**3. Results**

Crystals of LLHM were grown as described in the' Section 2. One crystal was used for the low temperature experiment, and another two were used in high pressure experiments in PIP and paraffin PTM. All crystals were selected using optical polarized microscopy.

#### *3.1. Room Temperature Raman Spectra and Vibrational Mode Assignment*

The crystal structure of LLHM contains six molecules in the asymmetric unit cell, resulting in 24 molecules in the full unit cell (Figure 2). Multiple H-bonds are located in directions not coinciding with cell axes or crystal faces, which limits the utility of polarized Raman spectroscopy.

**Figure 2.** Molecular (**left**) and crystal structure fragment of LLHM at 298 K (**right**), showing 12 molecules of L-leucine and maleic acid each in the unit cell (CCDC# 1889564). Hydrogen bonds are shown by dashed lines.

The complicated structure of LLHM significantly constrains precise band assignment in Raman spectra. Nevertheless, literature data and calculated gas-phase vibrational spectra of L-Leucine and maleic acid ions and their dimer helps to assign main band regions of obtained experimental spectra (Figure 3) [60–66]. All literature data except ref. [67], which contains multiple inaccuracies, confirm the suggested band assignment.

**Figure 3.** Experimental Raman spectra bands assignment in LLHM crystal structure at 298 K. Calculated gas-phase vibrational spectra are presented in Figure S1 (please see Supplementary Materials).

Main changes are expected in the region before 200 cm<sup>−</sup><sup>1</sup> (lattice vibrations) and 3000–3400 cm<sup>−</sup><sup>1</sup> (valence –OH and –NH3 vibrations). A significant change in mode position or appearance of new modes is key evidence of phase transition, while slight changes

in peak positions or their intensities are traditional for low temperature or high-pressure behavior of the original phase.

#### *3.2. Low Temperature Study*

Low temperature Raman spectra of LLHM crystal were recorded in the temperature range of 300–11 K, cooling down the sample. No additional peaks of a new phase were found in spectra (Figure 4). No crystal changes were also found using optical microscopy on cooling.

**Figure 4.** LLHM Raman spectra at low temperatures, showing no phase transition on cooling. Lone spurious peaks in the region of 2000–2500 cm<sup>−</sup><sup>1</sup> at temperatures 40 and 100 K were not vanished from spectra to preserve original data. Same is true for spurious peaks at 40 K in the region between 3100–3250 cm<sup>−</sup>1.

Wide bands split on cooling due to the thermal motion decrease. At low temperatures, the motions of functional groups in the molecule (e.g., different CH3 groups motion in L-Leucine ion) become distinguishable in Raman spectra. Moreover, vibrations of the same groups in symmetry unequal molecules are close in spectra, but they have slightly different frequencies (2–10 cm<sup>−</sup>1) because of the crystalline environment and become distinguishable at low temperatures as well. This is a typical behavior of molecular crystals, especially with a high Z' number [68–70]. Low and high-frequency regions are shown in detail in Figure S2. Stretching vibration of CO2− group (1699 cm<sup>−</sup><sup>1</sup> and 1734 cm<sup>−</sup><sup>1</sup> at 298 K, see Figure 3) has a different intensity ratio, which changes at 160 K and 80 K, and may be evidence of a phase transition, e.g., a doubling of the unit cell. Nevertheless, we assume change of this vibration intensity is the result of structure shrinking and corresponding intermolecular interaction changes, but not phase transition. SCXRD in ref. [34] showed no phase transition at 160 K or at the 0–200 cm<sup>−</sup><sup>1</sup> region in Raman spectra. Based on scrupulous analysis of Raman spectra at low temperatures, one can sugges<sup>t</sup> no phase transition on cooling. This coincides well with our previous X-Ray study in the temperature range of 100–300 K [34]. Summing up these two experiments, LLHM plasticity preservation can be proposed below 77 K down to liquid helium temperatures.

#### *3.3. High Pressure Study*

High pressure experiments were provided in different PTMs using DAC as reported in the Section 2. Usage of SCXRD was limited due to the poor diffraction data, which is a result of the nature of the LLHM crystal structure (defining plasticity) and DAC construction. Thus, only Raman spectra were recorded for all high-pressure experiments.

Surprisingly, the behavior of LLHM crystals differs significantly in paraffin and PIP. An effect of PTM, as well as experiment protocol on molecular crystals phase transition at high pressure, is a documented phenomenon [43,71,72]. The low-frequency region in Raman spectra shows no phase transition in paraffin up to 2.9 GPa (close to pressure limit for paraffin) and some changes in LLHM crystal in PIP at 1.35 GPa (Figure 5).

**Figure 5.** Raman spectra of LLHM at multiple pressures at (**<sup>a</sup>**,**<sup>c</sup>**) low-frequency and (**b**,**d**) highfrequency regions, showing different behavior in paraffin (**left**) and PIP (**right**) PTM.

The high-frequency Raman region is not very informative, lacking -OH and -NH3 vibrational modes information at high pressures [73,74]. Nevertheless, some changes in -CHx vibration modes confirm crystal changes in PIP in contrast to paraffin (full Raman spectra at all pressures are shown in Figure S3). We also report spectra of LLHM crystal in PIP at 0 GPa before pressure impact and after relaxation from 6.15 Gpa (Figure 6). Significant background level (halo) may be explained with possible amorphization of plastic LLHM crystal at high pressure or luminescence, which was not observed before pressure impact.

Possible phase transition in PIP was additionally confirmed by optical microscopy, which recorded crystal destruction at 1.35 GPa (Figure 7). No obvious changes of LLHM crystal in paraffin occurred in the whole pressure range according to optical microscopy. This confirms different behavior of LLHM crystals under pressure in different media.

An absence of SCXRD did not allow for the report of phase transition in LLHM crystal at high pressure in PIP unequivocally. Nevertheless, relevant changes in optical microscopy and Raman spectra allowed us to speculate about crystal destruction because of one or a cascade of phase transitions in the crystal structure or amorphization of the LLHM sample.

**Figure 6.** Raman spectra of LLHM at PIP PTM at 0 GPa before (bottom black line) and after (upper red line) pressure impact. \* Asterisk mark the signal from DAC.

**Figure 7.** Photographs showing LLHM crystal destruction in PIP at pressure 1.35 GPa. LLHM crystal at 0 GPa (**left**) and 1.35 GPa (**right**). Crystal size is 0.3 mm × 0.05 mm × 0.02 mm.
