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. 2009 Oct 26;2009:413175. doi: 10.1155/2009/413175

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

Ahlam J Abdul-Ghani 1, Asmaa M N Khaleel 1,*
PMCID: PMC2766752  PMID: 19865487

Abstract

Three new Schiff bases of N-substituted isatin LI, 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.

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.

Scheme 1

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Schiff bases of isatin derivatives.

2. Experimental/Materials and Methods

All chemicals used were of analytical reagent grade (AR) except dto 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 (μ eff. 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.

Scheme 2

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The structures of the prepared ligands LI, 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) and dto (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) and dto (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) and dto (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

  1. A solution mixture of the ligands LI 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 (C24H18N6O4S4 Co2Cl3)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 [(C24H18N6O4S4 NiCl2)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)%.

  2. To a solution mixture of N-acetyl, N-benzyl, or N-benzoylisatin (0.02 mmol) 0.0037, 0.0047, and 0.005 g, respectively, with dto (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 (C24H18N6O4S4 Co2Cl3)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 against Aspergillus 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 Aspergillus colony (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 of ν C=N of azomethine group [4, 6, 26–28], (ν C–N, δ NH), (ν C–N, ν C–S), ν C–S, and ν C=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 ν NH vibrations of the cyclic rings was dependent on their environment. ν NH of LII and LIII were observed at lower frequencies compared with that of LI (Table 1) [27, 32]. The latter exhibited bands assigned to ν C=O and ν NH 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 ν OH and ν C=N (azomethine) vibrations. The latter two complexes together with Ni(II) complex showed additional shifts in ν NH 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 ν C=O and ν NH2 vibrations (Table 1). This may be attributed to cleavage of thioamide ring on complexation leading reappearance of ν C=O and ν NH2 of both C-2 and NH2 of isatin and dto moieties, respectively. Shifts in ν NH2 (compared with ν NH2 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 ν C=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 ν C=N (azomethine) in all complexes except that of Cu(II). The latter complex exhibited shift of ν C=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 ν C=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 ν C=N was observed in the spectra of Co(II) and Ni(II) complexes. Shifts in the position of ν NH amide and ν C=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).

Symbol ν OH ν N–H ν C=O ν C=N Thioamide ν M–O ν M–N ν M–Cl
Band I Band II Band III Band IV
ν C–N + δ NH ν C–N + ν C–S ν C–S ν C=S
LI 3400 3298 1710 1650 1540 1465 1170 881 — — —
C1a 3344 3295 1718 1631 1545 1460 1162 877 559 389 277*
Co(II)
C1b 3350 3295 1718 1631 1545 1460 1165 877 559 389 277*
Co(II)
C2 3402 3227 1706 1631 1540 1396 1165 880 — 335 320
Ni(II)
C3 3347 3260 1716 1627 1520 1450 1150 780 408 350 339
Cu(II)
C4 3395 3250 1720 1630 1573 1458 1170 889 586 350 331
Pd(II)
C5 3400 3295 1715 1666 1510 1483 1134 850 — 340 300
Pt(IV)
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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−1 ν M-S, C3 and C5 = 345 and 370 cm−1 respectively, *bridging.

(b).

Symbol ν NH2 ν C=O ν C=N Thioamide H2O Lattice ν M-O ν M-N ν M-Cl
Band I Band II Band III Band IV
ν C–N + δ NH ν C–N + ν C–S ν C–S ν C=S
LII — — 1604 1554 1461 1170 848 — — — —
C6a 3255 1724 1612 1555 1446 1165 868 3417 547 466 273
Co(II) 3160 401
C6b 3250 1720 1612 1560 1450 1180 864 3450 493 450 230
Co(II) 3155 385
C7 3450 1750 1620 1550 1448 1150 870 — 520 400 316
Ni(II) 3348
C8 3224 1751 1589 1548 1448 1188 817 3450 560 478 —
Cu(II) 3132 385
C9 3147 1720 1612 1550 1465 1180 856 — 500 400 —
Pd(II) 3047 380
C10 3294 1720 1612 1548 1472 1170 850 — 500 400 330
Pt(IV) 3147 370
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ν OH, LII = 3400 cm−1; ν NH, LII = 3145 cm−1; Lattice butanol, C6b = 3550 cm−1 ν M-S, C8 = 320 cm−1.

(c).

Symbol ν N–H amide ν C=O amide ν N–H lactam ν C=O lactam ν c=N Thioamide group ν M–O ν M–N ν M–S
Band I Band II Band III Band IV
ν C–N + δ NH ν C–N + ν C–S ν C–S ν C=S
LIII 3394 1635 3247 1674 1600 1535 1465 1103 880 — — —
C11a 3410 1625 3247 1674 1587 1535 1450 1095 830 590 480 320
Co(II)
C11b 3410 1620 3247 1674 1580 1535 1450 1100 840 600 480 300
Co(II)
C12 3456 1625 3250 1670 1589 1535 1450 1100 860 580 450 308
Ni(II)
C13 3386 1620 3250 1666 1600 1535 1473 1095 850 617 401 310
Pd(II)
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Lattic H2O, C11a, C11b = 3500 cm−1

The electronic spectra of LI, 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(ν 1), 4A2 → 4T1(F)(ν 2), and 4A2 → 4T1(P)(ν 3). 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.

Symbol Band positions (cm−1) Assignment Dq/B¯ (β) B¯ (cm−1) 10Dq (cm−1) μ eff (B.M) Suggested structure Molar conductivity S ⋅ mol−1 ⋅ cm2 in DMF and DMSO*
ν 1 6388 (cal.) 4A2 → 4T2 470.2 6112 4.5 Tetrahedral 32.12*
C1a ν 2 10752 4A2 → 4T1 (F) 1.3
Co(II) ν 3 16930 (avr.) 4A2 → 4T1 (P) (0.484)
ν 4 21008 L → M (C.T)
ν 1 6388 (cal.) 4A2 → 4T2 470.2 6112 4.61 Tetrahedral 29.7*
C1b ν 2 10752 4A1 → 4T1 (F) 1.3
Co(II) ν 3 16930 (avr.) 4A2 → 4T1 (P) (0.484)
ν 4 21881 L → M (C.T)
C2 ν 1 12345 3A2g → 3T2g 2.8 454.2 12717 3.31 Octahedral 46.45
Ni(II) ν 2 16806 3A2g → 3T1g (F) (0.440)
ν 3 27035 (cal.) 3A2g → 3T1g (P)
ν 1 12150 2B1g → 2A1g 2.36 Octahedral 68.19
C3 ν 2 16666 2B1g → 2B2g
Cu(II) ν 3 18761 2B1g → 2Eg
ν 4 19646 L → M (C.T)
C4 ν 1 12048 1A1g → 1A2g Diamagnetic Square planar 60.37
Pd(II) ν 2 16949 1A1g → 1B1g
ν 3 20618 1A1g → 1Eg
C5 ν 1 17825 1A1g → 3T1g (H) Diamagnetic Octahedral 154.13
Pt(IV) ν 2 22371 1A1g → 3T2g
ν 1 6535 (cal.) 4A2 → 4T2 487.3 6091 4.21 Tetrahedral 34.3*
C6a ν 2 10526 4A2 → 4T1 1.25
Co(II) ν 3 16666 4A2 → 4T1 (P) (0.501)
ν 4 21551 L → M (C.T)
ν 1 6389 (cal.) 4A2 → 4T2 488.5 6107 4.30 Tetrahedral 30.52*
C6b ν 2 10504 4A2 → 4T1 (F) 1.25
Co(II) ν 3 16612 4A2 → 4T1 (P) (0.503)
ν 4 20876 L → M (C.T)
ν 1 5473 (cal.) 3T1(F) → 3T2 (F) 721.5 5768 2.73 Tetrahedral 7.9*
C7 ν 2 11074 3T1 (F) → 3A2 (F) 0.82
Ni(II) ν 3 15873 3T1 (F) → 3T1 (P) (0.70)
ν 4 18867 L → M (C.T)
C8 ν 1 13440 2B1g → 2A1g 1.84 Square planar 155.8
Cu(II) ν 2 19230 2B1g → 2B2g
C9 ν 1 16949 1A1g → 1A2g Diamagnetic Square planar 125.4
Pd(II) ν 2 21367 1A1g → 1B1g (C.T)
C10 ν 1 14388 1A1g → 3T1g Diamagnetic Octahedral 196.6
Pt(IV) ν 2 20576 1A1g → 3T2g (C.T)
C11a ν 1 6410 (cal.) 4A2 → 4T2 1.5 436.8 6552 3.959 Tetrahedral 143.5
Co(II) ν 2 10000 4A2 → 4T1 (F) (0.449)
ν 3 15641 (avr.) 4A2 → 4T1 (P)
C11b ν 1 6410 (cal.) 4A2 → 4T2 1.5 436.8 6552 3.997 Tetrahedral 150.6
Co(II) ν 2 10000 4A2 → 4T1 (F) (0.449)
ν 3 15641 (avr.) 4A2 → 4T1 (P)
C12 ν 1 4994 (cal.) 3T1 (F) → 3T2 (F) 0.74 673.1 4980 2.746 Tetrahedral 159.4
Ni(II) ν 2 10482 3T1 (F) → 3A2 (F) (0.653)
ν 3 15483 (avr.) 3T1 (F) → 3T1 (P)
C13 ν 1 12820 1A1g → 1A2g Diamagnetic Square planar 148.2
Pd(II) ν 2 16666 1A1g → 1B1g
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Scheme 3.

Scheme 3

Scheme 3

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Suggested structures of studied compounds.

The electronic spectra and magnetic moments (μ eff 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 ν 1 for Co(II) complexes (C1, C6, C11) and Ni(II) complexes (C7, C12) and ν 3 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(ν 1), 2B1g → 2B2g(ν 2) and 2B1g → 2Eg(ν 3) 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(ν 1), and 2B1g → 2B2g(ν 2). These bands were attributed to square planar Cu(II) complexes [44] (Scheme 3). Magnetic moment (μ eff = 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(ν 1) and 1A1g → 1B1g(ν 2) and the additional band 1A1g → 1Eg(ν 3) 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]Cl Temperature range of decomposition °C %Weight loss found (calc.)
M ⋅ wt = 841.8
–2Cl
–2ph 251–369 41.128 (41.45)
–C5H6N2O2
–OH 370–421 2.798 (2.01)
–2Cl 465–547 7.932 (8.43)
–(C7H3N4OS4)2Co 48.25 (48.08)
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(b).

C3
[LICuCl(H2O)]Cl.0.5BuOH Temperture range of decomposition °C %Weight loss found (calc.)
M ⋅ wt = 480.5
–BuOH 356–476 36.592 (36.94)
–Cl
–H2O
–CS
–C2H3O
–C2NS 477–630 18.008 (17.68)
–NH
–(phCHNO) CuCl 45.41 (45.36)
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(c).

C4
[(LI)2PdCl]Cl Temperture range of decomposition °C %Weight loss found (calc.)
M ⋅ wt = 759
–2Cl 145–219 14.925 (15.01)
–C2H3O
–phC3H4NO2 219–351 21.189 (21.34)
–ph 482–568 10.538 (10.01)
–CN 679–735 3.188 (3.42)
–(C6H3N4OS4) Pd 50.096 (50.197)
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(d).

C7
[LIINiCl2] Temperture range of decomposition °C %Weight loss found (calc.)
M ⋅ wt = 468.7
–CO 50–127 9.183 (9.38)
–NH2
–phCH2 239–377 19.672 (19.415)
–2Cl 432–565 34.42 (34.35)
–phN
–(C3NS2)Ni 36.858 (36.84)
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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.

Compounds Staphylococcus aureus inhibition Proteus vulgris inhibition Candida albecans inhibition Aspergillus niger growth
diameter (mm) 1000 ppm diameter (mm) 1000 ppm diameter (mm) 1000 ppm diameter (mm) 1000 ppm
DMSO Zero Zero Zero 25
Isatin 3 8 6
N-acetylisatin 4 Zero 5
N-benzylisatin 5 5 6
N-benzoylisatin 5 5 Zero
LI 8 5 Zero 9
C2 (Ni(II)) 4 8 Zero
C3 (Cu(II)) 9 5 5
C4 (Pd(II)) 18 5 Zero 9
LIII 6 8 Zero 9
C11 (Co(II)) 3 10 14 9
C12 (Ni(II)) Zero 12 11
C13 (Pd(II)) 3 Zero 11
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8. Conclusions

  1. Condensation reaction of N-acetyl, N-benzyl, and N-benzoyl isatins with dto gave Schiff base ligands LI–LIII, as was confirmed by 1H, 13C NMR, and IR spectra.

  2. The formation of the Schiff base ligand LIII 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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