Design, Synthesis, and Structures of a New Series of Supramolecular Gelators Derived from Variously Substituted Hydrazine-Carboxamides: Toward Developing Antimelanoma and Antibacterial Topical Gels

Abstract Supramolecular gels are emerging materials for various applications in chemistry, materials science, and biology. However, the a priori design of functional supramolecular gels remains an elusive goal. In this study, we disclose a crystal engineering-inspired supramolecular synthon strategy to synthesize a series of variously substituted hydrazine-carboxamides as supramolecular topical gels for antimelanoma and antibacterial applications. Nearly 89% of the hydrazine-carboxamides synthesized herein were gelators for a binary solvent system of DMSO/water. Single-crystal and powder X-ray diffraction (SXRD and PXRD, respectively) studies corroborated well with the design strategy employed herein. Among the hydrazine-carboxamides reported herein, two DMSO/water (1:1) gels derived from 4-NO2Ph_Inz and 4-NO2Ph_Bhyd were selected for drug delivery applications because of their better flow properties conducive to topical application. In vitro loading and release of an antineoplastic drug, namely, doxorubicin (DOX), within and from the gel matrix of 4-NO2Ph_Inz were more efficient compared to that of 4-NO2Ph_Bhyd; the former was also pH-responsive, resulting in an even more efficient release of DOX, making it suitable for effective release of the drug within the acidic microenvironment of cancer cells. DOX-loaded xerogel 4-NO2Ph_Inz_XG@DOX effectively induced apoptosis in B16–F10 melanoma cells, as confirmed by MTT assay, scratch assays, and various other pertinent experiments (vide infra). Both the DMSO/water (1:1) gels were able to act as media for the in situ synthesis of silver nanoparticles (AgNPs), and the resulting gel-embedded AgNPs turned out to be antibacterial against Staphylococcus aureus and E. coli. Overall, this study highlights the merit of a supramolecular synthon-based design strategy in discovering hitherto unknown hydrazine-carboxamide supramolecular gels with promising potential for drug delivery applications.