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

Area of Science:

• Supramolecular chemistry
• Crystal engineering
• Materials science
• Medicinal chemistry

Background:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) like flufenamic acid (FA) are widely used.
• Developing novel materials with specific properties, such as gelation, is crucial for various applications.
• Understanding structure-property relationships is key to designing functional molecules.

Purpose of the Study:

• To synthesize and characterize novel primary ammonium monocarboxylate (PAM) salts from flufenamic acid (FA) and its β-alanine monopeptide derivative (FM).
• To investigate the gelation behavior of these PAM salts in various solvents, including those relevant to topical formulations.
• To explore the potential anticancer activity of the synthesized gelator salts against aggressive cancer cell lines.

Main Methods:

• Supramolecular synthon rationale and crystal engineering principles were applied for salt synthesis.
• Gelation studies were performed using various solvents, including water and methyl salicylate.
• Structure-property correlations were analyzed using single-crystal X-ray diffraction (SXRD) and powder X-ray diffraction (PXRD).
• Anticancer activity was assessed using MTT, PEG2, and cell migration assays on MDA-MB-231 cells.

Main Results:

• A series of PAM salts were successfully synthesized from FA and FM.
• Approximately 90% of the synthesized PAM salts exhibited gelation properties in diverse solvents.
• SXRD and PXRD data provided insights into the gel network's supramolecular structure.
• One specific gelator salt (S7) showed significant anticancer effects on the MDA-MB-231 human breast cancer cell line.

Conclusions:

• The synthesized PAM salts demonstrate promising gelation capabilities, applicable in topical formulations.
• The study highlights the potential of supramolecular chemistry in designing functional materials from NSAIDs.
• The identified gelator salt (S7) warrants further investigation for its therapeutic potential as an anticancer agent.