INTRODUCTION:

Sulpha drugs show important biological activity e.g mechanism of action is based on the competitive antagonism of PABA (p-amino benzoic acid) and the sulfanilamide (Obaleye, 1996). They are a group of compounds used for eliminating a wide range of infections in human and other animal systems. Many chemotherapeutically important sulpha drugs like sulphadiazine, sulphathiazole, sulphamerazine and so forth, possess SO2NH moiety which is an important toxophoric function (Jain and Singh, 2006). The heterocyclic compounds with both sulphur and nitrogen atoms in the ring system have also been used in the synthesis of biologically active complexes. It is however noteworthy that the biological activity gets enhanced on undergoing complexation with metals. The complex formation between metal ions and sulpha drugs has attracted much attention recently due to their biological importance.

METHODS AND MATERIALS:

Detection of the Antibacterial Activity:

The antibacterial activities of the ligands and metal complexes were done by the well diffusion method described by Colins (1980), Obaleye and Famurewa (1989). The nutrient agar medium (Peptone beef extract NaCl and agar-agar) and 5mm diameter paper discs (whatman No 1) were used. The compounds were dissolved in DMSO in 50 and 100ppm concentration. The filter paper discs were soaked in different solution of the compounds, dried and then placed in the Petri dishes previously seeded with the test organisms (E.coli, S.aureus, K.pneumonia) obtained from Microbiogical laboratory, Lucknow. The plates were incubated for one to three days at 37°C and the inhibition zone around each disc was measured in mm using Zone Reader. The average zone of inhibition in millimeter was determined from the readings taken in triplicate. DMSO was used as a control.

RESULT AND DISCUSSIONS:

Magnetic susceptibility:

Magnetic moments of each of the complexes are given in Table 1. Examination of these data reveals that magnet moment of 0.4 B.M for Cd (II) complex confirms that the complex is essentially diamagnetic. The magnetic moment found for Co (II), Cu (II), Ni (II), Mn (II) complexes are 4.54, 2.24, 3.85 and 4.87 B.M respectively these values suggest octahedral geometry which is in good agreement with data of electronic transition. Fe (III) complex has magnetic moment of 5.75 BM the value is approximate to that found in literature for d5 high spin complex (Obaleye, 1996).

Table 1: Magnetic susceptibility and Conductivity Measurement of Sulphadimidine metal complexes.

Complexes	Magnetic moment μ (B.M)	Conductivity Ohm-1 cm2 mol-
[Co(SAD)2Cl2]	4.56	3.6
[Cu(SAD)2 (H2O)2]	2.24	4.8
[Ni(SAD)2Cl2]H2O	3.84	5.2
[Mn(SAD)2Cl2]	4.86	3.6
[Cd(SAD)2Br2]	0.5	3.4
[Fe(SAD)3](H2O)3	5.72	4.6

Antibacterial Screening:

The antibacterial screening data are presented in Table 2, where values are mean of 3 replicates ± SD. Values carrying superscripts different from their parent ligand for each microorganism are significantly different (P<0.05).

Table 2: Antibacterial screening data of the ligands and their complexes.

	E. coli		S. aureus		K. Pneumonia
Ligand/Complexes	50ppm	100ppm	50ppm	100ppm	50ppm	100ppm
SAD	14 + 0.97a	20 + 1.20a	14 + 0.98a	16+ 1.11a	12 + 1.00a	18 + 0.96a
[Co(SAD)2Cl2]	18 + 1.11b	20 + 1.23a	15 + 1.04a	18 + 1.18a	12 + 0.98a	20 + 1.06a
[Cu(SAD)2 ( H2O)2]	16 + 1.12b	25 + 1.27b	15 + 1.08a	17 + 1.23a	15 + 1.01a	23 + 1.50b
[Ni(SAD)2Cl2 ]H2O	19 + 1.19b	23 + 1.85a	17 + 1.11a	22 + 1.40b	22 + 1.05b	21 + 1.60a
[Mn(SAD)2Cl2]	16 + 1.08b	22 + 1.90a	15 + 1.12a	21+ 1.08b	22 + 1.05b	24 + 1.95b
[Cd(SAD)2Br2]	19 + 1.31b	23 + 1.92a	17 + 1.18a	20+ 1.88a	22 + 1.31b	20 + 1.09a
Fe(SAD)3(H2O)3	20 + 1.84b	25 + 2.00b	18 + 1.31a	25+ 1.89b	21 + 2.00b	16 + 0.86b

The antibacterial activities of the ligands and their complexes were tested on Gram positive bacteria: Staphylococcus aureus and Gram negative bacteria: Klebsiella pneumonia and Escherichia coli. The antibacterial activities of the complexes were evaluated by measuring inhibition zone observed around the tested materials.

The increase of the zone of inhibition for metal complexes when compared with corresponding ligands as shown in Table 3 is an indication that the metal complexes are able to decrease the population of bacterial species. It is also an indication that the metal complexes are more effective than their corresponding ligand. The results are in agreement with the finding of Casanova et al (1993). They reported that metal chelates of sulfa drugs were more bacteriostatic than the drugs themselves. This is significant in the light of increasing bacterial resistance to antibacterial drugs. The chelation increases the lipophilic nature of the central atom which subsequently favour its permeation through the lipid layer of the cell membrane (Chaudhary and Singh, 2002). The chelation theory accounts for the increased activities of the metal complexes. The chelation reduces considerably the polarity of the metal atom mainly because of the partial sharing of its positive charge with the donor group and possible p electron delocalization within the whole chelating ring (Baluja et al (2006). The increase in lipophilic character of these complexes seems to be responsible for their enhanced antibacterial activity. It may be suggested that these complexes deactivate various cellular enzymes, which play a vital role in various metabolic pathways of these microorganisms.

It has also been proposed that the ultimate action of the toxicant is the denaturation of one or more proteins of the cell, which as a result, impairs normal cellular processes. Since the metal complexes inhibit the growth of microorganisms, it is assumed that the production of enzymes is being affected and hence the microorganism is unable to utilize the food for itself or the intake of nutrient in suitable forms decrease and consequently the growth of microorganism is arrested, while the higher concentration proves fatal (Fahmi et al (1993). The result shows that most of the compounds possess higher inhibitory activity against the bacterial species at 100ppm concentration than at 50ppm concentration

CONCLUSION:

In all the complexes, the ligand is bidentate, sulphadimidine coordinates with metal ions either through pyrimidine N and sulfonyl N atom or through NH₂ group and oxygen atom of the sulphoxide. All the complexes have octahedral geometry except Cd (II) sulphadimidine which has tetrahedral geometry. The free ligand and its respective metal chelates were screened against bacteria to assess their potential as antimicrobial agent. The complexes showed greater activity against the three micro-organisms when compared to parent compound. The stability constant data revealed the possibility of using the ligand as antidote or chelating agent for medical treatment of metals overload or poisoning.

REFERENCES:

1. Obaleye JA (1996): Nigerian Journal Pure and Applied Sciences, 11: 441.

2. Jain M, Singh RV (2006): Bioinorg Chem Appl, ID13734, 1.

3. Casanova J, Alzuet G, Ferrer S, Borras J, Garcia–Granda S and Perez–Carreno E (1993): J Inorg Biochem, 51, 689.

4. Chaudhary AS and Singh R (2002): Biol Soc Quim, 47, 203.

5. Baluja S, Solanke A and Kachhadia N (2006): J Iran Chem Soc, 4, 312.

6. Fahmi N, Jadon SCS and Singh RV (1993): Phosphorus, Sulfur Silicon Relat Elem, 81, 133

Received on 25.09.2020 Modified on 26.10.2020

Research J. Science and Tech. 2021; 13(1):41-43

DOI: 10.5958/2349-2988.2021.00007.3