1 Introduction

The greater importance of using isatine (1H-indole-2,3-dione) and its derivatives is due to their pharmaceutical applications and biological activity (Ali et al. 2011; Singh et al. 2010). Hydrazone compounds have played an important role in the development of coordination chemistry, due to their ability to form a range of stable complexes which have applications in different fields. These include their role in biological, medical and environmental sciences (Cohen 1967; Tarafder et al. 2002). Schiff-base ligands containing an azomethine group (–C=N–) are considered as an important class of compounds because of their capability to stabilize different metals in various oxidation states, and their complexes are extensively studied due to synthetic approach flexibility. Furthermore, the hydrazone Schiff-base ligands are a very important species for synthetic inorganic chemists as they are widely used to design compounds for biological modelling applications, in catalysis, and in the preparation of liquid crystals (Larson and Pecoraro 1991; Ramade et al. 1997; Hoshino 1998). Schiff-base ligands containing various donor atoms (such as N, O, S, etc.) show broad biological activities, and are of special interest because of the variety of ways in which they are bonded to the transition metal ions (Shi et al. 2009; Zhao et al. 2001). In this article, we have reported the synthesis and spectral characterisation of new isatinic hydrazone Schiff-base compounds (L1, L2 and L3) and their metal complexes with Co(II), Zn(II) and Cd(II) ions. In addition, biological experiments on both Gram-positive (G+) and Gram-negative (G−) strains of bacteria were also carried out.

2 Experimental

2.1 Materials

All reagents were commercially available and used without further purification. Solvents were distilled from appropriate drying agents immediately prior to use.

2.2 Physical Measurements

Melting points were obtained on a Buchi SMP-20 capillary melting point apparatus and are uncorrected. IR spectra were recorded as KBr discs using a Shimadzu 8400 S FTIR spectrophotometer in the range 4000–400 cm−1. Electronic spectra of the prepared compounds were measured in the region 200–1100 nm for 10−3 M solutions in DMSO at 25 °C using a Shimadzu 160 spectrophotometer with 1.000 ± 0.001 cm−1 matched quartz cell. 1H and 13C NMR spectra were acquired in DMSO–d6 solutions using a Jeol 400 MHz spectrometer with tetramethylsilane (TMS) as an internal standard for 1H NMR. Metals were determined using a Shimadzu (A.A) 680 G atomic absorption spectrophotometer. Chloride was determined using potentiometer titration method on a (686–Titro processor–665Dosimat–Metrohm Swiss). Conductivity measurements were made with DMSO solutions using a PW 9526 digital conductivity meter and room temperature magnetic moments were measured with a magnetic susceptibility balance (Johnson Matthey Catalytic System Division).

3 Synthesis

3.1 Preparation of Ligands

The isatinic hydrazone ligands were synthesised adopting a conventional procedure published in literature (Menger et al. 1975), and as follows:

3.1.1 Preparation of L1

A solution of isatine (1.0 g, 6.79 mmol) in methanol (5 mL) was added dropwise with stirring to a mixture of furan-2-carboxylic acid hydrazide (0.85 g, 6.79 mmol) in methanol (5 mL), and 4 drops of glacial acetic acid was added to the reaction mixture. The mixture was allowed to reflux for 4 h, and then filtered off. The filtrate was allowed to slowly evaporate at room temperature to give the required compound as a pale yellow solid. Yield: 0.93 g (%54), m.p = 183 °C. IR data (cm−1): 3410, 3199 ν(N–H) of isatine and hydrazinic, 1697 ν(C=O) of isatine, 1670 ν(C=O) of hydrazone and 1622 ν(C=N). NMR data (ppm), δ H (400 MHz, DMSO-d6): 6.78 (C2–H), 6.91 (N–H) of hydrazinic, 6.96 (C11–H), 7.06 (C3–H), 7.38 (C12–H), 7.48 (C10–H), 7.63 (C13–H), 7.95 (C1–H) and 8.05 (H–N–C=O of isatine); δ C (100.63 MHz, DMSO-d6, ppm): 131.22 (C1), 116.17 (C2), 111.37 (C3), 132.49 (C4), 170.05 (C5), 155.36 (C7), 152.08 (C6), 129.24 (C8), 122.45 (C9), 123.72 (C10), 123.35 (C11), 124.25 (C12), 119.46 (C13).

3.1.2 Preparation of L2

The method used to prepare thiophene-2-carboxylic acid (2-oxo-1,2-dihydro-indol-3-ylidene) hydrazide (L2) was similar to that for L1, but with thiophene-2-carboxylic acid hydrazide (0.97 g, 6.79 mmol) in place of furan-2-carboxylic acid hydrazide. The quantities of other reagents used were adjusted accordingly. An identical work-up procedure gave the required compound as a pale brown solid. Yield: 1.26 g (% 68), m.p = 170 °C. IR data (cm−1): 3398, 3184 ν(N–H) of isatine and hydrazinic, 1693 ν(C=O) of isatine, 1663 ν(C=O) of hydrazide,1622 ν(C=N). NMR data (ppm), δ H (400 MHz, DMSO-d6): 6.85 (N–H) of hydrazinic, 6.94 (C11–H), 7.08 (C2–H), 7.28 (C12–H), 7.34 (C10–H), 7.47 (C3–H), 7.60 (C1–H), 7.72 (C13–H) and 8.02(–H–N–C=O of isatine); δ C (100.63 MHz, DMSO-d6, ppm): 129.59 (C1), 124.50 (C2), 132.18 (C3), 148.58 (C4), 166.96 (C5), 151.56 (C6), 161.34 (C7), 133.72 (C8), 116.11 (C9), 125.37 (C10), 123.09 (C11), 128.65 (C12), 110.61 (C13). The mass spectrum of L2 showed several peaks corresponding to successive fragmentations of the molecule. Peak detected at m/z 271.30 (4%) (M)+ represents the molecular ion peak of the ligand. Other distinct peaks were observed in the spectrum at m/z 144.13 (5%), 75.09 (40%), assigned to the [M-(C5H5NOS)]+ and [M–(C5H5NOS) + (C2HN2O)]+ fragments, respectively.

3.1.3 Preparation of L3

The method used to prepare 2-(pyridine-2-yl-hydrazono)-1,2-dihydro-indol-3-one) (L3) was analogous to that for L1, but with 2-hydrazino pyridine (0.74 g, 6.79 mmol) instead of furan-2-carboxylic acid hydrazide. The quantities of other reagents were adjusted accordingly, and an identical work-up procedure gave the required compound as a pale brown solid. Yield: 0.89 g (%55), m.p = 189 °C. IR data (cm−1): 3300, 3151 ν(N–H), 1689 ν(C=O), 1622 ν(C=N). NMR data (ppm), δ H (400 MHz, DMSO-d6): 7.78 (C1–H), 6.93 (C2–H), 7.28 (C3–H), 7.01 (C4–H), 7.44 (C10–H), 7.05 (C11–H), 7.10 (C–12), 7.48 (C13–H), 7.84 (N–H), 8.14 (C–N–H); δ C (100.63 MHz, DMSO-d6, ppm): 118.29 (C4), 119.72 (C2), 121.87 (C13), 122.57 (C9), 123.21 (C11), 125.14 (C10), 130.21 (C12), 131.12 (C3), 139.28 (C8), 148.72 (C1), 151.18 (C6), 155.26 (C7), 157.11 (C5). The mass spectrum of L3 ligand showed peak at m/z 238.24 (3%) (M)+ related to the molecular ion peak of the ligand. Peaks detected at m/z 148.13 (5%), 79.09 (40%), were attributed to the [M–(C5H2N2)]+ and [M–(C5H2N2) + (C2HN2O)]+ fragments, respectively.

3.2 General Synthesis of the Complexes

A methanolic solution (10 mL) of the metal chloride salt (1 mmol) was added with stirring into methanolic solution of the isatinic hydrazone ligand (2 mmol) in methanol (15 mL). The reaction mixture was then refluxed for 2 h on a water bath until a coloured precipitate formed, which was collected by filtration, washed with cold ethanol (5 mL) and dried at room temperature. Elemental analysis data, colours, and yields for the complexes are given in Table 1.

3.3 Determination of Bacteriological Activity

Bioactivities were investigated using agar-well diffusion method (Rahman 2001). The wells were dug in the media with the help of a sterile metallic borer with centres at least 24 mm. Recommended concentration (100 μL) of the test sample 1 mg/mL in DMSO was introduced in the respective wells. The plates were incubated immediately at 37 °C for 20 h. Activity was determined by measuring the diameter of zones showing complete inhibition (mm). To clarify the role of DMSO in the biological screening, separate studies were carried out with the DMSO solutions only and they showed no activity against any bacterial strains.

4 Results and Discussion

4.1 Chemistry

The reaction of isatine with furan-2-carboxylic acid hydrazide, thiophene-2-carboxylic acid hydrazide and hydrazino pyridine in mole ratios 1:1 resulted in the formation of L1, L2 and L3, respectively (see Scheme 1). The isatinic Schiff-base ligands were characterised by elemental analysis (Table 1), IR (Table 2), UV–Vis (Table 3) spectroscopy, 1H–, 13C-NMR and mass spectroscopy for L2 and L3 spectra. The di-electrolyte metal complexes were synthesised by mixing at reflux 2 mol of the ligands with 1 mol of the appropriate metal chloride. Monomeric complexes of the general formulae [M(Ln)2]Cl2 (where M = CoII, ZnII and CdII; n = L1, L2 and L3) were obtained (Scheme 2). The complexes are air-stable solids, soluble in DMSO and DMF. The complexes are sparingly soluble in MeOH, EtOH and not soluble in other common organic solvents. The coordination geometries of the complexes were deduced from their spectra. The analytical data (Table 1) agree well with the suggested formulae. Conductivity measurements of the complexes in DMSO solutions lie in the 68–79 cm2Ω−1mol−1 range, indicating their 1:2 electrolytic behaviours (Geary 1971) (Table 1).

Scheme 1
scheme 1

Synthesis route of hydrazone Schiff-bases

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Table l Colours, yields, elemental analyses, and molar conductance values
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Table 2 IR frequencies (cm−1) of the compounds
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Table 3 U.V–Vis spectral data in DMSO solutions
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Scheme 2
scheme 2

Proposed structures of complexes

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4.2 IR and NMR Spectra

The important infrared bands for the ligands and their complexes together with their assignments are listed in Table 2. The IR spectra of the ligands show characteristic bands at 1697, 1693 and 1689 cm−1 due to ν(C=O) of isatine moiety. Bands due to ν(C=O) of hydrazone group were observed at 1670 and 1663 in the L1 and L2, respectively (see supporting information(SI), Figures SI 1–3). The bands of ν(C=N) imine functional groups appeared at ca. 1622 cm−1. Bands at 3410; 3199, 3398; 3184 and 3331; 3151 cm−1 were assigned to the ν(N–H) stretching group of isatine and hydrazinic for ligands L1, L2 and L3, respectively (Al-Dulaimi et al. 2011; Al-Jeboori et al. 2005; Nakomoto 1996). The IR spectra of the complexes exhibited ligand bands with the appropriate shifts due to complex formation (Table 2). The ν(C=O) of the isatine group and ν(C=N) imine bands appeared at lower frequency and were observed in the -range 1682–1693 and 1603–1616 cm−1, respectively, compared with that detected in the free ligands in the range 1689–1697 and 1620–1622 cm−1 for the ν(C=O) and ν(C=N) groups, respectively. The shift of these bands to lower frequencies is due to reduced bond order in L1, L2 and L3. This can be attributed to delocalisation of metal electron density (t 2g) to the π-system of the ligand (Al-Jeboori et al. 2009; Livingstone et al. 1975), indicating coordination oxygen of carbonyl group and nitrogen of the C=N moieties to the metal atoms (El-Sonbati et al. 2002). The ν(C–O) and ν(C–S) of the furan and thiophene groups which were detected at 1238 and 1384 cm−1 in L1 and L2, respectively, were shifted to lower frequencies and appeared at 1219–1223 and 1378–1381 cm−1 for the complexes of L1 and L2, respectively, indicating coordination of the oxygen and the sulphur of the rings to the metal atoms. The ν(C=N) stretching of pyridine at 1587 cm−1 in L3 is shifted to higher frequency and observed around 1593–1598 cm−1 for the complexes, indicating coordination of nitrogen of the C=N pyridine moiety to the metal atoms (Al-Jeboori et al. 2010). Further, the IR spectra of the complexes display characteristic bands for ν(M–O) and ν(M–N) vibration mode around 628–598, 623–607, 614–634 and 517–5553, 519–563, 523–561 cm−1 for ligands L1, L2 and L3, respectively (Al-Jeboori et al. 2009). These bands indicated that the imine nitrogen and the oxygen of the carbonyl for the ligands are involved in coordination with metal ion. The 1H NMR spectra of the ligands in DMSO-d6 showed peaks at 6.78–7.95, 7.8–7.60 and 6.93–7.78 ppm assigned to protons of furan, thiophene and pyridine ring for L1, L2 and L3, respectively. Peaks at chemical shifts 6.91–7.84 and 8.02–8.14 ppm were assigned to N–H of hydrazinic and isatine groups, respectively (see supporting information, Figures SI 7, 9, 11). The 13C NMR spectra of the ligands in DMSO-d6 showed peaks at 152.08, 151.56 and 151.18 assigned to C6 in L1, L2 and C5 in L3, respectively. Signals resonances at 155.36, 161.34 and 157.11 were attributed to C7 in L1, L2 and C6 in L3, respectively (see supporting information, Figures SI 8, 10, 12).

The 1H NMR spectrum of the [Zn(L1)2]Cl2 complex in DMSO-d6 showed peaks at 7.27, 7.32 and 7.79 ppm assigned to furan ring protons. These resonances shifted downfield compared with that in free ligand, due to complex formation. The recorded peaks at 7.30, 7.52, 7.65 and 7.76 ppm were assigned to aromatic ring of isatine. The N–H of hydrazinic and isatinic groups was observed at δ = 8.17 and 8.43 ppm, respectively, which are deshielded compared with that in the free ligand. This is due to coordination of carbonyl group through the lone pair electron of oxygen, and subsequently electron withdrawing from carbonyl group towards metal centre caused decrease in electron density on the N–H group (see supporting information, Figures SI 13).

4.3 Mass Spectra

The mass spectra of the ligands were also consistent with the proposed structural formulae (see “Experimental” section). The positive ion ES mass spectra for L2 and L3 are reported. The mass spectrum of L2 showed several peaks corresponding to successive fragmentations of the molecule. Peak detected at m/z 271.30 (4%) (M)+ represents the molecular ion peak of the ligand. Other distinct peaks were observed in the spectrum at m/z 144.13 (5%), 75.09 (40%), assigned to the [M–(C5H5NOS)]+ and [M–(C5H5NOS) + (C2HN2O)]+ fragments, respectively (see supporting information, Figure SI 14).

L3 ligand showed peak at m/z 238.24 (3%) (M)+1 related to the molecular ion peak of the ligand. Peaks detected at m/z 148.13 (5%), 79.09 (40%) were attributed to the [M–(C5H2N2)]+ and [M–(C5H2N2) + (C2HN2O)]+ fragments, respectively (see supporting information, Figure SI 15).

4.4 Electronic Spectra and Magnetic Measurement

The UV–Vis spectra of the ligands exhibit high intense absorption peaks around 250-267 and 314-376 nm, assigned to π → π * and n → π *, respectively (Silverstein 2005) (see supporting information, Figures SI 4-6). The electronic spectra of the cobalt (II) complexes with L1 and L2 exhibit high intense peaks at 268 and 214, respectively, due to ligand field. While in L3 the spectrum shows peaks at 265–300 nm related to the intra-ligand. Bands detected at 379, 369 and 375 nm were attributed to charge transfer transition for L1, L2 and L3, respectively. The electronic spectra of the Co(II) complexes for L1, L2 and L3 exhibited band which can be attributed to 4T1g(F) → 4A2g(F) transition that is consistent with octahedral assignment. The magnetic moment of these complexes is typical for a high spin distorted octahedral structure (Lever 1984; Figgis 1967; Nasman 2008). The spectra of the Zn and Cd(II) complexes for L1, L2 and L3 exhibited bands were assigned to π → π* and L → M charge transfer (Lever 1984; Aly et al. 1985).

4.5 Antimicrobial Activity

The free hydrazone Schiff-base ligands and their metal complexes were screened against Bacillus (G+) and Ecoli (G−) to assess their potential as an antimicrobial agent by disc diffusion method, Table 4. The effects of prepared compounds depend on the type of tested bacteria. It is clear that the ligands showed different activity effect on both types of the Gram-positive (G+) and Gram-negative (G−) of the tested bacteria. L1 appears to be highly active against Gram-negative (G−) strain. However, L3 is shown to be highly active against Gram-positive (G+) strain. In general, complexes display a range of activity against tested strains of bacteria. [CoII(L1)2]Cl2 complex showed the highest activity against both strains, the negative Gram (G−) and the positive Gram (G+), among L1-complexes. On the other hand, the Zn-complexes for L2 and L3 showed the highest activity against both strains of bacteria (Chohan et al. 2004).

Table 4 Antibacterial activities of the synthesised Hydrazone Schiff-bases and their metal complexes
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5 Conclusion

In this paper, we have explored the synthesis and coordination chemistry of some complexes derived from the hydrazone Schiff-base ligands (L1, L2 and L3). The complexes were prepared by mixing at reflux 2 mmol of the Schiff-base ligand with 1 mmol of the appropriate metal chloride. Complexes of the general formulae [M(Ln)2]Cl2 [where M=Co(II), Zn(II) and Cd(II)] were obtained. Physico-chemical analysis indicated the formation of six coordinate dicationic metal complexes. Biological activities revealed that the ligands and their metal complexes showed different activity effect on both types of the Gram-positive (G+) and Gram-negative (G−) of the tested bacteria.