Further insights into the environmental effects on the computed hyperfine coupling constants of nitroxides in aqueous...

We investigated the main two factors influencing the mean hyperfine coupling constants of small nitroxide radicals in aqueous solution, i.e., the out-of-plane displacement of their nitrogen atom and the environmental effects (solvent effects), by means of the approach we previously developed and fine-tuned to study the solvation of the dimethyl nitroxide radical. Our methodology efficiently combines classical molecular dynamics based on a polarizable force field at the nanosecond scale and quantum mechanics/molecular mechanics (QM/MM) computations to account for the bulk instantaneous electrostatic environmental effect. Our method has been applied to five small nitroxides, namely methyl nitroxide, ethyl nitroxide, dimethyl nitroxide, di-tert-butyl nitroxide, and PROXYL. The theoretical nitrogen hyperfine coupling constant values for the five nitroxides in solution are in good agreement with experiment (difference of 0.3 G on average). Our approach showed that the solvent shift in nitroxide hyperfine coupling constants is almost constant whatever the nitroxide, and, particularly, whatever the nitroxide NO moiety's accessibility to the solvent. This result contrasts with earlier results derived from 10 ps scale trajectories based on Car-Parrinello molecular dynamics approach. However, we show that if we consider on average these latter results, they are in agreement with our conclusion. We also present an attempt to identify the origin of this result by analyzing the solvent contributions in terms of effects of the nitroxide first hydration shell and of the bulk, and by investigating the relation between these two contributions and the solvent structure at the vicinity of the NO moiety.