Synthesis , spectroscopic characterization , crystal structure and Hirshfeld surface analysis of Co ( III ) , Ni ( II ) and VO ( IV ) metal complexes with a novel Schiff base ligand and their antimicrobial activities

© 2019 by the authors; licensee Growing Science, Canada.


Introduction
Schiff bases derived from an amino and carbonyl compound are an important class of ligands that coordinate to metal ions via azomethine nitrogen and have been studied extensively.In azomethine derivatives, the C=N linkage is essential for biological activity, several azomethine have been reported to possess remarkable antimicrobial, 1 anticancer 2 and antimalarial activities. 3,4or the past two decades, Schiff bases were in constant emergence because of their simplicity in preparation and diversity in reactions. 5In comparison to 4d or 5d metal complexes, complexes of 3d transition metal ion exhibit beneficial properties as low toxicity and easily penetrate to the cell membrane of microbes. 6Literature survey shows that Schiff bases show bacteriostatic and bactericidal activity. 7Schiff bases containing o-vanillin possesses antifungal, antibacterial properties 8 and it acts as a weak inhibitor of tyrosinase, display both antimutagenic and co-mutagenic properties in E.coli. 9mines are possess antibacterial and more antifungal activities.The compounds having antimicrobial activity may act either by killing the microbe or by inhibiting multiplication of the microbe by blocking their active sites. 10Schiff bases derived from salicylaldehydes are well known as polydentate ligands, coordinating as deprotonated or neutral forms. 11Thus, the chemical literature prompted us to prepare the transition metal complexes with new Schiff base ligand, here we present the synthesis and characterization of new Schiff base ligand derived from 2-amino-3-benzyloxypyridine and 5-bromo salicylaldehyde as well as its Co(III), Ni(II) and VO(IV) metal complexes.Further, the structures of the complexes are elucidated by various spectral techniques.The bio-relevancy of these complexes have been professionally studied and explored by antimicrobial studies.The crystal structure of the HL ligand was studied by X-ray analysis and to same is reported.

Results and discussion
The obtained complexes are coloured powders, stable in air, insoluble in water and other common solvents but are easily soluble in polar coordinating solvents such as DMF and DMSO.Elemental analysis of the complexes indicates the stoichiometry to be 1:2 metal: ligand for C1, C3 and C5 and 1:1:1 metal: ligand: 1, 10-phenanthroline for C2, C4 and C6.The analytical data of the ligand and metal complexes are given in Table 1 and are in good agreement with the proposed formulation.The molar conductivity values corresponding to the Co(III), Ni(II) and VO(IV) complexes at 10 -3 M in DMSO in the range of 9.37-17.55Ω -1 cm 2 mol -1 and in this way a structural formula of non-electrolyte for these complexes can be assigned.

Description of the X-ray structure of HL
Single crystal X-ray diffraction analysis confirms the molecular structure of the title ligand HL.ORTEP view structure of the title ligand is shown in Fig. 1.The optimized parameters (bond lengths and bond angles) are in good agreement with the standard values, the list of selected bond lengths and bond angles are given in Tables 2 and Table 3.The title ligand exists in orthorhombic crystal system with Pca21 space group.The unit cell parameters are a = 14.240(3)Å, b = 16.090(3)Å, c = 7.2170 (13)  Å and V= 1653.5(5)Å 3 .The average length of the N1=C7 bond is 1.289(15) Å, and bond angle of N1-C7-C6 is 120.0(9)°obtained.In the crystal, two types of intermolecular hydrogen-bonding interactions are present (Table 4).The primary strong O2-H2---N1 hydrogen bond between the imine group and a carbonyl group generates butterfly structure along the b-axis direction and the secondary weak methyl C19-H19---O1 i and C19-H19---O2 i (where, i=-x+1,-y+1,-z+1/2) hydrogen-bonding interactions as depicted in Fig. 2.

Hirshfeld-surface analysis
Hirshfeld surface analysis is an effective tool for exploring packing modes and intermolecular interactions in molecular crystals, as they provide a visual picture of intermolecular interactions and of molecular shapes in a crystalline environment.Surface features characteristic of different types of intermolecular interactions can be identified, and these features can be revealed by colour coding distances from the surface to the nearest atom exterior (de plots) or interior (di plots) to the surface.This gives a visual picture of different types of interactions present and also reflects their relative contributions from molecule to molecule.
Hirshfeld surfaces and their associated two-dimensional fingerprint plots have been used to quantify the various intermolecular interactions in the title ligand. 12,13The two dimensional fingerprint plots from Hirshfeld surface analyses along with the electrostatic potential plots, illustrate the difference between the intermolecular interaction patterns and the relative contributions to the Hirshfeld surface (in percentage) for the major intermolecular contacts associated with the title ligand.

FTIR spectra
The relevant FTIR data for the ligand and its metal complexes are given in Table 5.The strong band is observed at 1617 cm −1 in the spectra of the free Schiff base ligand is a characteristic of the azomethine ν(C=N) stretching vibrations and it is disappeared upon coordination with metal ion. 14The shifting of this group to lower frequency (1564-1591 cm -1 ) in the metal complexes suggest the bonding of unsaturated nitrogen of the azomethine group of HL to the metal ions.The presence of a broad peak in the range 3500-3450 cm -1 indicates the presence of water molecule.The band for phenolic oxygen ν(Ph-O) occurs at 1277 cm -1 , whereas in complexes, this band is shifted to different frequency showing a strong band at around 1262-1274 cm -1 region indicates that there existed phen Ocoordination and involved in coordination with metal ion.The characteristic frequency for ligand corresponding to ether C-O showing a band around 1230 cm -1 , which is unaltered in the spectra of complexes.It shows that the ether C-O is not involved in the coordination. 15,16The metal-terminal oxygen ν(V=O) of the complexes C5 and C6 occurs at 974 and 969 cm -1 regions, respectively, which imitates the most of the oxidovanadium(IV) complexes.The new bands existed in the range 467-488 cm -1 and 515-549 cm −1 provides an additional proof for M-N and M-O, respectively.The appearance of νM-N and νM-O vibrations supports the proposed mode of coordination as depicted in Fig. 5.

Electronic spectra and magnetic moment Studies
The UV-Vis spectra of complexes in DMSO were recorded in the range of 200-800 nm as shown in Fig. 6.The geometry of metal complexes has been deduced from electronic spectra data of the complexes.The electronic spectra of Co(III) complexes shows a broad band at around 259-272, 304-341 and a shoulder at 574-616 nm, which may tentatively be assigned to 4 T1g(F)→ 4 T1g(P) and 4 T1g(F)→ 4 A2g(F), respectively, indicating an octahedral configuration around cobalt ion. 17The electronic spectra of Ni(II) complexes are measured in DMSO exhibits bands at 254-258, 307-347 and 592-612 nm assigned to the π→π* intraligand transition band charge transfer transition 3 A2g(F)→ 3 T2g(F) from the metal to antibonding orbital of the ligand and 3 A2g(F)→ 3 T1g(P) transitions, respectively, in an octahedral geometry around Ni(II) ion. 18The observed magnetic moment values were found in the range of 3.3-3.4BM, which is in the usual range of reported octahedral around the Ni(II) ion. 19The electronic spectra of VO(IV) complexes show low intensity d-d bands at 257-274, 321-341 and 569-583 nm assigned to 2 b2→ 2 e, 2 b2→ 2 b1 and 2 b2→ 2 a1 transitions, respectively, and it is in conformity with square pyramidal geometry around VO(IV). 20The room temperature μeff value for the vanadium complexes were found in the range 1.71-1.74B.M. The magnetic susceptibilities of the complexes are consistent with square-pyramidal geometry around the central metal ion.

Thermal analysis
Thermogravimetric analysis of representative samples has been studied as a function of temperature from room temperature to 800 °C under a nitrogen atmosphere at a heating rate of 10 °C /min.In the cobalt -complexes the first weight loss of 6.57% (calcd.6.69%) in the 157-229 °C range indicates the loss of coordinated water and chlorine molecules.The second and third steps correspond to the complete loss of the ligand molecule in the temperature range between 230-480 and 481-567 °C with a mass loss of 27.62% (calcd.27.89) and 17.39% (calcd.17.75%), respectively.Finally the most stable CoO is formed.Thermal analysis of Ni-complexes can be divided into three stages.In the first stage, weight loss is in the range 50-130 °C having mass loss of 13.27% (calcd.13.98%) due to loss of coordinated water and chloride ion.In continuation to the first stage, gradual weight loss in the range 150-370 °C having mass loss of 35.77% (calcd.36.05%)shows partial decomposition of the ligand moiety around the metal ion.The degradation stage is in the range of 390 -550 °C with an estimated mass loss of 33.27% (calcd.33.77%).This mass loss corresponds to the pyrolysis of ligand molecules leaving NiO as a residue.And, one 1, 10-phenanthroline moiety were decomposed at 560-660 °C, with mass losses of 29.07%(calcd.29.57%) and 30.62% (calcd.31.17%) leaving behind the corresponding metal oxide respectively.The vanadium-complexes decomposes in two stages.The first stage degradation starts at 190-244 °C with an estimated weight loss of 35.07%(calcd.35.68%) due to loss of phenanthroline.Further decomposition occurs in the temperature range of 250-460 °C having mass loss of 42.57% (calcd.42.79) indicates the loss of coordinated ligand.Further decomposition occurs in the temperature range of 550-670 °C corresponds to the final residue estimated as free vanadium oxide 22 and is shown in Fig. 7. On the basis of above facts, the proposed structure of metal complexes are presented in Fig. 8.

. Antimicrobial activity
The synthesized compounds of cobalt, nickel and vanadium complexes were screened for antibacterial activities against Gram positive bacteria Bacillus subtilis (ATCC 21332), Staphylococcus aureus (ATCC 25923) and Gram negative bacteria Salmonella typhi (19430), Escherichia coli (ATCC 25922) and antifungal activities against Aspergillus niger (MTCC 1881), Aspergillus lavus (MTCC 873), Candida albicans (MTCC 227) and Alternaia Solani (MTCC 4634) by well diffusion method. 23hloramphenicol and fluconazole were used as standards drugs for the comparison of the results.The minimum inhibitory concentration (MIC) profile of the entire compounds against bacteria and fungi are summarized in Tables 6 and Table 7. Four bacterial stains were incubated for 24 h at 37 °C, and fungal stains were incubated for 48 h at 37 °C along with standard antibacterial drug under similar conditions for comparison.The fungi were subcultured in potato dextrose agar medium, and the standard antifungal drug, fluconazole was used for control.Stock solution (10 −3 M) was prepared by dissolving the compounds in DMSO.Development of any turbidity illustrated that the compound was not able to inhibit the growth, while no turbidity indicated the inhibition of microorganism by the sample.All the studies were performed in triplicates and the average zone of inhibition was taken as the final reading.The outcome in the above studies shows that the activity of the complexes is higher than that of the corresponding ligand and this activity enhanced on coordination with metal ions.This enhancement in the activity may be rationalized on the basis that ligands mainly posses C=N bond.The enhanced antimicrobial activity of the complex compared with its ligand can be explained using chelation theory. 24The increase in antimicrobial activity may be considered in light of Searl's concept and Tweedy's chelation theory. 25,26,27

Conclusion
In the present work, Co(III), Ni(II) and VO(IV) complexes were prepared from novel Schiff base and are characterized using various spectral techniques.The IR spectral data demonstrate that the ligand acts as a bidentate, coordinating through azomethine nitrogen and carbonyl oxygen atoms.Thermal data provided the number of coordinated and lattice water molecules in the complexes.Magnetic and electronic spectral studies revealed octahedral geometry for Co(III) and Ni(II) complexes and square-pyramidal for VO(IV) complexes.The crystal structure of ligand HL has also been determined by Xray diffraction studies.The ligand and its Co(III), Ni(II) and VO(IV)complexes were tested for antimicrobial activity against some pathogen.Antimicrobial study reveals that, metal complexes have more biological activity than free ligand.

Materials and methods
All the reagents, starting materials as well as solvents were purchased commercially and used without any further purification.1, 10-phenanthroline monohydrate and CoCl2.6H2O,NiCl2.6H2O and VOSO4.2H2Oobtained from Merck Specialties Private Limited, Mumbai were used.Melting point was determined in open capillary tube using Precision Digital Melting Point Apparatus and is uncorrected.Elemental analysis was performed on Perkin Elmer 240 CHN-analyzer. 1 H and 13 C NMR spectra were obtained on Varian-400 MHz spectrometer using TMS (Tetra methyl silane) as an internal reference (Chemical shifts in δ, ppm) in CDCl3 solvent.Electrospray ionization (ESI) mass spectra were recorded using a 2010EV LCMS Shimadzu spectrometer.Infrared spectra were measured using Perkin Elmer Spectrum Version 10.03.09.in the range of 4000-400 cm -1 .The magnetic susceptibility of the solid complexes was determined by Gouy method at room temperature (27±3°C) using Hg[Co(SCN)4] as the standard.Molar conductance in ~10 -3 M DMSO solution was recorded using an Elico Cm-180 conductometer.Electronic spectra of the complexes in the UV-visible region (200-800nm) were measured using an ELICO SL 117 double beam spectrophotometer with quartz cells.TG and DTA measurements for the complexes were recorded in nitrogen atmosphere on TGA Q50 instrument keeping the final temperature at 800 °C with the heating rate of 10 °C/min.

Synthesis of ligand and its complexes 4.2.1. Synthesis of (E)-2-((3-(benzyloxypyridinylimino) methyl)-4-bromophenol (HL)
A new Schiff base was prepared (as shown in scheme, Fig. 9) by the condensation of equimolar amounts of 2-amino-3-benzyloxypyridine (0.002 mol) and 5-bromo salicylaldehyde (0.002 mol) were taken in round bottom flask containing minimum quantity of ethanol.The reaction mixture was refluxed with a catalytic amount of glacial acetic acid (1-2 drops) for about 7-8 h on a water bath at a temperature of 70-80 °C.The progress of the reaction was monitored by TLC.On completion of the reaction, the product was separated by filtration, washed and dried over anhydrous CaCl2 in desiccator and recrystallized from ethanol.Mass spectrum, 1 H NMR, 13   The ethanolic solutions of corresponding metal salts (1 mmol) were added slowly to a hot ethanolic solution of Schiff base ligand HL (2 mmol).The reaction mixture was refluxed for 6 h at 70 °C on water bath.The precipitate obtained was filtered, washed with ethanol and dried in desiccators using calcium chloride.

Preparation of complexes C2, C4 and C6 in the ratio of 1:1:1
The complexes were prepared by mixing equimolar ethanolic solutions of metal salts (1 mmol) and ligand (1 mmol) with stirring for 30 minutes.A solution of 1, 10-phenanthroline monohydrate (Phen) (1 mmol) dissolved in 10 ml ethanol was added to the reaction mixture.It was continued to reflux for 6 h on water bath.Then evaporated the solvent and the resulting complexes were used for further analysis.The development of single crystal of the metal complexes is unsuccessful.

Crystal structure determination by X-ray crystallography
Single crystal X-ray diffraction data of the Schiff base ligand HL was collected on a Bruker, Microstar Proteum 8 diffractometer, with Cu-Kα radiation (λ=1.54178°A) at 296 K.The structure was solved by direct methods using SHELXS-86 and refined by full-matrix technique using SHELXL-2014. 28,29All the non-hydrogen atoms were refined anisotropically.The summary of pertinent crystal data along with further details of structure determination and refinement are given in Table 8.The ORTEP, planes and packing diagrams were generated using the Mercury 3.8 software.

Fig. 2 .
Fig. 2. Crystal packing diagram viewed along b with O2-H2--N1 intermolecular hydrogen bond is shown as a light blue dashed line The intermolecular interactions of the title ligand are shown in the 2D fingerprint plots shown in Fig.4.H---H (34.20%) contacts make the largest contribution to the Hirshfeld surfaces, while the N---H, O--H, H--Br and C---H interactions which make up 7.0, 8.2, 13.3 and 27.9 %of the surface.Plots also reveal the information regarding the intermolecular hydrogen bonds thus supporting for O-H…N intermolecular interactions.This intermolecular contact is highlighted by conventional mapping of dnorm on molecular Hirshfeld surfaces and is shown in Fig.3.The red spots over the surface indicate the inter contacts involved in hydrogen bond.The dark-red spots on the dnorm surface arise as a result of the short interatomic contacts, i.e., weak C-H…O hydrogen bonds, while the other intermolecular interactions appear as light-red spots.

Fig. 3 .
Fig. 3. Hirshfeld surface mapped with a) dnorm for visualizing the intermolecular interactions of the HL b) Shape index property for a compound HL c) Hirshfeld surface mapped over curvedness

Fig. 4 .
Fig. 4. d) Fingerprint plots and corresponding surface area of the title compound showing the individual contribution of each interaction.di is the closest internal distance from a given point on the Hirshfeld surface and de is the closest external contacts.

Table . 1
. Elemental analysis and physical data of Schiff base ligand and its metal complexes.

Table . 5
. FTIR spectral data of the Schiff base ligand [HL] and its metal complexes %TFig. 5. IR spectra of HL and its metal complexes

Table . 6
. Antimicrobial results of the Schiff base ligand and its metal complexes.

Table . 7
. MIC [μg/ml] values for antimicrobial activity of Schiff base ligand and its corresponding metal complexes C NMR and FT IR spectrum of HL are depicted in Figs.(10-13).The developed single crystal was used to elucidate the structure of HL by single crystal X-ray diffractometer.

Table . 8
. Crystal data and structure refinement parameters of the HL.