SYNTHESIS, SPECTRAL STUDIES AND ANTIMICROBIAL SCREENING OF SOME TRANSITION METAL COMPLEXES WITH SUBSTITUTED ACETOPHENONE THIOSEMICARBAZONE

SYNTHESIS, SPECTRAL STUDIES AND ANTIMICROBIAL SCREENING OF SOME TRANSITION METAL COMPLEXES WITH SUBSTITUTED ACETOPHENONE THIOSEMICARBAZONE

Shyam Kumar Meena* and Meenakshai Jain

Department of Chemistry, Govt. P.G. College Dholpur, Rajasthan, India.

Department of Chemistry, University of Rajasthan, Jaipur, Rajasthan, India.

ABSTRACT: Complexs of Fe, Cu and Zn have been prepared by reacting metal chloridesulphate with p-hydroxyacetophenone thiosemicarbazone, p-fluoroacetophenone thiosemicarbazone, p-bromoacetophenone thiosemicarbazone as ligands and their complexes were screened for their IR, NMR, and antifungal and antibacterial studies. . Acetophenone thiosemicarbazone ligands were prepared by the reaction of substituted acetophenone with thiosemicarbazone in the presence of hot ethanol. All the transition-ligands 1:2 complexes have been isolated in the solid state, are stable in air, and characterized on the basis of their elemental and spectral data. They were found to be active against influenza, protozoa, small pox, and certain kinds of tumor.  Their metal complexes were used, in various biological systems, polymers, dyes, anti-inflammatory, analgesic and anti-oxidative action. The Schiff bases and their metal complexes were used in various biological activities such as antimicrobial, antifungal, antiviral, insecticides, and antitumor activity.

activity.

INTRODUCTION:The Schiff^’s base and their metal chelates is effective anticancer, antitumor, anti tuberculosis, antipyretic agent as well as anti fertility. Schiff^’s base possess industrial application as catalysts, dyes, fiber, perfumes an aesthetic, plant growth inhibitors cosmetics corrosion inhibitors, oxygen absorbents, polymers, lubricating agents, for removing metal impurities of oil and drying accelerators.^1-7.

The metal complexes with Schiff^’s base derived from chalcone and thiosemicarbazone have been extensively studied and have exhibited medicinal properties ⁸. Copper (II) complexes have found possible medicinal uses in the treatment of many diseases including cancer.⁹ Semicarbazone of various transition metals have been investigated owing to their coordination capability and pharmaceutical activity^10-12. Schiff^’s bases make them more effective in attaining high coordination structure¹³. Since Domagk’s original report¹⁴ on the anti-tubercular activity of thiosemicarbazones, the number of papers on the pharmacology of these compounds has expanded dramatically. They have also been found to be active against influenza ^15, small pox ¹⁶, and certain kinds of tumor¹⁷ and have been suggested as possible pesticides and fungicides ¹⁸. Their activity has frequently been thought to be their ability to chelate with tracer metal.

MATERIALS AND METHODS:

The transition metal complexes of substituted acetophenone thiosemicarbazone were derived from the reaction an aqoues solution of metal salt. Acetophenone thiosemicarbazone ligands were prepared by the reaction of substituted acetophenone with thiosemicarbazone in the presence of hot ethanol. All the transition-ligands 1:2 complexes have been isolated in the solid state, are stable in air, and characterized on the basis of their elemental and spectral data.

Thiosemicarbazone ligands behave as bidentate ligands by coordinating through the Sulfur of the isocyanides group and nitrogen of the cyanide residue.The acetophenone thiosemicarbazone ligands and their transition complexes have been screened for their IR, NMR, and antifungal and antibacterial studies.

Synthesis of substituted acetophenone thiosemicarbazones (2a-d) Table-1

P-Fluoroacetophenonethiosemicarbazone

P-Fluoroacetophenonethiosemicarbazone was prepared after the method of compainge and Archer.¹⁹ F- Fluoroacetophenone (2.52 ml, 20 mmol) was dissolved in ethanol (50ml) in a round bottomed flask and heated on a water bath for 5-10 minutes. This hot solution was treated with a hot ethanolic solution (50 ml) of thiosemicarbazone (1.80g, 20mmol) and refluxed for 4-5 hrs on water bath using reflux water condenser. The change in color of solution indicates the formation of P-Fluoroacetophenone thiosemicarbazone (2a-d). on cooling the reaction mixture the cream coloured product crystallized out which was filtered off under water suction and further recrystallized from absolute ethanol and finally dried over anhydrous cacl₂ in a vacuum desiccators.

FIG: 1

FIG: 2

Synthesis of 4-subsitituted aceto phenone thio semicarbazones metal complexes (3a-d):

Bis (F-Fluoroacetophenonethiosemicarbazone) iron (II)

P-Fluoroacetophenonethiosemicarbazone (1.816g, 8mmol) was dissolved in ethanol (20ml) and heated on a water bath. This solution was slowly treated with an aqueous solution of metal salt Feso₄.6H₂0 (0.6076g, 4mmol) in 2:1 molar ratio with string. Reaction mixture was refluxed on water bath for 1-2 hrs and left overnight to yield the crystalline dark green coloured crystals, which was filtered off under suction washed with water till filtrate become colourless. The product was finally washed with dilute ethanol and dried over fused cacl₂ in vacuum desiccators.

FIG: 3

BIS(PCHLOROACETOPHENONETHIOSEMICARBAZONE) CUPPER (II) (3A-D) TABLE-2

FIG: 4

BIS(PFLUOROACETOPHENONETHIOSEMICARBAZONE) IRON (II) (4A-D) TABLE-3

RESULTS AND DISCUSSION:

Substituted acetophenones

In the IR spectra of substituted acetophenone a sharp absorption band from 1780-1650 cm_1 is observed due to acetophenone >C=O and at 1620 cm-1 due to >C=C< stretching vibration.

Substituted acetophenonethiosemicarbazones

Formation of substituted acetophenones thiosemicarbazone was confirmed by the disappearance of absorption band from  1720-1650 cm-1 due to carbonyl group (>C=O) and appearance of new absorption bands from 3400-3350,3320-2800,and 1200-1045 cm_1 assinged to –NH₂, -NH and >C=S stretching vibrations, respectively in their IR spectra. Similarly, in 1H NMR spectra an additional broad singal at δ 2.85 ppm appears due to –NH₂ and a sharp singlet at δ 10.82 ppm due to –NH- protons are observed which further support the formation of compounds.(2a-d).

Metal complexes of substituted acetophenone thiosemicarbazone

In the IR spectra of the ligands and complexes only selected absorption peaks are discussed, which are important for ascertaining the doner sites of ligands. In the in spectra of metal complexes of substituted acetophenone-thiosemicarbazones the presence of absorption band at 3380cm-1 due to –NH₂ (symmetric) and at 3380cm-1due to-NH₂ (asymmetric) modes remain almost unaltered. This clearly indicates the noninvolvement of this group in complexation reaction ^20-21 but slight displacement of these frequencies is due to increased positive charge on nitrogen atom arising from the donation of electron pair from sulfur of thioamide moiety which is involved in chelation ^22-23.  Sharp absorption band from 3280-2850cm-1 which was due to NH- in ligands disappear in complexes indicating possible deprotonation on the β-nitrogen after complextion with metal ion ^24-27.A new absorption band in the complexes at 445-432 due to (M-N) confirm the metal nitrogen bond in the complexes ^28-29.

All compounds have been characterized on the basis of spectral (IR, NMR) studies and elemental analysis. IR spectra (400-4000cm-1) were recorded using a KBr. Central drug research institute (CDRI), Lucknow and Department Of Chemistry, University of Rajasthan, Jaipur. 1H NMR spectra were recorded on Brucker spectrometer (300 MHz) at CDRI, Lucknow using CDCl₃/DMSO as solvent. TMS was taken as internal standard.  C, H, N and s analysis of these compounds have been done using Coleman C and H analyzer. Melting points were determined in open glass capillaries and are uncorrected. The purity of compounds was checked by TLC using silica gel-G as adsorbent and visualization was accomplished by UV light or iodine adsorption.

All compounds are crystalline dark coloured solides, have fairly high melting points and are sparingly soluble in common organic solvents and are insoluble in water.

TABLE 1: ANALYTICAL AND PHYSICAL DATA OF SUBSTITUTED ACETOPHENONETHIOSEMICARBAZONES [Y-AR-C (CH₃) =N-NH-CS-NH₂]

TABLE 2: ANALYTICAL AND PHYSICAL DATA OF CU (II) COMPLEXES OF SUBSTITUTED ACETOPHENONETHIOSEMICARBAZONE [Y-AR-C (CH₃) =N-NH-CS-NH₂]₂ CU (II)

TABLE 3: ANALYTICAL AND PHYSICAL DATA OF FE (II) COMPLEXES OF SUBSTITUTED ACETOPHENONETHIOSEMICARBAZONE [Y-AR-C (CH₃) =N-NH-CS-NH₂]₂FE (II)

 TABLE 4: CHARACTERISTIC IR SPECTRAL DATA OF SUBSTITUTED ACETOPHENONE THIOSEMICARBAZONE AND THEIR METAL COMPLEXES

TABLE 5: CHARACTERISTIC ¹H NMR SPECTRAL DATA OF SUBSTITUTED ACETOPHENONE THIOSEMICARBAZONE AND THEIR METAL COMPLEXES

BIO-EFFICACY: Some representative compounds were screened for their antibacterial  and antifungal efficacy. Bis (F-Fluoroacetophenonethiosemicarbazone) iron (II)

  FIG: 5       ANTIBACTERIAL SPECIEES-E.COLI                   

FIG: 6 ANTIBACTERIAL SPECIEES-STREPTOMYCES

FIG:7ANTIBACTERIAL SPECIEES-BACILLES CEREUS         

 FIG:8 ANTIBACTERIAL SPECIEES-STREPTOCOCCUS

                            AUREUS      

FIG: 9 ANTIFUNGAL SPECIES-FUSARIUM                      

FIG: 10 ANTIFUNGAL SPECIES-PENECILLUM

FIG: 11ANTIFUNGAL SPECIES- A.NIGER

FIG: 12

ACKNOWLEDGEMENT: Authors are thankful to Head Department of Chemistry, University of Rajasthan, Jaipur for providing research facilities.  Central Drug Research Institute (CDRI), Lucknow, Seminal Applied Science Pvt. Ltd Jaipur for providing research facilities.

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    How to cite this article

    Meena SK and Jain M: Synthesis, Spectral Studies and Antimicrobial Screening of Some Transition Metal Complexes with Substituted Acetophenone Thiosemicarbazone. Int J Pharm Sci Res 2014; 5(11): 4880-86.doi: 10.13040/IJPSR.0975-8232.5 (9).4880-86.

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