Hydrogen-Bond Network in Equimolar N -Methylacetamide–Water: Integrated Neutron Scattering, Molecular Dynamics, DFT–NBO–AIM, and Machine Learning Analysis

An equimolar N -methylacetamide–water (NMA–W) mixture was re-examined by combining molecular dynamics (MD) simulations, DFT-based Natural Bond Orbital (NBO) and Atoms-in-Molecules (AIM) analyses, and data-driven reconstruction of previously reported neutron scattering functions of the NMA–W liquid. MD simulations, using an AMBER-based force field for NMA and the SPC/E model for water, reproduce reasonably well the experimental structure factors and pair correlation functions of the liquid. In parallel, a Random Forest Regressor is employed as a nonparametric data-driven reconstruction tool, showing that the main features of the structural data can be represented as a continuous numerical representation of the scattering vector Q, providing a continuous numerical representation for comparison purposes. Three representative NMA–water clusters previously identified as the most probable local arrangements governing the liquid structure are further analyzed using NBO and Atoms-in-Molecules (AIM) approaches. The analysis provides additional information on hydrogen-bond electronic structure, including charge-transfer effects, electron density at bond critical points, and topological characteristics of intermolecular interactions. Comparison with MD-derived lifetimes shows that stronger electronic interactions do not always correspond to longer-lived hydrogen bonds, reflecting the role of local network topology and dynamical fluctuations.