Abstract
Cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes with two new unsymmetrical ligands, isatin salicylaldehyde oxalic acid dihydrazide (isodh) and isatin salicylaldehyde malonic acid dihydrazide (ismdh) were synthesized and characterized by elemental analyses, electrical conductance, magnetic moments, electronic, NMR, ESR and IR spectral studies. The isodh acts as a dibasic tetra dentate ligand bonding through two >C=N-, a deprotonated phenolate and deprotonated indole enolate groups to the metal. The ismdh ligand shows monobasic tetra dentate behaviour in bonding with metal ion through two >C=N-, indole >C=O and a deprotonated phenolate group. The electronic spectral data suggest 4-coordinate square planar geometry for Co(II), Ni(II) and Cu(II) complexes of isodh, whereas, 6-coordinate octahedral structure for the ismdh complexes. The ESR studies also indicate a square planar and distorted octahedral environment around Cu(II) for isodh and ismdh complexes, respectively. Most of the metal complexes show better antifungal activity than the standard and a significant antibacterial activity against various fungi and bacteria.
Introduction
Acylhydrazones of various aldehydes and ketones occupy a special place among the biologically important organic ligands containing a variety of donor groupsCitation1. These Schiff bases are able to change their coordination behaviour depending on the starting reagents, pH of the medium and reaction conditions. The acylhydrazone derivatives are of considerable interest because of their chemistry and potentially beneficial biological activitiesCitation2. The bio-activity may be due to the presence of multi-coordination centres having the ability to form stable chelates with the essential metal ions which the organism need in their metabolism. Studies on biological activity of Schiff bases derived from isatin and their metal complexes showed significant enhancement of antibacterial and antifungal activity of the isatin derivatives on complexationCitation3.
Over the recent years, more attention has been focused on the coordination chemistry and biological properties of different metal complexes of isatin-thio-semicabazonesCitation4,Citation5, bis-(thio-semicarbazonesCitation6), semicarbazonesCitation7 and hydrazonesCitation8,Citation9 in order to establish a possible relationship between chemical structure and biological activity. Schiff and Mannich bases of isatin were reported to possess antibacterialCitation10, antifungalCitation11, antiviralCitation12, anti-HIVCitation13, anti protozoalCitation14, antiviralCitation15 and anticancerCitation16. Within the context of enzyme inhibitors, isatin derivatives have found recent applications in the inhibition of cysteine and serine proteasesCitation17,Citation18. Recently, isatin hydrazone derivative complexes of Cu(II), Ni(II) and Zn(II) have been reported to exhibit potential anti-tumour activity evaluated on human leukemic cellsCitation19.
Although metal complexes of mono-hydrazones derived from isatin have been extensively investigated, those of bis-hydrazones have received little attention and unsymmetrical dihydrazones have not been reported so far. Synthesis of such ligands is rather difficult compared to their symmetrical counterparts because simple condensation methodology can no longer be applied with three components. Instead, it is usual to obtain first the mono-condensation product of the dihydrazide with a carbonyl compound, in which one primary amino group forms an azomethine bond and the other remains unchanged. It is subsequently condensed with another carbonyl group containing compound to form the desired ligandCitation20. In this paper, we have synthesized two new unsymmetrical isatin salicylaldehyde acyldihydrazones ligands by condensing isatin, salicylaldehyde and dihydrazides. The Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes with above ligands were prepared in order to obtain functional complexes that could display suitable keto–enol equilibria in aqueous solution. The ligands and their complexes have been characterized by various physico-chemical and spectral techniques. We have also described the study of antibacterial and antifungal properties of all the synthesized compounds. They were assayed in vitro for antimicrobial activity against representative strains of gram positive bacteria (Bacillus subtilis), Gram-negative bacteria (Escherichia coli) and antifungal activity against Aspergillus sp., Pseudocercospora sp. and Trichoderma sp. by minimal inhibitory concentration (MIC) method. The standard agent Ampicillin for antibacterial activity and Miconazole for antifungal activity were also screened under identical conditions for comparison.
Experimental
Materials
Commercial reagents have been used without further purification and all experiments have been carried out in the open atmosphere. The metal salts, isatin, salicylaldehyde and solvents were purchased from SD Fine Chemicals, India, and were used as such. Diethyl oxalate, diethylmalonate and hydrazine hydrate (Merck Chemicals, India) were used in synthesis.
The precursor oxalic acid dihydrazide, (CONHNH2)2 and malonic acid dihydrazide, CH2(CONHNH2)2 were prepared by the reported procedureCitation21 by reacting diethyl oxalate and diethylmalonate with hydrazine hydrate, respectively, in 1:2 molar ratio in a beaker containing 10 mL ethanol.
Synthesis of isatin salicylaldehyde oxalic acid dihydrazone (isodh)
Isatin (10 mmol, 1.47 g) in ethanol (25 mL) was reacted with 25 mL hot aqueous solution of oxalic acid dihydrazide (10 mmol, 1.18 g) in a round bottom flask by stirring on a magnetic stirrer for 30 min at 60°C. Now, 10 mL ethanolic solution of salicylaldehyde (10 mmol, 1.22 mL) was added to this solution and refluxed for 5 h. A light orange coloured precipitate was obtained on cooling the above solution. The product was filtered by suction on a Buckner funnel and purified by washing several times with hot water followed by ethanol and finally with diethyl ether. The purity of the product was monitored by TLC. The compound was dried in desiccator over anhydrous calcium chloride at room temperature.
Synthesis of isatin salicylaldehyde malonic acid dihydrazone (ismdh)
Isatin salicylaldehyde malonic acid dihydrazone was prepared by reacting isatin (10 mmol, 1.47 g) in ethanol (25 mL) with 25 mL solution of malonic acid dihydrazide (10 mmol, 1.32 g) in aqueous ethanol (50%, v/v) in a round bottom flask and stirred for 1 h on a magnetic stirrer. Ten millilitre ethanolic solution of salicylaldehyde was added in the above solution drop wise with shaking. An orange–yellow precipitate was obtained on refluxing the solution for 3 h. The precipitate was filtered by suction and washed thoroughly with aqueous ethanol and finally with diethyl ether. The purity of the product was checked by TLC. The pure compound was dried in desiccator over anhydrous calcium chloride.
The ligands could not be crystallized because of their highly insoluble nature in organic solvents. However, they were characterized by elemental analyses (C, H, N), melting points, NMR (1H & 13C) and IR spectra.
Synthesis of the metal complexes
Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of isodh and ismdh ligands were synthesized by reacting 25 mL aqueous ethanolic solutions (50%, v/v) of each metal(II) chloride salts (10 mmol) with 25 mL partially dissolved ethanolic solution of isodh (10 mmol, 3.51 g) or ismdh (10 mmol, 3.65 g) separately, in 1:1 (M:L) molar ratio in a round bottom flask. On heating, the reactants dissolved initially at boiling temperature and the complexes were precipitated after refluxing the solution for 2 h for Cu(II) and Zn(II) and 4–6 h for other complexes of both the ligands. The complexes were filtered in a glass crucible and washed several times with hot aqueous ethanol to remove the unreacted reactants. Finally, they were dried in a desiccator over anhydrous calcium chloride at room temperature.
Physico-chemical measurements
The metal and chloride contents were analyzed gravimetrically using standard literature proceduresCitation22. C, H and N contents were determined on an Exeter Analytical Inc. CHN Analyzer (Model CE-440). The molar conductance of 10−3 M solutions of the complexes soluble in DMSO was measured at room temperature on a Eutech Con 510 Conductivity meter. 1H & 13C NMR spectra of the ligands were recorded in DMSO-d6 on a JEOL AL-300 FT-NMR multinuclear spectrometer. Chemical shifts were reported in parts per million (ppm) using tetramethylsilane as an internal standard. All exchangeable protons were confirmed by addition of D2O. Infrared spectra were recorded in KBr on a Varian 3100 FT-IR spectrophotometer in the 4000–400 cm−1 region. Electronic spectra of the complexes were recorded on a Shimadzu spectrophotometer, model, Pharmaspec UV-1700 in nujol. Magnetic susceptibility measurements were performed at room temperature on a Faraday balance using Hg[Co(SCN)4] as the calibrant. The X-band ESR spectra of Cu(II) complexes were recorded on a EMX 1444 EPR spectrometer at room temperature (300 K) in solid state using TCNE as g marker (g = 2.00277).
Biological activity
Antifungal activity
The ligands as well as their complexes were screened for their antifungal activity against various fungi viz. Aspergillus sp., Pseudocercospora sp. and Trichoderma sp. These species were isolated from the infected organs of the host plants on potato dextrose agar (potato 250 g + dextrose 20 g + agar 20 g) medium. The cultures of the fungi were purified by single spore isolation technique.
The solution in different concentrations 0.5, 1 and 1.5 mg/mL of each compound in DMSO were prepared for testing against spore germination. A drop of the solution of each concentration was kept separately on glass slides. The conidia, fungal reproducing spores (approx. 200) lifted with the help of an inoculating needle, were mixed in every drop of each compound separately. Each treatment was replicated thrice and a parallel DMSO solvent control set was run concurrently on separate glass slides. All the slides were incubated in humid chambers at 25 ± 2°C for 24 h. Each slide was observed under the microscope for spore germination and percent germination was finally calculated. The results were also compared with a standard antifungal drug Miconazole at the same concentrations.
Antibacterial activity
The antibacterial activity of the ligands and their complexes was studied against E. coli and B. subtilis bacteria. Each of the compounds was dissolved in DMSO and solutions of the concentration 1 mg/mL and 2 mg/mL were prepared separately. Paper discs of Whatman filter paper (No. 42) of uniform diameter (2 cm) were cut and sterilized in an autoclave. The paper discs soaked in the desired concentration of the complex solutions were placed aseptically in the petridishes containing nutrient agar media (agar 20 g + beef extract 3 g + peptone 5 g) seeded with E. coli and B. subtilis bacteria separately. The petridishes were incubated at 37°C and the inhibition zones were recorded after 24 h of incubation. Each treatment was replicated nine times.
The antibacterial activity of a common standard antibiotic Ampicillin was also recorded using the same procedure as above at the same concentrations and solvent. The % Activity Index for the complex was calculated by the formula as follows:
Determination of MIC value
The antibacterial screening concentrations of the compounds to be used were estimated from the MIC value. The MIC was determined using the disc diffusion technique by preparing discs containing 0.1 to 1.0 mg/mL of each compound against both the bacteria and applying the protocol. All the compounds were more effective at 1.0 and 2.0 mg/mL concentrations. Consequently, all the compounds were screened at these concentrations against both the bacteria.
Results and discussion
Analysis of complexes
It appears that the asymmetric ligands, isodh and ismdh are formed by two-step synthesis. In first step, isatin reacts with the dihydrazide in 1:1 molar ratio to form mono isatin dihydrazone in solution, which further reacts with salicylaldehyde, in second step, to form isatin salicylaldehyde dihydrazone. The analytical data show that these ligands deprotonate their phenolic protons during complexation with metal(II) chloride and form 1:1 (M:L) complexes. At the same time, isodh ligand enolizes its >C=O group of indole ring and form doubly deprotonated complexes of general composition [M(isodh-2H)]. The reactions may be written as follows:
MCl2.xH2O + isodh → [M(isodh-2H)] + 2HCl + xH2O
where, M = Co(II), Ni(II), Cu(II), Zn(II) and Cd(II)
MCl2.xH2O + ismdh → [M(ismdh-H)(H2O)n]Cl + HCl + (x-n)H2O
where, n = 2 for M = Co(II), Ni(II), Cu(II); n = 0 for M = Zn(II) and Cd(II)
All the metal complexes are coloured powdery solids. The cobalt(II) complexes are orange–brown, nickel(II) complexes are orange and yellow–green, copper(II) complexes are brown, zinc(II) complexes are yellow–orange and cadmium(II) complexes are light orange in colour. The metal complexes are insoluble in water and less polar organic solvents like ethanol, methanol, chloroform, benzene, acetone and diethyl ether but are soluble in highly polar solvents DMF and DMSO. The ligands as well as their metal complexes decompose at the temperature between 178 and >300°C without melting. The molar conductance values of 10−3 M solutions of the isodh complexes in DMSO at room temperature are observed in the range 5.69–10.10 ohm−1 mol−1 cm2 suggesting that they are non-electrolytesCitation23. However, all the ismdh complexes are 1:1 electrolytes as indicated by their molar conductance values observed in the range 52.54–62.43 ohm−1 mol−1 cm2 ().
Table 1. Analytical data of the ligands and their metal complexes.
Magnetic moments and electronic spectra
The room temperature magnetic moment data of copper(II) complexes of isodh and ismdh, in the present study, show μeff values 1.78 and 1.85 B.M., respectively, corresponding to one unpaired electron. [Cu(isodh-2H)] complex shows a broad band centred at 690 nm similar to [Cu(NH3)4]2+ at 625 nm, suggesting a square planar geometry for the complex with 2Eg → 2T2g transitionCitation24. [Cu(ismdh-H)(H2O)2]Cl shows three bands at 660, 468 and 408 nm, which may be assigned to 2B1g → 2A1g, → 2B2g and → 2Eg transitions indicating a distorted octahedral geometry for the complex.
The electronic spectra of [Cu(isodh-2H)] shows weak bands at 830, 520 and 390 nm corresponding to 1A1g → 1B1g, → 1B2g and a charge transfer band similar to that reported for nickel(II) acetyl acetone bis-acylhydrazoneCitation25 and many other Ni(II) complexes with square planar geometryCitation26. The square planar geometry of this complex is further confirmed by its diamagnetic nature. Nickel(II) octahedral complexes generally show three bands due to 3A2g (F) → 3T2g (F) (ν1), → 3T1g (F) (ν2) and → 3T1g (P) (ν3) transitions. [Ni(ismdh-H)(H2O)2]Cl shows three transitions at 883, 595 and 403 nm suggesting an octahedral geometry for the complex. Above nickel(II) complex shows μeff value 3.12 B.M. corresponding to two unpaired electrons in an octahedral environment.
[Co(isodh-2H)] complex shows μeff value 2.16 B.M. corresponding to one unpaired electron and suggests a low spin square planar geometry for the complexCitation27. The electronic spectral bands observed for this complex () are in good agreement with the bands reported for cobalt(II) square planar complexes. [Co(ismdh-H)(H2O)2]Cl shows three bands at 1020, 532 and 438 nm indicating an octahedral geometry and are assigned as 4T1g (F) → 4T2g (F) (ν1), → 4A2g (F) (ν2) and → 4T1g (P) (ν3). This complex shows μeff value 4.90 B.M. and is fairly close to those reported for three unpaired electrons in an octahedral environmentCitation28.
Table 2. Magnetic moments, electronic spectral bands of the complexes and their assignments.
The magnetic moment and electronic spectral studies clearly indicate a 4-coordinate square planar geometry for all isodh complexes, whereas ismdh complexes of Co(II), Ni(II) and Cu(II) form a 6-coordinate octahedral structure including two water molecules in bonding. Since the coordination of ismdh ligand results the formation of a large eight-membered ring around metal ion, there is enough space to accommodate water molecules (). However, Zn(II) and Cd(II) complexes generally prefer to form 4-coordinate complexes.
Figure 1. Representative structures of the metal complexes.
ESR spectra
ESR spectra of [Cu(isodh-2H)] in solid state at 300 K shows an isotropic intense broad signal with no hyperfine structure. The giso value of 2.1066 suggests a square planar geometry involving grossly misaligned tetragonal axes. However, [Cu(ismdh-H)(H2O)2]Cl exhibits an axial signal with two g values, gII = 2.4318 and g⊥ = 2.0277. These values are consistent with copper(II) in an elongated tetragonally distorted octahedral environment with all the principal axes aligned parallelCitation29.
Improved resolution of g and hyperfine anisotropy of the copper(II) ion are observed in the frozen DMSO solution spectra of the complexes at 77 K (). Both the copper(II) complexes show a well-defined hyperfine structure of four lines due to coupling of the electron with copper(II) nuclei (I = 3/2) on the lower field region. The gII, g⊥, AII and A⊥ values are measured accurately (). The gav and Aav values are calculated using the equations gav = (gII + 2g⊥)/3; Aav = (AII + 2A⊥)/3. These values suggest an elongated tetragonally distorted octahedral geometry for ismdh complex in DMSO solution. In particular, the high field region of the spectra of [Cu(isodh-2H)] complex is partially resolved into its gx and gy components (gx = 2.0469, gy = 2.0215) and the average g⊥ value is calculated by the expression g⊥ = ½ (gx + gy). This may be due to a small orthorhombic component superimposed on the perpendicular component, thereby lowering the equatorial symmetryCitation30. The observed g and A values for isodh complex suggest a square planar geometry around Cu(II) ion. Moreover, the observation gII >g⊥ >ge (2.0023), shows that the unpaired electron is in the dx2-y2 orbital of copper(II) ionCitation31,Citation32. No ΔMs = 2 transition at half field was observed for any of these complexes, ruling out the possibility of dimeric forms.
Figure 2. ESR spectra of copper(II) complexes (A) in solid state (B) in DMSO solution.
Table 3. ESR spectral parameters for copper(II) complexes.
1H and 13C NMR
The 1H NMR spectrum of isodh exhibits signals due to aromatic protons as multiplet at δ 6.83–7.70 (8H), three >NH protons as singlet at 8.10 (1H), 8.30 (1H) and 8.33 (1H),−CH=N- proton as singlet at 9.02 (1H), Ar-OH as singlet at 10.31 (1H) ppmCitation33. In the spectra of [Zn(isodh-2H)], only two >NH proton signals are observed at a slightly downfield shift as compare to isodh, which is indicative of deshielding of >NH proton and in turn shows interaction of the two >C=N- groups with the metal ion. The disappearance of >NH proton signal of indole ring indicates its involvement in enolization of endole >C=O group and deprotonates during complexation. The signals for aromatic protons show a minor shift in their position in the complex. A significant downfield shift in -CH=N- signal is characteristic of the involvement of the -CH=N- group in bonding with the metal ion. The ismdh exhibits signals for >CH2 as singlet at δ 4.03 (2H), aromatic protons as multiplet at 6.82–7.76 (8H), three >NH protons as singlet at 8.17 (1H), 8.50 (1H) and 8.53 (1H), -CH=N- as singlet at 9.90 (1H) and Ar-OH as singlet at 11.00 (1H) ppm. The downfield shift of two amide >NH protons from 8.17, 8.50 to 8.22, 8.60 ppm in its Zn(II) complex suggests the coordination of the two >C=N- nitrogen to the metal ion. However, the unshifted position of indole ring >NH proton signal in the Zn(II) complex of ismdh indicates the non- involvement of this group in bonding. There is minor shift in the position of signals of >CH2 and aromatic protons (). The absence of the resonance signal due to Ar-OH proton in Zn(II) complexes of both the ligands provides an evidence for the deprotonation of the phenolic -OH group of ligand during complexation as inferred from IR spectral data also. The disappearance of >NH, -CH=N- and Ar-OH protons in both the ligands in their D2O exchanged 1H NMR spectra confirm their assignments.
Table 4. 1H NMR spectra of ligands and their complexes.
In Zn(II) complexes of isodh and ismdh ligands, the bonding through phenolate oxygen has been inferred from the deshielding observed in >C-O− carbon as compared with the ligands. The appearance of an additional >C-O− carbon signal in Zn(II) isodh complex indicates the enolization of indole >C=O group during complex formation. Only a minor shift in the positions of two amide >C=O carbon signals in Zn(II) complexes of both the ligands indicates that these groups do not participate in bonding. The bonding of the ligands through two >C=N- nitrogen is indicated by the deshielding observed in >C=N- carbons in their complexes ().
Table 5. Citation13C NMR spectra of ligands and their complexes.
IR spectra
The ligands show broad bands centred at 3222 and 3180 cm−1 for isodh and at 3226 and 3184 cm−1 for ismdh assigned as ν(NH) due to presence of two amide >NH and one indole ring >NH groups in each ligand. These ligands also show a broad band ν(OH) at 3446 cm−1 in isodh and at 3452 cm−1 in ismdh due to phenolic−OH group. The absence of ν(OH) band in all the metal complexes suggests deprotonation of the phenolic proton during complexation. This is further confirmed by the appearance of a new band assigned as ν(C-O)− between 1263 and 1280 cm−1. In the metal complexes, ν(NH) for amide either occur at the same frequency as in parent ligands or shifted very slightly from their position suggesting no participation of the two amide >NH groups in bondingCitation34. However, ν(NH) for indole ring disappears in all the isodh complexes indicating that indol >NH group is involved in enolization of indole >C=O group and deprotonates during complex formation.
The ligands show two ν(C=O) bands at 1729 and 1690 cm−1 for isodh and at 1719 and 1679 cm−1 for ismdh due to presence of an indole >C=O and two amide >C=O groups, respectively. In metal complexes, the ν(C=O) due to two amide >C=O groups occur nearly at the same wave number as in parent ligands, suggesting non-involvement of the two amide >C=O groups in bonding. The minor shifted position of ν(C-N) bands in the metal complexes as compared to the ligands also support the non-involvement of the two amide >C=O groups in bonding. However, the other ν(C=O) band due to indole >C=O group is considerably shifted to lower frequency by 19–23 cm−1 in all ismdh complexes, indicating the participation of indole >C=O group in bonding with metalCitation35. The disappearance of ν(C=O) of indole ring in all the isodh complexes suggests the enolization of indole ring >C=O group during complexation ().
Table 6. Important IR spectral bands (cm−1) and their assignments.
The ν(C=N) bands observed at 1627 and 1622 cm−1 in the spectra of isodh and ismdh, respectively, shifted to lower frequency by 10–15 and 9–16 cm−1 in their metal complexes suggesting coordination through the two azomethine groupsCitation36. A weak band due to ν(N-N) observed at 961 cm−1 in isodh and 968 cm−1 in ismdh shifts to higher frequency by 35–41 and 37–40 cm−1, respectively, in their complexes indicates the coordination of one of the nitrogen atom of the N-N group with metal. All the metal complexes also show weak bands in the ranges 529–545 and 457–487 cm−1, which may be tentatively assigned to ν(M-O) and ν(M-N), respectively. Co(II), Ni(II) and Cu(II) complexes of ismdh show a broad ν(OH) band due to water in the range 3460–3476 cm−1. These complexes also show weak bands in the ranges 947–961, 749–760 and 651–666 cm−1 due to presence of coordinated water molecules. On the basis of above discussion, general structures for the metal complexes are proposed ().
Antifungal activity
The antifungal experimental data () indicate that the ligands as well as their complexes show an appreciable activity against Aspergillus sp., Pseudocercospora sp. and Trichoderma sp. at 0.5, 1.0 and 1.5 mg/mL concentration. Comparative analysis shows a higher antifungal activity for the metal complexes than the free ligandsCitation37. The activity is appreciably enhanced at the higher concentration of the compounds. DMSO control has shown a negligible activity as compare to the metal complexes and ligands. The metal complexes show better activity against Trichoderma sp. [Cd(isodh-2H)] complex shows the highest activity (100%) against Trichoderma sp. among all the complexes at the concentration of 1.5 mg/mL. [Cu(ismdh-H)(H2O)2]Cl shows the highest activity (98%) against Aspergillus sp. The antifungal activity of the present complexes generally varies in the following order of fungal species.
Table 7. Antifungal activity of the ligands and their complexes.
Trichoderma sp. > Aspergillus sp. > Pseudocercospora sp.
All the metal complexes exhibited greater antifungal activities against Trichoderma sp. as compared to the standard drug Miconazole. The ligand isodh and its complexes are more effective as compared to ligand ismdh and its complexes. The activity varies in the following order of metal ions:
Cd > Zn > Cu > Co > Ni
The increase in antimicrobial activity of metal complexes may be explained on the basis of chelation theory. On chelation, the polarity of the metal ion will be reduced to a greater extent due to the overlap of the ligand orbital and partial sharing of the positive charge of the metal ion with donor groupsCitation38. Further, the mode of action of the compounds may involve the formation of a hydrogen bond through the azomethine group with the active centre of cell constituents, resulting in interference with the normal cell processCitation39. The toxicity of the complexes can be related to the strength of the metal-ligand bond, besides other factors such as size of the cationCitation40 receptor sites, diffusion and a combined effect of the metal and ligands for inactivation of the bio-molecules.
Antibacterial activity
The metal complexes, ligands, standard drug Ampicillin and control were screened separately for their antibacterial activity against E. coli (gram negative) and B. subtilis (gram positive). The activity of the complexes has been compared with the activity of a common standard antibiotic Ampicillin and % Activity Index has been calculated for the complexes. It has been observed that the metal complexes are more active than the ligands and the activity increases with increasing the concentration of the complexesCitation41. The antibacterial results () suggest that the ligands and their complexes show a significant antibacterial activity against both the bacteriaCitation42 as compared to the standard drug (Ampicillin). However, the complexes are more effective against B. subtilis than E. coli. The % Activity Index data indicate that [Cu(ismdh-H)(H2O)2]Cl shows the highest antibacterial activity (94%) against B. subtilis at the concentration of 2.0 mg/mL, whereas [Zn(ismdh-H)]Cl shows the highest activity against E. coli (Activity Index = 94%).
Table 8. Antibacterial activity of the ligands and their complexes.
Conclusions
The present paper includes the novel synthesis of two biologically relevant unsymmetrical Schiff bases, isatin salicylaldehyde oxalic acid dihydrazone and -malonic acid dihydrazone. The Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of above ligands have been synthesized and characterized using various spectral techniques. The IR and NMR spectra show that the isodh bonds with the metal ion through deprotonated indole enolate, deprotonated phenolate and two >C=N groups, whereas ismdh through two >C=N-, indole >C=O and a deprotonated phenolate group. Electronic and ESR spectral studies indicate square planar environment in solid state for Co(II), Ni(II), Cu(II) complexes of isodh and octahedral for ismdh complexes. The complexes show an appreciable antifungal and antibacterial activity.
Acknowledgments
The authors thank the Head, S.A.I.F., Indian Institute of Technology, Mumbai, for recording ESR spectra, Prof. Nand Lal, Department of Life Sciences, CSJM University, Kanpur, for the help in biological screening.
Declaration of interest
The authors V.P.S and D.P.S. are grateful to UGC, New Delhi, and CSIR, New Delhi, respectively, for financial assistance.
Related Research Data
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