Accurate prediction of bulk properties in hydrogen bonded liquids: amides as case studies

Abstract

In this contribution we show that it is possible to build accurate force fields for small organic molecules allowing the reliable reproduction of a large panel of bulk properties, which are seldom addressed in the same context. Starting from the results obtained in recent studies, we developed a protocol for charge estimation and virtual site generation for the amide class of molecules. The parametrization of electrostatic properties is based on population analysis and orbital localization of quantum mechanical computations rooted in density functional theory and the polarizable continuum model, without any additional external information. The new protocol, coupled to other recent studies in our group targeted at an accurate fitting of internal degrees of freedom, makes available a method for building force fields from scratch (excluding for the moment intermolecular van der Waals interactions) with focus on reproducing the structure and dynamics of hydrogen bonded liquids, yielding results that are in line or better than those delivered by current general force fields. The approach is tested on the demanding series formed by formamide and its two N-methyl derivatives, N-methylformamide and N,N-dimethylformamide. We show that the atomistic structure of the liquids arising from classical molecular dynamics (MD) simulations employing the new force field is in full agreement with X-ray and neutron diffraction experiments and the corresponding spatial distribution functions are in remarkable agreement with the results of ab initio MD simulations. It is noteworthy that the latter result has never been obtained before without using ad hoc (and system dependent) scale factors and that, in addition, our parameter-free procedure is able to reproduce static dielectric constants over a wide range of values without sacrificing the force field accuracy with respect to other observables. Finally, we are able to explain the trend of static dielectric constants followed by the three amides in terms of properties obtained from the simulations, namely hydrogen bond patterns and reorientational lifetimes.