Institute of Applied Chemistry, Guizhou University, Guiyang, 550025, P. R. China.
Org Biomol Chem. 2011 Feb 21;9(4):1041-6. doi: 10.1039/c0ob00114g. Epub 2010 Dec 14.
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.
化学研究表明，抗结核药物异烟肼的酰化抗性是由于葫芦[n]脲（n=6 或 7）的包含或排除所致。（1）H NMR 谱分析表明，异烟肼与两种葫芦[n]脲的不同相互作用模型取决于主体的空腔大小。密度泛函理论方法的量子化学计算表明，异烟肼与两种葫芦[n]脲的相互作用是通过在气相和水溶液中通过葫芦[n]脲的端口羰基上的氢键通过热力学稳定化来实现的。电子吸收滴定光谱表明，主体和客体以 1:1 的比例相互作用，具有中等的结合常数。在葫芦[n]脲存在下，用各种酰化剂对异烟肼进行酰化动力学研究表明，抗性仅取决于主体-异烟肼的比例，而与葫芦[n]脲的大小和酰化剂的种类无关。
