Extension of the AMBER force-field for the study of large nitroxides incondensed phases: an ab initio parameterization

The popular AMBER force-field has been extended to provide an accurate description of largeand flexible nitroxide free-radicals in condensed phases. New atom types have been included, andrelevant parameters have been fitted based on geometries, vibrational frequencies and potentialenergy surfaces computed at the DFT level for several different classes of nitroxides, bothin vacuo and in different solvents. The resulting computational tool is capable of providingreliable structures, vibrational frequencies, relative energies and spectroscopic observables forlarge and flexible nitroxide systems, including those typically used as spin labels. The modifiedforce field has been employed in the context of an integrated approach, based on classicalmolecular dynamics and discrete–continuum solvent models, for the investigation ofenvironmental and short-time dynamic effects on the hyperfine and gyromagnetic tensors ofPROXYL, TEMPO and INDCO spin probes. The computed magnetic parameters are in verygood agreement with the available experimental values, and the procedure allows for an unbiasedevaluation of the role of different effects in tuning the overall EPR observables.