A new series of Cu(II) and Ni(II) complexes of NO bidentate 4-NO$_{2}$-benzoylhydrazones: synthesis, characterization, and biological studies

Turk J Chem (2015) 39: 939 – 954 Turkish Journal of Chemistry http://journals.tubitak.gov.tr/chem/ c TÜBİTAK ⃝ doi:10.3906/kim-1502-122 Research Article A new series of Cu(II) and Ni(II) complexes of NO bidentate 4-NO 2 -benzoylhydrazones: synthesis, characterization, and biological studies Hatice BAŞPINAR KÜÇÜK1,∗, Emel MATARACI KARA2 , Berna ÖZBEK ÇELİK2 1 Department of Chemistry, İstanbul University, İstanbul, Turkey 2 Department of Pharmaceutical Microbiology, İstanbul University, İstanbul, Turkey Received: 28.02.2015 • Accepted/Published Online: 22.05.2015 • Printed: 30.10.2015 Abstract: A series of new nickel(II) and copper(II) hydrazone complexes 1–14, containing a bidentate NO-donor hydrazone ligand, derived from 4-nitrobenzoylhydrazide and several aliphatic and aromatic aldehydes were synthesized, and their chemical structures were confirmed by means of FT-IR, UV-Vis, 1 H and 13 C NMR, mass spectral data, conductance measurements, and elemental analyses. The spectral data of the newly synthesized complexes show the formation of a 1:2 [metal:ligand] ratio. The ligands and their complexes were also investigated for their possible in vitro antimicrobial activities against S. aureus, S. epidermidis, E. coli, K. pneumonia, P. aeruginosa, P. mirabilis, E. faecalis, and C. albicans. Among the fourteen new complexes synthesized, complex Cu(L 4 )2 (7) containing a direct aromatic moiety in the ligand (HL 7 ) was found to be most active against selected test microorganisms. Key words: Hydrazone derivatives, bidentate Schiff base ligand, copper complex, nickel complex, antimicrobial activity 1. Introduction Schiff bases are an important class of nitrogen-donor ligands, pioneered by Hugo Schiff (1834–1915) with the discovery of them in 1864. 1 From the coordination chemistry perspective, hydrazone-type Schiff bases are multidentate ligands, i.e. they have multiple coordinating sites. For example, acylhydrazone Schiff base complexes are extensively investigated in the form of coordination polymers. 2 Analytical chemistry also uses these kinds of compounds as metal-chelating agents. 3 The keto-enol tautomerism is important for forming complexes with usual and unusual properties due to different donation properties and adopting unusual coordination numbers. 4 Using various hydrazides and carbonyl compounds, the resulting ligands and complexes thereby formed by these ligands have suitable structural and functional variations. 5 Schiff base complexes with transition metals are useful model compounds of the active parts of biologically important complexes. Reported biological and pharmaceutical activities of hydrazone-type Schiff base complexes include antimicrobial, antituberculostatic, anticancer, and antioxidant behaviors. 6,7 Aroylhydrazone complexes of transition metals are also an interesting class with amebicidal, antibacterial, and antileukemic activities with potential activities for antineoplastic, antiviral, and antiinflammatory effects. 8−10 It is reported that the long list of biological activities of Schiff base complexes can also include antifungal activity. 11 Insecticidal and herbicidal activities are other interesting outcomes of Schiff base complexes. 12 Inhibition of lipid peroxidation and enzymes was also reported for this versatile class of compounds. 13−15 ∗ Correspondence: 939 BAŞPINAR KÜÇÜK et al./Turk J Chem Technological applications of hydrazone-based Schiff base complexes include, but are not limited to, light emission diodes (LEDs), 16 corrosion inhibitors, 17 potentiometric sensors, 18 synthetic intermediates to heterocyclic compounds, and conjugate azomethine-based polymers. 19 With some postsynthetic modification, hydrazone-based Schiff base metal complexes can be varied for further applications such as energy transfer cassettes, 20 fluorogenic or chromogenic probes, and metal complex dyes. 21 According to the literature, numerous metal complexes were synthesized employing several hydrazone ligands. In these hydrazone ligands, the pyridine nitrogen or hydroxyl moiety bound to the aromatic ring are extra donor groups, as expected. 8,22−26 Singh et al. synthesized metal complexes in which the ligand was 2-acetylthiophene benzoyl hydrazone. 27 The originality of our study is that we have used, for the first time, 4-nitrobenzoylhydrazone as the precursor to the ligand to have a tetradentate fashion without using the aforementioned pyridine or hydroxy moieties. To investigate the relationship between the structure of the metal complex and the biological activity it possesses, we have used aliphatic and aromatic substituted 4-nitrobenzoylhydrazone ligands. The present work intends to describe new candidates of this class, and this work reports the synthesis and spectral characterization (including 1 H and 13 C NMR, FT-IR, UV-Vis and ESI-MS analyses) of seven hydrazone-based Schiff base ligands (HL n ; n = 1–7) and their Cu(II) and Ni(II) metal complexes 1–14 [in the form of Cu(L n )2 and Ni(L n )2 ; n = 1–7], along with an overview of their biological activities against eight well-known microorganisms in the presence of several antibiotics. 2. Results and discussion The ligands were synthesized by condensation of 4-nitrobenzoylhydrazide with several aliphatic and aromatic aldehydes (Scheme 1). The reaction of these ligands with metal salts in a 1:2 metal:ligand molar ratio in methanol yielded four coordinate complexes M(L n )2 (M = Cu(II), Ni(II); n = 1–7) (Scheme 2) and in the complexes, the ligands are enolized and deprotonated during complexation (Scheme 1). 28,29 The presence of the nitro group in the hydrazone is crucial; instead of 4-NO 2 -benzoylhydrazones, we have also attempted to synthesize 4-Hbenzoylhydrazones. A quick comparison yields the observation that if there is an electron-withdrawing NO 2 group in the aromatic ring, the Cu complexes are formed instantly whereas the Ni complexes require 1 h to complete. The analytical data and physical properties of the ligands and coordination compounds are listed in Table 1. All of the synthesized compounds are quite stable in air at room temperature without decomposing for a long time. The metal complexes have been obtained as colored solids and decompose at the temperature range between 209 and >380 ◦ C without melting. As far as solubility is concerned, the metal complexes 2, 4, 6, and 8 are fully soluble in most common organic solvents such as chloroform, methylene chloride, diethyl ether, and acetone, but other Ni(II) complexes 10, 12, and 14 and all Cu(II) complexes 1, 3, 5, 7, 9, 11, and 13 are insoluble in most common organic solvents except DMF and DMSO. The 10 −3 M solutions of the complexes in DMSO show low molar conductance values in the range of 6.2–11.8 Ω−1 cm 2 mol −1 (Table 1). These values indicated that all synthesized complexes are nonelectrolytes. 30−32 Our attempts to obtain single crystals of the compounds failed, so we had to characterize our ligands and (...truncated)