Circular dichroism spectra calculation of diastereomeric c-7 pentacyclic oxindole alkaloids using density functional theory and time-dependent density functional theory methods / Yusri Mohd Yunus

Density Functional Theory (DFT) and time-dependent density functional theory (TD-DFT) are reliable methods to calculate circular dichroism (CD) spectra in assigning the absolute configuration (AC) of chiral compounds. It requires choosing the correct level of theory that includes basis set, exchange-correlation functional and solvation model. Well established AC of diastereomeric pentacyclic oxindole alkaloids (POAs), isopteropodine and pteropodine were tested to find suitable level of theory. Both isopteropodine and pteropodine were purified by recycling HPLC and the nonempirical correlation between their experimental and computational CD data was studied. A series of Pople’s basis set (6-31G, 6-31G*, 6-31+G, 6-31+G*, 6-31+G**, 6-311+G**) exchange-correlation functionals (PBEPBE, MPW1PW91, BVP86, B3LYP, CAM-B3LYP) and polarizable continuum solvation models (IEF-PCM, I-PCM, C-PCM), which are commonly used for natural product, were assessed. It was found that a double zeta basis set with an additional diffuse and polarization functions as 6-31+G** was sufficient for the electronic circular dichroism (ECD) spectra simulation. The calculation inclusive of solvation model is significant to be included and the IEF-PCM is the best solvation model. Although both B3LYP and CAM-B3LYP hybrid functionals could model the ECD data for isopteropodine, however the former functional failed in predicting the critical Cotton effect (CE) of the n→π∗ electronic transition in pteropodine. This was nevertheless solved by the latter long-range correction properties functional. Thus, the suitable level of theory proposed to model the CD data for POAs system is TD-DFT/ CAM-B3LYP/6-31+G**/IEF-PCM with similarity factor of more than 0.9. The reliability on this optimised computational CD method was verified through consistency in simulating ECD data of three new POAs in establishing their AC.