Structural Variety of Alkali Hydrogen Maleates at High Pressure

Studies regarding the effect of pressure on the structure of pharmaceutical excipients, such as hydrogen maleates, can provide useful information about their stability in the formulation and overall chemical interactions with active ingredients. Hydrogen maleates, with small (lithium, sodium, potassium, and ammonium) cations that are stable at ambient pressure, are shown to undergo various structural changes upon compression. Depending on the cation size, the nature of the cations’ interaction with the anion, and the extent of hydration, the response of hydrogen maleates to pressure leads to hydrogen bond rearrangement, phase transitions, cation coordination number increases, anion packing transformations, and, eventually, crystal structure collapse. Initially, the symmetric intramolecular hydrogen bonds in hydrogen maleates localize under pressure on one of the oxygens, leading to a break in crystal symmetry. This proton-transfer points to a pressure-driven change of reactivity in this simple system, which acts as a prototype for biologically active enzymatic centers.