An Imidazole Functionalized Hf(IV) Metal-Organic Framework for Multi-Component Biginelli and Hantzsch Condensation Reactions and Fluorometric Sensing of Anticancer Drug Raloxifene.

The growing global population and rising demand for pharmaceuticals highlight the need for efficient drug synthesis and detection methods. This study presents a bifunctional imidazole-functionalized Hf(IV)-based metal-organic framework (MOF), 1 as a heterogeneous catalyst for synthesizing 1,4-dihydropyridines (1,4-DHPs), which are key moieties in the synthesis of drugs used for cardiovascular treatments. The solvent-free activated form of 1, labeled as 1' catalyzes both Biginelli and Hantzsch reactions under mild conditions. The Biginelli reaction using aldehyde, ethyl acetoacetate, and urea proceeded at 80 °C in 0.5 h with a 99% yield, while the Hantzsch reaction with aldehyde, ethyl acetoacetate, and ammonium acetate occurred at room temperature in ethanol within 1 h, also achieving a 99% yield. Compound 1' showed broad substrate compatibility in both reactions. Additionally, the MOF exhibited excellent sensing ability for the anticancer drug raloxifene (RLX), showing a fast turn-off fluorescence response (within 5 s), a low detection limit (9 nM), and a high Stern-Volmer constant (Ksv, 2 × 106 M⁻¹), enabling sensitive detection in diverse environments, including wastewater and biofluids. Detailed investigations into catalytic mechanisms and detection capabilities provide valuable insights for advancing drug synthesis and analytical methodologies. The study provides valuable insights into both the catalytic and sensing capabilities of 1', demonstrating its potential for advanced pharmaceutical synthesis and real-time drug monitoring.