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Supramolecular modification of baclofen in the solid state
Author(s)
Malapile, Ramokone Junia
Date Issued
2020
Type
Thesis
Publisher
Cape Peninsula University of Technology
Abstract
Baclofen (BAC, (R/S)-4-amino-3-(4-chlorophenyl)butanoic acid), a γ-amino acid, was used to
form multicomponent crystals (MCCs) with coformers (CFs) of different acidic strength and
molecular size. Crystallisation of BAC with oxalic acid (OXA), salicylic acid (SAL),
phenoxyacetic acid (POA), 2,4-dichlorophenoxyacetic acid (2,4ClPOA), 4-picoline (4PIC) and
3,4-lutidine (3,4LUT) yielded seven MCCs, [BAC+][OXA-]·w, BAC·SAL·w, [BAC+][POA-],
[BAC+][2,4ClPOA-], [BAC+][2,4ClPOA-]·w, 2BAC(4PIC)·w and 2BAC(3,4 LUT)·w, respectively.
The bulk materials were analysed by thermoanalytical methods (thermogravimetry and
differential scanning calorimetry), powder X-ray analysis and Fourier transform infrared
spectrometry. Liquid assisted grinding (LAG), as a green chemistry method, was also applied
to form the MCCs.
X-ray analysis of the single crystal structures revealed that BAC exists in zwitterionic or
cationic form in these crystals, and the MCCs represent a large variety of crystal classes,
such as salts, salt solvates, cocrystal salt solvates or solvates with different stoichiometry. It
was noted that BAC appeared in many different conformations in the MCCs and the crystal
[BAC+][2,4ClPOA-] represents a new conformer of BAC found in the solid state.
Comparative crystal packing analysis revealed similarities in the packing arrangement of the
MCCs, with the exception of the oxalate salt, where the hydrogen bonded layers formed by
the polar functional groups of the BAC and the CFs alternating with the hydrophobic
aromatic layers. Contrarily, the polar layers show great variety in their hydrogen bonding
pattern.
In conclusion, BAC is a good candidate to form MCCs with the selected CFs, but the
predictability of the nature of interactions formed between the BAC moieties or between
the BAC and CF molecules are poor and this makes BAC a challenging target when crystal
engineering techniques are used.
form multicomponent crystals (MCCs) with coformers (CFs) of different acidic strength and
molecular size. Crystallisation of BAC with oxalic acid (OXA), salicylic acid (SAL),
phenoxyacetic acid (POA), 2,4-dichlorophenoxyacetic acid (2,4ClPOA), 4-picoline (4PIC) and
3,4-lutidine (3,4LUT) yielded seven MCCs, [BAC+][OXA-]·w, BAC·SAL·w, [BAC+][POA-],
[BAC+][2,4ClPOA-], [BAC+][2,4ClPOA-]·w, 2BAC(4PIC)·w and 2BAC(3,4 LUT)·w, respectively.
The bulk materials were analysed by thermoanalytical methods (thermogravimetry and
differential scanning calorimetry), powder X-ray analysis and Fourier transform infrared
spectrometry. Liquid assisted grinding (LAG), as a green chemistry method, was also applied
to form the MCCs.
X-ray analysis of the single crystal structures revealed that BAC exists in zwitterionic or
cationic form in these crystals, and the MCCs represent a large variety of crystal classes,
such as salts, salt solvates, cocrystal salt solvates or solvates with different stoichiometry. It
was noted that BAC appeared in many different conformations in the MCCs and the crystal
[BAC+][2,4ClPOA-] represents a new conformer of BAC found in the solid state.
Comparative crystal packing analysis revealed similarities in the packing arrangement of the
MCCs, with the exception of the oxalate salt, where the hydrogen bonded layers formed by
the polar functional groups of the BAC and the CFs alternating with the hydrophobic
aromatic layers. Contrarily, the polar layers show great variety in their hydrogen bonding
pattern.
In conclusion, BAC is a good candidate to form MCCs with the selected CFs, but the
predictability of the nature of interactions formed between the BAC moieties or between
the BAC and CF molecules are poor and this makes BAC a challenging target when crystal
engineering techniques are used.
Additional information
Thesis (Master of Applied Science in Chemistry)--Cape Peninsula University of Technology, 2020
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