Covalent molecular hybridization of heterocyclic hydrazides with hexamolybdates: Structural, electronic, and antitubercular properties

To explore new organically derivatized polyoxymetalates (POMs), three heterocyclic hydrazide-functionalized hexamolybdates—1: (TBA)₃[Mo₆O₁₈(=N=NCOC₅H₄N)], 2: (TBA)₃[Mo₆O₁₈(=N=NCOC₄H₃S)], and 3: (TBA)₃[Mo₆O₁₈(=N=NCOC₄H₃N₂)]; (TBA = tetrabutylammonium)—were synthesized by refluxing the corresponding heterocyclic hydrazides with octamolybdates in dry acetonitrile. Their structures were elucidated by single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, ultraviolet–visible spectrscopy, electrospray ionization mass spectrometry, and ¹H nuclear magnetic resonance spectroscopy. In all compounds, one terminal oxo atom of the hexamolybdate is replaced by a heterocyclic hydrazide via a Mo=N multiple bond. Compound 1 contains three conformational isomers of [Mo₆O₁₈(=N=NCOC₅H₄N)]³⁻ with approximate C_s or C₁ symmetry, whereas compound 2 contains a single [Mo₆O₁₈(=N=NCOC₄H₃S)]³⁻ anion with C_s approximate symmetry. Antitubercular activity assays show that all three compounds exhibit enhanced inhibitory activity compared with hexamolybdate and the thiophene-2-carbohydrazide (L2) ligand, although their activity remains lower than that of isoniazid(L1) and pyrazine-2-carbohydrazide (L3). Given their large molecular weights, the molar inhibitory activities of compounds 1–3 are close to or superior to the corresponding ligands alone. Overall, this work demonstrates that molecular hybridization of organic drug molecules with POMs via covalent bonds provides a promising strategy for developing POM-based agents with enhanced biological activity.