基于密度泛函活性理论研究降糖药SGLT2的端基异构效应

Generalized anomeric effect from DFRT approach on SGLT2

在密度泛函活性理论(DFRT)框架下,应用能量分解分析法,结合新近发展起来的信息理论(IT),以2-F-α-D-吡喃型葡萄糖为SGLT2模型分子,在DFT M06-2X/cc-pVDZ水平上优化并计算了80对分子的能量及其分能量.能量分解分析显示,有27对出现端基异构现象,但还有53对不符合这个经验规则.它们的总偶极矩差值(ΔDe),而不是超共轭效应差(Δh),可以作为一项合理的总能量差相关指标.借助于双组分能量"立体位阻能和静电势能"组合模型,或者"交换相关能与静电势能"组合模型,能较好地预测模型分子的一般端基异构体的能量差.用密度泛函框架下的信息理论,计算了27对正端基异构体的8个信息量指数,未找到相关性强的单个信息量指数.探讨了模型分子端基异构效应的本质和起源,证实了它们的复杂属性.

The nature and origin of the generalized anomeric effect is investigated with energy components and information-theoretic quantities from density functional reactivity theory(DFRT)and Information-theoretic Approach.In the framework of DFRT,the energy decomposition analysis and the newly developed information theory(IT)were used to study the generalized anomeric effect of 2-F-α-D-glucopyranose as SGLT2 model molecule on the level of DFT M06-2 X/cc-pVDZ,and the information energy index of 80 isomers and their sub-isomers were calculated.The total energy decomposition of the 80 conformations shows that the anomeric heterogeneity is statistically significant(ie,27 matches the rule),but another 53 does not conform to this rule.Their total dipole moments difference(ΔDe),rather than the superconjugation effect difference(Δh),can be used as a reasonable total energy difference correlation index.The origin of the generalized anomeric effect were explored with eight information indices,which confirmed the origin of their complex effect.This paper provides a hypothesis of the origin of the electrostatic-stereoscopic effect consistent with the traditional chemical beliefs,that is,the two-component new-density functional energy analysis,which can better explain the energy difference of the general anomeric effect of SGLT2 molecules.