Solvent-Based NMR Approaches for the Assessment of Molecular Interactions: A Review of Current Practices

The structure, dynamics, and reaction kinetics exhibited by molecules in the solution state are essentially governed by their interactions with the solvents. Solvents influence solute structure, stability, aggregation, and binding through noncovalent solute-solvent interactions. Hence, understanding solute-solvent interactions is essential for elucidating the molecular behavior in solution. Traditionally, solute-solvent interactions are studied experimentally via solute properties, while theory examines both solute and solvent behavior. Nuclear magnetic resonance (NMR) spectroscopy offers a gamut of experimental methods for probing molecular interactions in condensed phase. Solvent-based NMR methods have become powerful tools to experimentally detect and quantify solute-solvent interactions. The present review highlights the solvent-detected as well as solvent-mediated NMR approaches discussed in literature in the past two decades portraying the dynamicity of solvents in shaping solute behavior-affecting structure, conformational flexibility, and intermolecular interactions. Solvents used in solution NMR experiments offer a plethora of NMR active nuclei both dipolar and quadrupolar in nature that can be efficiently probed to unveil molecular dynamics and interactions. NMR solvent-based methods, from simple to complex systems, are more efficient than other spectroscopic techniques. Solvent relaxation, magnetization transfer, and dynamic nuclear polarization effectively capture subtle solute-solvent interaction changes. These methods are reviewed in specifics to emphasize the potential of solvent-based NMR.