Cucurbituril-resisted acylation of the anti-tuberculosis drug isoniazid via a supramolecular strategy.

ABSTRACT

A chemical investigation reveals that the resistance to acylation of an anti-tuberculosis drug, isoniazid is a consequent result of the inclusion or exclusion of cucurbit[n]urils (n = 6 or 7). The (1)H NMR spectra analysis shows that the different interaction models of the isoniazid with the two cucurbiturils are dependent on the cavity size of the hosts. Quantum chemistry calculations with density functional theory method indicate that the interaction of the isoniazid with both cucurbiturils is through thermodynamic stabilization in both the gas phase and aqueous solution through hydrogen bonding on the portal carbonyls of the cucurbiturils. Electronic absorption titration spectra suggest the hosts and guest interact in a ratio of 1 1 with moderate binding constants. Acylation kinetics of isoniazid with various acylating agents in the presence of the cucurbiturils revealed that resistance is only dependent on the host-isoniazid ratio, and independent on the size of the cucurbiturils and the species of acylating agents.