Simulation and Software Development of Electronic Circular
Dichroic Spectrum
XU Fan2, SU Jun-kui1, WEN Yan1, GAN Li-she1, 2*
1. School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China
2. Institute of Modern Chinese Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Abstract：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 theoretical spectrum. The software can adjust simulation parameters in real-time and compare them with the experimental curve, facilitating the data processing and result evaluation of the calculated ECD.
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