On the mechanism of solid-state phase transitions in molecular crystals – the role of cooperative motion in (quasi)racemic linear amino acids

Abstract

During single-crystal-to-single-crystal (SCSC) phase transitions, a polymorph of a compound can transform to a more stable form while remaining in the solid state. By understanding the mechanism of these transitions, strategies can be developed to control this phenomenon. This is particularly important in the pharmaceutical industry, but also relevant for other industries such as the food and agrochemical industries. Although extensive literature exists on SCSC phase transitions in inorganic crystals, it is unclear whether their classications and mechanisms translate to molecular crystals, with weaker interactions and more steric hindrance. A comparitive study of SCSC phase transitions in aliphatic linear-chain amino acid crystals, both racemates and quasi-racemates, is presented. A total of 34 transitions are considered and most are classified according to their structural change during the transition. Transitions without torsional changes show very different characteristics, such as transition temperature, enthalpy and free energy, compared with transitions that involve torsional changes. These differences can be rationalized using classical nucleation theory and in terms of a difference in mechanism; torsional changes occur in a molecule-by-molecule fashion, whereas transitions without torsional changes involve cooperative motion with multiple molecules at the same time.

The mechanism driving a solid–solid phase transition in a biomacromolecular crystal

“…Mnyukh argued that all SSPTs are first order in nature and follow a mechanism of continuous nucleation and growth (molecule-by-molecule). Similar to the study by Smets et al (2020), however, our results demonstrate that the nucleation-and-growth process of the SSPT in riboA crystals is not mutually exclusive to the cooperative motions of subdomains of molecules. Importantly, the mechanism of these changes is not theoretical, but is directly observable and measurable using the combination of PVM, AFM and TRX.…”

“…The most recent studies in nonbiological systems show that SSPTs triggered by heating or photons can occur via a metastable liquid phase (Peng et al, 2015;Smets et al, 2020;Pogatscher et al, 2016;Mohammadi et al, 2018;Taniguchi et al, 2019). In crystals of linear amino acids, synchronous cooperative motion of molecules was shown to be only one of many possible transition mechanisms (Smets et al, 2020). The first-order (continuous) or second-order (discontinuous) classificaitons of SSPTs by Ehrenfest have since been challenged (Mnyukh, 2009).…”

“…From general thermodynamic studies of oscillators to current investigations on neural oscillations in the brain (Brochini et al, 2016), SSPTs have been a topic of great interest. Well known examples are phase changes in shape memory alloys caused by temperature variation (Otsuka & Wayman, 1998), or in small organic molecular crystals by heat or light exposure (Etter & Siedle, 1983;Skoko et al, 2010;Smets et al, 2020). Notably, in shape memory alloys, the challenge between increased entropy and intrinsic order in a crystal drives the molecular rearrangement to overcome the heat applied (Everhardt et al, 2019).…”

“…However, mechanisms of SSPTs in organic and inorganic crystals at the molecular and atomic levels are relatively poorly understood due to technical challenges, but frequently involve dislocation generation and motion. A very recent study of organic molecular crystals illustrates the cooperative motion in phase transitions (Smets et al, 2020).…”

Crystal engineering in IUCrJ: from `the' crystal structure to `a' crystal structure

“…In keeping with the theme of 'structure' a number of papers dealt with cocrystals both in the pharmaceutical context (Fatima et al, 2020;Ranjan et al, 2020) and in a more general sense (Rajkumar & Desiraju, 2021). Other areas addressed included charge density (Chodkiewicz et al, 2020;Sanjuan-Szklarz et al, 2020;Duverger-Né dellec et al, 2020), phase transformations (Smets et al, 2020;Rekis et al, 2021), crystals obtained under exotic conditions (Buganski & Bindi, 2021;Hu et al, 2020;Né meth, 2020), and MOFs (Yadava et al, 2020;Park et al, 2020) apart from core papers on supramolecular synthons and synthetic strategy.…”