A refined general AMBER force field for liquid acetonitrile: Development and validation

Abstract

GAFF-ACN, a refined general AMBER force field specific for liquid acetonitrile, is introduced aiming for accurately reproducing both the experimental density and static dielectric constant using classical NPT molecular dynamics (MD) simulations. Its parameterization combines a quantum-mechanically derived geometry with restrained electrostatic potential charges in a polarizable continuum model, standard GAFFv2.11 parameters, and enforced molecular linearity. GAFF-ACN reproduces a broad set of macroscopic and microscopic properties of liquid acetonitrile. The density agrees closely with experiment (−0.4% relative error), and the static dielectric constant differs by 13%, representing, to the best of our knowledge, the most accurate dielectric constant reported to date for a fixed-charge model. GAFF-ACN also reproduces (i) key thermodynamic observables, i.e., heat of vaporization, surface tension, isothermal compressibility, and thermal expansion coefficient; (ii) mass transport coefficients, viz. self-diffusion and shear viscosity; and (iii) structural aspects including pairwise radial distribution functions and coordination numbers. All results are obtained using standard simulation protocols, enabling reproducibility and straightforward adoption across common MD packages. GAFF-ACN, therefore, provides an accurate and practical acetonitrile model for the solvation of GAFF-parameterized organic solutes.