Studies on Synthesis, Characterization and Biological Activity of Salicylic acid Containing Mixed Ligand Complexes of Zn(II)ion

 

Md. Zakirul Islam¹, Shejutyaktar¹, Md. Shiraj-U-Ddaula¹,Md. Masuqul Haque¹,

Md. Faruk Hossen¹, Md. Akhter Farooque¹ and Md. Kudrat-E-Zahan²*

¹Inorganic Research Laboratory, Department of Chemistry, University of Rajshahi, Rajshahi-6205, Bangladesh.

²Dept. of Chemistry, Faculty of Science, Rajshahi University, Rajshahi-6205, Bangladesh.

*Corresponding Author E-mail: kudrat.chem@ru.ac.bd

The flexibility of zinc coordination, which allows different coordination modes and fast ligand exchange, has been suggested to be one key catalytic feature of the zinc ion which makes it an invaluable metal in biological catalysis. Mixed ligand Complexes of the Schiff base Zn(II) metals sources have been synthesized and characterized using FTIR,UV-visible spectra, metal estimation, TLC and magnetic moments measurements. Antimicrobial activity of the prepared complexes were measured as resistance to antimicrobial agents is emerging in a wide variety of nosocomial and community-acquired pathogens. The results of the study infers though zinc and salicylic acid individually demonstrated potential biological activities, however, when they were in the form of complex the biological activities were found inferior.

 

 

1. INTRODUCTION:

Zinc is relatively abundant in biological materials. Approximately 10% of the total human proteome have been identified to bind with zinc in vivo from a bioinformatics investigation, [1] and they play very crucial roles in all forms of life [2-6].The different coordination modes and fast ligand exchange of zinc coordination has been suggested to be one key catalytic feature of the zinc ion which makes it an invaluable metal in biological catalysis [7]. However, partly because of the well-known difficulties for zinc to be characterized by spectroscopy methods, evidence for dynamic nature of the catalytic zinc coordination has so far mainly been indirect.

 

Biological activity describes the beneficial or adverse effects of a drug on living matter. Metal coordination complexes have been widely studied for their antimicrobial activity [8]. Further, a number of Zn(II) complexes with variety of ligand show antimicrobial, anticarcinogenic, veterinary, anthelmintic, and poliovirus inhibitor activities [9–12]. So, there remain scope for synthesis of new complexes of Zn(II) and substantial improvement of their clinical utility.

 

Salicylic acid was targeted as one of ligand because (i) they display wide variety of chemotherapeutic properties such as antibacterial and antiphrastic activity [13-14] and (ii) they possess a wide variety of coordination modes [15-16] which can be useful in the construction of organic frameworks. Moreover, It has been suggested that the coordination of carboxylate to zinc could be dynamic in the catalytic process, known as carboxylate shift, which has been suggested to be important in the function of zinc enzymes [17-21].

 

Our group has previously studied electronic properties of N₂O₄schiff base ligand containing metal complexes of Cd(II), Pd(II), Hg(II) and Zr(IV) [22-24]. In this contest, we report here the synthesis and characterization of zinc(II) complexes containing salicylic acid and their biological activity.

 

2. EXPERIMENTAL:

2.1 Measurements and materials

Electronic spectra were recorded on a Thermoelectron Nicolet evolution 300 UV-Vis spectrophotometer. All chemicals were commercial products and were used as supplied.

 

 

2.2 Synthesis of [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)]:

About 2.6975g of Zinc sulfate monohydrate ZnSO₄.H₂O was dissolved in 5ml of distilled water, ethanol solution of 2.0571g ofAnthranilic acid and 2.0718g of Salicylic acid were taken in 2:1:1 molar ratio. The three solutions were mixed, stirred for 2 hours at ambient temperature and allowed to stand for 24 hour. A white precipitate was observed. The precipitate was filtrated off on a filter paper and dried in a vacuum desiccator over anhydrous CaCl₂.

 

Figure 1:  Structure of Complex [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)]

[Zn(C₁₂H₈N₂)(C₇H₄O₃)] and [Zn(SCN)₂(C₇H₄O₃)] were prepared followingthe above procedure. Where,C₇H₄O₃^2- = salicylate ion, NH₂.C₆H₄.COO^- = anthranilate, and C₁₂H₈N₂ = 1, 10 – phenanthroline

 

3. RESULTS AND DISCUSSION:

3.1 Physical properties of the complexes:

Some physical properties of the complexes are shown in the (Table 1). The molar conductance values are in the region range 0.2 to 1.5 Ω^‑1_cm² _mol^-1, suggesting that all the synthesized complexes are non-electrolyte. The observed values of effective moment (µ_eff) of the complexes at room temperature shown that all the complexes are diamagnetic except [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)] which is paramagnetic in nature. The melting point ranges from 230-255. The percentage of zinc obtained by metal estimation were found good agreement with calculated values.

 

3.2 Infrared spectra

IR spectral data are shown in (Table 2). The strong bands obtained at 3300, 1615 and 16320 cm^-1 due to υ (-NH), υ (C-O) and υ (C-H) respectively. The presence of metal ligand bonding is evident from the appearance of υ (M-O) and υ (M-N) at around 750 and 390 cm^-1 respectively in the spectra of the complexes.

 

3.3 Electronic spectral studies

The observed electronic spectrum of [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)] in ethanolis shown in Figure 2. The results showed that after the complex formation through carboxylate group the absorbance maxima at 340 cm^-1 which is due to salicylate ion shifted towards lower wave length.

 

4. ANTIBACTERIAL SCREENING:

In testing antibacterial activity of these complexes we used more than one test organism to increase the chance of detecting antibiotic principles in the test materials. The sensitivity of microorganisms to antibiotics and other antimicrobial agents can be determined by disc diffusion assay [25,26]. Antibacterial activities of complexes

 

A = [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)],

B= [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)],

C = [Zn(SCN)₂(C₇H₄O₃)], were observed A total of six Gram positive and Gram negative bacteria were used in this antimicrobial screening. Complexes A-C (30mg/disc) were prepared by dissolving with dimethyl sulfoxide (DMSO).

 

To compare the antibacterial activity, kanamycin (30mg/disc) was used as standard antibiotic. As a negative control, a blank disc impregnated with solvent, DMS followed by drying off was used. 

 

4.1 Minimum inhibitory concentration (MIC) assay

The minimum inhibitory concentrations (MIC) were determined by serial dilution technique [Table 3] (26,27) in the presence of standard Kanamycin. bacterial inocula were prepared at 5×10⁶ - 5×10⁷cfu/ml. Final adjustment were made using optical density measurement for bacteria (absorbance 0.05 at a wavelength of 660 nm).

Table 1: Physical properties of complexes

Compounds	Colour	Melting point (±50C)	Molar conductance Ohm -1cm2mol-1	µeff (B.M)	%Zinc
					Calculated	Found
[Zn(NH2.C6H4.COO)(C7H4O3)]	White	250	1.058	2.10	19.20	19.02
[Zn(C12H8N2)(C7H4O3)]	White	255	1.210	-	17.04	16.88
[Zn(SCN)2(C7H4O3)]	White	230	1.486	-	20.47	20.27

Where, C₇H₄O₃^2- = salicylate ion, NH₂.C₆H₄.COO^- = anthranilate, and C₁₂H₈N₂ = 1, 10 –phenanthroline

 

 

Table 2: Major IR spectral data (cm^-1) with their assignment and electronic spectral data of the Schiff base complexes

Where, C₇H₄O₃^2- = salicylate ion, NH₂.C₆H₄.COO^- = anthranilate, and C₁₂H₈N₂ = 1, 10 – phenanthroline

 

 

Figure 2: Electronic absorption spectra of (A) Salicylic acid (B) Antralinic acid (C) [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)] in ethanol.

 

 

Table 3: Antimicrobial activity of complexes and standard Kanamycin

Complexes A = [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)], B = [Zn(NH₂.C₆H₄.COO)(C₇H₄O₃)], C = [Zn(SCN)₂(C₇H₄O₃)],and K = Kanamycin.

 

Table 4: Minimum inhibitory concentrations (MIC) of complexes and standard Kanamycin

 

 

The minimum inhibitory concentrations (MIC) of complex A against Bacillus caerius, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Shigelladysenteriae and Shigella Sonnei were found to be 2, 4, 8, 8, 2 and 4mg/ml. respectively; that of 32, 64, 32, 32, 32 and 64 mg/ml, respectively for complex B; that of 8, 4, 8, 2, 8 and 4mg/ml, respectively for complex C, respectively [Table 4].

 

It is concluded all the tested complexes possesses very high antimicrobial activity with a minimum inhibitory concentration. Further investigations are required to explore the exact mechanism of their cytotoxic properties which may be helpful for exploring new type of potent cytotoxic agent(s) with the hope of adding novel and alternative chemotherapeutic agent(s) in clinical implications.

 

5. REFERENCES:

1.        Andreini, C.; Banci, L.; Bertini, I.; Rosato, A.J. Proteome Res., 5, 196–201 (2006).

2.        Odell, B. L. Nutr. Re V., 50 , 48–50(1992).

3.        Lipscomb, W. N.; Strater, N. Chem. Re V , 96 , 2375–2433(1996).

4.        Christianson, D. W.; Cox, J. D. Annu. Re V. Biochem.68, 33–57(1999).

5.        Parkin, G. Chem. Re V ,104, 699–767 (2004).

6.        Anzellotti, A. I.; Farrell, N. P. Chem. Soc. Re V.,37,1629–1651(2008).

7.        McCall, K. A.; Huang, C. C.; Fierke, C. A. J. Nutr. 130, 1437S–1446S (2000).

8.        Kamalakannan, P. and D. Venkappayya, J. biochem., 21; 90: 22-37(2002)

9.        S. Chandra, S. Parmar, and Y. Kumar,BioinorgChem and App., 2009, 6(2009).

10.     M. I. Zaidi, F. H. Wattoo, M. H. S. Wattoo, S. A. Tirmizi, and S. Salman,A. J. Microbio R, 6, 24, 5134–5137 (2012).

11.     S. S. Kukalenko, B. A. Bovykin, S. I. Shestakova, and A. M. Ometchenko, Rus Chem Rev, 54, 7, 676 (1985).

12.     Tamm, R. Bablanian, M. M. Nemes, C. H. Shunk, F. M. Robinson, and K. Folkers, J. Exp Med, 113, 625–656(1961).

13.     Wu, K. K. Anti-Inflammatory Anti-Allergy Agents Med. Chem. 6, 278 (2007).

14.     Thomas, M. R. In Kirk-Othmer Encyclopedia of Chemical Technology; Wiley: Hoboken, NJ, 2006.

15.     Yin, M.-C.; Ai, C.-C.; Yuan, L.-J. J. Mol. Struct. (THEOCHEM) 33, 691 (2004).

16.     Song, J.-F.; Chen, Y.; Li, Z.-G.; Zhou, R.-S.; Xu, X.-Y.; Xu, J.-Q.; Wang, T.-G. Polyhedron26, 4397(2007).

17.     Robert, V.; Lemercier, G.J. Am. Chem. Soc.,128,1183–1187 (2006).

18.     Sousa, S. F.; Fernandes, P. A.; Ramos, M. J.J. Am. Chem.Soc.,129, 1378–1385 (2007).

19.     Kimura, E. Acc. Chem. Res.,34, 171–179 (2001).

20.     Sousa, S. F.; Fernandes, P. A.; Ramos, M. J.Biophys. J.88, 483–494 (2005).

21.     Szeto, M. W. Y.; Mujika, J. I.; Zurek, J.; Mulholland, A. J.; Harvey, J. N.J. Mol. Struct.: Theochem898, 106–114 (2009).

22.     Md.Kudrat-E-Zahan and Hiroshi Sakiyama, Asian Journal of Research in Chemistry, 7(13): 278 (2014).

23.     Md.Anarul Islam, Roksanakhatun, M.Monirul Islam and Md. Kudrat-E-Zahan, Asian Journal of Research in Chemistry, 7(2): (2014).

24.     Md. Kudrat-E-Zahan, and Hiroshi Sakiyama, Asian Journal of Research in Chemistry, 6(11): 1072 (2013).

25.     W. Bauer, W. M. M. Kirby, J. C. Sherris, and M. Turck, Am. J. Clin. Pathol. 44, 493 (1966).

26.     R Schwalbe, L Steele-Moore, A C Goodwin: CRC Press, 53-79, (2007)

27.     Md. Kudrat-E-Zahan and Hiroshi Sakiyama, Asian Journal of Research in Chemistry, 7(13): 278 (2014).

 

 

 

 

Received on 18.08.2014         Modified on 15.11.2014

Accepted on 04.01.2015         © AJRC All right reserved