Time dependent density functional theory modeling of chiroptical properties of amino acids in solution
Kundrat, Matthew David
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Time Dependent Density Functional Theory (TDDFT) and the COnductor-like Screening MOdel (COSMO) of solvation were used to model the specific rotation and Optical Rotatory Dispersion (ORD) of various amino acids in solution. Zwitterionic, cationic, dicationic, anionic and dianionic forms of amino acids were investigated and the results compared with experimental literature data obtained in neutral, acidic and basic conditions, as appropriate. It was found that TDDFT modeled the specific rotation of all the forms of the amino acids with an approximately equal level of accuracy. One source of error encountered is that the model overestimated the extent of intramolecular hydrogen bonding for the zwitterions, affecting the calculated mole fractions of the different conformers thus having an impact on the specific rotation. The physical origin of the Clough-Lutz-Jorgensen's rule was investigated, a general property of alpha amino acids where the specific rotation of an acidified solution is nearly always more positive in value than the specific rotation of the amino acid by itself. Results were consistent with the functional side chains of the amino acids behaving similarly to negatively charged groups when the molecules were in their zwitterionic forms, while those same groups behaved in a fashion akin to positively charged perturbers in the cationic, protonated forms of the molecules. Finally, the specific rotation of amino acids has be calculated using explicit solvation molecules, as opposed to the continuum model that has been used previously. It was found that simple three-point charge models used in place of quantum mechanical waters were able to reproduce, to an extent, the inductive effects of those solvent molecules on the chiroptical responses of the solute amino acids.