Co(II) and Cd(II) Complexes Derived from Heterocyclic Schiff-Bases: Synthesis, Structural Characterisation, and Biological Activity

New monomeric cobalt and cadmium complexes with Schiff-bases, namely, N′-[(E)-(3-hydroxy-4-methoxyphenyl)methylidene]furan-2-carbohydrazide (L1) and N′-[(E)-(3-hydroxy-4-methoxyphenyl)methylidene]thiophene-2-carbohydrazide (L2) are reported. Schiff-base ligands L1 and L2 were derived from condensation of 3-hydroxy-4-methoxybenzaldehyde (iso-vanillin) with furan-2-carboxylic acid hydrazide and thiophene-2-carboxylic acid hydrazide, respectively. Complexes of the general formula [M(L)2]Cl2 (where M = Co(II) or Cd(II), L = L1 or L2) have been obtained from the reaction of the corresponding metal chloride with the ligands. The ligands and their metal complexes were characterised by spectroscopic methods (FTIR, UV-Vis, 1H, and 13C NMR spectra), elemental analysis, metal content, magnetic measurement, and conductance. These studies revealed the formation of four-coordinate complexes in which the geometry about metal ion is tetrahedral. Biological activity of the ligands and their metal complexes against gram positive bacterial strain Bacillus (G+) and gram negative bacteria Pseudomonas (G−) revealed that the metal complexes become less resistive to the microbial activities as compared to the free ligands.


Introduction
Schiff-base ligand is an interesting class of compounds which have played a key role in the development of coordination chemistry. Schiff-bases and their complexes have a variety of applications in the biological systems and industry [1][2][3][4][5][6]. Furthermore, Schiff-bases are very important materials for inorganic chemists as these are widely used in medicinal inorganic chemistry due to their diverse biological, pharmacological, antitumor activities and their excellent chelating ability. Schiff-bases have gained much importance in catalysis, biomimetic modelling applications, designing molecular magnet molecules, and in liquid crystals aspect [7][8][9]. Schiff-base ligands with heterocyclic molecule and/or containing heteroatoms such as N, O, and S show a broad biological activity and are of special interest because of the variety of ways in which they are interacted to transition metal ions [10,11]. Experimental studies related to DNA binding and cleavage were explored using a range of potent Cu(II) Schiff-base complexes. In addition, Schiff-base nickel(II) complexes have been regarded as models for enzymes such as urease [12]. Vanilline and furfurylamine Schiff-base derivatives are very useful biochemical materials having biological activities [13,14]. Structural characterisation of Schiff-bases and their metal complexes are well documented, including X-ray molecular structure [15][16][17][18][19]. In this paper, we report the synthesis of new Schiff-bases L 1 and L 2 , namely, N -[(E)-(3-hydroxy-4-methoxyphenyl)methylidene]furan-2-carbohydrazide and N -[(E)-(3hydroxy-4-methoxyphenyl)methylidene]thiophene-2-carbohydrazide, respectively, and their metal complexes with Co(II) and Cd(II) ions.

Experimental
2.1. Materials. All reagents were commercially available and used without further purification. Solvents were distilled from appropriate drying agents immediately prior to use.

Preparation of N -[(E)-(3-Hydroxy-4-methoxyphenyl)methylidene]thiophene-2-carbohydrazide (L 2 ).
The method used to prepare L 2 was similar to that used for L 1 but thiophene-2-carboxylic acid hydrazide (1.00 g, 0.007 mmoL) was used in place of furan-2-carboxylic acid hydrazide. The quantities of other reagents used were adjusted accordingly. An identical work-up procedure gave the title compound as an orange-yellow solid. Yield

General Synthesis of Complexes.
A methanolic solution (10 mL) of the hydrated metal salt (1 mmoL), MCl 2 ⋅XH 2 O (where M = Co II ; X = 6; Cd II ; X = 2), was stirred into methanolic solution of the Schiff-base ligand (2 mmoL) in methanol (15 mL). The reaction mixture was then refluxed for 2 h to give a coloured precipitate which was collected by filtration, washed with cold ethanol (5 mL), and dried at room temperature. Elemental analysis data, colours, and yields for the complexes are given in Table 1.

Determination of Bacteriological Activity.
Bioactivities were investigated using agar-well diffusion method [20]. The wells were dug in the media with the help of a sterile metallic borer with centers at least 24 mm. Recommended concentration (100 L) of the test sample 1 mg/mL in DMSO was introduced in the respective wells. The plates were incubated immediately at 37 ∘ C for 20 h. Activity was determined by measuring the diameter of zones showing complete inhibition (mm). In order to clarify the role of DMSO in the biological screening, separate studies were carried out with the solutions alone of DMSO and they showed no activity against any bacterial strains. Ligand found to be potentially active against these bacterial strains were compared with its complexes.

Results and Discussion
4.1. Chemistry. The reaction of 3-hydroxy-4-methoxybenzaldehyde with furan-2-carboxylic acid hydrazide or thiophene-2-carboxylic acid hydrazide in mole ratio 1 : 1 gave L 1 and L 2 , respectively (Scheme 1). The Schiff-bases were characterised by elemental analysis (Table 1), IR  (Table 2), UV-Vis spectroscopy (Table 3) [22][23][24]. The IR spectra of the complexes exhibited ligand bands with the appropriate shifts due to complex formation ( Table 2). The ] (C=O) and ] (C=N) stretching bands that appeared in the free ligands at ca. 1660 and 1620 cm −1 , respectively, are shifted to lower frequency in the complexes and observed in the ranges 1641-1649 cm −1 and 1600-1613 cm −1 for ] (C=O) and ] (C=N), respectively. These bands are assigned to a ] (C=O) and ] (C=N) stretches of reduced bond order. This can be attributed to delocalisation of metal electron density ( 2 ) to the -system of the ligand [25,26], indicating coordination of oxygen of C=O and nitrogen of the C=N moieties to the metal atoms [27]. The bands of ] (C-O) at ca. 1270 cm −1 in the free ligands are shifted to lower frequencies and appeared at 1203-1263 cm −1 for the complexes. At lower frequency the complexes exhibited bands around 540-549 and 404-416 cm −1 which could be assigned to ] (M-O) and ] (M-N) vibration mode [25]. These bands indicated that the imine, nitrogens and the oxygen of carbonyl group of the ligands are involved in coordination with metal ion. The IR spectra of the complexes show peaks in the range 3373-3529 and around 3203-3404 cm −1 assigned for the free O-H and N-H functional groups. 1 H, 13 C NMR spectra of L 1 and L 2 show the expected signals (see Section 2). 1 H NMR of the ligands show peaks at chemical shift ca. 3.84 ppm. This singlet peak with three proton integration has been assigned to the methyl moiety of the methoxy group (3H, s, CH 3 ). As expected this signal appeared downfield. The chemical shift for the O-H group was observed at 8.57 and 7.92 ppm for L 1 and L 2 , respectively. The deshielding of this group and shifted downfield may be due to hydrogen bonding to the NMR solvent, which lead to decrease of the density of electrons on the hydroxyl group. Signals at 7.0-7.4 ppm were assigned to protons of aromatic ring. The chemical shift at 8.74 and 8.34 ppm in L 1 and L 2 , respectively assigned to -CH=N-(imine) protons.

Electronic Spectra and Magnetic Moment Measurements.
The UV-Vis spectrum of L 1 exhibits a high intense absorption peak at 376 nm, with a shoulder at 270 nm, assigned to n → * and → * , respectively [28]. The spectrum for L 2 exhibits a high intense absorption peak at 314 nm, with a shoulder at 261 nm, assigned to n → * and → * , respectively. The electronic spectra of the cobalt(II) complex for 1 and 2 exhibit high intense peaks at 269 and 270 nm, respectively, due to ligand field. The absorption bands at 390 and 414 nm for 1 and 2, respectively, attributed to 4 T 1 g (F) → 4 T 1 g (P) transitions. The spectra of the Co(II) complex for 1 and 2 exhibited band which can be attributed to 4 T 1 g (F) → 4 A 1 g (F) transition, corresponding to tetrahedral Co(II) complexes [29][30][31][32]. The observed room temperature magnetic moment values 3.91 and 3.87 B.M for L 1 and L 2 Co-complexes, respectively confirmed their tetrahedral geometry. The slightly lower magnetic moment might be due to the slight deviation from the regular tetrahedral geometry. The spectra of the Cd(II) complex for 1 and 2 exhibited bands assigned to ligand → * and L → M charge transfer [29,33]. The metal normally prefers tetrahedral coordination.

Antimicrobial Activity
The free Schiff-base ligands and their metal complexes were screened against Bacillus (G+) and E. coli (G−) to assess their potential as an antimicrobial agent by disc diffusion method. The measured zone of inhibition against the growth of various microorganisms is listed in Table 4. It is found that the ligand has higher antimicrobial activity than its metal complexes. This can be explained as follows. The biological activity of the Schiff-base ligand is related to the imine moiety, which plays a key role in the inhibition of the tested bacteria. The lower antimicrobial activity of the metal complexes compared with that in the ligand may be due to the strong interaction between the imine moieties and the metal ions. Such interaction will reduce the activity of the imine moiety in the inhibition.

Conclusion
In this paper, we have explored the synthesis and coordination chemistry of cobalt and cadmium complexes derived from the Schiff-base ligands L 1 and L 2 . The complexes were prepared by mixing at reflux 2 mmole of the Schiffbase ligand with 1 mmole of the appropriate metal chloride.
Complexes of the general formulae [M(L) 2 ]Cl 2 (where M = Co(II) and Cd(II); L = L 1 and L 2 ) were obtained. Physicochemical analysis indicated the formation of four coordinate dicationic metal complexes. Biological activities revealed that the ligands have higher antimicrobial activity than their metal complexes.