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.

We present a computational methodology based on a polarizable Quantum Mechanical (QM)/Molecular Mechanics (MM) approach to accurately compute the Vibrational Optical Activity (VOA) spectra of chiral systems. This approach is applied for the calculation of Infrared (IR), Vibrational Circular Dichroism (VCD), Raman and Raman Optical Activity (ROA) spectra of aqueous solutions of (l)-methyl lactate and (S)-glycidol. Remarkable agreement between calculations and experiments is reported, showing the reliability and accuracy of the methodology, especially with respect to standard continuum solvation approaches.

We present a computational study on the spectroscopic properties of UV-Vis absorbing dyes in water solution. We model the solvation environment by using both continuum and discrete models, with and without polarization, to establish how the physical and chemical properties of the solute-solvent interaction may affect the spectroscopic response of aqueous systems. Seven different compounds were chosen, representing different classes of organic molecules. The classical atomistic description of the solvent molecules was enriched with polarization effects treated by means of the fluctuating charges (FQ) model, propagated to the first-order response function of the quantum-mechanical (QM) solute to include its effects withing the modeling of the electronic excitations of the systems. Results obtained with the QM/FQ model were compared with those from continuum solvation models as well as nonpolarizable atomistic models, and then confronted with the experimental values to determine the accuracy that can be expected with each level of theory. Moreover, a thorough structural analysis using molecular dynamics simulations is provided for each system. K E Y W O R D S excitation energies, QM/FQ, QM/MM, QM/PCM, solvent effects, TD-DFT 1 | I N TR O DU C TI O N One-photon absorption spectroscopy within the UV-Visible range is often the most direct and inexpensive analytical tool that can be used to study the electronic properties of a system. Most commonly, such measurements are carried out on solvated samples, with water being a ubiquitous choice.With the gradual increase in the complexity of the systems under investigation, the correct interpretation of experimental data is increasingly reliant on their calculated ab initio counterparts. Many theoretical models based on quantum mechanics (QM), accompanied by their computational implementations, have been presented over the years offering different levels of compromise between the computational cost and the accuracy of the results. [1][2][3] At present, methods based on density functional theory (DFT) and its time-dependent counterpart (TD-DFT) have become the most popular choice for the simulation of absorption spectra of medium-large organic molecular systems thanks to their versatility stemming from the freedom of choice of density functional and basis set, as well as the favorable scaling with system size which allows their application to increasingly large systems. [1,[4][5][6] Many benchmarks studies have been presented elaborating on the merits and limitations of TD-DFT for the simulation of UV-Vis spectroscopy, as well as on the most appropriate choice of functional and basis set combination for different types of system. [6][7][8][9][10][11][12][13][14][15][16] And though many computational studies are carried out on isolated systems, solvent effects should not be neglected for the presence of the solvation environment can significantly alter the electronic absorption properties of a system, both qualitatively and quantitatively. [17][18][19][20][21][22][23][24][25][2...