Ab Initio and Density Functional Theory Modeling of the Chiroptical Response of Glycine and Alanine in Solution Using Explicit Solvation and Molecular Dynamics

Abstract

We investigate ways in which simple point charge (SPC) water models can be used in place of more expensive quantum mechanical water molecules to efficiently model the solvent effect on a solute molecule's chiroptical responses. The effect that SPC waters have on the computed circular dichroism of a solvated glycine molecule are comparable to, albeit somewhat weaker than, that of quantum mechanical waters at the coupled cluster CC2 level of theory. The effects of SPC waters in fact correlate better with QM-CC2 waters than quantum mechanical waters computed with density functional theory (DFT) methods, since they do not promote spurious charge transfer excitations that are a known deficiency with most popular density functionals. Furthermore, the near zero order scaling of point charge waters allows multiple layers of explicit solvation to be modeled with negligible computational cost, which is not practical with CC2 or DFT levels. As a practical example, we model the molar rotations of glycine and alanine, and track their convergence.

Comprehensive Studies on the Free Energies of Solvation and Conformers of Glycine: A Theoretical Study

“…[1][2][3][4][5][6][7][8][9] High-level ab initio studies demonstrated that the neutral form (NE) of glycine exists in the gas phase but the zwitterionic form (ZW) is unstable in vacuo. [11][12][13][14][15][16][17][18][19][20]27,[30][31][32][33] However, as is well known, the ZW of glycine predominates in crystalline or in aqueous solution, 2 and hence the solvent (or environmental) effects should be included in the theoretical studies to explore the glycine chemistry correctly. Therefore the theoretical studies of glycine in aqueous solution have been mainly carried out by three different approaches; (i) calculations of the solute surrounded by some discrete water molecules [10][11][12][13][14][15][16][17][18][19][20][21] (ii) calculations by statistical approaches such as Monte Carlo (MC) 25 or molecular dynamics (MD), 14,19,[22][23][24] and (iii) calculations by use of a dielectric continuum methodology.…”

“…[11][12][13][14][15][16][17][18][19][20]27,[30][31][32][33] However, as is well known, the ZW of glycine predominates in crystalline or in aqueous solution, 2 and hence the solvent (or environmental) effects should be included in the theoretical studies to explore the glycine chemistry correctly. Therefore the theoretical studies of glycine in aqueous solution have been mainly carried out by three different approaches; (i) calculations of the solute surrounded by some discrete water molecules [10][11][12][13][14][15][16][17][18][19][20][21] (ii) calculations by statistical approaches such as Monte Carlo (MC) 25 or molecular dynamics (MD), 14,19,[22][23][24] and (iii) calculations by use of a dielectric continuum methodology. [26][27][28][29][30][31][32][33] Nevertheless, the experimental findings 1-9 could not be successfully reproduced by most of these approaches, although some qualitative characteristics were consistent with the experimental findings.…”

“…On the other hand, a great number of water molecules could be treated by using the MC or MD simulations, 14,19,[22][23][24][25] and some works on the ZW of glycine in water have been reported. [13][14][15][16][17][18][19][20][21][22][23][24][25] However, these simulations could be difficult to apply directly to a chemical process such as the intramolecular proton transfer of glycine, since the potential energy functions employed in these approaches might be hardly suitable to a chemical process. Recently, the mixed quantum mechanical/molecularmechanical methods (QM/MM) have been developed to overcome these limitations, 69 but the methods could still include some inaccuracies associated with the MM region and the approximate treatment of electrostatic interactions at the boundaries between QM and MM regions.…”

Conformational behavior of simple furanosides studied by optical rotation

“…Kundrat and Autschbach has shown the simple point charge water molecules to be a computationally very efficient alternative to using quantum mechanical waters in modeling the solvent effect on a solute's chiroptical responses. 40 With a limited success, Ruud et al also studied the solvent influence on the zero-point vibrational corrections to optical rotation of S-methyloxirane. 36 They also found the solvent effect on the vibrational corrections to be relatively constant within the whole frequency range, contrary to the electronic (equilibrium) component which decreases in solvent with increasing frequency.…”

Concentration Dependent Specific Rotations of Chiral Surfactants: Experimental and Computational Studies

“…[36][37][38][39][40] These studies involved simulations of small molecules in water to account for solvent effects. After the simulation, the coordinates of the molecule(s) are exported at regular time intervals called snapshots.…”