药物小分子化学位移的量子化学计算研究

核磁共振的谱峰归属对分子结构的确定至关重要，用理论计算方法预测化学位移对谱峰的正确归属是极其有帮助的. 我们用量子化学的方法预测了乙酰水杨酸及其衍生物分子上碳原子的化学位移，并通过比较计算值和实验值得到不同理论计算方法的误差范围. 用HF和DFT理论计算芳环碳的化学位移时，CSGT方法比GIAO方法更为准确. 与其它方法相比，B3PW91//CSGT 在6-311G(d，p)基组下得到的芳环碳的化学位移最接近实验值. 采用B3LYP//GIAO计算时， 使用不同的基组 6-31G(d，p)和6-311++G(3df，3pd)得到的化学位移计算值只有δ 0.01~2.04的差异. MP2方法非常耗时，且对于计算精度的改善并不显著; 并且，由于电子相关性的影响，碳原子周围的电子环境对化学位移计算的准确性影响很大. 与实验值比较，HF方法由于忽略电子相关效应所以表现较差. 另外，碳链的增长对计算准确性也存在一定影响. 

Quantum Chemical Calculation on 13C NMR Shifts of Small Drug Molecules

Prediction of chemical shifts using quantum chemical calculation is helpful for assigning NMR spectra, and of great importance in structure determination. In this paper, we evaluated the performance of different quantum chemical methods for calculating 13C chemical shifts of acetylsalicylic acid and its derivatives. When Hartree-Fock (HF) and density functional theories (DFT) were used to compute phenyl 13C chemical shifts, both the CSGT method and the GIAO method yielded results that agreed reasonably well with the experimental values, while the former method often showed better performance than the latter. Calculated phenyl 13C chemical shifts showed excellent agreement with the experimental results when B3PW91//CSGT at 6-311G(d, p) level was used. When the B3LYP//GIAO method was used for calculation, the difference between the results obtained by applying 6-31G(d, p) and 6-311++G(3df, 3pd), respectively, was only δ 0.01~2.04. The MP2 method was often more time-consuming, but the results it gave show only marginal improvement in terms of calculation accuracy. It was found that the greater effect of electronic correlation, the more the electronic atmosphere of C atoms affects the accuracy of chemical shift calculation. For the reason, the HF method performed not so well because the calculation did not take electronic correlation into account. It was also found that the length of C chain also has effects on the calculated results.