug inclusion complexes generally lies in the intermediate region, where ωτ ≈ 1, and the standard methods of studying these interactions, i.e., NOE and chemical shift monitoring, suffer from insufficient output information. The sensitivity of LLS toward the environmental changes is utilized here to gain insights into the drug assemblies formed by β-CD. One can use change in relaxation of LLS to study the structural changes during complexation. The examples of β-CD with the drugs indomethacin, paracetamol, gliclazide, and CI-933 (a precursor 4-methoxybenzamide) were studied. Indomethacin, paracetamol, and 4-methoxybenzamide show strong interaction through the para-substituted benzene ring, unlike gliclazide. Relaxation of LLS in β-CD-drug complexes is modeled using standard Redfield Relaxation Theory. Computational studies performed support the experimental observations. Docking and molecular dynamics simulation provided the explanation of the relaxation properties of these drug molecules.