AMOEBA force field parameterization of the azabenzenes

Assessment of chemical properties can often require a computationally costly sampling of a high-dimensional phase space in order accurately to predict ensemble-averaged values. Molecular mechanics simulations offer an efficient way to sample such ensembles, with the quality of the results depending on the ability of the force field adequately to describe the energetics of the system under the conditions of the simulation. The range of applicability of a particular force field depends both upon its functional form (e.g., the degree to which it employs harmonic terms vs anharmonic, and the degree to which it includes crossterms (which couple different internal coordinates), highorder electric multipoles, or polarization) and its various parameters. Force fields are usually made more accurate through the proliferation of atom types, i.e., atoms of the same element that, as a consequence of belonging to different chemical functional groups, have interaction energies that are computed using different parameters. One such force field, AMOEBA, was originally devoted to water and biomolecules, but it now also finds use for more general applications involving organic molecules. We here present an extension of AMOEBA through a complete parameterization of the stable azabenzene series, i.e., six-membered N-heterocyclic rings incorporating varying numbers of N atoms from 1 to 4. Such heterocycles are found widely in various pi-conjugated systems [1] and their derivatives are ubiquitous in biological [2] and pharmaceutical [3] compounds, as well as a number of metal–organic cages [4–6] and frameworks [7–9]. Thus, we focus here on Abstract We present an extension of the AMOEBA force field to several common organic heterocycles, namely pyridine, pyrazine, pyrimidine, pyridazine, the three unique triazines, and the two unique tetrazines. Atomic multipoles for newly defined atom types were obtained from quantum chemical calculations on the isolated molecules. Atomic polarizability parameters are maintained at their standard AMOEBA values for corresponding atomic classes while standard van der Waals parameters are rescaled to reproduce CCSD(T) intermolecular interaction energies of selected dimer structures. In order to improve vibrational frequencies that are important both spectroscopically and for flexible dynamics, parameters for covalent terms, i.e., bond-stretching, angle-bending, and stretch-bend terms, were optimized and added to the existing AMOEBA force field. We validate our force field through comparison of molecular structural, vibrational, electrostatic, and energetic properties—including intermolecular interaction energies—to reliable quantum chemical data for the various systems of interest.