 Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

We review a mixed quantum-classical theoretical model and computational technique designed to accurately reproduce spectral signals of aqueous systems and provide a rationalization for the underlying physics.

The novel polarizable FQFμ force field is proposed and coupled to a quantum mechanical (QM) SCF Hamiltonian. The peculiarity of the resulting QM/FQFμ approach stands in the fact the polarization effects are modeled in terms of both fluctuating charges and dipoles, which vary as a response to the external electric field/potential. Remarkably, QM/FQFμ is defined in terms of three parameters: electronegativity and chemical hardness, which are well-defined in density functional theory, and polarizability, which is physically observable. Such parameters are numerically adjusted to reproduce full QM reference electrostatic energy values. The model is challenged against test molecular systems in aqueous solution, showing remarkable accuracy and thus highlighting its potentialities for future extensive applications.

A methodology to account for nonelectrostatic interactions in Quantum Mechanical (QM)/Molecular Mechanics (MM) approaches is developed. Formulations for Pauli repulsion and dispersion energy, explicitly depending on the QM density, are derived. Such expressions are based on the definition of an auxiliary density on the MM portion and the Tkatchenko-Scheffler (TS) approach, respectively. The developed method is general enough to be applied to any QM/MM method and partition, provided an accurate tuning of a small number of parameters is obtained. The coupling of the method with both nonpolarizable and fully polarizable QM/fluctuating charge (FQ) approaches is reported and applied. A suitable parametrization for the aqueous solution, so that its most representative features are well reproduced, is outlined. Then, the obtained parametrization and method are applied to calculate the nonelectrostatic (repulsion and dispersion) interaction energy of nicotine in aqueous solution.

In this paper, we have extended to the calculation of hyperfine coupling constants, the model recently proposed by some of the present authors [Giovannini et al., J. Chem. Theory Comput. 13, 4854–4870 (2017)] to include Pauli repulsion and dispersion effects in Quantum Mechanical/Molecular Mechanics (QM/MM) approaches. The peculiarity of the proposed approach stands in the fact that repulsion/dispersion contributions are explicitly introduced in the QM Hamiltonian. Therefore, such terms not only enter the evaluation of energetic properties but also propagate to molecular properties and spectra. A novel parametrization of the electrostatic fluctuating charge force field has been developed, thus allowing a quantitative reproduction of reference QM interaction energies. Such a parametrization has been then tested against the prediction of EPR parameters of prototypical nitroxide radicals in aqueous solutions.