**1. Introduction**

Studying molecular crystals and their phase transitions is of grea<sup>t</sup> importance for many scientific fields such as crystallography [1,2], thermodynamics [3,4], computational [5–7] and solid state chemistry [8–10], etc. Solid forms of many organic molecules are being developed, studied, and produced in the pharmaceutical industry [11–15] and in arising subfields of materials science [16–18]. The last one, among others, focuses the attention on the mechanical properties of molecular crystals [19–25] and metal-organic complexes [26–28]. Several dozens of organic crystals show anomalous plasticity and elasticity at ambient and extreme conditions under mechanical stress [29–33]. L-Leucinium hydrogen maleate (LLHM) is a unique example of organic crystals that preserves plasticity at a cryogenic temperature [34]. This phenomenon was studied and explained recently using a mainly crystallographic approach [34,35].

One of the methods to understand the nature of an important property of molecular crystal is to apply significant outside impact—low temperature, hydrostatic pressure, mechanochemical stress, etc. [36–39]. These methods help to follow the behavior of the systems at changing environments at macroscopic (thermodynamics) and microscopic (molecular contacts) levels, depending on the availability of experimental and theoretical techniques [40–47]. Moreover, low temperatures and high pressures often trigger phase transitions, resulting in new solid forms, including polymorphs. The application of extreme conditions is a powerful tool to find and sometimes stabilize new forms of organic molecules.

**Citation:** Skakunova, K.D.; Rychkov,D.A. Low Temperature and High-Pressure Study of Bending L-Leucinium Hydrogen Maleate Crystals. *Crystals* **2021**, *11*, 1575. https://doi.org/10.3390/ cryst11121575

Academic Editors: Ulrich Prahl, Sergey Guk and Faisal Qayyum

Received: 23 November 2021 Accepted: 14 December 2021 Published: 16 December 2021 Corrected: 21 April 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Thus, studies of new forms of molecular crystals using extreme conditions [11,37,48] as well as a search of new bending crystals [30,49,50] are of grea<sup>t</sup> interest for modern science. Nevertheless, the interrelation of these two areas is just an emerging field. There are very few works that search for new forms of plastic crystals at high pressures or low temperatures [34,35,51]. To fulfill this gap, in this work we applied low temperatures and high pressures to crystals of LLHM, chasing new forms of these bending crystals. In this work we continue examination of the LLHM system at different conditions, reporting experimental behavior of this crystal at extreme conditions.

L-Leucinium hydrogen maleate crystals were grown for the first time by Arkhipov et al. [52] as an individual system in a series of amino acid maleates. Providing single crystal X-ray diffraction (SCXRD) experiments, the plasticity of LLHM was noted and formulated as "interesting mechanical behavior: mechanical action on crystals of (LLHM) results in elastic, and then plastic bending". Further, a detailed study showed that crystals preserve their plasticity at temperatures down to 77 K. It was proven using video and photo recording of the bending process [34]. Using SCXRD, authors showed that no significant changes in crystal structure of LLHM occurred during the cooling down to 100 K, preserving the layered structure [34]. The system behavior on bending was also investigated using optical and scanning electron microscopy, as well as SCXRD [35]. Scrupulous analysis of crystal structure allows authors to provide a simple model for bending LLHM crystals—layers of L-Leucinium cations and maleic acid anions connected via H-bonds (forming *bc* planes) were stacked over *a* direction (interacting with weak VdW interactions). This results in the possible slipping of layers along b direction (Figure 1).

**Figure 1.** Crystallographic (**left**) and schematic (**right**) representation of the layered structure of LLHM, showing layers that shift resulting in plasticity under mechanical stress (adapted from [34,35]). Layers' shifts are marked with an arrow sign depending on the direction of displacement.

Nevertheless, no experiments below 100 K and high pressures were provided before, leaving an opportunity for a combined study of possible phase transitions at extreme conditions using powerful methods of XRD and Raman spectroscopy.

#### **2. Materials and Methods**

## *2.1. Crystal Growth*

Crystals of LLHM were obtained by slow evaporation of an equimolar aqueous solution of L-leucine and maleic acid using the 'sitting-drop' approach [53] as described in previous work [34]. L-leucine (>98%, HPLC) and maleic acid (>99%, HPLC) were purchased from Sigma-Aldrich (St. Louis, MO, USA) and used without further purification. The crystallization procedure leads to 'hedgehog' polycrystalline material as presented in [35]. This bulk material was used to find and cut single crystals for low-temperature and high-pressure experiments. Crystals were operated with care at every stage of isolation and setting to the diamond anvil cell (DAC) to avoid accidental bending.

#### *2.2. High-Pressure Generation and Measurement*

Hydrostatic pressure was generated in diamond-anvil cells (DAC) of 'Almax–Boehler' type without beryllium backing plates [54] with natural diamonds suitable both for X-ray

diffraction and for Raman experiments. Paraffin (ROTH GmbH, Karlsruhe, Germany, hydrostatic limit ~3 GPa) and a 1:1 stoichiometric pentane–isopentane mixture (PIP) (hydrostatic limit 7 GPa) were used as a pressure-transmitting medium (PTM) in two separate experiments [55]. A special chamber was used to facilitate the DAC loading [56]. Pressure measurement was done with a precision of 0.05 GPa using the ruby fluorescence method [57,58].

## *2.3. Optical Microscopy*

Optical microscopy was provided using the OLYMPUS BX41 microscope (Olympus, Tokyo, Japan) with a MPlan N 10×/0.25 FN22 objective. Euromex fiber optic light source EK-1 was used for illumination.

#### *2.4. Single-Crystal X-ray Diffraction (SCXRD)*

Data were collected using an Oxford Diffraction Gemini R Ultra X-ray diffractometer (Crawley, Australia) with a CCD area detector and Mo Kα radiation. The quality of data was not high enough to refine the atomic coordinates or determine unit cell parameters, mainly because of the DAC usage. It was mentioned before that the diffraction of LLHM crystals is not very high for accessible laboratory instruments either. [34]

## *2.5. Raman Spectroscopy*

Raman experiments were performed for low-temperature and high-pressure samples. Raman spectra were recorded using a LabRam HR 300 spectrometer from HORIBA Jobin Yvon (Edison, NJ, USA) with a CCD detector. For spectral excitation, a 488 nm line of an Ar+ laser was used with a beam size of ~1 μm at the surface of the sample and a power of ~8 mW. All data were collected using a Raman microscope in backscattering geometry. The spectral resolution was ~2 cm<sup>−</sup><sup>1</sup> providing seven scans 30 s each for every spectrum.

Raman spectra of LLHM were recorded in the temperature range of 300–11 K during cooling without repeating on heating.

Two distinct experiments were performed for samples at high pressures. Raman spectra for LLHM in PIP were recorded at pressures of 1.35, 2.03, 2.48, 3.06, 3.63, 4.05, 4.48, 5.03, 5.50, and 6.15 GPa on loading and 3.05, 1.82, 1.15, 0.41, and 0 GPa on pressure release. Spectra for LLHM in Paraffin were recorded at pressures of 0, 0.38, 2.55, and 2.90 GPa.

## *2.6. Computational Methods*

Gas-phase calculations of vibrational spectra (both IR and Raman) were done for L-leucine cation, Maleic acid anion, and LLHM dimer to provide a more reasonable assignment of experimental modes. Ions of L-Leucine, maleic acid, and their dimer were extracted from the LLHM crystal structure from [34] and were further freely optimized at B3LYP/6-311+G(d,p) level of theory, providing vibrational calculations subsequently. None of the atoms or groups were fixed for gas-phase optimization, making possible the ion formation of L-Leucine and Maleic acid in the gas phase calculations. Gaussian09 package was used for all calculations [59]

Solid state calculations, as suggested in literature, were attempted to perform for the simulation of high-pressure behavior [3,7,46] and the vibrational band assignment. Nevertheless, even the usage of supercomputers (80 cpu, 384 Gb RAM, max time for task without interruption—240 h) did not allow for the performance of such calculations in reasonable time, providing the 'simple' optimization of one full unit cell in several months. Thus, only gas-phase calculations were used for this work.
