AT1受体拮抗剂缬沙坦化学位移的量子化学计算研究

Quantum Chemical Calculation on 1H NMR Chemical Shifts of Valsartan——An AT1 Receptor Antagonist

核磁共振波谱实验能够通过谱峰化学位移归属确定化合物分子结构,同时理论计算预测化学位移有助于核磁共振对化合物的谱峰归属.该文基于李芳等人的核磁共振实验以及分子动力学模拟结果,采用量子化学方法预测了缬沙坦(Valsartan)在SDS胶束中2种构象的化学位移.通过比较不同量子化学方法和基组的计算结果,特别是采用了ONIOM模型考虑了胶束环境对药物分子化学位移的影响,表明Valsartan在SDS胶束溶液中所存在的2种构象可以通过理论计算加以区分,且这2种构象的化学位移理论预测值与NMR实验值吻合得很好.本工作表明在计算复杂体系化合物的化学位移时,理论模型应该考虑环境效应的影响.

Prediction of chemical shifts using quantum chemical calculations is a useful tool for NMR spectra assignment. In this work, the protons chemical shifts of Valsartan dissolved in sodium dodecyl sulfate （SDS） micelle were calculated and compared with those obtained from NMR experiments. The computational results, especially those obtained with the ONIOM method, could distinguish the two conformations dissolved in the SDS micelle, and the theoretical values of chemical shifts are in reasonable agreement with those obtained with NMR experiments. Our study showed that in the calculations of chemical shifts of complex system, the environment should be considered in the theoretical model.