Xiannong Chen

Molecular simulation of alkyl boronic acids: molecular mechanics and solvation free energy calculations

The alkyl boronic acid moiety is incorporated into many biologically interesting structures. To provide parameters for molecular mechanics and dynamics studies of compounds containing this group, we performed ab initio calculations at the 6‐31G* level to obtain bond stretching, bending, and torsion constants. The hydrodynamic formulation of the time‐dependent density functional theory was used to calculate the attractive part of van der Waals (VDW) 6–12 potential. The geometry of boronic acid moiety of the 6‐31G* optimized methyl boronic acid was similar to that of the X‐ray crystal structure of phenyl boronic acid. To test the reliability of nonbonded parameters, Monte Carlo free energy perturbation simulations and the thermodynamic cycle approach were used to estimate the differences in solvation free energy between alkyl alcohol and alkyl boronic acid, both in water and in chloroform. These free energy differences were also obtained experimentally by measuring the vapor–water and water–chloroform partition coefficients. The close agreement between experimental values and the results of our simulations suggests the reliability of new molecular mechanics force‐field parameters for alkyl boronic acids.