Deconstructing ¹H NMR Chemical Shifts in Strong Hydrogen Bonds: A Computational Investigation of Solvation, Dynamics,...

This study provides the first quantitative dissection of the factors influencing ¹H NMR chemical shifts δ_H in strong hydrogen-bonded systems, focusing on solvation, nuclear dynamics, and nuclear delocalization. A novel computational framework was developed, combining static quantum chemical calculations (nonrelativistic and relativistic), ab initio molecular dynamics (AIMD), and three-dimensional numerical solutions of the Schrödinger equation. This multiscale approach was applied to three model systems: the bifluoride anion (FHF)^-, the Zundel cation (H₅O₂)⁺, and the pyridine-pyridinium cation (PyHPy)⁺. Our results reveal that nuclear dynamics and delocalization are the dominant factors determining δ_H in complexes with short, strong hydrogen bonds. Solvation effects, while critical for defining the hydrogen-bonding environment, play a secondary role. By isolating the contributions of each factor, we demonstrate that traditional methods often underestimate the quantum mechanical nature of the proton. The application of three-dimensional Schrödinger equation solutions represents a significant methodological advancement, enabling deeper insights into proton behavior in hydrogen bonds. This work not only enhances our understanding of NMR parameters in challenging systems but also establishes a robust framework for modeling complex interactions in chemical and biological environments.