Synthesis, Characterization and Biological Activity of Mixed Ligand Complexes of Isatin

 

A. Anto Arockia Raj¹*, J.Vinnarasi¹, Dr. R. Venkataraman²

¹Department of Chemistry, St. Xavier’s College (Autonomous), Palayamkottai-627 002, Tamil Nadu, India.

²Department of Chemistry, Sri Paramakalyani College, Alwarkurichi – 627 412, Tirunelveli, Tamil Nadu, India

*Corresponding Author E-mail: antset.anto@gmail.com

 

Complexes of Mn (II), Co (II), Ni (II), Cu (II) and Zn (II) were synthesized using isatin and p-phenylenediamine ligands. The characterization and nature of bonding have been deduced from molar conductivity, FT-IR, UV-Visible and magnetic studies. The results obtained from these studies were used to arrive at the structures of the complexes. Molar conductance values indicate that all the complexes were non-electrolytic in nature. The study of electronic spectra along with magnetic moments suggests that these complexes have distorted octahedral geometry. Mixed ligand complexes have been screened for their invitro antibacterial (Proteus vulgaris, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Micrococcus and Salmonella typhi “H”) activities by zone of inhibition method. The copper complex possesses enhanced activity towards Escherichia coli.

 

 

 

INTRODUCTION:

Oxindole are endogenes compound with a long history and found in mammalian body fluids and tissues, ubiquitously distributed in the central nervous system, that have shown an extensive range of biological effects including antibacterial¹, antifungal², anticonvulsant³, antiviral⁴ and antiproliferative activity⁵. Metal complexes may act as a pro-drug. Metal complexes with Schiff bases of Isatin derivatives exhibited remarkable biological activity. Isatin and its derivatives have important biological activities like anticonvulsant³, antiviral⁴, insecticide, fungicide, anti-inflammatory⁶, analgesic⁷, anti-tubercular⁸, antibacterial¹ and anti-depressant⁹. Isatin is present in the brain and other tissues in human and the oxindole moiety is also found in natural products in some plants.

 

3-thiosemicarbazones of Isatin were previously found to be active in the treatment of smallpox¹⁰. Copper (II), nickel (II) and zinc (II) Isatin-hydrazone complexes had their potential activity as antitumor agents evaluated on diverse human leukemic cells¹¹.

 

Metal complexes may act as a pro-drug. Metal complexes with Schiff bases of Isatin derivatives exhibited remarkable biological activity. A considerable number of metal complexes are now to possess antitumor activity ¹². Isatin metal complexes exhibited invitro antibacterial against E.coil, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus anthracis, Staphylococcus faecalis, Proteus mirabilis and Entrobacter sp.

 

Keeping these facts in mind, in the present work, a series of M(II) complexes of metal ions like Mn²⁺, Co²⁺, Ni²⁺,Cu²⁺ and Zn²⁺ ions with isatin and p-phenylenediamine ligands have been synthesized and characterized.

 

MATERIAL AND METHODS:

All chemicals used in the present work, viz., Isatin, p-Phenylenediamine (PPD), metal salts and solvents were of analytical reagent(A.R.) grade. The melting points were determined by open capillary tube method. The electronic spectra of metal complexes in methanol were recorded in the range of 200nm-800nm on the Shimadzu spectrophotometer. FT-IR spectra of mixed ligand complexes were recorded using KBr discs in the range of 400-4000cm^-1 on a Shimadzu spectrophotometer.

 

Preparation of metal Complexes:

The synthesis of metal-mixed ligand complexes are presented in Scheme1. The ethanolic solution of Isatin (0.001M) and ethanolic solution of PPD (0.001M) were mixed slowly to a solution of metal (II) chloride (Mn, Co, Ni, Cu and Zn) (0.002M) in ethanol. The mixture was stirred using magnetic stirrer for 2 hours at 60˚C. After cooling the precipitated complex was filtered, washed with absolute ethanol and dried.

 

Antibacterial activity determination:

We have recorded the antibacterial activity of mixed ligand complexes against micro organism, using ceftazidime as standard and Disc Diffusion Method was adopted, run plate for 24 hours.

 

Preparation of test Sample:

10 mg of each sample was taken and fractions were separately dissolved in 1 μl water to obtained corresponding stock solution of 10 μl.

 

Disc Diffusion Method:

The pathogenic culture is spread in sterile Muller Hinton Agar Plates (MHA) medium. Whatman no. 1 filter paper is used to prepare disc with the help of punching machine. The discs are sterilized in autoclave and loaded with suitable concentration of test extracts. The test extract loaded discs are placed in bacterial culture lawn on nutrient agar plates. Then the plates are incubated at 37º C for 2-3days. After incubation the zone of inhibition is measured and recorded.

 

RESULTS:

The electronic absorption spectra of isatin metal complexes in the range of 200nm-800nm in methanol were recorded on the Shimadzu spectrophotometer. The yield of the complexes, melting points and their electronic absorption spectra, were tabulated in table-1.Isatin has the following stretching frequencies as ν_{- NH}  = 3190 cm^-1,ν_{- CO} = 1740 & 1620cm^-1,ν_{- NH}   = 1400-1100 cm^-1 (bending vibration). IR frequencies (cm^-1) for metal complexes were shown in table-2.From the IR data we conclude that the metal binds with both the nitrogen atom of p-phenylenediamine (-NH₂ ) and -C = O of Isatin. The IR absorption for the M-N, M-X and M-O also confirm the structure of the complexes. The low molar conductance values recorded that indicate all the complexes are non-electrolytic in nature. The µ_eff values of Mn (II), Co (II), Ni (II) and Cu (II), revealed that these are paramagnetic and Zn (II) complex is diamagnetic. The magnetic moment value of Cu (II) complex 1.78 BM suggests a distorted octahedral geometry^{13, 14} around the metal ion. The magnetic moment for Co (II) complex is 4.72 BM indicates the high spin six-coordinated octahedral arrangement^{15, 16} of ligand molecules around the metal ion. The Ni (II) complex has magnetic moment value of 2.8 BM indicating a spin-free octahedral^{17, 18}configuration. The Zn (II) complex is found to be diamagneticas expected for d¹⁰ configuration.

 

The antibacterial activity of the synthesized metal complexes against Proteus vulgaris, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Micrococci and Salmonella typhi “H” micro organisms by zone of inhibition studies, revealed that copper (II) complex was found to have higher activity against Staphylococcus aureus compared to other micro-organisms. The maximum activity was observed at 10μl concentration by zone of inhibition studies. The metal complexes of manganese and zinc are found to possess activity against Klebsiella pneumonia and nickel, copper and zinc complexes are found to have activity against Escherichia coli.

 

Illustrations:

 

Scheme1

 

Table 1:-Electronic absorption spectra and physical properties of metal-mixed ligand complexes

S.No	Complexes	λmax(nm)	Colour	M.Point (0C)	Percentage of  Yield(%)
1	(IP)Mn	301	Orange red	250	84
2	(IP)Co	305	Reddish brown	271-274	96
3	(IP)Ni	301	Yellowish brown	220-222	91
4	(IP)Cu	305	Black	240	85
5	(IP)Zn	300	Brown	254-260	85

 

Table 2:-IR spectral frequencies (cm ^-1) for Metal Complexes

S.No	Complexes	ν –NH	ν –CO	ν M-O	ν M-N	ν M-X
1	(IP) Mn	3124	1725 1597	425	485	368
2	(IP) Co	3150	1689 1612	425	486	375
3	(IP) Ni	3250	1705 1612	425	509	364
4	(IP) Cu	3200	1728 1612	460	455	360
5	(IP) Zn	3217	1728 1765	655	540	372

 

Table 3:-Conductivity and Magnetic Moment measurements

S.No	complexes	Molar conductance  ohm-1 cm2mol-1	µeff  (B.M)	Magnetic behavior
1	(IP)Mn	13.62	5.19	Paramagnetic
2	(IP)Co	11.7	4.72	Paramagnetic
3	(IP)Ni	11.2	2.8	Paramagnetic
4	(IP)Cu	12.5	1.78	Paramagnetic
5	(IP)Zn	10.6	-	Diamagnetic

(IP)Mn -Manganese Complex,(IP)Co – Cobalt Complex, (IP)Ni – Nickel Complex, (IP)Cu – Copper complex and(IP)Zn – Zinc Complex

Fig. 1

 

DISCUSSION:

Based on conductivity, magnetic moment, IR, and electronic studies, the structure of the complexes may be a distorted octahedral geometry. Figure 1 represents the structure of the complexes. The Cu (II) complex has higher activity against Escherichia coli.

 

REFERENCES:

1.        Daisley R.W and Shah V K. J. Pharm. Sci., 73; 1984: 407.

2.        Piscopo B, Diumo M V, Godliardi R, Cucciniello M and Veneruso G.Bol. Soc. Ital. Sper. 63; 1987:827.

3.        Gursoy A, Karali N, Buyuktimakin S, Demirayak S, Ekinci A C and  Ozer H, Farmaco.39; 1996: 5072.

4.        Pandeya S N, Sriram D, Nath G and DeClercq E. Eur. J. Pharm. Sci. 9;1999:  25-31.

5.        Silva JF, M Garden S J and Pinto A C.J. Braz. Chem. Soc. 12;2001:273.

6.        Alagarsamy V and Ramseshu K V. Pharmazie. 58; 2003: 233-36.

7.        Sridhar S K and Sreenivasulu M. Indian drugs. 38;2001: 531-34.

8.        Tran V H, Nguyen Q D and Le N V, Tap. Chi. Dou Hoc. 8; 2002:15-17.

9.        Popp F D, Parson R and Donigan B E. J. Pharm. Sci, 69; 1980: 1235-1237.

10.     Ferrari M B, Pelizzi C, Pelosi G and Rodríguez-Argüelles C. Polyhedron. 21;2002: 2593.

11.     Rodrigues-Arguelles M C, Ferrari M B, Bisceglie F, Pelizzi C, Pelosi G, Pinelli S and  Sassi  M. J. Inorg. Biochem. 98; 2004: 313.

12.     Kosturiak A, Polavka J, Valko L, Slama J,Gruskova A and Miglierini M J. Magn. Mater. 153; 1996: 184.

13.     Figgis B N and Lewis J.  Modern coordination chemistry, Wiley Interscience, New York. 1960.

14.     Sabastiyan A and Venkappayya D. J. IndianChem. Soc.67;1990:584

15.     Konig E. Structure and bonding. SpringerVerlag, Berlin. 1971.

16.     Rana A K and Shah J R. Indian J. Chem. A20; 1981:142.

17.     Cotton F A and Wilkinson G. Advanced inorganic chemistry, Wiley Interscience, New York. 1962.Figgis B N, An introduction to ligand fields. Wiley Eastern, New Delhi. 1976.

 

 

 

Accepted on 01.08.2013         © RJPT All right reserved