International Journal of Applied Science - Research and Review Open Access

Keywords

Schiff base ligands; Transition metals;2, 2'-Bipyridine; Isoniazid; Antibacterial activity

Introduction

Study of coordination chemistry of transition metal ions with various types of ligands has been enhanced by the current advancements in the fields of bioinorganic chemistry and medicine [1]. Through the years, Schiff bases have played a special role as chelating ligands in main group and transition metal coordination chemistry, due to their stability under a variety of oxidative and reductive conditions, and to the fact that imine ligands are borderline between hard and soft Lewis bases [2-4].

Schiff bases that arise from amino and carbonyl compounds are an important class of ligands that coordinate to metal ions through azomethine nitrogen and have been studied widely [5]. In azomethine derivatives, the (CN) linkage is necessary for biological activity; numerous azomethines have been reported to have marked antifungal, antibacterial, anticancer and antimalarial activities [6-14]. A large number of Schiff bases and their complexes have been studied for their interesting and significant properties, e.g. their ability to reversibly bind oxygen [15,16], catalytic activity in hydrogenation of olefins [17] photochromic properties [18] and complexing ability towards some toxic metals [19].

Mixed ligand complexes also play an important role in the biological field as exemplified by many ways in which enzymes are known to be activated by metal ions [20]. Schiff bases derived from heterocyclic compounds such as P- anisaldehyde and furan? 2?carbaldehyde have attracted an increased interest in the bioinorganic chemistry field [21-23]. Isoniazid (INH), also known as isonicotinylhydrazide (INH), is a known tuberculostatic agent used as a first-line agent for the prevention and treatment of both latent and active tuberculosis. It forms metal chelates with many bivalent ions having moderate to better biological significance [24,25]. Since the discovery of bipyridine at the end of the nineteenth century, the bipyridine ligand has been used extensively in the complexation of metal ions due to its strong redox stability and ease of functionalization [26,27]. The biological activities of the Schiff base and its mixed ligand complexes were also investigated herein.

Experimental

All used chemicals were purchased from Merck and Loba chemicals. All the melting points were determined on a digital melting point apparatus. Products were characterized by comparison of spectroscopic data (UV-Visible and FT-IR) and melting points with authentic samples. The wavelength of absorbance was determined by UV-Visible spectrophotometer [JASCO 503] using a quartz cuvette and ethanol as the reference. The IR spectrums were recorded on FT-IR spectrophotometer [JASCO, FT-IR/4100] Japan using dry KBr as the standard reference. The magnetic susceptibility of the complexes was measured at room temperature using a Gouy balance.

General Procedure for Synthesis of N-(4 methoxybenzylidene) isonicotinohydrazone Schiff base Ligand as the Primary Ligand, L1

INH (1.37 g, 10.0 mmol) was mixed with absolute ethanol (15 mL) and the mixture brought to the boil, producing a slurry. Barely sufficient additional ethanol was then added to give a homogeneous solution at reflux. P-anisaldehyde (1.22 mL, 10 mmol) was added drop-wise over 5 minutes and washed with 5 mL of ethanol. The reaction mixture was refluxed for 4 hours then allowed to cool slowly and to stand overnight. Finally, it produces a white crystalline solid which was filtered off and dried (Scheme 1).

Scheme 1: Synthesis of Schiff base ligand L1.

Experimental procedure for synthesis of mixed ligand complexes

To the warm methanolic solution (10 mL) of primary ligand L1 (0.255 g, 1 mmol), 10 mL warm methanolic solution (0.257 g, 1 mmol) of nitrate salt of metal Cu(II) and Ni(II) were added. After 30 minutes 5 mL warm methanolic solution of 2,2′?bipyridine (0.156 g, 1 mmol) was added drop-wise as a secondary ligand (L2) and the resulting mixture was refluxed for about 3-4 hours. The obtained precipitate was filtered, washed with methanol and dried under vacuum on anhydrous CaCl₂.

Antimicrobial activity

The ligand (L1) and its mixed ligand complexes with (L2) were screened for in vitro antimicrobial activity in DMSO against gramnegative Escherichia coli (E. coli) and gram-positive Bacillus cereus (B. cereus) strains by Kirby Bauer’s disc diffusion technique. A uniform suspension of test organism of 24 hours old culture was prepared in a test tube containing the sterile saline solution. Sterile nutrient agar was then added in each of the Petri dishes. The dishes were related to ensuring the uniform mixing of the microorganism in the agar medium which was then allowed to solidify. Sterile Whatmann filter paper discs were dipped in the solution of each compound and placed on the labeled plates. The DMSO was used as a control of the solvent. Kanamycin was used as a standard compound for comparison. Plates were kept in the refrigerator for half an hour for diffusion and incubated at 37°C for 24 hours. The diameter of the zone of inhibition around each disc was measured by scale and results were recorded in terms of mm. The observed data of antimicrobial activity of the L1, mixed ligand complexes and the standard drugs are given in Tables 4.

Results and Discussion

By the reaction of Cu(II) and Ni(II) with ligand (L1)and 2,2′? bipyridine (L2), complexes of the type [M(L1)(L2)]2+ were obtained. These complexes have a different color, stable at room temperature, insoluble in common polar solvent but soluble in DMSO and DMF, do not have the sharp melting point but decompose above 250°C. The measurement of molar conductivity at 10-3 M concentration carried out in DMSO at room temperature. The molar conductivity values show that the nitrate complexes were 1:2 electrolytes [28]. The analytical and physical data (color, melting point, molar conductivity and magnetic moment) of the complex are given in Table 1. For the Cu(II) and Ni(II) complexes the magnetic moments were 1.83 BM and 0.22 BM indicating paramagnetic and diamagnetic nature respectively. These values correspond to the square- planar geometry of both the mixed ligand complexes [29,30].

Symbol of Compounds	Complexes	M.P or De (Decomposition Temp) / °C	Solubility			µeff in B.M
			Color	DMSO & DMF	Molar conductance ohm-1 cm2mol-1
Ligand (L1)	C14H13N3O2	143	White	(+) ve	5
[Cu(L1)(L2)] (NO3)2	[Cu(C14H13N3O2)(C10H8N2)] (NO3)2	275 (De)	Brown	(+) ve	156	1.83
[Ni(L1)(L2)] (NO3)2	[Ni(C14H13N3O2)(C10H8N2)] (NO3)2	285 (De)	Yellow	(+) ve	149	Dia

Table 1 Analytical and physical properties data of L1 and its mixed ligand complexes with L2.

IR spectral studies

The IR spectrum of the primary ligand (L1) showed in Table 2 and Figure 1, exhibited characteristic bands at 1658.84.5 cm^-1 and 1598.69 cm^-1 assigned to ?(C=O) and ?(C=N) respectively Figures 1-4 [31]. The band at 1658.84.5 cm^-1 attributable to the ν(C=O) stretching vibration of the Schiff base ligand is shifted to another region 1628– 1637 cm^-1 in the complexes of Cu(II) and Ni(II) indicating coordination of the carbonyl oxygen to the metal ions (Figures 2-3). The presence of band at 528– 535 cm^-1 in the IR spectra of complex is due to M–O stretching vibration [28,32]. The azomethine band at 1598.69 cm^-1 of Schiff base was shifted to lower frequency ranging of 1571–1593 cm^-1 in the spectra of the complexes, confirming the participation of the azomethine nitrogen atom in the coordination of the metal ion. In the IR spectra of this complex, the new bands which appear in the 426– 434 cm^-1 region are assigned to the ν(M–N) vibration [28,32]. The strong sharp band observed at 1384 cm^-1 in the complex can be assigned to uncoordinated nitrate ion [28]. The band at 650 cm^-1 is assigned to ν(C=N) of pyridine for secondary ligand, L2. This band is shifted to 671-682 cm^-1 for mixed ligand complexes [33,34]. All of these IR data confirm ligands coordinated in Cu(II) and Ni(II) metal complexes through their O and N atoms respectively.

Symbol of Compound	Compound	ν (C=O)	ν (C=N)	ρ(Py) bending	V (M-O)	ν (M- N)
Ligand (L1)	C14H13N3O2	1658.84	1598.69
Ligand L2	C10H8N2		1642 m	650
[Cu(L1)(L2)](NO3)2	[Cu(C14H13N3O2)(C10H8N2)] (NO3)2	1636.35	1592.95	678.73	528.02	433.99
[Ni(L1)(L2)](NO3)2	[Ni(C14H13N3O2)(C10H8N2)] (NO3)2	1628.82	1571.41	681.68	534.71	426.92

Table 2 Key infrared bands (cm^-1) of L1 and its mixed ligand complexes with L2.

Figure 1: IR Spectrum of L1.

Figure 2: IR Spectrum of [Cu(L1)(L2)](NO₃)2.

Figure 3: IR Spectrum of [Ni(L1)(L2)](NO₃)2

Figure 4: UV- Visible Spectrum of the L1 and its Mixed Ligand Complexes.

UV- visible spectra

The UV-Visible spectra of the ligand L1 shows two bands at 281 and 347 nm which are assigned to π- π* and n-π* transition respectively. All the complexes showed the charge transfer transitions which can be assigned to charge transfer from the ligand to metal (LMCT) and vice versa. For complexes, absorption bands at the range of 367– 370 nm may be associated with L→M charge transfer and vice versa (M→L ) [29,30]. In the UV-region, the complexes showed absorption band at 269–270 nm (Figure 4) which may be assigned to π −π * transition. The spectra of all the complexes exhibiting bands assigned to π −π and M→L charge transfer, the metals normally prefer squareplanar geometry [29,30]. All observations were summarized in the Table 3.

Symbol of Compound	Compound	λ in nm	Assignment
Ligand (L1)	C14H13N3O2	283 333	π-π* n-π*
[Cu(L1)(L2)](NO3)2	[Cu(C14H13N3O2)(C10H8N2)] (NO3)2	270 367	π -π* C.T
[Ni(L1)(L2)](NO3)2	[Ni(C14H13N3O2)(C10H8N2)] (NO3)2	269 370	π -π* C.T

Table 3 UV- Visible spectrum of the Ligand L1 and its mixed ligand complexes with L2.

Antimicrobial screening result

The Schiff-base ligand L1 and its mixed ligand complexes with L2 reported here were evaluated for antibacterial activity against Escherichia coli and Bacillus cereus. The values of zone inhibition were measured in millimeter. The data of antibacterial activities of ligand L1 and its mixed ligand complexes with L2 are given in Table 4.

Antibacterial Zone of Inhibition (in mm)
Compounds	Gram Negative	Gram Positive
	Escherichia coli	Bacillus cereus
Kanamycin	32	35
Ligand (L1)	4	4
[Cu(L1)(L2)](NO3)2	20	22
[Ni(L1)(L2)](NO3)2	18	15

Table 4 Antibacterial screening results of Ligand L1 and its mixed ligand complexes with L2.

Based on the above results the expected structures of the Schiff base complexes may be represented as shown in the Figure 5.

Figure 5: The proposed geometry of M- mixed ligand complexes for L1 and L2 (where, M= Cu(II) and Ni(II)).

The inhibitory zone data reveals that the ligand L1, as well as its mixed ligand complexes with L2, shows good to moderate good antibacterial activity. The biological activity of Schiff base ligand arises from the presence of imine group which imports in elucidating the mechanism of transformation reaction in biological systems. However, mixed ligand complexes with L2 showed remarkable antibacterial activity as a result of chelation of metal with organic ligands synergistically increasing its effect [28,31,32,35]. The DMSO control did not show any antimicrobial activity against the tested bacterial strains whereas the tested compounds were found to be active.

Conclusion

The Schiff base ligand L1 and its Cu(II) and Ni(II) mixed ligand complexes with L2 were prepared and characterized using various spectral and other techniques. The IR spectral data indicated that Schiff base (L1) and 2,2′?bipyridine (L2) ligand coordinated to the metal ions bycarbonyl oxygen, N of azomethine and pyridine respectively indicating the square- planar geometry of the complexes. It has been observed that the mixed ligand complexes showed more antibacterial activity than Schiff base ligand L1. Although with respect to standard, the tested compounds were found to be moderately active.

Acknowledgement

We are grateful thank to Department of Chemistry, Rajshahi University , Rajshahi, Bangladesh, for providing necessary materials and we are also grateful thank to Department of Pharmacy, Rajshahi University, Rajshahi, for providing Antibacterial activities.

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