Effect of Hydration on the Barrier to Internal Rotation in Formamide. Quantum Mechanical Calculations Including Explicit Solvent and Continuum Models

The effect of hydration upon the barrier to rotation in formamide has been predicted using both continuum models and those that consider the solvent molecules explicitly. The continuum calculations are based upon the polarizable continuum model, while the simulation calculations employ a Monte Carlo (MC) treatment. Variants of the MC method are studied employing classical and quantum mechanical (both semiempirical and ab initio ) descriptions of the solute. All methods suggest a different transition state structure in water compared to the gas phase and show the importance of solute polarization. The calculated free energy barrier to rotation is in good agreement with the experimental data in all cases.