Bivalent metal complexes of a novel modified nicotinic acid hydrazide drug: Synthesis, characterization, and anti-tubercular studies

Abstract

Iron(II) and manganese(II) complexes of N'-(1-(pyridin-2-yl)ethylidene)nicotinohydrazide (LH) have been synthesized and characterized by elemental analysis, IR, and ¹H NMR spectroscopy. The crystal structure of the ligand has been determined by single crystal X-ray diffraction and electronic spectroscopic techniques. Crystal data for LH, C₁₃H₁₂N₄O: Orthorhombic, space group Pbcn (no. 60), a = 18.0824(3) Å, b = 7.86555(14) Å, c = 16.1614(3) Å, V = 2298.60(7) Å³, Z = 8, T = 103 K, μ(Mo Kα) = 0.093 mm^-1, Dcalc = 1.388 g/cm³, 36729 reflections measured (5.042° ≤ 2Θ ≤ 54.966°), 2633 unique (R_int = 0.0224, R_sigma = 0.0124) which were used in all calculations. The final R₁ was 0.0383 (F²>2σ(F²)) and wR₂ was 0.0988 (all data). The ligand was found to chelate to the metal ions through the azomethine nitrogen and amide oxygen atoms in a bidentate manner. The anti-tubercular activity of the ligand, its iron (II) and manganese (II) complexes were studied against Mycobacterium tuberculosis (ATTC 27294). The results revealed higher activity of the iron (II) complex with MIC value of 8.00±0.83 µM and a moderate activity of the manganese (II) complex having MIC value of 14.20±1.40 µM, compared to the reference drugs having MIC values of 9.41±0.92, 10.74±1.02, 25.34±2.6 µM and parent ligand with MIC value of 17.60±1.80 µM.