Synthesis, Characterization, X-Ray Crystal Structures and Antibacterial Activities of Oxidovanadium(V) Complexes with Hydrazone and Hydroxamate Ligands

Two new oxidovanadium(V) complexes, [VOL1L] (1) and [VOLL]·CH3OH (2·CH3OH), where L1 and L2 are the dianionic form of N’-(3-bromo-2-hydroxybenzylidene)picolinohydrazide (H2L) and 2-chloro-N’-(2-hydroxy-3-methoxybenzylidene)benzohydrazide (H2L), respectively, and L is the monoanionic form of 2-hydroxybenzohydroxamic acid (HL), were prepared and characterized by elemental analysis, infrared and electronic spectroscopy. Structures of the complexes were further confirmed by single crystal X-ray determination. The V atoms in the complexes are in octahedral coordination. The hydrazone ligands coordinate to the V atoms through the phenolate O, imino N, and enolate O atoms. The hydroxamate ligand coordinates to the V atom through the carbonyl and hydroxy O atoms. The complexes show effective antibacterial activity against B. subtilis, S. aureus and E. coli. The presence of Cl substitute group in the complex may enhance the antibacterial activity.


Introduction
Schiff bases and their metal complexes have received considerable interest in coordination, catalytic, biological and medicinal chemistry. 1Vanadium acts as essential role in humans and many living organisms.The biological and pharmacological effects of vanadium element include coordination capability and chemical similarity between vanadate and phosphate. 2Some inorganic vanadates show insulin-mimetic properties, as well as antitumor activities.
A number of vanadium complexes with various types of organic ligands are reported to possess interesting antidiabetic activity. 3In pursuit of new vanadium compounds with decreased toxic side effects and enhanced bioavail-ability, a great number of organic ligands and vanadium complexes have been investigated. 4The metal complexes of vanadium have the ability to normalize blood glucose level, thus, they can act as models of the haloperoxidases. 5oreover, the metal complexes of vanadium possess interesting antimicrobial activities. 6In recent years, much attention has been focused on the biological properties of vanadium complexes. 7Some metal complexes of vanadium with hydrazone ligands have been reported for their antibacterial activities by our research group. 8In pursuit of new vanadium-based biocidal agents, we report here two new vanadium(V) complexes, [VOL 1

1. Materials and Measurements
3-Bromo-2-hydroxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde, picolinohydrazide and 2-chlorobenzohydrazide were purchased from Aldrich and used as obtained.Other solvents and reagents were made in China and used as received.C, H and N elemental analyses were performed with a Perkin-Elmer 240 elemental analyzer.Infrared spectra were recorded on a Nicolet AVATAR 360 spectrometer as KBr pellets in the 4000-400 cm -1 region.UV-Vis spectra were recorded on a Lambda 900 spectrometer.

4. X-ray Crystallography
Diffraction intensities for the complexes were collected at 298(2) K using a Bruker D8 VENTURE PHOTON dif- fractometer with MoKα radiation (λ = 0.71073 Å).The collected data were reduced using SAINT, 9 and multi-scan absorption corrections were performed using SADABS. 10tructures of the complexes were solved by direct methods and refined against F 2 by full-matrix least-squares methods using SHELXTL. 11All of the non-hydrogen atoms were refined anisotropically.The amino H atoms were located from different Fourier maps and refined isotropically, with N-H distances restrained to 0.90(1) Å.The other hydrogen atoms in both compounds were placed in idealized positions and constrained to ride on their parent atoms.Crystallographic data for the complexes are summarized in Table 1.
A stock solution of the synthesized compound (1000 μg mL -1 ) in DMSO was prepared and graded quantities of the test compounds were incorporated in specified quantity of sterilized liquid LB medium.Suspension of the microorganism was prepared and applied to 96-well assay plate with serially diluted compounds to be tested.10 μL of tested samples at pre-set concentrations were added to wells with penicillin as a positive reference and with the solvent control (5% DMSO) in medium and incubated at 37 °C for 24 h.
After 24 h exposure, 10 μL of PBS (phosphate buffered saline 0.01 mol L -1 , pH 7.4) containing 4 mg mL -1 of MTT was added to each well.After 4 h, the medium was replaced by 150 μL DMSO to dissolve the complexes.The absorbance at 492 nm of each well was measured with an ELISA plate reader.The IC 50 value was defined as the concentration at which 50% of the bacterial strain could survive.

IR and UV-Vis Spectra of the Complexes
The ν(C=N) absorptions are observed at 1607 cm -1 for complex 1 and 1618 cm -1 for complex 2. 13 The intense bands indicative of the C=O vibrations are absent in the complexes, indicating the enolization of the hydrazone ligands.The sharp bands indicative of the N-H vibrations are located at 3272 cm -1 for complex 1 and 3252 cm -1 for complex 2. The weak peaks in the low wave numbers in the region 450-700 cm -1 may be attributed to V-O and V-N bonds in the complexes.Complexes 1 and 2 exhibit typical bands at 953 cm -1 , which are assigned to the V=O vibrations. 14he UV-Vis spectra of the complexes were recorded in 10 -5 mol L -1 in ethanol, in the range 200-800 nm.The weak bands centered at 326 nm for complex 1 and 335 nm for complex 2 are attributed to intramolecular charge transfer transitions from the p π orbital on the nitrogen and oxygen to the empty d orbitals of the metal. 15The intense bands observed at about 275 nm for the complexes are assigned to intraligand π-π* transition. 15The bands centered at 580 nm for complex 1 and 570 nm for complex 2 are attributed to the ligand-to-metal charge transfer transitions (LMCT). 16

4. Antibacterial Activities
The complexes were screened for antibacterial activities against two Gram-positive bacterial strains (B.subtilis and S. aureus) and two Gram-negative bacterial strains (E. coli and P. aeruginosa) by MTT method.The IC 50 values of the complexes against the bacteria are presented in Table 4. Penicillin G was tested as a reference drug.Complex 1 exhibited effective activity against B. subtilis, and weak activity against S. aureus, while no activity against Gram-negative bacteria E. coli and P. aeruginosa.Complex 2 exhibited effective activity against B. subtilis and S. aureus, weak activity against E. coli, while no activity against P. aeruginosa.In general, complex 2 has stronger activity against B. subtilis, S. aureus and E. coli than complex 1, which might be caused by the existence of the biological active substitute group, Cl.Both the free hydrazones H 2 L 1 and H 2 L 2 , and the hydroxamic acid HL have no or very weak activities on the bacteria.VO(acac) 2 has weak activities on B. subtilis, S. aureus and E. coli, and no activity on P. aeruginosa.

Conclusion
Two new oxidovanadium(V) complexes were obtained and structurally characterized.The complexes show superior antibacterial activities against B. subtilis, S. aureus and E. coli than the free ligands and VO(acac) 2 .Complex 2 Qian: Synthesis, Characterization, X-Ray Crystal Structures ... has similar activities against B. subtilis when compared with penicillin G.The presence of Cl substitute group in the complex may enhance the antibacterial activity.
Scheme 1.The synthetic method of the complexes.

Fig. 1 .
Fig. 1.Molecular structure of complex 1, showing the atom-numbering scheme.Displacement ellipsoids are drawn at the 30% probability level.

Fig. 3 .
Fig. 3. Crystal packing structure of complex 1, viewed along the a axis.Hydrogen bonds are shown as dashed lines.

Fig. 4 .
Fig. 4. Crystal packing structure of compound 2 • CH 3 OH, viewed along the c axis.Hydrogen bonds are shown as dashed lines.

Table 1 .
Crystallographic data and refinement parameters for complexes 1 and 2 • CH 3 OH