Rational Approach Towards Designing Metallogels From a Urea‐Functionalized Pyridyl Dicarboxylate: Anti‐inflammatory, Anticancer, and Drug Delivery

Abstract

A structural rationale was adopted to design a series of metallogels from a newly synthesized urea-functionalized dicarboxylate ligand, namely, 5-[3-(pyridin-3-yl)ureido]isophthalic acid (PUIA), that produces metallogels upon reaction with various metal salts (Cu^II , Zn^II , Co^II , Cd^II , and Ni^II salts) at room temperature. The gels were characterized by dynamic rheology and transmission electron microscopy (TEM). The existence of a coordination bond in the gel state was probed by FTIR and ¹ H NMR spectroscopy in a Zn^II metallogel (i.e., MG2). Single crystals isolated from the reaction mixture of PUIA and Co^II or Cd^II salts characterized by X-ray diffraction revealed lattice inclusion of solvent molecules, which was in agreement with the hypothesis based on which the metallogels were designed. MG2 displayed anti-inflammatory response (prostaglandin E₂ assay) in the macrophage cell line (RAW 264.7) and anticancer properties (cell migration assay) on a highly aggressive human breast cancer cell line (MDA-MB-231). The MG2 metallogel matrix could also be used to load and release (pH responsive) the anticancer drug doxorubicin. Fluorescence imaging of MDA-MB-231 cells treated with MG2 revealed that it was successfully internalized.