High-pressure XAS experiments on sulfamide: a tool to study hydrogen bond interactions to optimize drug design

Hydrogen bond interactions are pivotal in the pharmaceutical industry, influencing drug-target binding, solubility, and formulation. Crystal engineering optimizes drugs using these bonds, with sulfonamides historically crucial in antimicrobial applications. High-pressure studies on sulfamide have revealed structural phase transitions due to modifications in the hydrogen-bond interactions. The transition affects the electronic density of sulfur atoms, making sulfamide the ideal compound to study changes in hydrogen bond interactions by an element-specific technique (i.e., XAS). Among all the beamlines, ID12 emerges as the best choice for studying this compound, as it is the only beamline where measurements of XAS at high pressures are routinely performed in the required X-ray energy range. If successful, these experiments could be potentially extended to other drugs and atoms beyond sulfonamides and sulfur, allowing the design and development of improved therapeutic agents.