Fluorine-induced perturbations in hydrogen bond networks: Insights from FT-IR, Raman, and AIMD simulations

Abstract

Hydrogen bonds (HBs) govern molecular recognition, catalysis, and self−assembly, yet their strength can be tuned dramatically by subtle changes in electron density distribution. Fluorine, owing to its high electronegativity and low polarizability, perturbs HB networks in a uniquely position−dependent manner. We present an integrated vibrational spectroscopy (IR and Raman) and ab initio molecular dynamics (AIMD) protocol that quantifies HB donor and acceptor strengths of functional groups in solution. Monofluoroaniline isomers were investigated in an HB donor solvent (CH₃OH) and an acceptor solvent (DMSO). Meta − fluorine withdraws electron density most strongly, weakening O–D···N interactions by Δν = +22 cm⁻¹ and simultaneously enhancing NH donation in DMSO by Δν = 3 cm⁻¹. Ortho − fluorine increases acceptor strength (−1 cm⁻¹ in νOD) but its intramolecular N–H···F contact reduces intermolecular N–H···O bonding. Para − fluorine leaves both modes essentially unchanged. The workflow furnishes solvent−resolved HB parameters that can feed directly into pharmacophore scoring, next−generation force−field parametrization, and any modeling framework that requires accurate donor/acceptor descriptors – ranging from drug−target docking, through electrolyte and polymer design, to supramolecular host−guest engineering and catalytic reaction modeling.