Prediction of nitroxide hyperfine coupling constants in solution from combined nanosecond scale simulations and quantum computations

Abstract

We present a combined theoretical approach based on analyzing molecular dynamics trajectories (at the nanosecond scale) generated by use of classical polarizable force fields and on quantum calculations to compute averaged hyperfine coupling constants. That method is used to estimate the constant of a prototypical nitroxide: the dimethylnitroxide. The molecule is embedded during the simulations in a cubic box containing about 500 water molecules and the molecular dynamics is generated using periodic conditions. Once the trajectories are achieved, the nitroxide and its first hydration shell molecules are extracted, and the coupling constants are computed by considering the latter aggregates by means of quantum computations. However, all the water molecules of the bulk are also accounted for during those computations by means of the electrostatic potential fitted method. Our results exhibit that in order to predict accurate and reliable coupling constants, one needs to describe carefully the out-of-plane motion of the nitroxide nitrogen and to sample trajectories with a time interval of 400 fs at least to generate an uncorrelated large set of nitroxide structures. Compared to Car-Parrinello molecular dynamics techniques, our approach can be used readily to compute hyperfine coupling constants of large systems, such as nitroxides of great size interacting with macromolecules such as proteins or polymers.

Quantitative evaluation of the aqueous dihydronitroxide nitrogen hyperfine coupling constant from QM/MM//MD computations

“…In a recent study, we have addressed the three above points by investigating the properties of the solvated dimethylnitroxide (CH 3 ) 2 NO radical [25]. In particular, we demonstrated that it is possible to accurately reproduce the (CH 3 ) 2 NO a N value (within about 2%) with the following strategy:…”

Effects of molecular dynamics and solvation on the electronic structure of molecular probes

“…The molecular properties of these nitroxides strongly depend on the chemical environment, and recent theoretical simulations have achieved a detailed characterization of such dependencies for isotropic solutions in non-polar/ polar and protic/aprotic solvents [18][19][20][21][22]. Besides the effects of complex chemical environment, ESR parameters are also affected by intra-molecular dynamics.…”

Assessing the accuracy of a QM/MM//MD combined protocol to compute spectromagnetic properties of polyfunctional nitroxides in solution

“…Recently, we proposed such a protocol to compute hyperfine coupling constants (hcc's) of flexible nitroxides in water [1,2]. It is based on combining nanosecond-scale classical molecular dynamics (MD) with large-scale QM/MM computations on small nitroxide/ water clusters extracted along the MD trajectories.…”