Solid-state NMR characterization of weak interactions in molecular crystals

Weak non-covalent interactions, including hydrogen bonds, π–π stacking, and the diverse family of σ-hole interactions (halogen, chalcogen, pnictogen, tetrel, osme, and matere bonds), govern the structure, stability, and properties of molecular crystals. Solid-state Nuclear Magnetic Resonance (SSNMR) spectroscopy provides an unparalleled means of probing these interactions at the atomic level by directly sensing local electronic environments, independent of long-range order. This review surveys recent advances (approximately since 2020) in SSNMR methodologies for detecting, characterizing, and quantifying weak interactions in molecular solids. Particular emphasis is placed on developments in high-field and ultrafast magic-angle spinning (MAS) instrumentation, as well as novel pulse sequences that enhance access to key nuclei involved in non-covalent bonding. SSNMR observables, such as chemical shifts, dipolar and J couplings, quadrupolar parameters, and relaxation rates, are shown to provide quantitative insight into the interaction strength, geometry, and dynamics of hydrogen-bonded, π-stacked, and σ-hole-bonded systems. The review also discusses the synergistic integration of SSNMR with diffraction (single-crystal and powder X-ray diffraction, electron diffraction) and computational methods (Crystal Structure Prediction, DFT calculations, molecular dynamics simulations, machine learning models), yielding a multidimensional framework for elucidating structure–property relationships in both crystalline and disordered materials. Special attention is devoted to complex environments such as multicomponent crystals, host–guest assemblies, and amorphous dispersions. Looking ahead, continued advances in ultrahigh-field instrumentation, pulse-sequence design, and NMR crystallography promise to transform SSNMR from a diagnostic into a predictive tool for supramolecular chemistry and crystal engineering, bridging microscopic interactions with macroscopic material behaviour.