LAUSR

Theoretical calculations of optical rotation (OR), although important to predict absolute configurations (ACs) and corroborate experiments, require efficient methodology able to reproduce enantiomer specificity and real OR values. Also, troublesome molecules are recurring in the literature, such as (S)-methyloxirane and (1R,5R)-β-pinene. This study evaluates DFT functionals B3LYP, CAM-B3LYP, ωB97X-D, M06-2X, and PBE0 considering basis sets aug-cc-pVDZ, aug-cc-pVTZ, 6-311++G(2d,p), and 6-311++G(3df,2p) in OR prediction of 42 rigid organic molecules assessing cases with wrong enantiomeric determination comparing to available experimental data at wavelengths 355, 589, and 633 nm. Functionals CAM-B3LYP and ωB97X-D with aug-cc-pVTZ are indicated here to reproduce experimental values more accurately considering fewer number of wrong AC predictions, normalized RMSD values below 0.70, and a good approximation to experimental values in hierarchical cluster analysis. Methyloxirane AC was reproduced in CAM-B3LYP and PBE0, with [ α ] 355 = 6 . 94 $$ {\left[\alpha \right]}_{355}=6.94 $$ for CAM-B3LYP/aug-cc-pVTZ close to experimental value [ α ] 355 = 7 . 49 ± 0 . 30 $$ {\left[\alpha \right]}_{355}=7.49\pm 0.30 $$ . Good results were found for AC of β-pinene in M06-2X, CAM-B3LYP, and ωB97X-D while the latter in 6-311++G(3df,2p) obtained OR values of [ α ] 589 = 3 . 44 $$ {\left[\alpha \right]}_{589}=3.44 $$ and [ α ] 689 = 4 . 20 $$ {\left[\alpha \right]}_{689}=4.20 $$ close to experimental values [ α ] 589 = 2 . 8 $$ {\left[\alpha \right]}_{589}=2.8 $$ and [ α ] 689 = 4 . 66 ± 0 . 60 $$ {\left[\alpha \right]}_{689}=4.66\pm 0.60 $$ . The two molecules aforementioned are, for the first time, reported to give valid theoretical OR values in such simple methodologies. OR calculations were all performed after geometry optimization at the same level of theory, and analysis of different functional combinations for each step in β-pinene showed it can interfere with AC prediction even in rigid molecules.