New Molecular-Mechanics Model for Simulations of Hydrogen Fluoride in Chemistry and Biology

• Published in: Journal of chemical theory and computation Vol. 16; no. 8; pp. 5105 - 5126
• Main Authors: Orabi, Esam A, Faraldo-Gómez, José D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11.08.2020
• Subjects: Amino acids; Biomolecules; Clusters; Computational fluid dynamics; Computer simulation; Dimers; Fluorides; Halides; Hydrofluoric Acid - chemistry; Hydrogen; Hydrogen bonding; Hydrogen fluoride; Lipids; Mechanics; Mechanics (physics); Molecular Dynamics Simulation; Molecular Mechanics; Molecular structure; Quantum chemistry; Quantum Theory; Simulation; Solvation; Thermodynamic properties; Thermodynamics; Toxicity; Vapor phases
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/acs.jctc.0c00247

Hydrogen fluoride (HF) is the most polar diatomic molecule and one of the simplest molecules capable of hydrogen-bonding. HF deviates from ideality both in the gas phase and in solution and is thus of great interest from a fundamental standpoint. Pure and aqueous HF solutions are broadly used in chemical and industrial processes, despite their high toxicity. HF is a stable species also in some biological conditions, because it does not readily dissociate in water unlike other hydrogen halides; yet, little is known about how HF interacts with biomolecules. Here, we set out to develop a molecular-mechanics model to enable computer simulations of HF in chemical and biological applications. This model is based on a comprehensive high-level ab initio quantum chemical investigation of the structure and energetics of the HF monomer and dimer; (HF) n clusters, for n = 3–7; various clusters of HF and H2O; and complexes of HF with analogs of all 20 amino acids and of several commonly occurring lipids, both neutral and ionized. This systematic analysis explains the unique properties of this molecule: for example, that interacting HF molecules favor nonlinear geometries despite being diatomic and that HF is a strong H-bond donor but a poor acceptor. The ab initio data also enables us to calibrate a three-site molecular-mechanics model, with which we investigate the structure and thermodynamic properties of gaseous, liquid, and supercritical HF in a wide range of temperatures and pressures; the solvation structure of HF in water and of H2O in liquid HF; and the free diffusion of HF across a lipid bilayer, a key process underlying the high cytotoxicity of HF. Despite its inherent simplifications, the model presented significantly improves upon previous efforts to capture the properties of pure and aqueous HF fluids by molecular-mechanics methods and to our knowledge constitutes the first parameter set calibrated for biomolecular simulations.