Diltiazem-imprinted porphyrinic covalent organic frameworks as solid-phase extractants and fluorescent sensors

Diltiazem, which is a calcium channel blocker, is involved in the formation of covalent organic frameworks (COFs) through the Schiff base reaction of tetrakis (4-aminophenyl)-porphine (TAPP) and dihydroxynaphthalene-dicarbaldehyde (DHNDC) and the next enol-to-keto tautomerization. The diltiazem-imprinted COFs (DICOFs) were optimally formed using Sc(OTf)₃ as the catalyst, TAPP/DHNDC/diltiazem in a molar ratio of 2/3/4, N-methylpyrrolidone/mesitylene (v/v = 3/5) as the porogen, and a 1-h reaction with a high imprinting factor of 10.5 compared to the nonimprinted counterparts (NICOFs). The optimized DICOF exhibited a more amorphous XRD pattern, a larger surface area (1650 vs. 930 m²/g), a larger pore volume (1.33 vs. 0.75 cm³/g), and a finer porous SEM feature than NICOF. The selectivity of NICOF toward diltiazem and diazepam at 250 nM (α = 1.03, RSD = 1.3%) was smaller than the selectivity of DICOF (α = 2.94, RSD = 1.6%). The diltiazem samples (5.0-300 ng mL^-1) dynamically quenched the fluorescence of 15 μg/mL DICOF in 50 mM phosphate buffer at pH 6.5 at 8.0 min equilibrium; thus, Stern-Volmer plots were linearly constructed for sensing diltiazem with an LOD of 3.4 ng mL^-1 and an LOQ of 10.2 ng mL^-1. According to the plots, 30 ng mL^-1 diltiazem solutions that were diluted from 30 mg-specified tablets had an average measured concentration of 29.5 ng mL^-1 (σ = 1.3% and n = 5). In addition to application as fluorescent sensors, DICOFs (30 mg) could be used as dispersive extractants to recover 95.2% of 0.6 ng mL^-1 diltiazem from 25 mL phosphate buffer with quadruplicate uses of 0.5 mL methanol/acetic acid (v/v = 9/1) as the eluent. Langmuir and pseudo-second-order models were fitted to the isothermal and kinetic sorption mechanisms, respectively. The maximum sorption capacity of DICOF was ten times larger than that of NICOF (156 vs. 15.2 mg/g). The interday recoveries of 0.6 ng mL^-1 spiked in 20-fold diluted human urine, and 60-fold diluted human serum were 93.2% and 90.6%, respectively.