摘要
有机小分子化合物,尤其是天然产物具有复杂和多样的结构,且一般含有多个手性中心,确定其绝对构型一直是结构鉴定的难点之一。电子圆二色光谱(ECD)具有样品无损、曲线简洁等优势,是鉴定绝对构型的强有力的手段之一。利用密度泛函理论(DFT)和含时密度泛函理论(TDDFT)等量子化学理论以及计算机技术,对化合物的理论ECD计算模拟,与实验值对比确定绝对构型是目前主流技术。计算模拟流程如下:首先确定化合物的相对构型,其次运用构象搜索软件对化合物进行构象分析,然后对搜索得到的多个最低能量态构象(如能量阈值在2.0 kcal·mol^(-1)以内)进行几何优化和振动分析,将已经优化完成的优势构象投入ECD计算,计算ECD相关参数,得到电子激发能(eV)和转子强度(10^(-40) erg-esu-cm)等数据,最终根据数据进行多构象谱图拟合。该研究主要对ECD曲线的模拟方法、ECD计算结果的评价标准进行了全面总结。在此基础上,运用Python语言开发了一款自动化处理高斯ECD计算结果、模拟ECD曲线的软件,该软件能够对计算得到的输出文件进行定位,对于化合物几何优化和振动分析得到的输出文件,可以抓取各个构象的吉布斯自由能数据,并且依据此数据进行玻尔兹曼分布的加权,对于计算ECD相关性质的输出文件,可以抓取ECD计算相关的电子激发能和转子强度的数据,依据以上数据得到的ECD计算理论光谱图,能够进行实时模拟参数调节并与实测曲线对比,方便了计算ECD的数据处理和结果评价。
Organic small molecules,especially natural products,have complex and diverse structures and generally contain multiple chiral centers,so the determination of their absolute configuration has always been a challenge in structural elucidation.Electronic circular dichroism(ECD)is a powerful tool for identifying absolute configuration because of its concise curve and without sample loss.With effective use of computer technology and quantum chemistry theories such as density functional theory(DFT)and time-dependent density functional theory(TDDFT),the calculation of theoretical ECD spectrum and comparison with the experimental one has become a state-of-the-art technique for absolute configuration determination.The main process is as follows:First,the relative configuration of the compound needs to be determined before calculation.Conformation analyses are carried out to identify multiple lowest energy conformers,which are then subjected to geometric optimization and vibration analysis(such as the energy threshold within 2.0 kcal·mol^(-1)).ECD-related parameters,such as electronic excitation energy(eV)and rotor strength(10^(-40) erg-esu-cm),are further calculated for each lowest energy conformer.Finally,these data are processed according to Gaussian broadening function for spectrum fitting,and the calculated spectrum of all conformers is averaged according to their Boltzman weight.This article mainly summarizes the simulation method of the ECD curve and the evaluation standards of the ECD calculation result.Furthermore,software was developed for automatically processing Gaussian ECD calculation results and simulation of ECD curve based on Python language.The software can locate keywords in the output files.For the geometry optimization and vibration analysis output files,it can capture the Gibbs free energy data of each conformer and weight the Boltzmann distribution.The ECD-related properties output files can capture the excitation energy(eV),the corresponding oscillator and rotatory strength,and simulate the theoret
作者
许范
苏俊奎
文燕
甘礼社
XU Fan;SU Jun-kui;WEN Yan;GAN Li-she(School of Biotechnology and Health Sciences,Wuyi University,Jiangmen 529020,China;Institute of Modern Chinese Medicine,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China)
出处
《光谱学与光谱分析》
SCIE
EI
CAS
CSCD
北大核心
2024年第2期434-438,共5页
Spectroscopy and Spectral Analysis
基金
国家自然科学基金项目(22077111,81872756)资助。
