Synthesis, characterization, and pharmaceutical activities of new metallated ionic chitosan Schiff base hydrogels as potential chemotherapeutic agents

Abstract

Facile and green protocols were used to synthesize a novel series of metallated ionic chitosan Schiff base hydrogels (ICSBHs) by grafting low-molecular-weight chitosan (LMC) with salicylaldehyde-imidazolium/thiazolium ionic liquids (Me₂ImSal⁺MCl_x⁻ and MeThSal⁺MCl_x⁻, 2a-f) (M = Ti, x = 6; M = Pd and x = 4). Physical characterization of the new hydrogels was performed based on solubility, sol-gel fractions, and solvent uptake measurements. Meanwhile, these hydrogels were structurally and morphologically characterized using microanalytical and spectral analyses (FTIR, NMR (¹H NMR, ¹³C NMR, and ¹H¹⁵N HMBC NMR), EDX, ESI-MS, and SEM). Interestingly, PdCl₄ ion performs better than TiCl₆ as a crosslinking agent for cationic chitosan Schiff base, as revealed from the higher crosslinking levels and, consequently, porosity of PdCl₄-based hydrogels compared to TiCl₆-based hydrogels. Interestingly, the PdCl₄-based hydrogel (ICSBH₆) exhibited significant antimicrobial potential, outperforming the clinical drug ciprofloxacin (CIP) (MIC/MBC values of ICSBH₆ were 15.85 /31.7, while the values were 33.4/66.8 for CIP, against S. aureus). Meanwhile, ICSBH₆ showed superior antibiofilm and anticancer potentials. The MTT assay findings revealed ICSBH₆ as a promising and safe anti-hepatocarcinoma chemotherapeutic agent with a significantly low IC₅₀ value of 3.79 μg/mL against Huh-7 cancer cells, while a high IC₅₀ value (48.87 μg/mL) against normal BNL cells. According to the results of in silico studies, ICSBH₆ exhibits higher binding affinities for bacterial biofilm formation and antibiotic resistance-induction proteins (6M3A/ 7C7R) (−11.1/−11.77 kcal/mol) than CIP.