Design, Spectral and Antibacterial Investigations of Some Mixed Ligand Metal Complexes

Introduction

Benzimidazole is a bicyclic compound containing two nitrogen atoms at alternate positions fused to the benzene ring. It is used as an important precursor for the synthesis of various biologically active heterocyclic compounds. Its derivatives have been found to display remarkable antiviral [1], antimicrobial [2], antioxidant[3], anticancer [4] and antiulcer [5] activities. The effectiveness of such compounds increases when coordinated to metal ions [6-8]. Now-a-days, mixed ligand metal complexes have received considerable attention for their wide range of applications in analytical and biological chemistry [9-12].

Furthermore, the mixed ligand metal complexes of 2,2’-bipyridine have also been reported [13-15]. Considering the versatile nature of such compounds and our ongoing work on them [16-19], we have made an effort to report the synthesis of some ternary complexes having benzimidazole moiety. Moreover, these ternary compounds exhibited moderate antibacterial activity when screened against some selected strains; B. subtilis, E. coli and S. typhi.

Materials and Methods

The chemicals and reagents were obtained from Sigma Aldrich and used as such.

Preparation of Ligand

The precursor 2-hydrazinobenzimidazole was prepared as reported previously [8]. The Schiff base ligand; 2-(o-vanillinidenehydrazino)benzimidazole was prepared by condensing 2-hydrazinobenzimidazole with o-vanillin [8].

Yield 80%, color yellow; Anal. Calc. (%): C, 63.83; H, 4.96; N, 19.86, Found (%): C, 63.76; H, 4.92; N, 19.82. 

Preparation of Mixed Ligand Complexes

Hot ethanolic solution of the Schiff base (0.01 mol, 20 mL), metal(II) chloride (0.01 mol, 20 mL) and 2,2’-bipyridine (0.01 mol, 20 mL) in 1:1:1 molar ratio are mixed with stirring. The resulting mixture was refluxed for 2 hours at pH 7-8 by adding 0.25 g of solid NaOH. It was filtered, washed and finally, dried in vacuo. The schematic representation for the synthesis of mixed ligand complexes is shown in Fig. 1.

Figure 1: Scheme for the preparation of metal complexes Click here to View Figure

Analysis and Physical Measurements

The UV and FTIR spectra were obtained from Perkin-Elmer and Varian FTIR spectrophotometer, respectively. The CHN analysis was done in MLW-CHN micro analyzer. The ¹H-NMR spectra in DMSO-d6 were recorded on JEOL GSX-400 equipment. Thermal analysis was carried out by Netzch-429 thermal analyser and ESR spectra were recorded on E-112 EPR Spectrophotometer.

Results and Discussion

These compounds were stable, non hygroscopic and soluble in DMSO and DMF. The physico-analytical data for them is shown in Table 1.

Table 1: Physico-analytical data of the compounds

Compounds	Yield (%)	Λam	C Found (Calcd)	H Found (Calcd)	N Found (Calcd)	M Found (Calcd)
[CoL1L2] 2H2O	67	10.2	52.82 (52.86)	4.37 (4.40)	14.75 (14.80)	10.33 (10.39)
[CuL1L2] 2H2O	65	11.4	52.41 (52.45)	4.35 (4.37)	14.64 (14.68)	11.05 (11.10)
[ZnL1L2] 2H2O	61	7.5	52.28 (52.31)	4.31 (4.36)	14.78 (14.65)	11.27 (11.33)

^aOhm^-1 cm² mole^-1

IR Spectra

The coordination of phenolic oxygen is confirmed from the disappearance of band at ~3300 cm^-1 due to phenolic -OH vibration for metal complexes. The band for vN-H (exocyclic) remains unchanged in the metal complexes, indicates non-involvement of imino nitrogen in coordination. Further, the non coordination of ring nitrogen atom (-C=N) of benzimidazole moiety in the complexes is also ascertained as there is no change in the positions of bands at ~ 1540 and ~ 1320 cm^-1 was observed. On the other hand, the band at ~3150 cm^-1 for benzimidazole νN-H group shifted to lower frequency region by ~20 cm^-1, indicated the involvement of -NH group in coordination. Besides the above, the coordination of azomethine nitrogen is also identified due to shifting of bands for vC=N (azomethine) and vN-N vibrations. Further, an additional band was appeared at ~2840 cm^-1 for –OCH₃ group in all the compounds, which remain unaltered. The absorption band for vO-H (lattice water) is assigned at ~3500 cm^-1. In addition, a sharp band at 670–685  cm^-1 for ν(C═N) of pyridine is also observed for ternary complexes.[20] Some importantIR data for the ternary compounds are listed in Table 2. The representative IR spectrum of [ZnL1L2]2H₂O is shown in Fig. 2.

Table 2: Important IR data for the ternary compounds

[CoL1L2] 2H2O	[CuL1L2] 2H2O	[ZnL1L2] 2H2O	Assignments
3500	3510	3510	νO-H (lattice water)
~3140	~3140	~3130	νN-H (benzimidazole)
~ 1525	~ 1530	~ 1520	νC=N (benzimidazole)
~ 1320	~ 1335	~ 1340	vC-N (cyclic)
1610	1615	1610	νC=N (azomethine)
655	660	668	νC=N (pyridine)
1270	1270	1282	νC-O (phenolic)
580	570	585	νM-N
490	495	510	νM-O
348	345	330	νM-Cl

Figure 2: IR spectrum of [ZnL1L2] 2H2O Click here to View Figure

Thermal Analysis

The TGA data for the ternary complexes are listed in Table 3. The compounds displayed similar type of thermal decomposition and remains unaffected up to ~50  followed by a slight depression up to ~110 . This confirms the presence of lattice water in the metal complexes. The anhydrous metal complexes showed rapid degradation after 270  for organic constituents and continues up to ~600  as indicated in the plateau of the thermo gram. Finally reaches to the corresponding stable metal oxide.

Table 3: TGA data for the ternary compounds

Compounds	Temp. range of Water loss ()	% of water       loss		Decomposition Temperature       ()	% of residue		Composition of the residue
		Found	Calc.		Found	Calc.
[CoL1L2] 2H2O	50-110	6.28	6.34	260	13.17	13.21	CoO
[CuL1L2] 2H2O	60-110	6.25	6.29	270	13.85	13.90	CuO
[ZnL1L2] 2H2O	55-100	6.24	6.27	245	14.08	14.12	ZnO

 

Electronic Spectra

The mixed ligand Co(II) complex displayed two main bands around ~10,800 cm^-1 (broad) and ~22,500 cm^-1 (strong) under octahedral symmetry. The magnetic moment value for the Co(II) complex is obtained at 4.8 B.M. The Cu(II) complex in DMSO displayed two bands at ~14,600 cm^-1 and ~16,750 cm^-1. In this case, the band for ²B_1g®²A_1g is not observed. The magnetic moment value for Cu(II) complex is obtained at 1.85 B.M. The data supports hexa coordinated environment for the compounds. The electronic data for the ternary complexes are listed in Table 4.

Table 4: Electronic data for the ternary compounds

Compounds	ν (cm-1)	Transition	Geometry	μeff (BM)
[CoL1L2] 2H2O	~10,800 (broad)	4T1g(F)®4T2g(F) (v1)	Octahedral	4.8
	~22,500 (strong)	4T1g(F)® 4T1g (P) (v3)
[CuL1L2] 2H2O	~14,600	2B1g®2B2g (v2)	Distorted octahedral	1.85
	~16,750	2B1g®2Eg (v3)

¹H NMR Spectra

The ¹H NMR spectra of HL1 (Fig. 3) and Zn(II) complex displayed a multiplet at δ 7.4-8.5 ppm for aromatic protons of phenyl groups.  The signals at δ 6.7 ppm and δ 9.0 ppm are due to ring NH and exocyclic NH protons, respectively. Also the signals for -OCH₃ and azomethine protons appeared at δ 4.5 ppm and δ 8.7 ppm, respectively. The downfield shift of ring -NH and azomethine protons indicates their participation in coordination. Furthermore, the disappearance of the signal due to phenolic -OH proton in the metal complexes confirms its participation in co-ordination through deprotonation.

Figure 3: 1H NMR spectrum of HL1 Click here to View Figure

Electron Spin Resonance (ESR) Spectra

The ESR spectrum of Cu(II) complex at 300 K displayed a well resolved four line spectrum for the compound. Also the data supported mononuclear nature of the compound. The spin Hamiltonian parameters were determined, which showed g‖ = 2.25 > g_┴ = 2.07 > 2.0023. The data suggests octahedral geometry for the chelate [21]. Also, g‖ < 2.3 suggests covalent nature of metal-ligand bond and the unpaired electron is present in dx2-y2 orbital [22]. In addition, the exchange interaction term G (3.66) was determined.

In Vitro Antibacterial Activity

The in vitro antibacterial activities of these studied compounds were reported at 100 μg mL^-1 concentrations by Agar Well method [23] against B. subtilis, E. coli and S. typhi. The zone of inhibition is shown in Table 5 and Fig. 4. The standard antibacterial drug ciprofloxacin was also screened as above. The Schiff base ligand showed moderate activity against all organisms, whereas the ternary complexes displayed greater activity. This will be explained by chelation theory and C=N bonds. Moreover, other factors such as solubility, dipole moment, nature of the ligand and geometry may contribute towards the higher activity [24, 25].

Table 5: Antibacterial activity of the compounds

Compounds	B. subtilis	E. coli	S. typhi
HL1	13.54	13.26	14.92
[CoL1L2] 2H2O	17.25	19.38	22.34
[CuL1L2] 2H2O	21.48	20.62	24.52
[ZnL1L2] 2H2O	14.75	17.56	19.15

Figure 4: Antibacterial activity of the compounds Click here to View Figure

Electrostatic Potential

The ESP surface of HL1 ligand was analyzed by using ArgusLab 4.0.1 software and shown in Fig. 5. The surface contains number of possible sites for electrophilic attack. The study displayed very specific data about the charge distribution. The negative regions are mainly over -OCH₃ group oxygen, phenolic oxygen, azomethine nitrogen and benzimidazole nitrogen atoms as shown by red colour. The -OCH₃ group oxygen atom is not involved in coordination due to steric effect, which was confirmed earlier.

Figure 5: The ESP surface of Schiff base Click here to View Figure

Conclusion

The foregoing observations suggest that all the mixed ligand complexes are neutral in nature and contain lattice water molecules. The spectral study revealed octahedral geometry for all the metal complexes in which the primary ligand behaves as tridentate chelation with the metal ion. The metal complexes showed moderate antibacterial activity compared to the Schiff base ligand. The higher activity is due to the enhanced lipophilic property of the central metal ion for chelation. Moreover, the electrostatic potential surface of the Schiff base is analyzed, which also confirms tridentate chelation of the ligand.

Acknowledgement

The authors are highly thankful to the authorities of Centurion University of Technology and Management, Odisha, India for providing necessary facilities with financial assistance.

Conflicts of Interest

There are no conflicts to declare.

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