Abstract
We developed a quantitative approach to quantum chemical microsolvation. Key in our methodology is the automatic placement of individual solvent molecules based on the free energy solvation thermodynamics derived from molecular dynamics (MD) simulations and grid inhomogeneous solvation theory (GIST). This protocol enabled us to rigorously define the number, position, and orientation of individual solvent molecules and to determine their interaction with the solute based on physical quantities. The generated solute–solvent clusters served as an input for subsequent quantum chemical investigations. We showcased the applicability, scope, and limitations of this computational approach for a number of small molecules, including urea, 2-aminobenzothiazole, (+)-syn-benzotriborneol, benzoic acid, and helicene. Our results show excellent agreement with the available ab initio molecular dynamics data and experimental results.
Highlights
Molecules 2021, 26, 1793. https://Solvents play a pivotal role in solution phase chemistry
We find a very good agreement between the water positions obtained with our Free Energy Based Identification of Solvation Sites (FEBISS) algorithm and the high-density water locations determined with the 3-dimensional reference interaction site model (3D-RISM) calculation
We devised a computational protocol to quantum chemical microsolvation, where the location, orientation, and interaction of individual solvent molecules with the solute are automatically calculated based on molecular dynamics (MD) and grid inhomogeneous solvation theory (GIST)
Summary
Solvents play a pivotal role in solution phase chemistry. The chemically relevant solution phase conformations of the reactants, intermediates, and products may differ significantly from their gas phase or solid-state counterparts and can even depend on the specific solvent [5]. This is in particular true for bio- or biomimetic molecules and biochemical reactions that take place in water. To accurately account for the reactivity in the condensed phase, a reliable characterization is necessary. Theoretical investigations are an attractive alternative to fill this gap, but the accurate treatment of (explicit) solvation is still an active field of research in computational chemistry [5,6,7,8]
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