Structural Variety of Alkali Hydrogen Maleates at High Pressure

Abstract

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.

Actual Symmetry of Symmetric Molecular Adducts in the Gas Phase, Solution and in the Solid State

“…There are three groups of crystals in which the deviation of the proton position from the H-bond center is below 0.06 Å, about 0.2 Å, and about 0.3 Å [51]. The symmetry of these H-bonds changes under pressure [59].…”

Crystal structure of cyclohexylammonium hydrogen maleate salt hemi-hydrated

“…Poreba and al. 12 have reported structures of alkali hydrogen maleates. Thus, to better understand the mode of formation of maleates and hydrogen maleates, this new salt CyNH3[HOOC(CH)2COO]•H2O (1) was isolated as a suitable crystal by reacting the maleic acid, the cyclohexylammonium and SnPh3Cl in one "pot" process.…”

Kilobytes of kilopascals: high-pressure depositions of the Cambridge Structural Database

“…It is well established that compression of materials can lead to solid-to-solid phase transitions (Goryainov et al, 2005;Zakharov & Boldyreva, 2013;Fisch et al, 2015;Zakharov et al, 2016;Novelli et al, 2020; or visible changes in the morphology (Patyk et al, 2016;Cai et al, 2015) and colour of the crystal (Andrzejewski & Katrusiak, 2017a,b;Li et al, 2019). High-pressure conditions can modify the crystallization preference, leading to new crystal forms, such as polymorphs and solvates (Podsiadło et al, 2017a;Safari et al, 2020;Olejniczak et al, 2019;Pore ˛ba et al, 2020), or they can affect different properties of crystalline solids (Isnard et al, 2011;Runowski et al, 2017;Patyk-Kaz ´mierczak et al, 2017). Moreover, high-pressure techniques enable the crystallization of compounds with low melting points, existing in the gaseous or liquid state under ambient conditions, thus providing structural data that would otherwise be difficult to access (Oswald et al, 2005;Boldyreva, 2008;Marciniak et al, 2016;Sutuła et al, 2017;Podsiadło et al, 2012Podsiadło et al, , 2013Podsiadło et al, , 2017a.…”