Carboxylated Pillar[5]arene Meets Medicinal Biguanides: Host−Guest Complexes with Alexidine and Phenformin in the Crystal and Solution/Gas Phase
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Date
2023-10-12
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American Chemical Society
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Abstract
Here we discuss crystal and solution/gas phase complexes of carboxylated pillar[5]arene with two cationic guests, alexi-dine and phenformin, revealing host-guest and assembly curiosities, the role of hydrogen bonding and cavity inclusion versus exo-mode binding. We show that the combination of carboxylated pillar[5]arene with bis(biguanidinium) guest alexidine results in the crystallization of open-type supramolecular architecture. This is also the first crystal structure of alexidine ever reported. The crystallization of pillar[5]arene with biguanidinium drug phenformin effects a rare solid state complex comprising two cavity inclusion modes within the same crystal lattice. The winner in the competition between ethanol molecules and organic cation (phenformin) for the access to the cavity of pillar[5]arene is undecided, visualized as ‘snapshot’ of these two inclusion possibilities in one crystal structure. Our results demonstrate that carbox-ylated pillar[n]arenes can be useful addition to the macrocyclic toolkit for the facilitation of the crystallization of bio(macro)molecules. Moreover, the IM-MS analysis of the pre-crystallization solutions of pillar[5]arene host and bigua-nide guests have shown the presence of structures and conformations closely related to those observed in the crystal forms. The most intriguing results obtained for pillar[5]arene-alexidine complex imply a conformational evolution of the complex over 24 h. The IM-MS analysis complemented by theoretical calculations may be applied to predict and examine the crystallization process of host-guest systems, complementing crystallographic studies
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Cryst. Growth Des. 2023. Publication Date: October 12, 2023. https://doi.org/10.1021/acs.cgd.3c00942