Vladimir Damjanović

Copper(II) complexes with benzhydrazone-related ligands: synthesis, structural studies and cytotoxicity assay

The dinuclear copper(II) complexes [Cu2(LH)2] (1), [Cu2(L3OMe)2] (2), [Cu2(L4OMe)2] (3) as well as the tetranuclear complex [Cu4(L3OMe)4]·4MeOH·2H2O (2a·4MeOH·2H2O), (where LH = 2-oxybenzaldehyde benzhydrazonato, L3OMe = 3-methoxy-2-oxybenzaldehyde benzhydrazonato or L4OMe = 4-methoxy-2-oxybenzaldehyde benzhydrazonato) were synthesized by reacting copper(II) acetate with the corresponding aroylhydrazone. Reactions in the presence of N-donor ligands D (pyridine, 4,4′-bipyridine or 1,10-phenanthroline) afforded complexes with different nuclearities and Cu : L : D ratios. They can be classified as dinuclear, [Cu2(LH)2(py)2] (1py), [Cu2(L3OMe)2(py)2]·3H2O (2py·3H2O), [Cu2(L4OMe)2(py)2] (3py), [{Cu(LH)}2(bpy)] (1bpy), [{Cu(L3OMe)}2(bpy)] (2bpy), and [{Cu(L4OMe)}2(bpy)] (3bpy), mononuclear [Cu(LH)(phen)] (1phen), [Cu(L3OMe)(phen)] (2phen) and [Cu(L4OMe)(phen)] (3phen), and polynuclear [{Cu(LH)}2(bpy)]n·2nMeOH (1bpy*·2MeOH) complexes. Conversion of complexes 1py–3py to complexes 1–3 proceeded via solid state reactions. The crystal and molecular structures of 2a·4MeOH·2H2O, 2py·3H2O, 3py, 1bpy*·2MeOH, 2bpy, 1phen and 3phen were determined by the single crystal X-ray diffraction method. All complexes were characterized by means of elemental and thermogravimetric analysis, FT-IR spectroscopy and the powder X-ray diffraction method. In vitro cytotoxicity of benzhydrazone-related ligands and their copper(II) complexes against THP-1 and HepG2 cells demonstrated that the complexes are significantly more cytotoxic than the corresponding ligands.

Spectroscopic Studies of Methimazole Reactivity toward the Aquapentacyanoferrate (II) Ion in Aqueous Solutions

Methimazole (2-mercapto-1-methylimidazole, MMI) and its pentacyanoferrate (II) complex have been charac- terized by means of UV/Vis, Raman, and NMR spectroscopy. The reaction of MMI with aquapentacyanoferrate (II), (Fe(CN)5(H2O)) 3� , in buffered aqueous solutions yielded the (Fe(CN)5(MMI)) 3� complex. It was found that only thione tautomer of MMI coordinates to the iron (II). The exceptionally stabile and inert complex was produced.

Comparative studies on conventional and solvent-free synthesis toward hydrazones: Application of PXRD and chemometric data analysis in mechanochemical reaction monitoring

Synthesis of hydrazones was performed via both conventional and solvent-free routes using the corresponding hydrazide (isonicotinic hydrazide, nicotinic hydrazide, 2-aminobenzhydrazide or 4-aminobenzhydrazide) and appropriate aldehyde (salicylaldehyde, 3-methoxysalicylaldehyde or 4-methoxysalicylaldehyde). A systematic study dedicated to solvatomorphism or polymorphism screening resulted in the formation of twelve novel crystalline forms, and eight of these were characterized via the single crystal X-ray diffraction method. In all studied structures, the molecules were assembled into endless supramolecular chains, discrete rings, chains of rings or nets. The mechanochemical synthesis employing liquid-assisted grinding was also applied and the nicotinic- and isonicotinic-based hydrazones were found to form readily from their corresponding precursors. The chemometric study using principal component analysis for mechanochemical synthesis monitoring was implemented for the first time to provide an insight into the reaction profiles. A thoughtful combination of ex situ powder X-ray diffraction and chemometric analysis was essential to identify a stepwise mechanism for the hydrazone formation via an intermediate phase. In five investigated reactions the first principal component accounted for at least 75% of the total variance, whereas in the case of two reactions this component accounted for 69.72 and 46.23% of the total variance. The hydrazones were also evaluated for cytotoxic activity in vitro. All compounds exhibited weak to moderate cytotoxicity against THP-1 and no cytotoxicity against HepG2 cells. Substantial antibacterial activity was obtained against Moraxella catarrhalis while no growth inhibition of Staphylococcus aureus, Enterococcus faecalis and Escherichia coli was observed.