Solvent Dependence of ¹⁴N Nuclear Magnetic Resonance Chemical Shielding Constants as a Test of the Accuracy of the Computed Polarization of Solute Electron Densities by the Solvent

Ribeiro, R. F.; Marenich, A. V.; Cramer, C. J.; Truhlar, D. G.
J. Chem. Theor. Comput. 2009, 5, 2284.

Although continuum solvation models have now been shown to provide good quantitative accuracy for calculating free energies of solvation, questions remain about the accuracy of the perturbed solute electron densities and properties computed from them. Here we examine those questions by applying the SM8, SM8AD, SMD, and IEF-PCM continuum solvation models in combination with the M06-L density functional to compute the ¹⁴N magnetic resonance nuclear shieldings of CH₃CN, CH₃NO₂, CH₃NCS, and CH₃ONO₂ in multiple solvents, and we analyze the dependence of the chemical shifts on solvent dielectric constant. We examine the dependence of the computed chemical shifts on the definition of the molecular cavity (both united-atom models and models based on superposed individual atomic spheres) and three kinds of treatments of the electrostatics, namely the generalized Born approximation with the Coulomb field approximation, the generalized Born model with asymmetric descreening, and models based on approximate numerical solution schemes for the nonhomogeneous Poisson equation. Our most systematic analyses are based on the computation of relative ¹⁴N chemical shifts in a series of solvents, and we compare calculated shielding constants relative to those in CCl₄ for various solvation models and density functionals. While differences in the overall results are found to be reasonably small for different solvation models and functionals, the SMx models SM8, and SM8AD, using the same cavity definitions (which for these models means the same atomic radii) as those employed for the calculation of free energies of solvation, exhibit the best agreement with experiment for every functional tested. This suggests that in addition to predicting accurate free energies of solvation, the SM8 and SM8AD generalized Born models also describe the solute polarization in a manner reasonably consistent with experimental ¹⁴N nuclear magnetic resonance spectroscopy. Models based on the nonhomogeneous Poisson equation show slightly reduced accuracy. Scaling the intrinsic Coulomb radii to larger values (as has sometimes been suggested in the past) does not uniformly improve the results for any kind of solvent model; furthermore it uniformly degrades the results for generalized Born models. Use of a basis set that increases the outlying charge diminishes the accuracy of continuum models that solve the nonhomogeneous Poisson equation, which we ascribe to the inability of the numerical schemes for approximately solving the nonhomogeneous Poisson equation to fully account for the effects of electronic charge outside the solute cavity.