Synthesis of Co (II) complex of some novel 5-nitroimidazole derivatives for its antibacterial activity

DG Desai; DK Sureja; AK Seth; BR Prajapati; KI Molvi

doi:10.4103/2347-6486.240040

ORIGINAL ARTICLE

Year : 2016 | Volume : 4 | Issue : 1 | Page : 26-30

Synthesis of Co (II) complex of some novel 5-nitroimidazole derivatives for its antibacterial activity

DG Desai¹, DK Sureja², AK Seth³, BR Prajapati⁴, KI Molvi⁵
¹ Professor, Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Waghodia, Vadodara, Gujarat, India
² Associate Professor, Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Waghodia, Vadodara, Gujarat, India
³ HOD, Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Waghodia, Vadodara, Gujarat, India
⁴ >Assistant Professor, Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
⁵ Assistant Professor, Ibn Sina National College for Medical Studies, Al-Mahjar, Jeddah - 22421, KSA

Date of Web Publication

29-Aug-2018

Correspondence Address:
D G Desai
Professor, Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Waghodia, Vadodara, Gujarat
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2347-6486.240040

Abstract

Background: The development of resistant with the current antibiotics increases the need for discovery of more efficient drugs for the treatment of infections. Several studies have demonstrated an increase in antibacterial activity following the interaction of several compounds with metal ions.
Objective: The aim of the present work was to synthesize a novel series of Cobalt (II) complexes of 2-(1- substituted-5-nitro-1H-imidazol-2-yl)-1-substitutedethanone and evaluate their in-vitro antibacterial activity.
Methods: Reaction of 2-(1-substituted-5-nitro-1H-imidazol-2-yl)-1-substitutedethanone with cobalt nitrate hexahydrate under reflux condition in alkaline medium yielded metal-ligand complexes in good yield. The antibacterial activities of metal-ligand complexes were evaluated in-vitro against selected bacteria and fungi by agar well diffusion method. The zone of inhibition in mm was determined for all the ligand-metal complexes.
Results: All newly synthesized metal-ligand complexes were characterized by physical and spectral analysis. Some of the investigated complexes displayed moderate inhibitory activity against gram (+)ve bacteria. None of the Co (II) complex showed inhibitory effect against gram (-)ve bacteria.
Conclusion: Co (II) complexes of 2-(1-substituted-5-nitro-1H-imidazol-2-yl)-1-substitutedethanone have been synthesized and characterized. The antibacterial activity of the compounds is related to the cell wall structure of the bacteria as the results indicated that some of the tested complexes were active against gram-positive bacteria only.

Keywords: Cobalt (II) complex; 5-nitroimidazole; Antibacterial activity

How to cite this article:
Desai D G, Sureja D K, Seth A K, Prajapati B R, Molvi K I. Synthesis of Co (II) complex of some novel 5-nitroimidazole derivatives for its antibacterial activity. J Integr Health Sci 2016;4:26-30

How to cite this URL:
Desai D G, Sureja D K, Seth A K, Prajapati B R, Molvi K I. Synthesis of Co (II) complex of some novel 5-nitroimidazole derivatives for its antibacterial activity. J Integr Health Sci [serial online] 2016 [cited 2023 Jun 9];4:26-30. Available from: https://www.jihs.in/text.asp?2016/4/1/26/240040

Introduction

It is well known that a number of 5-nitroimidazole derivatives have been used in the treatment of tropical diseases, in protozoa, anaerobic bacteria and the eradication of Helicobacter pylori infections.^[1],[2],[3] The interaction of imidazole derivatives with metal ions is a subject of continuous interest. Furthermore, these molecules may easily coordinate to transition metal ions, giving stable coordination compounds. The nitro group adjacent to imidazolic nitrogen may occupy a coordination site, stabilizing chelate metal complexes.

Cobalt (II) ion is one of the most important trace elements in biological systems, since it is an essential micro nutrient for all living organisms. In the form of vitamin B₁₂ (Cobalamin), this metal plays a number of crucial roles in many biological functions. Nowadays, transition metals and their complexes are widely used as drugs and diagnostic agents to treat a variety of diseases.^[4],[5],[6] In the Co (II) coordination compounds, the imidazole nitrogen atom and its neighboring nitro group are active sites for binding the Co+² atom, giving place to mono- or bi-dentate coordination modes, therefore stabilizing tetrahedral or octahedral geometries.

Literature survey shows that Co (II) complexes of azole drugs are more active antibacterial and antifungal agents than the metal-free azole drugs.^[7],[8],[9] The enhancing effect of metals, particularly Co (II), on the antifungal and antibacterial activity has also been found in studies on a number of compounds.^{[10],[12],[13]}

Previously, we have investigated the antibacterial activity of transition metal complexes of 2-(1- substituted-5 -nitro- 1,H-imidazol-2-yl)-1 - substitutedethanone with Cu (II) and Ni (II).^[14],[15] So in search of better antibacterial agent, we are herewith reporting the synthesis, structural characterization and antibacterial activity of Co (II) coordination compounds of some novel 2-(1- substituted-5 -nitro- 1,H-imidazol-2-yl)-1 - substitutedethanone derivatives.

Methodology

Chemicals and reagents

All the chemicals and solvents (reagent grade) were obtained commercially from Loba company and used without further purification. The ligands were synthesized and characterized according to previously published method.^[15]

Physical measurements

The melting points were determined in open capillaries and are uncorrected. The electronic spectra of the compounds were recorded on Shimandzu 1800 UV-Vis spectrophotometer. The infrared spectra were recorded in KBr on Shimadzu Fourier Transform Infrared 8400S spectrophotometer. ¹H NMR measurements were carried out in DMSO-d₆ on Bruker Advance II spectrometer at 400 MHz with TMS as an internal reference and the chemical shift are expressed in ppm. Mass spectra were recorded on Micromass Q- T, TOF MS ES+4.73e³. The conductivity measurements were carried out at room temperature using a Conductivity Bridge, Systronics.

General procedure for the synthesis of metal complexes:

A solution of the ligand was prepared by dissolving different ligands (10 mM) in methanol (50 mL). Then solution of Co(NO₃)₂ 6H₂O (5 mM) in hot methanol (50 mL) was added to the ligand solution with stirring. The pH of reaction mixture then adjusted to 8-10 by adding conc. ammonia. The obtained colored solution was further stirred under reflux for 4-5 h and then allowed to stand at room temperature for 24 h to crystallize. The product was removed by filtration, washed with cooled methanol, recrystallized from methanol and dried under vacuum.

[Co(NIMP)2]:

Dark brown crystals; Yield: 75%; m.p. 262-264 °C; UV (λmax, nm): 240, 315, 484; IR (KBr, cm^-1): 3650, 3500, 2977, 2800, 2270, 1570, 1365, 495; MF: C³⁰H³⁴CoN⁶O¹⁰S² (761.69); Λm (Ω¹cm²mol⁻¹): 1.40.

[Co(NIMPCl)2]:

Light brown crystals; Yield: 87%; m.p. 275-277 °C; UV (λmax, nm): 240, 305, 484; IR (KBr, cm^-1): 3600, 3500, 2980, 2850, 2250, 1500, 1365, 550; MF: C³⁰H³²CoCl²N⁶O¹⁰S² (830.58); Λm (Ω¹cm²mol⁻¹): 0.70.

[Co(NIMMCl)2]:

Earthy brown crystals; Yield: 72%; m.p. 237-239 °C; UV (λmax, nm): 240, 305, 484; IR (KBr, cm^-1): 3610, 3300, 2900, 2850, 2250, 1570, 1350, 516; ¹H NMR (DMSO-d₆, δ): 1.28 (t, 6H, -SO2CH2CH3), 3.20 (q, 4H, -SO2CH2CH3), 3.72 (t, 4H, - CH2CH2SO2C2H5), 4.30 (s, 4H, N=C-CH2-COAr), 4.90 (t, 4H, N-CH2CH2SO2C2H5), 7.60-7.84 (m, 8H, Ar-H), 7.87 (s, 2H, C-4 of imidazole); MF: C³⁰H³²CoCl²N⁶O¹⁰S² (830.58); Λm (Ω¹cm²mol⁻¹): 0.55.

[Co(NIMOCl)2]:

Red crystals; Yield: 69%; m.p. 211-213 °C; UV (λmax, nm): 240, 305, 464; IR (KBr, cm^-1): 3650, 3450, 2900, 2850, 2230, 1550, 1345, 520; MF: C30H32CoCl2N6O10S2 (830.58); MS: m/z 830 (M+), 832 (M+²), 834 (M+⁴); Λm (Ω¹cm²mol⁻¹): 0.67.

[Co(NIMF)2]:

Dark brown crystals; Yield: 72%; m.p. 208-209 °C; UV (λmax, nm): 240, 345, 484; IR (KBr, cm^-1): 3630, 3430, 2980, 2900, 2250, 1545, 1360, 510; ¹H NMR (DMSO-d₆, δ): 1.32 (t, 6H, -SO2CH2CH3), 3.15 (q, 4H, -SO²CH²CH³), 3.66 (t, 4H, - CH²CH²SO²C²H⁵), 4.26 (s, 4H, N=C-CH2-COAr), 4.96 (t, 4H, N-CH²CH²SO²C²H⁵), 6.54 (d, 2H, C-4 of furan), 6.75 (d, 2H, C-3 of furan), 7.59 (s, 2H, C- 5 of furan), 8.10 (s, 2H, C-4 of imidazole); MF: C²⁶H³⁰CoN⁶O¹²S² (741.61); Λm (Ω¹cm²mol⁻¹): 0.69.

[Co(NIMDF)2]:

Brown crystals; Yield: 72%; m.p. 205-207 °C; UV (λmax, nm): 240, 315, 484; IR (KBr, cm^-1): 3500, 3300, 2980, 2900, 2270, 1545, 1360, 525; ¹H NMR (DMSO-d₆, δ): 3.79 (s, 6H, N-CH3), 4.26 (s, 4H, N=C-CH2-COAr), 6.54 (d, 2H, C-4 of furan), 6.75 (d, 2H, C-3 of furan), 7.59 (s, 2H, C-5 of furan), 7.98 (s, 2H, C-4 of imidazole); MF: C²⁰H¹⁸CoN⁶O⁸ (529.33); Λm (Ω¹cm²mol⁻¹): 1.30.

[Co(NIMDP)2]:

Red crystals; Yield: 85%; m.p. 222-225 °C; UV (λmax, nm): 240, 300, 484; IR (KBr, cm^-1): 3500, 3400, 2980, 2900, 2280, 1555, 1340, 512; MF: C²⁴H²²CoN⁶O⁶ (549.40); MS: m/z 781 (M+); Λm (Ω^{- 1}cm²mol⁻¹): 1.20.

Results and Discussion

Synthetic approach

The synthesis of metal complexes were obtained in good yield by in situ reaction of respective 2-(1- substituted – 5 – nitro - 1H - imidazol – 2 – yl)-1- substitutedethanone with cobalt nitrate hexahydrate under reflux condition in alkaline medium. A synthetic route is shown in [scheme 1]. All the complexes were light to dark brown in color and were soluble in DMSO, DMF and insoluble in all other solvents. The complexes were stable crystalline solids with melting point ranging from 205 to 277 °C.

Characterization

The characterization of complexes have been achieved by satisfactory physical methods and spectral (UV, IR, ¹H NMR, mass and molar conductance) studies.

The UV spectra reveal three absorbance maxima for the metal complexes at 240, 315 and 480 nm. It is observed that UV-vis spectra of metal-ligand complex shows absorption bands of increasing wavelengths due to π-π* and n-π* transitions.

The IR spectra of the prepared metal-ligand complex showed C-H stretching (3096-2800 cm^-1), C=O stretching (2250-2000 cm^-1), NO₂ asymmetric and symmetric stretching (1570-1540 and 1366-1358 cm^-1), M-O (600-480 cm^-1). By comparing the IR spectra of metal-ligand complexes with the spectrum of the free ligand, the shifting of carbonyl signal of the free ligand was observed, which indicates the involvement of carbonyl oxygen with the electron- rich Co metal during the complex formation. This bonding weakens the C=O bond and shifts the stretching frequencies. Two new bands in the range 600-480 cm^-1 were also observed. These two bands were observed in the complexes and not found in the free ligand and they are attributed to M-O and M-N bonds in the complexes respectively. So, IR spectral data supports the formation of the metal-ligand complexes from respective ligand.

The ¹H NMR spectra of ligand-metal complex in DMSO-d6 shows triplet and quartet at δ 1.28-1.40 and 3.15 ppm confirms the presence of ethyl group (-SO2C2H5). Two triplets at δ 3.66-3.89 and 4.96 ppm indicates presence of two methylene groups (N-

CH2CH 2SO2CH2CH3). Two singlets at δ 4.26-4.30 and 7.87-8.1 ppm arises due to the methylene group (-N=C-CH2) and C-4 proton of imidazole ring respectively. All the aromatic protons were found between δ 6.54 to 7.94 ppm as multiplet.

In the mass spectra of all metal-ligand complex, higher molecular weight (double the molecular weight of ligand) confirms that metal to ligand ratio is 1:2. The mass spectrum also supports the proposed molecular formula of the metal-ligand complex. The fragmentation routes primarily involved losses of NO (M-30), NO2 (M-46) and HNO₂ (M-47) molecules from the molecular ion.

The molar conductance values of the synthesized ligand metal complexes of 10^-3 M (dissolved in DMF) at room temperature were found in the range of 0.55 - 1.50 Ω⁻¹cm²mol⁻¹, which indicates that all the metal complexes have conductivity values in the range characteristic for non-electrolytic nature.^[16]

Antibacterial activity

The in vitro antibacterial activity of metal complexes of 2-substituted 5-nitroimidazole was evaluated against gram positive (B. pumilus and S. aureus) and gram negative (S. aboney) bacteria by cup plate method^[17] using Ciprofloxacin (100 μg/mL) and Tinidazole (100 μg/mL) as a standard drugs. The metal complexes were dissolved in minimum amount of DMF and diluted with water. Agar medium and nutrient broth were prepared with the standard preparatory techniques. The results of antibacterial activity are recorded in the form of zone of inhibition in mm at 100 μg/mL concentration and are presented in [Table 1]. Four out of seven metal complexes did not show any inhibitory activity on the growth of all tested bacteria, while three metal complexes display zone of inhibition against gram positive bacteria only. By considering results, it can be concluded that substituted ligands and the metal moiety along with the cell wall structure of the bacteria may play a role in determining the antibacterial activity. The differences in cell wall structure of bacteria can produce differences in antibacterial susceptibility and some antibiotics can kill only gram-positive bacteria and is ineffective against gram-negative pathogens.

Table 1: Antibacterial activity of metal-ligand complexes

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Conclusion

The antibacterial activity of Co (II) complexes of 2- (1- substituted – 5 – nitro - 1H – imidazol – 2 - yl)- 1-substitutedethanone derivatives was tested against very persistent microorganisms: B. pumilus, S. aureus and S. aboney. Some of the metal complexes displayed moderate in vitro inhibitory activity. Amongst the two series, 2-(1-methyl-5-nitro-1H- imidazol-2-yl)-1 -substitutedethanone derivatives formed Co (II) complexes were active than the complexes of 2-(1-(2-(ethylsulfonyl)ethyl)-5-nitro- 1H-imidazol-2-yl)-1-substitutedethanone. It may be concluded that the antibacterial activity of the compounds is related to the cell wall structure of the tested bacteria.

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