Absolute Configuration Determined by Chiroptical Calculations

Simulation Methods

Optimisation

First of all, the basic molecular structures are either builded by Molecular Mechanics or using the CIF file from Cambridge Structural Database. After the initial model is builded, the molecular geometry is optimised again using DFT methods. The basis set used starts from small one and increases step by step untile the level of theory for the later calculations. (e.g. M062X/6-311++G(d,p) is chosen for the ECD calculation, the optimisation should also compute at the same level of theory.) My personal preference are 3-21G → 6-31G → 6-31G(d,p) → 6-31++G(d,p) → 6-311++(d,p). B3LYP is a very efficient functional, so I prefer to optimise the geometry using B3LYP functional first, then move to the chosen DFT methods for later calculations.

Electronic Circular Dichroism Calculations

The detailed ECD calculation methods and Gaussian key words can be found in here. My personal preference of DFT method for ECD calculation is M062X/6-31+G(d,p)with CPCM. Larger basis sets can be used if the resulting spectrum is not conclusive, but from my experence, this DFT method could satisfy most of molecules. If the calculated spectrum is not in good agreement with the literature, you should always re-exam the optimised geometry.

Specific Rotation Calculations

I personally do not trust the specific rotation calculations. In most of cases, it gives useless results and I have to avoid to discuss the calculated specific rotation in the report or paper. The detailed method to compute specific rotation is here. I have not found any perticular DFT method that would normally produce reliable results yet. There is one review paper talked about the current state of Ab initio calculation of optical rotation and electronic circular dichroism.

NMR Calculations

The detailed simulation method is here. M062X/pcS-2 is my personal favourate DFT method. PcS-2 is a special basis set designed for NMR calculations. It can be downloaded in EMSL Basis set Exchange website.

Selected Molecules

Brevianamide_A: ECD calculations, Specific Rotation Calculations, ¹³C NMR Calculations