# Synthesis and Characterization of New Schiff Bases Derived from N (1)-Substituted Isatin with Dithiooxamide and Their Co(II), Ni(II), Cu(II), Pd(II), and Pt(IV) Complexes

Authors: Ahlam J. Abdul-Ghani; Asmaa M. N. Khaleel
Journal: Bioinorganic Chemistry and Applications
 (2009)

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## Abstract

Three new Schiff bases of N-substituted isatinLI, LII, and LIII = Schiff base of N-acetylisatin, N-benzylisatin, and N-benzoylisatin, respectively, and their metal complexes C1a,b=[Co2(LI)2Cl3]Cl, C2=[Ni(LI)2Cl2]0.4BuOH, C3=[CuLICl(H2O)]Cl·0.5BuOH,
C4=[Pd(LI)2Cl]Cl, C5=[Pt(L1)2Cl2]Cl2·1.8EtOH.H2O, C6a=[CoLIICl]Cl·0.4H2O·0.3DMSO, C6b=[CoLIICl]Cl·0.3H2O·0.1BuOH, C7=[NiLIICl2], C8=[CuLII]Cl2·H2O, C9=[Pd(LII)2]Cl2, C10=[Pt(LII)2.5Cl]Cl3, C11a=[Co(LIII)]C12·H2O, C11b=[Co(LIII)]Cl2·0.2H2O, and C12=[Ni(LIII)2]Cl2, C13=[Ni(LIII)2]Cl2 were reported. The complexes were characterized by elemental analyses, metal and chloride content, spectroscopic methods, magnetic moments, conductivity measurements, and thermal studies. Some of these compounds were tested as antibacterial and antifungal agents against Staphylococcus aureus, Proteus vulgaris, Candida albicans, and Aspergillus niger.


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## Body

## 1. Introduction

Isatin (indole-2,3-dione) and its derivatives have shown a wide scale of biological activities such as antibacterial [1–3], antifungal [1, 3–5], anticonvulsant [2, 6], anti-HIV [7], anticancer [1, 2], antiviral [1], and enzyme inhibitors [2]. The Schiff bases (a) and (b) (Scheme 1) derived from isatin and its derivatives with different amines have been studied [1, 2, 6, 8–13]. The reaction of N-acetyl, N-benzoyl, and N-tosylisatin and their Schiff base derivatives (c) and (d) (Scheme 1) with ethanol, methanol, isopropyl alcohol, allyl alcohol, TsNH2, pyrrolidine, and water yield products resulting from nucleophilic attack at the C-2 carbonyl that leads to heterocyclic ring cleavage [8, 14]. The present work aims to study the synthesis and antibacterial activity of three new ligands derived from condensation of N-acetyl, N-benzyl, and N-benzoylisatin with the chelating agent dithiooxamide (ethanedithioamide or rubeanic acid) dto and their metal complexes. The Schiff bases of dithiooxamide and their complexes have received most of the attention because of the semiconductive, magnetic, spectroscopic, and thermal properties [15–17] as well as being used as semiconductors antibacterial and antifungal agents [18–20].Scheme 1
Schiff bases of isatin derivatives.


## 2. Experimental/Materials and Methods

All chemicals used were of analytical reagent grade (AR) exceptdto and ethanol which were purified prior to use [21]. FTIR spectra were recorded on SHIMADZU FTIR-8400S, Fourier Transform, Infrared spectrophotometer. The electronic spectra (λ(200–1100) nm) in different solvents were recorded on Shimadzu (UV-Vis)-160 spectrophotometer. Elemental microanalyses were performed on Euro vector EA 3000 A. The metal contents of the complexes were determined by atomic absorption technique using Varian-AA775, Atomic Absorption Spectrophotomer. Mass spectra were recorded on Shimadzu QP 5050A. 1H NMR was performed by using Bruker Ultra Sheild 300 MHz NMR spectrophotometer. Thermal analyses (TG and DTG) were carried out by using Shimadzu Thermal Analyzer Type 50 H. Electrical conductivity measurements for complexes (10-3 M) in DMF and DMSO at room temperature were carried out by using Hunts Capacitors Trade Mark British made. Magnetic moments (μeff. B.M) for the prepared complexes in the solid state at room temperature were measured by using Bruker Magnet B.M-6. The chloride content for complexes was determined by Mohr’s method. N-acetylisatin, N-benzylisatin, N-benzoylisatin, and PdCl2(phCN)2 were prepared by methods reported in literature [6, 22–25].


## 3. Synthesis of Ligands

All attempts to prepare 1-(9a-Hydroxy-2,3-dithiooxo-1,2,3,9a-tetrahydro-1,4,9-triaza-fluoren-9-yl)-ethanone (LI) (Scheme 2) and 9-Benzyl-9a-hydroxy-9,9a-dihydro-1H-1,4,4-triaza-fluorene-2,3-dithione (LII) (Scheme 2) in solutions were unsuccessful; therefore solid reaction was carried out to prepare the two ligands.Scheme 2
The structures of the prepared ligandsLI, LII, and LIII.


### 3.1. Schiff Base of N-Acetylisatin: 1-(9a-Hydroxy-2,3-dithiooxo-1,2,3,9a-tetrahydro-1,4,9-triaza-fluoren-9-yl)-ethanone (LI)

A powdered mixture of N-acetylisatin (0.3092 g, 1.6 mmol) anddto (0.0983 g, 0.8 mmol) in a sealed Carius tube was heated in a stirred oil bath at 160–170°C for 2 hours. The melt colour was changed from orange to dark brown. After cooling to room temperature, the solid product was ground and dissolved in butanol, followed by precipitation with ether. A black precipitate was formed. The product was filtered off and washed several times with ether to remove the unreacted materials giving brown crystals. Yield (0.116 g, 48.76%), m.p (220°C decomp.). 1H NMR data δ(ppm), (CDCL3): 2.508 (3H,s,CH3); 3.34 (2H,s,OH and NH thioamide); 7.074–7.853 (4H, m, aromatic protons). MS(EI), m/z(%): 207(21), 161(10), 146(23), 133(9), 92(10), 78(59), 63(84), 44(100). Anal. for C12H9N3O2S2 Calcd. C, 49.48; H, 3.09; N, 14.43%; Found: C, 50.54; H, 3.22; N, 13.23%.


### 3.2. Schiff Base of N-Benzylisatin: 9-Benzyl-9a-hydroxy-9,9a-dihydro-1H-1,4,4-triaza-fluorene-2,3-dithione (LII)

A powdered mixture of N-benzylisatin (0.829 g, 3.5 mmol) anddto (0.85 g, 7 mmol) was heated in a sealed Carius tube in an oil bath at 140°C for 10 hours. Colour of melt was changed from orange to dark brown. After cooling to room temperature, a solid mass was formed. The product was ground and purified several times in refluxing ethanol, filtered off, washed with hot ethanol followed by acetone and dried, giving dark brown crystals. Yield (0.2679 g, 22.3%), m.p (>250°C). 1H NMR data δ(ppm), (DMSO): 3.45(2H, s, OH and NH thioamide); 5.1(2H, w, CH2 benzyl); 6.9–7.2(9H, m, aromatic protons). MS(EI), m/z(%): 156(11), 149(15), 127(13), 105(11), 78(100), 63(100). Anal. for C17H13N3OS2 Calcd.: C, 60.17; H, 3.83; N, 12.38%; Found: C, 61.10; H, 3.43; N, 12.98%.


### 3.3. Schiff Base of N-Benzoylisatin: N-[2-(3-oxo-5,6-dithioxo-3,4,5,6-tetrahydro-pyrazin-2-yl)-phenyl] benzamide (LIII)

Equimolar amounts of benzoylisatin (0.2 g, 0.79 mmol) anddto (0.0957 g, 0.79 mmol) in butanol (2 cm3) containing 4 drops of piperidine were heated under reflux with stirring for 5 hours during which the colour of solution was changed from orange to brown. The solution mixture was left to stand overnight and then cooled down to 0°C. Cold ether was added until a dark brown precipitate was formed. The product was filtered off, washed several times with acetone followed by ether. Yield (0.0857 g, 30.51%), m.p. (250°C decomp.), 1H NMR data (ppm), (DMSO): 4.902–5.101(1H, b, NH thioamide); 7.144–7.860(9H, m, aromatic protons); 10.124(1H, b, NH benzoyl moiety). MS(EI), m/z(%): 296.6(13), 267.5(7), 232.6(20), 195.6(15), 149.5(6), 104.4(27), 83.4(6). Anal. for C17H11N3O2S2 Calcd.: C, 57.79; H, 3.11; N, 11.89%; Found: C, 57.39; H, 3.54; N, 11.30%.


## 3.1. Schiff Base of N-Acetylisatin: 1-(9a-Hydroxy-2,3-dithiooxo-1,2,3,9a-tetrahydro-1,4,9-triaza-fluoren-9-yl)-ethanone (LI)

A powdered mixture of N-acetylisatin (0.3092 g, 1.6 mmol) anddto (0.0983 g, 0.8 mmol) in a sealed Carius tube was heated in a stirred oil bath at 160–170°C for 2 hours. The melt colour was changed from orange to dark brown. After cooling to room temperature, the solid product was ground and dissolved in butanol, followed by precipitation with ether. A black precipitate was formed. The product was filtered off and washed several times with ether to remove the unreacted materials giving brown crystals. Yield (0.116 g, 48.76%), m.p (220°C decomp.). 1H NMR data δ(ppm), (CDCL3): 2.508 (3H,s,CH3); 3.34 (2H,s,OH and NH thioamide); 7.074–7.853 (4H, m, aromatic protons). MS(EI), m/z(%): 207(21), 161(10), 146(23), 133(9), 92(10), 78(59), 63(84), 44(100). Anal. for C12H9N3O2S2 Calcd. C, 49.48; H, 3.09; N, 14.43%; Found: C, 50.54; H, 3.22; N, 13.23%.


## 3.2. Schiff Base of N-Benzylisatin: 9-Benzyl-9a-hydroxy-9,9a-dihydro-1H-1,4,4-triaza-fluorene-2,3-dithione (LII)

A powdered mixture of N-benzylisatin (0.829 g, 3.5 mmol) anddto (0.85 g, 7 mmol) was heated in a sealed Carius tube in an oil bath at 140°C for 10 hours. Colour of melt was changed from orange to dark brown. After cooling to room temperature, a solid mass was formed. The product was ground and purified several times in refluxing ethanol, filtered off, washed with hot ethanol followed by acetone and dried, giving dark brown crystals. Yield (0.2679 g, 22.3%), m.p (>250°C). 1H NMR data δ(ppm), (DMSO): 3.45(2H, s, OH and NH thioamide); 5.1(2H, w, CH2 benzyl); 6.9–7.2(9H, m, aromatic protons). MS(EI), m/z(%): 156(11), 149(15), 127(13), 105(11), 78(100), 63(100). Anal. for C17H13N3OS2 Calcd.: C, 60.17; H, 3.83; N, 12.38%; Found: C, 61.10; H, 3.43; N, 12.98%.


## 3.3. Schiff Base of N-Benzoylisatin: N-[2-(3-oxo-5,6-dithioxo-3,4,5,6-tetrahydro-pyrazin-2-yl)-phenyl] benzamide (LIII)

Equimolar amounts of benzoylisatin (0.2 g, 0.79 mmol) anddto (0.0957 g, 0.79 mmol) in butanol (2 cm3) containing 4 drops of piperidine were heated under reflux with stirring for 5 hours during which the colour of solution was changed from orange to brown. The solution mixture was left to stand overnight and then cooled down to 0°C. Cold ether was added until a dark brown precipitate was formed. The product was filtered off, washed several times with acetone followed by ether. Yield (0.0857 g, 30.51%), m.p. (250°C decomp.), 1H NMR data (ppm), (DMSO): 4.902–5.101(1H, b, NH thioamide); 7.144–7.860(9H, m, aromatic protons); 10.124(1H, b, NH benzoyl moiety). MS(EI), m/z(%): 296.6(13), 267.5(7), 232.6(20), 195.6(15), 149.5(6), 104.4(27), 83.4(6). Anal. for C17H11N3O2S2 Calcd.: C, 57.79; H, 3.11; N, 11.89%; Found: C, 57.39; H, 3.54; N, 11.30%.


## 4. Preparation of Metal Complexes

(A)
A solution mixture of the ligandsLI and LII (0.01 mmol) (0.0029, 0.0033 g), respectively, with the metal salts CoCl2·6H2O, NiCl2·6H2O, and CuCl2·2H2O (0.01 mmol) and (0.02 mmol) (0.0058, 0.0067 g) of LI and LII, respectively, with the metal salts PdCl2(phCN)2 and K2PtCl6 (0.01 mmol), in DMF (C1), butanol (C2 and C3), or DMSO (C4–C10) was heated under reflux for four hours. Precipitation of LI complexes took place within 30 minutes, while those of LII was precipitated at the end of reflux time. The products were filtered, washed with hot ethanol and acetone, followed by ether and vacuum dried. Complexes of LIII were prepared in the same manner using a mixture of LIII (0.01 mmol, 0.0035 g) with the metal salts CoCl2·6H2O, NiCl2·6H2O (0.01 mmol), and (0.02 mmol, 0.007 g) of LIII with PdCl2(phCN)2 (0.01 mmol). “C1a”: colour(dark brown) Yield (26.24%). Anal. for (C24H18N6O4S4Co2Cl3)Cl Calcd.: C, 34.21; H, 2.13; N, 9.97; S, 15.20%; Found: C, 34.32; H, 2.50; N, 9.42; S, 15.13%. M, 13.99(Calcd), 14.0(Found)%; Cl, 16.86(Calcd), 16.20(Found)%. “C2”: colour(dark brown). Yield (23.51% ). Anal. for [(C24H18N6O4S4NiCl2)0.4(C4H10O)] Calcd.: C, 47.63; H, 5.75; N, 8.33%; Found: C, 48.32; H, 5.45; N, 8.83%. M, 5.82(Calcd), 5.72(Found)%. “C3”: colour(dark brown). Yield (23.35%). Anal. for [(C12H9N3O2S2CuCl (H2O))Cl.0.5(C4H10O)] Calcd.: C, 34.96; H, 3.32; N, 8.74%; Found: C, 34.01; H, 3.72; N, 9.73%. M, 13.21(Calcd), 13.85(Found)%. Cl, 14.77(Calcd), 14.70(Found%). “C4”: colour(dark brown). Yield (35.18%). Anal. for [(C24H18N6O4S4PdCl)Cl] Calcd.: C, 37.94; H, 2.37; N, 11.06; S, 16.86%; Found: C, 38.40; H, 2.38; N, 11.15; S, 16.78%. M, 13.96(Calcd), 13.71(Found)%. Cl, 9.35(Calcd), 10.5(Found)%. “C5”: colour(brown). yield (19.08%). Anal. for [(C24H18N6O4S4PtCl2)Cl2·1.8(C2H6O)·H2O] Calcd.: C, 32.47; H, 3.02; N, 8.23%; Found: C, 32.85; H, 3.27; N, 9.16%. M, 19.12(Calcd), 19.10(Found)%. “C6a”: colour(dark brown). Yield (36.06%). Anal. for [(C17H13N3OS2CoCl)Cl·0.4(H2O)·0.3(C2H6SO)] Calcd.: C, 42.28; H, 3.12; N, 8.40; S, 12.81%; Found: C, 41.85; H, 2.72; N, 8.15; S, 12.00%. M, 11.79(Calcd), 12.11(Found)%; Cl, 14.21(Calcd), 14.58(Found)%. “C7”: colour(dark brown). Yield (45.30%). Anal. for [C17H13N3OS2NiCl2] Calcd.: C, 43.52; H, 2.77; N, 8.96%; Found: C, 44.20; H, 3.05; N, 9.24%. M, 12.52(Calcd), 12.23(Found)%; Cl, 15.14(Calcd), 15.47(Found)%. “C8”: colour(dark brown). Yield (45.39%). Anal. for [(C17H13N3OS2Cu)Cl2·H2O)] Calcd.: C, 41.50; H, 3.05; N, 8.54%; S, 13.02%; Found: C, 42.15; H, 2.74; N, 8.16; S, 12.94%. M, 12.91(Calcd), 13.12(Found)%; Cl, 14.44(Calcd), 14.55(Found)%. “C9”: colour(dark brown). Yield (43.38%). Anal. for [(C34H26N6O2S4Pd)Cl2)] Calcd.: C, 47.71; H, 3.04; N, 9.82%; S, 14.97%; Found: C, 47.75; H, 3.11; N, 9.69; S, 15.52%. M, 12.39(Calcd), 13.00(Found)%; Cl, 8.30(Calcd), 8.47(Found)%. “C10”: colour(dark brown). Yield (32.42%). Anal. for [((C17H13N3OS2)2.5PtCl)Cl3] Calcd.: C, 43.05; H, 2.74; N, 8.86%; S, 13.50%; Found: C, 43.84; H, 2.55; N, 9.17; S, 14.09%. M, 16.46(Calcd), 15.87(Found)%. “C11a”: colour(brown). Yield (33.43%). Anal. for [(C17H11N3O2S2Co)Cl2·H2O] Calcd.: C, 40.72; H, 2.59; N, 8.38 %; Found: C, 40.05; H, 2.34; N, 7.82;%. M, 11.75(Calcd), 12.25(Found)%. Cl, 14.17(Calcd), 14.85(Found)%. “C12”: colour(brown). Yield (34.37%). Anal. for [(C34H22N6O4S4Ni)Cl2] Calcd.: C, 48.82; H, 2.63; N, 10.05%; Found: C, 49.62; H, 2.46; N, 9.41; %. M, 7.02(Calcd), 7.50(Found)%. Cl, 8.49(Calcd), 8.56(Found)%. “C13”: colour(brown). Yield (34.03%). Anal. for [(C34H22N6O4S4Pd)Cl2] Calcd.: C, 46.20; H, 2.46; N, 9.51; S, 14.49%; Found: C, 46.47; H, 2.66; N, 9.79; S, 14.78%. M, 12.00(Calcd), 11.50(Found)%. Cl, 8.04(Calcd), 8.63(Found)%.(B)
To a solution mixture of N-acetyl, N-benzyl, or N-benzoylisatin (0.02 mmol) 0.0037, 0.0047, and 0.005 g, respectively, withdto (0.01 mmol) (0.0012 g), (0.04 mmol) (0.0048 g), and (0.02  mmol) (0.0024 g), respectively, in butanol was added a solution of CoCl2·6H2O (0.02 mmol) in butanol. The mixture was heated under reflux. Precipitation took place immediately. Heating was continued for 4 hours to achieve complet precipitation. The product was filtered, washed with hot butanol, followed by ethanol, acetone, ether, and vacuum dried. “C1b”: colour(dark brown). Yield (25.15%). Anal. for (C24H18N6O4S4Co2Cl3)Cl Calcd.: C, 34.21; H, 2.13; N, 9.97; S, 15.20%; Found: C, 34.15; H, 1.95; N, 10.31; S, 15.07%. M, 13.99(Calcd), 13.30(Found)%; Cl, 16.86(Calcd), 16.19(Found)%. “C6b”: colour(dark brown). Yield (71.42%). Anal. for [(C17H13N3OS2CoCl) Cl·0.3(H2O)·0.1(C4H10O)] Calcd.: C, 43.34; H, 3.03; N, 8.71; S, 13.28%; Found: C, 43.89; H, 3.35; N, 8.54; S, 13.48%. M, 12.22(Calcd), 12.25(Found)%; Cl, 14.73(Calcd), 14.44(Found)%. “C11b”: colour(brown). Yield (41.72%). Anal. for [(C17H11N3O2S2Co)Cl2·0.2H2O] Calcd.: C, 41.93; H, 2.34; N, 8.63%; Found: C, 42.56; H, 2.53; N, 8.73; %. M, 12.10(Calcd), 12.11(Found)%. Cl, 14.59(Calcd), 14.71(Found)%.


## 5. Microbiological Test Methods

The two following methods were used to perform the antimicrobial tests.


### 5.1. Agar Diffusion Method

In this method the colonies of the selected bacteria, namely,Staphylococcus aureus (G+), Proteus vulgaris (G-), and the fungus Candida albicans were spread on the surface of solidified nutrient agar. Suitably separated 7 mm diameter holes were made in each agar plate. Each hole was injected with 0.1 mL of 150, 350, 650, and 1000 ppm of the studied compound in DMSO. The agar plates were incubated at 37°C for 24 hours. Diameters of growth inhibition zones were measured in mm depending on diameter and clarity.


### 5.2. Agar Dilution Method

In this method the antifungal activity of 250 ppm of some selected compounds in DMSO was screened againstAspergillus niger. 2.5 cm3 of 2000 ppm of tested solution was added to 20 cm3 of hot agar solution. The homogenized mixture was then poured into petridish and left to solidify. The Aspergilluscolony (9 mm diameter) was fixed on the solidified agar, and the medium was incubated at 37°C for 8 days.


## 5.1. Agar Diffusion Method

In this method the colonies of the selected bacteria, namely,Staphylococcus aureus (G+), Proteus vulgaris (G-), and the fungus Candida albicans were spread on the surface of solidified nutrient agar. Suitably separated 7 mm diameter holes were made in each agar plate. Each hole was injected with 0.1 mL of 150, 350, 650, and 1000 ppm of the studied compound in DMSO. The agar plates were incubated at 37°C for 24 hours. Diameters of growth inhibition zones were measured in mm depending on diameter and clarity.


## 5.2. Agar Dilution Method

In this method the antifungal activity of 250 ppm of some selected compounds in DMSO was screened againstAspergillus niger. 2.5 cm3 of 2000 ppm of tested solution was added to 20 cm3 of hot agar solution. The homogenized mixture was then poured into petridish and left to solidify. The Aspergilluscolony (9 mm diameter) was fixed on the solidified agar, and the medium was incubated at 37°C for 8 days.


## 6. Results and Discussion

The IR spectra showed that the three ligands exhibited vibrational modes ofνC=N of azomethine group [4, 6, 26–28], (νC–N, δNH), (νC–N, νC–S), νC–S, and νC=S of dto moiety [29, 30] (Table 1). Spectra of LI and LII showed vibrational bands related to stretching modes of OH groups [31, 32]. The position of the bands assigned to νNH vibrations of the cyclic rings was dependent on their environment. νNH of LII and LIII were observed at lower frequencies compared with that of LI (Table 1) [27, 32]. The latter exhibited bands assigned to νC=O and νNH of amide and lactam rings [6, 27, 31, 32]. The spectra of LI complexes with Co(II), Cu(II), and Pd(II) ions exhibited shift in νOH and νC=N (azomethine) vibrations. The latter two complexes together with Ni(II) complex showed additional shifts in νNH to lower frequencies while no significant changes were observed on vibrational modes of C=O group which rules out coordination with carbonyl oxygen. Shifts of thioamide bands (III and IV) were observed in the spectra of Cu(II) and Pt(IV) complexes and were attributed to coordination of metal ion with sulfur atom [33]. Metal complexes of LII showed bands assigned to νC=O and νNH2 vibrations (Table 1). This may be attributed to cleavage of thioamide ring on complexation leading reappearance of νC=O and νNH2 of both C-2 and NH2 of isatin and dto moieties, respectively. Shifts in νNH2 (compared with νNH2 of the free dto (3296, 3203 cm-1)) [34] to lower frequencies were observed in all spectra of complexes except that of Ni(II) which was shifted to higher frequency. Bands related to νC=O vibrations in spectra of both Ni(II) and Cu(II) complexes were shifted to higher frequencies while spectra of the other complexes showed shifts to lower frequencies. Additional shifts were observed in the bands assigned to νC=N (azomethine) in all complexes except that of Cu(II). The latter complex exhibited shift of νC=S band to lower frequency which refers to coordination of sulfur to Cu(II) ion [33]. The spectra of LIII metal complexes exhibited shifts in vibrational modes of νC=O and band IV of thioamide group as a result of coordination with metal ions [33, 35]. Additional shift in position of bands assigned to νC=N was observed in the spectra of Co(II) and Ni(II) complexes. Shifts in the position of νNH amide and νC=O of lactam ring were observed in the spectra of the Pd(II) complex as a result of coordination. Bands related to vibrational modes of lattice solvent, coordinated water were observed at 3500-3400 cm-1 [36–38]. Bands appeared at lower frequencies were refered to M–O, M–N, M–S, and M–Cl stretching modes [36–38]. Further data are collected in (Table 1).Table 1
FTIR vibrations for the ligands and their metal complexes.
(a)SymbolνOHνN–HνC=OνC=NThioamideνM–OνM–NνM–ClBand IBand IIBand IIIBand IVνC–N+δNHνC–N+νC–SνC–SνC=SLI3400329817101650154014651170881———C1a3344329517181631154514601162877559389277*Co(II)C1b3350329517181631154514601165877559389277*Co(II)C23402322717061631154013961165880—335320Ni(II)C33347326017161627152014501150780408350339Cu(II)C43395325017201630157314581170889586350331Pd(II)C53400329517151666151014831134850—340300Pt(IV)Lattice butanol, C2, C3= 3500, 3750 cm-1, Lattice ethanol, C5 = 3495 cm-1 Coord·H2O, C3 = 3456, 750, 675; Lattice H2O, C5 = 3425 cm-1νM-S, C3 and C5 = 345 and 370  cm-1 respectively, *bridging.(b)SymbolνNH2νC=OνC=NThioamideH2O LatticeνM-OνM-NνM-ClBand IBand IIBand IIIBand IVνC–N+δNHνC–N+νC–SνC–SνC=SLII——1604155414611170848————C6a3255172416121555144611658683417547466273Co(II)3160401C6b3250172016121560145011808643450493450230Co(II)3155385C7345017501620155014481150870—520400316Ni(II)3348C83224175115891548144811888173450560478—Cu(II)3132385C9314717201612155014651180856—500400—Pd(II)3047380C10329417201612154814721170850–500400330Pt(IV)3147370νOH, LII = 3400 cm-1; νNH, LII = 3145 cm-1; Lattice butanol, C6b = 3550 cm-1νM-S, C8 = 320  cm-1.(c)SymbolνN–H amideνC=O amideνN–H lactamνC=O lactamνc=NThioamide groupνM–OνM–NνM–SBand IBand IIBand IIIBand IVνC–N+δNHνC–N+νC–SνC–SνC=SLIII33941635324716741600153514651103880———C11a34101625324716741587153514501095830590480320Co(II)C11b34101620324716741580153514501100840600480300Co(II)C1234561625325016701589153514501100860580450308Ni(II)C1333861620325016661600153514731095850617401310Pd(II)LatticH2O , C11a, C11b=3500 cm-1Theelectronic spectra ofLI, LII, and LIII exhibited high-intensity multiple bands in DMF and DMSO at 36231–20000 cm-1. These bands were assigned to π→π* transition of conjugated system. LIII exhibited additional low-intensity band which was assigned to n→π* transition. Changes in positions and profile (C8–C10) of bands were observed in the spectra of metal complexes. Bands related to the (CT) transition were observed as a shoulder on the ligand band in the spectra of C1, C3, C6, C7, C9, and C10 complexes (Table 2). The bands observed in the spectra of Co(II) complexes in the visible region were assigned to 4A2→4T2(ν1), 4A2→4T1(F)(ν2), and 4A2→4T1(P)(ν3). The magnetic moment values of Co(II) complexes were in the range of (3.959–4.6 BM) (Table 2). This indicates tetrahedral geometry around Co(II) ions [36–39] (Scheme 3). The Ni(II) complex C2 gave a greenish yellow colour in DMF indicating the exchange of weak ligand atoms with solvent molecules [40–43]. The spectrum of this complex showed bands characteristic of octahedral Ni(II) complex [36–38, 40–43] (Table 2), while the other Ni(II) complexes (C7 and C12) showed tetrahedral geometries (Scheme 3).Table 2
Electronic spectra, spectral parameters and magnetic moment with suggested structures of LI, LII, and LIII complexes.
SymbolBand positions (cm-1)AssignmentDq/B¯ (β)B¯ (cm-1)10Dq (cm-1)μeff (B.M)Suggested structureMolar conductivity S·mol-1·cm2 in DMF and DMSO*ν1 6388 (cal.)4A2→4T2470.261124.5Tetrahedral32.12*C1aν2 107524A2→4T1(F)1.3Co(II)ν3 16930 (avr.)4A2→4T1(P)(0.484)ν4 21008L→M (C.T)ν1 6388 (cal.)4A2→4T2470.261124.61Tetrahedral29.7*C1bν2 107524A1→4T1(F)1.3Co(II)ν3 16930 (avr.)4A2→4T1(P)(0.484)ν4 21881L→M (C.T)C2ν1 123453A2g→3T2g2.8454.2127173.31Octahedral46.45Ni(II)ν2 168063A2g→3T1g (F)(0.440)ν3 27035 (cal.)3A2g→3T1g (P)ν1 121502B1g→2A1g2.36Octahedral68.19C3ν2 166662B1g→2B2gCu(II)ν3 187612B1g→2Egν4 19646L→M (C.T)C4ν1 120481A1g→1A2gDiamagneticSquare planar60.37Pd(II)ν2 169491A1g→1B1gν3 206181A1g→1EgC5ν1 178251A1g→3T1g (H)DiamagneticOctahedral154.13Pt(IV)ν2 223711A1g→3T2gν1 6535 (cal.)4A2→4T2487.360914.21Tetrahedral34.3*C6aν2 105264A2→4T11.25Co(II)ν3 166664A2→4T1(P)(0.501)ν4 21551L→M (C.T)ν1 6389 (cal.)4A2→4T2488.561074.30Tetrahedral30.52*C6bν2 105044A2→4T1(F)1.25Co(II)ν3 166124A2→4T1(P)(0.503)ν4 20876L→M (C.T)ν1 5473 (cal.)3T1(F)→3T2(F)721.557682.73Tetrahedral7.9*C7ν2 110743T1(F)→3A2(F)0.82Ni(II)ν3 158733T1(F)→3T1(P)(0.70)ν4 18867L→M (C.T)C8ν1 134402B1g→2A1g1.84Square planar155.8Cu(II)ν2 192302B1g→2B2gC9ν1 169491A1g→1A2gDiamagneticSquare planar125.4Pd(II)ν2 213671A1g→1B1g (C.T)C10ν1 143881A1g→3T1gDiamagneticOctahedral196.6Pt(IV)ν2 205761A1g→3T2g (C.T)C11aν1 6410 (cal.)4A2→4T21.5436.865523.959Tetrahedral143.5Co(II)ν2 100004A2→4T1(F)(0.449)ν3 15641 (avr.)4A2→4T1(P)C11bν1 6410 (cal.)4A2→4T21.5436.865523.997Tetrahedral150.6Co(II)ν2 100004A2→4T1(F)(0.449)ν3 15641 (avr.)4A2→4T1(P)C12ν1 4994 (cal.)3T1(F)→3T2(F)0.74673.149802.746Tetrahedral159.4Ni(II)ν2 104823T1(F)→3A2(F)(0.653)ν3 15483 (avr.)3T1(F)→3T1(P)C13ν1 128201A1g→1A2gDiamagneticSquare planar148.2Pd(II)ν2 166661A1g→1B1gSuggested structures of studied compounds.The electronic spectra and magnetic moments (μeff B.M) (Table 2) of these complexes were consistent with these assignment [36–38, 40–43]. Spectral data (B′, Dq/B′, 10Dq and β) (Table 2), for the Co(II) and Ni(II) complexes were calculated by applying band energies on Tanaba Saugano diagrams. The energy of ν1 for Co(II) complexes (C1, C6, C11) and Ni(II) complexes (C7, C12) and ν3 for Ni(II) complex C2 were also calculated from the diagrams. The spectrum of the Cu(II) complex C3 exhibited three bands (Table 2) attributed to the spin allowed transitions 2B1g→2A1g(ν1), 2B1g→2B2g(ν2) and 2B1g→2Eg(ν3) of Jahn Teller tetragonally distorted octahedral Cu(II) complexes [34]. The magnetic moment of the complex (2.36 B.M) indicated paramagnetic character with a high spin orbital coupling [40–43]. The spectrum of Cu(II) complex C8 exhibited two bands (Table 2) which were assigned to 2B1g→2A1g(ν1), and 2B1g→2B2g(ν2). These bands were attributed to square planar Cu(II) complexes [44] (Scheme 3). Magnetic moment (μeff  =  1.84 B.M) of the complex supported such conclusion [36–38, 44]. The spectra of the diamagnetic Pd(II) complexes (C4, C9, and C13) showed two bands assigned to 1A1g→1A2g(ν1) and 1A1g→1B1g(ν2) and the additional band 1A1g→1Eg(ν3) for C4. These bands are attributed to square planar Pd(II) complexes [34–38, 40–43]. The spectra of the diamagnetic Pt(IV) complexes exhibited two bands which were assigned to forbidden transitions 1A1g→3T1g and 1A1g→3T2g showing octahedral geometry around Pt(IV) ion [40–43] (Scheme 3). The molar conductivities (Table 2) showed that electrolytic nature of the Pt(IV) complex (C10) was 1 : 3, Pt(IV), Cu(II), Pd(II), Co(II) and Ni(II) complexes (C5, C8, C9, C11, C12, and C13) 1 : 2, and Co(II), Cu(II), and Pd(II) complexes (C1, C3, C4, and C6) 1 : 1, while the Ni(II) complexes (C2 and C7) were nonelectrolyte [45]. From these observations, together with the results obtained from other analytical data, the sterochemical structures of the complexes were suggested (Scheme 3).Thermogravimetric analyses (TG and DTG) have been studied at heating range of 50–800°C for the complexes (C1, C3, C4, and C7) under nitrogen atmosphere. The following results (Table 3) were explained according to analytical suggestions mentioned in literature [46–48]. (i) Lattice water, free ions, and organic fragments that are not directly coordinated to the metal ions were found to leave the complex at earlier stages compared with coordinated fragments, (ii) The heating range (50–800°C) produced incomplete decomposition of metal complexes, and the final products were dependent on the type of metal ion and on (M-L) affinity [36–38, 46, 49] which reflects the stability of complexes.Table 3
Thermal decomposition of C1, C3, C4, and C7.
(a)C1[(LI)2Co2Cl3]ClTemperature range of decomposition °C%Weight loss found (calc.)M·wt = 841.8–2Cl–2ph251–36941.128(41.45)–C5H6N2O2–OH370–4212.798(2.01)–2Cl465–5477.932(8.43)–(C7H3N4OS4)2Co48.25(48.08)(b)C3[LICuCl(H2O)]Cl.0.5BuOHTemperture range of decomposition °C%Weight loss found (calc.)M·wt = 480.5–BuOH356–47636.592(36.94)–Cl–H2O–CS–C2H3O–C2NS477–63018.008(17.68)–NH–(phCHNO)CuCl45.41(45.36)(c)C4[(LI)2PdCl]ClTemperture range of decomposition °C%Weight loss found (calc.)M·wt = 759–2Cl145–21914.925(15.01)–C2H3O–phC3H4NO2219–35121.189(21.34)–ph482–56810.538(10.01)–CN679–7353.188(3.42)–(C6H3N4OS4)Pd50.096(50.197)(d)C7[LIINiCl2]Temperture range of decomposition °C%Weight loss found (calc.)M·wt = 468.7–CO50–1279.183(9.38)–NH2–phCH2239–37719.672(19.415)–2Cl432–56534.42(34.35)–phN–(C3NS2)Ni36.858(36.84)


## 7. Biological Screening

The antibacterial activity for precursors,LI and LIII, and some of their complexes was evaluated against Staphylococcus  aureus (G+) and Proteus vulgaris (G-) using the agar diffusion method. Diameter (mm) of growth inhibition zones was measured after incubation for 24 hours at 37°C. The results showed that no antibacterial action was recorded by the studied compounds using concentration of 150, 350, and 650 ppm. Using 1000 ppm (Table 4), LI and its complexes were more active against Staphylococcus aureus, while LIII and its complexes (except C13) were more active against Proteus vulgaris than the other studied compounds. The antifungal activity was evaluated against Candida albicans by the agar diffusion method and Aspergillus niger colony (9 mm diameter) by the agar dilution method using concentration of 250 ppm in DMSO. The results showed that LI and LIII were inactive against Candida albicans; Co(II) (C11), Ni(II) (C12), and Pd(II) (C13) complexes were more active than the parent ligand (LIII) while those of LI were inactive except Cu(II) complex (C3). LI, LIII, and C4 which were inactive against Candida albicans showed moderate activity against Aspergillus niger which refer to the effective selectivity of specific inhibitor on the microorganisms.Table 4
Antibacterial and Antifungal activities of studied compounds.
CompoundsStaphylococcus aureus inhibitionProteus vulgris inhibitionCandida albecans inhibitionAspergillus niger growthdiameter (mm) 1000 ppmdiameter (mm) 1000 ppmdiameter (mm) 1000 ppmdiameter (mm) 1000 ppmDMSOZeroZeroZero25Isatin386N-acetylisatin4Zero5N-benzylisatin556N-benzoylisatin55ZeroLI85Zero9C2 (Ni(II))48ZeroC3 (Cu(II))955C4 (Pd(II))185Zero9LIII68Zero9C11 (Co(II))310149C12 (Ni(II))Zero1211C13(Pd(II))3Zero11


## 8. Conclusions

(1)
Condensation reaction of N-acetyl, N-benzyl, and N-benzoyl isatins withdto gave Schiff base ligands LI–LIII, as was confirmed by 1H, 13C NMR, and IR spectra.(2)
The formation of the Schiff base ligandLIII took place with ring cleavage at C-2 of the heterocyclic ring of the benzoylisatin. Whereas the formation of LI and LII took place without ring cleavage.(3)
The presence of various donor atoms and the stereochemistry of the studied ligands enhanced different complexing behaviours and geometries using the studied metal ions.(4)
The results of the physical properties and spectral analyses of cobalt complexes prepared by template reaction demonstrated the recommendation of for synthesis of metal complexes of the studied ligands, due to less time consuming and in general more yield of products.(5)
The study of biological activity of the studied ligands and some of their metal complexes against bacteria and fungi showed selectivity nature of microorganism towards these compounds and indicated the possibility of using some of them as antibacterial and antifungal agents.



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*Source: 413175-2009-10-26.xml*