Synthesis, Characterization, and ADME/T Prediction of (2Z)-2-[2-(2,4-Dinitrophenyl)hydrazinylidene]-1,2-diphenyle -than-1-ol (DPHD) and Its Copper(II) Complex

Abstract

Abstract : The hydrazone ligand (2Z)-2-[2(2,4-dinitrophenyl)hydrazinylidene]-1,2-diphenylethan-1-ol (DPHD) and its Cu(II) complex were synthesized and characterized using physical and spectroscopic techniques. The newly synthesized compounds are coloured and crystalline with high yield (>70%) with melting points ≥ 100 ℃. The spectroscopic result has indicated a square planar geometry for the copper complex being coordinated by azomethine nitrogen, imine nitrogen, and two nitro groups. Both were soluble in dimethyl sulfoxide (DMSO), sparingly soluble in methanol and ethanol while being insoluble in hexane. The ligand was sparingly soluble in water while its complex was insoluble. SwissADME and ProTox-II in silico predictions of ADME/T showed that both DPHD and its copper complex showed compliance with the  Lipinski’s Rule of Five signifying promising oral drug-likeness. Complexation improved the gastrointestinal absorption and aqueous solubility of its copper complex, but it increased the predicted acute toxicity (LD₅₀ = 900 mg/kg) and synthetic complexity relative to the free ligand. Both drugs are not blood-brain-barrier permeant and have acceptable pharmacokinetic characteristics of possible drug-drug interaction via inhibitory effect on various cytochrome P450. These findings concluded that the copper complex has a better bioavailability but altered toxicity, highlighting the need for experimental toxicity testing and further recommends preclinical investigation of its therapeutic role