Supramolecular Gel Control of Cisplatin Crystallization: Identification of a New Solvate Form Using a Cisplatin-Mimetic Gelator

Dawn, Arnab; Andrew, Katherine S.; Yufit, Dmitry S.; Hong, Yuexian; Reddy, J. Prakasha; Jones, Christopher D.; Aguilar, Juan A.; Steed, Jonathan W.

Abstract

A series of platinum based low-molecular-weight urea-based gelators C1, C2, and C3, mimicking the structure of the anticancer drug cisplatin has been synthesized, as part of the development of a targeted, supramolecular gel phase crystallization and polymorphism screening strategy. Morphological and rheological studies established that inclusion of a longer spacer between the urea and cisplatin-mimetic regions of the gelator (C3) resulted in optimal gelation performance. Interfacial crystallization of cisplatin in a gel–sol biphasic system has been employed to address the insolubility of the drug molecule in organic solvents. A new N,N-dimethylacetamide (DMA) solvate of cisplatin has been identified and a crystal habit modification of the known N,N-dimethylformamide (DMF) solvate form of cisplatin has been observed on crystallization of cisplatin in C3 gels prepared in xylenes. While both targeted and nontargeted gels resulted in the formation of the new DMA solvate, only the targeted C3 gel resulted in high-quality single crystal suitable for characterization by single crystal crystallography. The high crystal quality is attributed to a close match between the core geometry of C3 with that of cisplatin together with local order in the gel fibers of C3.

Citation

Dawn, A., Andrew, K. S., Yufit, D. S., Hong, Y., Reddy, J. P., Jones, C. D., …Steed, J. W. (2015). Supramolecular Gel Control of Cisplatin Crystallization: Identification of a New Solvate Form Using a Cisplatin-Mimetic Gelator. Crystal Growth and Design, 15(9), 4591-4599. https://doi.org/10.1021/acs.cgd.5b00840

• Journal Article Type: Article
• Acceptance Date: Aug 10, 2015
• Publication Date: Sep 2, 2015
• Deposit Date: Oct 2, 2015
• Publicly Available Date: Aug 18, 2016
• Journal: Crystal Growth and Design
• Print ISSN: 1528-7483
• Electronic ISSN: 1528-7505
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 9
• Pages: 4591-4599
• DOI: https://doi.org/10.1021/acs.cgd.5b00840
• Public URL: https://durham-repository.worktribe.com/output/1421709