QSPR modeling of optical rotation of amino acids using specific quantum chemical descriptors

Many chemical phenomena occur in solution. Different solvents can change the optical activity of chiral molecules. The optical rotation angles of solutes of 75 amino acids in dimethylformamide, water and methanol were analyzed using the quantitative structure–activity relationships approach. For an accurate description of chirality, we used specific quantum chemical descriptors, which reflect the properties of a chiral center, and continuous symmetry measures. The set of specific quantum chemical descriptors for atoms located near the chiral center, such as Mulliken charges, the sum of Mulliken charges on an atom (with the hydrogen charges summed up with the adjacent non-hydrogen atoms), and nuclear magnetic resoncance tensors was applied. To represent solvent effects, we used mixture-like structural simplex descriptors and quantum chemical descriptors obtained for structures optimized for specified solvent using PBE1PBE/6-31G** level of theory with the polarizable continuum model. Multiple linear regression, M5P, and locally weighted learning techniques were used to achieve accurate predictions. The specific quantum chemical descriptors proposed here demonstrated high specificity in the majority of the developed models and established direct quantitative structure–property relationships.