Trivalent transition metal complexes derived from carbohydrazide and dimedone

2.1 Reagents

All the chemicals used in the study were of Anal R grade. Metal salts were purchased from E. merck and were used as received. All the solvents used were of high purity. Moisture was excluded from the glass apparatus using CaCl₂ glass tubes.

2.2 Isolation of complexes

All the complexes were synthesized by template method i.e., by the condensation of dimedone and carbohydrazide in the presence of respective trivalent metal salts. To a hot, well stirred methanolic solution (∼50 cm³) of carbohydrazide (10 mmol), was added trivalent chromium or iron salt (5 mmol) dissolved in minimum quantity of methanol (20 cm³). The resulting solution was refluxed for 0.5 h. After that dimedone (10 mmol) dissolved in ∼20 cm³ methanol was added in the refluxing mixture and the mixture was again refluxed for 6–8 h. The mixture was concentrated to half of its volume and kept in a desiccator overnight. On overnight cooling, colored complexes were obtained which were filtered, washed with methanol, acetone and diethylether, dried in vacuo. The syntheses of the complexes may be shown by the following scheme (Fig. 1).

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Figure 1

Synthesis of macrocyclic complexes derived from dimedone and carbohydrazide with trivalent metal salts.

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2.3 Analytical and physical measurements

The microanalyses of C, H and N were recorded at Elementar Vario EL III (Carlo Erba 1108) at Sophisticated Analytical Instrument Facility, CDRI, Lucknow. The magnetic susceptibility measurements were carried at SAIF, IIT Roorkee on a vibrating sample magnetometer. The IR spectra were recorded on Infrared spectrophotometer in the range 4000–200 cm⁻¹ using KBr pellets at Sophisticated Analytical Instrument Facility, Punjab University, Chandigarh. Electronic spectra (DMF) were recorded on Cary 14 spectrophotometer in the Department of Chemistry, IIT Roorkee. The conductivity was measured on a digital conductivity meter (HPG System, G-3001). Melting Points were determined using capillaries in electrical M.P. apparatus. The metal contents were determined by standard EDTA methods.

2.4 Biological activity of complexes

3.1 Infrared spectra

A pair of strong bands at ∼3215 and 3295 cm⁻¹ corresponding to ν(NH₂) which is present in the spectrum of carbohydrazide but absent in the spectra of all the complexes (Prasad, 2007). However a broad peak at 3340–3415 cm⁻¹ corresponding to ν(N–H) was observed in the spectrum of all the complexes (Khan, 1998; Singh, 2012). A strong peak at ∼1685 cm⁻¹ in the spectrum of carbohydrazide and all the complexes is attributed to the CO group of CONH moiety. A new strong absorption band in the region ∼1585–1615 cm⁻¹ was observed which may be attributed to ν(C⚌N) stretching vibration (Singh, 2004; Gupta and Chandra, 2006). This confirms the condensation of carbonyl group of dimedone and amino group of carbohydrazide (Prasad and Mathur, 2006; Zeng, 1999). These results provide strong evidence for the formation of macrocyclic frame (Mohamed, 1999). The lower value of ν(C⚌N) indicates coordination of azomethine nitrogen to metal (Lodeiro, 2003). The bands present at ∼1342–1020 cm⁻¹ may be assigned due to ν(C–N) vibration.

The Far infrared spectra show bands in the region ∼410–435 cm⁻¹ corresponding to ν(M–N) vibrations in all the complexes (Mohamed, 1997; Aqra, 1993). The presence of bands in all complexes in 410–435 cm⁻¹ region originate from ν(M–N) azomethine vibrational modes and give an idea about coordination of azomethine nitrogens (Rana, 1982). The bands present at 295–310 cm⁻¹ correspond to ν(M–Cl) vibrations Shakir, 1999; Chandra and Kumar, 2004. The bands present at 210–250 cm⁻¹ in all nitrato complexes are assignable to ν(M–O) Shakir, 1999.

3.2 Mass spectra

The mass spectra of trivalent chromium (III) and iron (III) macrocyclic complexes derived from dimedone and carbohydrazide have been recorded using NBA matrix. All the spectra exhibit parent peaks due to molecular ions [M]⁺ and [M+2]⁺. The proposed molecular formula of these complexes was confirmed by comparing their molecular formula weights with m/z values. The molecular ion peaks and other fragments arising from the thermal cleavage of the complexes have been given in Table 2.

3.3 Magnetic measurements and electronic spectra

The magnetic moment of chromium (III) complexes was found in the range 3.94–4.15 B.M. The electronic spectra of chromium (III) complexes show bands at ∼9165–9235 cm⁻¹ (ν₁), ∼13 115–13 420 cm⁻¹(ν₂) , ∼17 342–18 214 cm⁻¹(ν₃), ∼27 218–27 652 cm⁻¹(ν₄) and ∼34 773 cm⁻¹(ν₅) respectively. These spectral bands cannot be interpreted in terms of four or six coordinated environment around the metal atom. The spectra are comparable with that of five coordinated Cr (III) complexes Wood, 1972. Thus, keeping in view the analytical data and electrolytic nature of these complexes, five coordinated square pyramidal geometry can be assigned for these complexes. Thus, assuming the symmetry C_4V for these complexes (Chohan et al., 2006a), various spectral bands can be assigned as : ${}^4{\text{B}}_1\to {}^4{\text{E}}^a$ , (ν1), ${}^4{\text{B}}_1\to {}^4{\text{B}}_2$ , (ν₂), ${}^4{\text{B}}_1\to {}^4{\text{A}}_2$ ,(ν₃) and ${}^4{\text{B}}_1\to {}^4{\text{E}}^b$ (ν₄), respectively.

The magnetic moments of iron (III) complexes lay in the range 5.87–5.92B.M. The electronic spectra of iron (III) complexes show various bands at ∼9854–9946 cm⁻¹, 15 418–15 825 cm⁻¹ and 27 535–27 860 cm⁻¹. These bands do not suggest the octahedral or tetrahedral geometry of the complexes around the metal atom. The spectral bands are consistent with the range of spectral bands reported for five coordinated square pyramidal iron (III) complexes Chohan et al., 2006. Assuming C_4V symmetry for these complexes, various bands can be assigned as: d_xy → d_yz,xz and d_xy → d_z2. Any attempt to make accurate assignment is difficult due to interactions of the metal–ligand- bond systems lifting the degeneracy of d_{xz and} d_yz pair.

3.4 Biological assay results

All the synthesized macrocyclic complexes were tested for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of synthesized macrocyclic complexes has been evaluated by the agar well diffusion method. Minimum Inhibitory Concentration (MIC) of various complexes against various bacterial strains was tested through a macrodilution tube method. Standard antibiotics namely Linezolid and Cefaclor were used for comparison with antibacterial activities shown by these complexes. Linezolid showed MIC of 4, 4, 16 and 32 μg/ml against B. cereus, S. aureus, E. coli and S. typhi, respectively, while Cefaclor showed MIC of 8, 2, 8, 16 μg/ml against B. cereus, S. aureus, E. coli and S. typhi respectively. Some complexes of the tested series possessed good antibacterial activity against both Gram-positive and Gram-negative bacteria.

Complexes (2), (5) and (6) exhibited good antibacterial activity against both Gram (+) and Gram (−) bacteria with zone of inhibition in the range 26.0 to 26.6 mm. Complexes (1), (3) and (4) showed good activity. The values are comparable with the zone of inhibition shown by standard antibiotics Linezolid and Cefaclor.

Complex (3) showed MIC of 32 μg/ml against S. typhi which is equal to the MIC shown by the standard antibiotic Linezolid for the same bacterial strain. Complex (6) showed MIC of 16 μg/ml against S. typhi which is equal to the MIC shown by the standard antibiotic Cefaclor for the same bacterial strain. Complexes (2) and (6) showed MIC of 16 μg/ml against E. coli which is equal to the MIC shown by the standard antibiotic Linezolid for the same bacterial strain. Complexes (3) and (5) showed MIC of 8 μg/ml against E. coli which is equal to the MIC shown by the standard antibiotic Cefaclor for the same bacterial strain. Complex (6) showed MIC of 4 μg/ml against S. aureus, which is equal to the MIC shown by the standard antibiotic Linezolid for the same bacterial strain. Complex (1) showed MIC of 8 μg/ml against B. cereus, which is equal to the MIC shown by the standard antibiotic Cefaclor for the same bacterial strain.

It has been suggested that chelation/coordination reduces the polarity of the metal ion mainly because of partial sharing of its positive charge with donor group within the whole chelate ring system. This process of chelation thus increases the lipophilic nature of the central metal atom, which in turn, favors its permeation through the lipoid layer of the membrane thus causing the metal complex to cross the bacterial membrane more effectively thus increasing the activity of the complexes. Besides from this many other factors such as solubility, dipole moment, conductivity influenced by metal ion may be possible reasons for remarkable antibacterial activities of these complexes.(Chohan et al., 2006, 2006a) It also has been observed that some moieties such as azomethine linkage or heteroaromatic nucleus introduced into such compounds exhibit extensive biological activities that may be responsible for increase in hydrophobic character and liposolubility of the molecules in crossing the cell membrane of the microorganism and enhance biological utilization ratio and activity of complexes (Chohan et al., 2006, 2006a) (Fig. 2, Tables 3 and 4).

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Figure 2

Bar graph representation of antimicrobial activity of synthesized complexes. X axis: complexes/antibiotics; Y axis: MIC (μg/ml). a – Bacillus cereus (MTCC 1272), b – Staphylococcus aureus (MTCC1144), c – Escherichia coli (MTCC 739), d – Salmonella typhi (MTCC 733), Linezolid, Cefaclor – Standard antibiotics.

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3.5 Structural Studies

The structural properties of the complexes have been studied. The geometry optimized structure of the [Fe(C₁₈H₂₈O₂N₈)Cl] Cl₂, as shown in Fig. 3, has steric energy 14.98 kcal/mol. All other structural parameters, given in Table 5, also suggest a square pyramidal geometry.

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Figure 3

Geometry optimized Structure of macrocyclic complexes.

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