Supramolecular Gels Derived from Simple Organic Salts of Flufenamic Acid: Design, Synthesis, Structures, and Plausible Biomedical Application

Abstract

Following supramolecular synthon rationale in the context of crystal engineering, a nonsteroidal-anti-inflammatory-drug (NSAID), namely flufenamic acid (FA) and its β-alanine monopeptide derivative (FM), were converted to a series of primary ammonium monocarboxylate (PAM) salts. Majority of the PAM salts (∼90%) showed gelation with various solvents including water and methyl salicylate (important solvents in topical gel formulation). Structure–property correlation studies based on single-crystal X-ray diffraction (SXRD) and powder X-ray diffraction (PXRD) data provided intriguing insights into the structure of the gel network. Furthermore, one of the gelator salts (S7) displayed anticancer activity on a highly aggressive human breast cancer cell line (MDA-MB-231) ,as revealed by MTT, PEG2, and cell migration assays.

Acid⋅⋅⋅Amide Supramolecular Synthon for Tuning Amino Acid‐Based Hydrogels’ Properties

“…[4][5][6][7] An alternative approach recently envisaged the potential of noncovalent interactions involved in the crystal packing of supramolecular synthons, for predicting and modulating the macroscopic features of the corresponding gels. [8][9][10] Although the correlation between self-assembly in the solid state and in the gel phase is still under debate, [11] the application of crystal engineering principles to the design of LMWG afforded some promising results, [12][13][14][15] especially in the case of organic salts, [16][17][18][19] metallogels, [20][21] and sensing platforms for ions or bioactive molecules. [22][23][24] Among the reported classes of LMWG, N-fluorenylmethyloxycarbonyl (Fmoc) protected amino acids play a key role as biocompatible efficient gelators, owing to their π-π stacking interactions that facilitate molecular orientation and formation of carbamate hydrogen-bonded networks.…”

“…An alternative approach recently envisaged the potential of noncovalent interactions involved in the crystal packing of supramolecular synthons, for predicting and modulating the macroscopic features of the corresponding gels [8–10] . Although the correlation between self‐assembly in the solid state and in the gel phase is still under debate, [11] the application of crystal engineering principles to the design of LMWG afforded some promising results, [12–15] especially in the case of organic salts, [16–19] metallogels, [20–21] and sensing platforms for ions or bioactive molecules [22–24] …”

Supramolecular gel formation regulated by water content in organic solvents: self-assembly mechanism and biomedical applications

“…Supramolecular hydrogels fabricated from molecular self-assembly of low-molecular-weight gelators (LMWGs) are well known for their potential applications in biomedicine, 16 drug delivery, 17 catalysis, 18 chemical sensors, 19 materials synthesis, 20 environmental remediation, 21 etc. 22 The gelation and crystallization of LMWGs are two closely related types of non-equilibrium self-assembly processes; both take place in over-saturated solutions and undergo nucleation and growth processes.…”