Novel mono- and binuclear complexes derived from N-benzoyl-N-glycylthiourea (BGH) with some transition metal ions

1 Introduction

The metal complexes derived from amino acids and their derivatives have important pharmaceutical applications. They have been exploited in cancer multidrug resistance (Sharma and Pivnica-Worms, 1999), tested as antimalarial (Goldberg et al., 1997) and exhibit antitumor activity (Wang et al., 2005). Also, thiourea derivatives have several important uses in medicine as potent anti-cancer and antiinfluenza agents (Biot et al., 2007; Nair and Sobhia, 2008) but no studies have been carried out recently on the thiourea derivatives involving glycine. The present paper is devoted to study of the coordination chemistry and the spectroscopic behavior of the thiourea and its metal complexes, derived from the reaction of N-benzoyl-N-glycylthiourea (BGH) with Cu(II), Co(II), Ni(II), Zn(II) and Fe(III) chlorides and/or Cu(II), Co(II), Ni(II) and Zn(II) acetates. Also, this study is carried out to shed more light on the behavior of the ligand during complex formation at different pH’s.

2 Experimental

All the chemicals used in this investigation were of analytical grade and used without further purifications.

3 Results and discussion

All the metal complexes are colored, except the Zn(II) complex which was white. Also, they were stable against light and air for more than 12 months and insoluble in most common organic solvents but easily soluble in DMSO and DMF. The molar conductivities in DMF (10⁻³ M) at 25 °C for the Cu(II), Co(II), Ni(II) and Zn(II) acetate complexes fall in the range 1.0–10 Ω⁻¹ cm² mol⁻¹ indicating their non-electrolytic nature. On the other hand, the comparatively high values of molar conductivities of Cu(II), Co(II), Ni(II) and Zn(II) chloride complexes in DMF (40–80 Ω⁻¹ cm² mol⁻¹) suggested 1:1 and/or 1:2 electrolytes (Geary, 1971). The melting points of the metal complexes were in the range of 140–255 °C, except for Fe(III) complex which showed high melting point (>300 °C). Elemental analyses and some physical properties of the isolated solid complexes are listed in Table 1.

The most important IR spectral bands of the free ligand (BGH) and its metal complexes are recorded in Table 2. The free ligand can be represented in three tautomeric forms, the keto (1a) (free), (1c) (hydrogen-bonded) and the enol (1b) forms as shown in Fig. 1.

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Figure 1

Scheme represents the tautomeric forms of the ligand.

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On comparing the IR spectra of the free ligand with that of glycine in Nujol mull, we observed two strong bands at 1712 and 1666 cm⁻¹ in the spectrum of BGH (KBr) assignable to free υ(C⚌O) and hydrogen-bonded υ(C⚌O) vibrations, respectively. This indicates the existence of hydrogen bonding between the C⚌O and OH of the carboxylic group. The 1658 cm⁻¹ band is attributed to the C⚌O attached to –C₆H₅ group. The IR spectrum of the free ligand in KBr shows four bands at 3445, 2874, 3237 and 3167 cm⁻¹. The first two bands are assigned to the υ(OH-free) and υ(OH-hydrogen-bonded) vibrations while the other two bands are assigned to υ(NH–CO) and υ(NH–CS) vibrations, respectively. Finally, the two bands observed at 1182 and 783 cm⁻¹ are attributed to υ(C⚌S) (Nakamoto, 1970) vibrations. The hydrogen bonding between the C⚌O and the OH groups of the carboxylic moiety seems to be strong of the type O−H⋯O (Fig. 1c). This is approved by the negative acidity test when the ligand is dissolved in water. On the other hand, the IR spectrum of the free ligand in Nujol mull shows the obscurity of the hydrogen bonding together with the appearance of a strong band at 3631 cm⁻¹ due to the free υ(OH) vibration as well as the disappearance of the band at 2874 cm⁻¹ due to the hydrogen-bonded (OH) of the carboxylic group. The most important assignments of the free ligand and its metal complexes are listed in Table 2. The ¹H NMR spectrum of the free ligand in d₆-DMSO shows several signals at 4.3 (doublet), 7.5–8.5 (multiplet), 10.83 (singlet), 11.2 (singlet), 11.5 (singlet) and 13.8 (singlet broad) ppm, with respect to TMS, assigned to the protons of CH₂, C₆H₅, (NH–CH₂), (NH–CO), OH (free) and OH (hydrogen-bonded), respectively. These may be taken as additional evidence that the ligand is mainly existed in the keto form (Fig. 1a). The broad signal at 13.8 ppm suggests that the OH is hydrogen-bonded to the carbonyl oxygen (Fig. 1c). Also, this suggests that the ligand involves a strong hydrogen-bond even on dissolving in d₆-DMSO. The electronic spectrum of the free ligand in Nujol mull shows seven bands at 36496, 34483, 33557, 31447, 28763, 27933 and 23148 cm⁻¹ assigned to n → π^∗ (CO, COOH), n → π^∗ (CO, Ph), n → π^∗ (CS), π → π∗ (CO, carboxylic), π → π∗ (CO, Ph), π → π∗ (CS) and π → π∗ (C⚌C, Ph) (Rao, 1975), respectively. This refers to the existence of the free ligand in the keto form.

The modes of coordination in the metal complexes have been determined by comparing the IR spectra of the free ligand (BGH) with those of metal complexes and glycine (Nakamoto, 1970). First, the ligand behaves in a bidentate manner toward the mono-nuclear Cu(II) complex (Fig. 2). The IR spectrum in KBr of the Cu(II) chloride complex with the general formula,[Cu(H₂L)Cl(H₂O)₃]·½H₂O·Cl (1), shows that the ligand coordinates in a bidentate manner via the (CO) attached to the phenyl and the thione (CS) groups to the Cu(II) ion, without displacement of a hydrogen atom, forming a six-member ring around the Cu(II) ion. On the basis of the shifts of C⚌O and OH of the COOH groups from 1709 and 3445 cm⁻¹ to 1737 and 3450 cm⁻¹, respectively, indicate that these groups are excluded from bonding. Also, the (CO) attached to the phenyl group and the (CS) groups are shifted to lower wave-numbers at 1608 and 1473 cm⁻¹, respectively, indicating their participation in coordination. Also, the two NH bands are slightly shifted to lower wave-numbers due to their attachment to the donor groups (CO, CS). The observation of two new bands at 505 and 483 cm⁻¹ assigned to υ(M–O) and υ(M–S) vibrations (Ferraro, 1966), respectively, may be taken as an additional evidence for the participation of the (CO) and the CS groups in bonding. The electronic spectrum of the Cu(II) complex in Nujol shows a broad weak band centered at 12469 cm⁻¹ indicating the existence of a distorted-octahedral around the Cu(II) ion. This band is mainly attributed to ²E_g → ²T_2g transition in distorted-octahedral geometry around the Cu(II) ion (Lever, 1968). Also, the normal value of magnetic moment for the Cu(II) complex (1.7 B.M.) suggests the absence of any Cu–Cu interactions. On dissolution of the Cu(II) complex in DMF the above band is shifted toward lower value and observed at 11655 cm⁻¹ indicating the replacement of water by DMF molecules and the complex has also a distorted-octahedral geometry around the Cu(II) ion. Also, the band observed at 22727 cm⁻¹ in Nujol and DMF is assigned to charge-transfer of the type (Cu → Cl) (Rao, 1975). The TGA curve of the Cu(II) chloride complex shows that the complex decomposes in four steps. The first step (35–132 °C) corresponds to the loss of 2.5 molecules of water of hydration (found: 9.4%; calcd.: 10.3%). The second step (133–295 °C) corresponds to the loss of 2Cl, H₂O, CH₂COOH and phenyl group (found: 52.5%; calcd.: 51.6%). The third step (295–719 °C) stands for the loss of 2NH + CO (found: 13.8%; calcd.: 13.3%). Finally, the estimated residue corresponds to CuCS (found: 24.3%; calcd.: 24.7%).

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Figure 2

Structure of the Cu(II) complex,[Cu(H₂L)Cl(H₂O)₃]·½H₂O·Cl (1).

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The IR spectrum of the binuclear Co(II) complex with the general formula,[Co₂(H₂L)Cl₃(EtOH)]·H₂O·Cl (2), shows that the ligand coordinates to two Co(II) ions within the same complex. The first Co(II) ion coordinates to the (CS) and the (CO) groups attached to the phenyl moiety forming six-member ring while the second Co(II) ion is bonded to the (CO) and the (OH) groups of the carboxylic group without displacement of a hydrogen atom forming four-member ring around the second Co(II) ion (Fig. 3).

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Figure 3

Structure of the Co(II) complex,[Co₂(H₂L)Cl₃(EtOH)]·H₂O·Cl (2).

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The electronic spectrum of the Co(II) complex in Nujol mull shows two bands at 16287 and 15106 cm⁻¹ assigned to ⁴A₂ → ⁴T₁ (P) (υ₂) transitions in a tetrahedral geometries around the two Co(II) ions (Devillanova and Verani, 1979; Nicholls, 1986). The first band may be assigned to the tetrahedral geometry in case of the ring containing both the (CS) and (CO) groups while the second band is assigned to the second ring involving the carboxylic group. The values of υ₁, B and β for the first Co(II) ion were calculated and found to be 6898 cm⁻¹, 941 and 0.97, respectively. On dissolution of the Co(II) complex in DMF, the two bands observed at 16502 and 14837 cm⁻¹ are assigned to ⁴A₂ → ⁴T₁ (P) (υ₂) transitions in a tetrahedral geometries around the two Co(II) ions (Nicholls, 1986). The blue shift of these bands may be assigned to the substitution of ethanol by DMF molecule in a tetrahedral geometry around the two Co(II) ions. The value of the magnetic moment (4.5 B.M.) as well as blue color of the Co(II) complex is taken as strong evidences for the existence of a tetrahedral geometry around the Co(II) ion. The values of υ₁, B and β for the second Co(II) ion were calculated and found to be 6775 cm⁻¹, 857 and 0.88, respectively.

The IR spectrum of the binuclear Ni(II) complex with the general formula,[Ni₂(HL)Cl₂(H₂O)₆]·2H₂O·Cl (3), shows that the ligand acts as a mono negative tetradentate ligand coordinating to two Ni(II) ions within the same complex. The first Ni(II) ion is coordinated to the ligand through the (CS) and (CO) groups attached to the phenyl moiety forming six-member ring while the second Ni(II) ion is bonded to the (CO) and (OH) groups of the carboxylic group with displacement of a hydrogen atom forming four-member ring around the second Ni(II) ion. The ligand forms two octahedral geometries around the two nickel ions (Fig. 4).

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Figure 4

Structure of the Ni(II) complex,[Ni₂(HL)Cl₂(H₂O)₆]·2H₂O·Cl (3).

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The IR spectrum suggests the disappearance of the OH band of the carboxylic group together with the appearance of two new bands at 1630 and 1516 cm⁻¹ assigned to the υ_as(COO) and υ_s(COO) vibration, respectively. This indicates the participation of the carboxylic group in bonding with displacement of a hydrogen atom toward the second Ni(II) ion. Also, the spectrum shows the negative shifts of both the CO and CS groups to lower wave-numbers (Sallam et al., 2006; Cakir et al., 2001) suggesting the participation of these groups in coordination to the first Ni(II) ion. The electronic spectrum of the Ni(II) complex in Nujol mull shows bands at 27933, 23256, 16556 and 14245 cm⁻¹. The first and the third bands are attributed to υ₃ and υ₂ transitions for the first Ni(II) ion while the second and fourth bands are attributed to υ₃ and υ₂ transitions for the second Ni(II) ion. The values of υ₁, B and β for the first Ni(II) ion were calculated and found to be 6467 cm⁻¹, 995 and 0.95, while these values were calculated and found to be 7386 cm⁻¹, 995 and 0.95, respectively, for the second Ni(II) ion. The value of the magnetic moment for each Ni(II) ion (2.5 B.M.) was taken as an evidence for the existence of octahedral geometry around the two Ni(II) ions. Thermal analyses (TGA, DTG) of the Ni(II) chloride complex showed that the complex decomposes in five stages. The first step (30–91 °C) indicates the loss of 5H₂O molecules (found: 15.5%; calcd: 14.9%). The second step (91-265 °C) corresponds to the loss of 3H₂O of coordination and 3Cl ions in two successive stages (found: 26.1%; calcd.: 26.5%). The third step (266–441 °C) corresponds to the loss of CH₂COOH and NH moieties (found: 13.2%; calcd.: 12.2%). The fourth step (442–574 °C) indicates the loss of Ph and HN (found: 15.9%; calcd.: 15.2%). The residue is a mixture of NiCS and 6C (found: 29.4%; calcd.: 28.9%).

Also, BGH acts as a mono negative tetradentate ligand coordinating to two Fe(III) ions at the same time as in the Fe(III) complex,[Fe₂(HL)Cl₃(H₂O)₅]Cl₂·7H₂O (4). It binds to the first Fe(III) atom through the amidic carbonyl (CO) and (CS) groups, while it coordinates to the second Fe(III) atom through the carboxylate group after displacement of the hydrogen atom. This behavior is supported by the shifts of the bands in the regions, 1619–1630, 1662–1666, 1173–1178 cm⁻¹ and 779–789 to lower wave-numbers (Cakir et al., 2001) assigned to the C⚌S^∗, CO and CS groups, respectively. The new two bands in the 1690–1722 and 1442–1476 cm⁻¹ regions assigned to υ_as(COO) and υ_s(COO) groups, respectively, are taken as an evidence for the participation of the carboxylic group with replacement of a hydrogen atom (Fig. 5). The electronic spectrum of Fe(III) chloride complex in Nujol shows two bands at 16666 and 20746 cm⁻¹ assigned to d–d transitions and a band at 29325 cm⁻¹ assigned to LMCT (Lever, 1968; Sutton, 1968). The value of magnetic moment (3.13 B.M.) falls in between the values expected for the high spin Fe^III with S = 5/2 and for the low spin Fe(III) with S = 1/2 and the possibility of spin state equilibrium between ⁶A₂ and ²T₂ states (Sutton, 1968). The TGA of the ferric chloride complex shows six stages of decomposition. The first step (51–150 °C) is due to the loss of one molecule of water (found: 2.1%; calcd.: 2.4%). The second step (151–356 °C) indicates the loss of 11 H₂O molecules hydrated and coordinated molecules (found: 27.7%; calcd.: 26.7%). The third step (357–788 °C) corresponds to the loss of 3½Cl₂ (found: 15.7%; calcd.: 16.8%) leaving a residue (found: 54.5%; calcd.: 54.1%) corresponding to Fe₂C₁₀H₉O₃N₂SCl_1½.

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Figure 5

Structure of the Fe(III) complex,[Fe₂(HL)Cl₃(H₂O)₅]Cl₂·7H₂O (4).

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The high melting point of the Fe(III) (>300 °C) in comparison to the other metal complexes suggests the strong bonding between the Fe(III) ion and the ligand. The strong bond is also confirmed from the data of TGA which indicate that the complex is not completely decomposed up to 788 °C.

All the chloride complexes show the participation of the thioketo and the carbonyl oxygen (amidic) in bonding and the inertness of the carboxylic group toward coordination except for the Ni(II) and Fe(III) complexes. This can be explained on the basis of the low pH (1–1.5) of the solution during complex formation which prevented the removal of a hydrogen atom from the carboxylic group. On the other hand, the comparatively high pH value (∼4) for the Ni(II) and Fe(III) complexes assisted the participation of this group in bonding.

Also, the ligand (BGH) behaves as a binuclear binegative tetradenate ligand in the enol form as in case of the Cu(II), Co(II), Ni(II) and Zn(II) acetate complexes. The ligand coordinates to the first atom through the CS and (CO) groups in the enol form with replacement of a hydrogen atom from the enolized OH group and it coordinates to the second metal atom through the (COOH) with replacement of a hydrogen atom. This mode of coordination is supported by the disappearance of the band assigned to amidic carbonyl and the appearance of new band in the region 1568–1654 cm⁻¹ assigned to the (C⚌N^∗) group. Also, the shifts of the bands in the regions 1145–1180 and 751–786 cm⁻¹ are assigned to υ(CS) vibrations to lower wave- numbers. The ligand binds the second atom through carboxylic group after replacement of a hydrogen atom. The bands observed in the 1567–1600 and 1433–1460 cm⁻¹ regions are assigned to υ_as(COO) and υ_s(COO) vibrations. First, the IR spectrum of the Cu(II) acetate complex with the general formula,[Cu₂L(Ac)₂]·½H₂O (5), shows that the ligand coordinates to two Cu(II) ions. The results indicate that the ligand coordinates to the first Cu(II) ion through the thioketo (CS) and the enolized (C⚌O) with the displacement of a hydrogen atom from the latter group forming six-member ring around the first Cu(II) ion, while it coordinates to the second Cu(II) ion via the carboxylate group with displacement of a hydrogen atom forming four-member ring around the second Cu(II) ion. Also, the IR spectrum shows a broad band centered at 3406 cm⁻¹ assigned to υ(OH) vibration of the water molecule. The disappearance of the carbonyl oxygen at 1658 cm⁻¹ together with the appearance of a new band at 1624 cm⁻¹ assigned to the C⚌N^∗ group may be taken as an evidence for the enolization of the carbonyl oxygen together with the displacement of a hydrogen atom. The negative shifts of the CS groups at 1464 and 1166 cm⁻¹ to lower wave numbers (Table 2) suggest the participation of this group in bonding. On the other hand, the results show the obscurity of both the OH and the CO groups of the carboxylic group together with the appearance of two new bands at 1581 and 1433 cm⁻¹ assigned to υ_as(COO) and υ_a(COO) vibrations, respectively. The electronic spectrum of the Cu(II) complex, in Nujol mull, shows a broad band centered at 15290 cm⁻¹ which may be assigned to ²B_1g → ²E_g and ²B_1g → ²A_1g transitions in a square-planar geometries (Sutton, 1968) around the two Cu(II) ions. This band is blue shifted in DMF and observed at 15923 cm⁻¹. Also, the normal value of magnetic moment for the Cu(II) complex (1.74 B.M.) suggests the absence of any Cu–Cu interactions. All these foundations suggest a square-planar geometry around the two Cu(II) ions (Fig. 6).

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Figure 6

Structure of the Cu(II) acetate complex,[Cu₂L(Ac)₂]·½H₂O (5).

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Second, the electronic spectrum of Co(II) acetate complex of the general formula,[Co₂(L)(Ac)₂]·3½H₂O (6), in Nujol and DMF shows three bands at 19380, 16393 and 14970 cm⁻¹. These bands are assigned to ⁴A₂ → ⁴T₁ (P) transition in a tetrahedral geometry around the second Co^II ion (Sutton, 1968). The value of magnetic moment (4.1 B.M.) is taken as an evidence for the existence of a tetrahedral geometry around the two Co(II) ions (Fig. 7).

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Figure 7

Structure of the Co(II) acetate complex,[Co₂(L)(Ac)₂]·3½H₂O (6).

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The thermal analyses curves of Co(II) acetate complex show four stages of decomposition. The first step (40–109 °C) corresponds to the loss of one molecule of one and half water of hydration (found: 4.5%; calcd.: 5.0%). The second step (109–378 ^oC) corresponds to the loss of two coordinated water molecules, two acetate groups and CH₂COOH (found: 40.9%; calcd.: 39.8%). The third step (380–555 °C) stands for the loss of NH molecule (found: 3.1%; calcd.: 2.8%). The last step corresponds to the decomposition of the remaining organic ligand leaving a residue (found: 51.5%; calcd.: 52.4%) for Co₂C₈SNOH₅.

The UV spectra of Ni(II) acetate complex of the general formula,[Ni₂L(OH)₂(H₂O)₆]·4H₂O (7), in DMF and Nujol, show bands at 16611 and 23364 cm⁻¹ assigned to ³A_2g → ³T_1g (ν₂) and ³A_2g → ³T_1g(P) (ν₃) respectively. The presence of these bands suggests an octahedral geometry around Ni(II) ion (Fig. 8). Also, the spectrum shows a band at 29069 cm⁻¹ assigned to LMCT (Sutton, 1968). The relatively low magnetic moment value (2.5 B.M.) supports the absence of any Ni–Ni interaction (Nawar et al., 2001).

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Figure 8

Structure of the Ni(II) acetate complex,[Ni₂L(OH)₂(H₂O)₆]·4H₂O (7).

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The thermal analyses curves (TGA, DTG) show that the Ni(II) acetate complex decomposes in five steps. The first (38–122 °C) stands for the loss of two molecules of water of hydration (found: 6.3%; calcd.: 6.3%). The second step (123–241 °C) corresponds to the loss of 2H₂O one of them is hydrogen bonded but not participated in crystal lattice (Jasinski et al., 2003) (found: 7.0%; calcd.: 6.3%). The next step (243–381 °C) corresponds to the decomposition of 6H₂O + OH (found: 22.8%; calcd.: 22.1%). The fourth step (382–531 °C) stands for the loss of C₄H₄N₂O₄ (found: 25.6%; calcd.: 25.4%). The remaining corresponds to Ni₂C₆S (found: 38.3%; calcd.: 39.1%).

The IR spectrum shows that the ligand coordinates to Zn(II) acetate forming binuclear complex with the general formula,[Zn₂(L)(Ac)₂]·4EtOH (8). The ligand behaves as a mono-negative bidentate ligand in the enol form toward the first Zn(II) ion coordinating via the CS and C–OH groups with replacement of a hydrogen atom from the latter group. The second Zn(II) ion is coordinated to the ligand through the carboxylic group with replacement of a hydrogen atom. Also, the spectrum shows two bands in the region 1583 and 1423 cm⁻¹ assigned to the υ_as(COO) and υ_a(COO) vibrations, respectively. The difference between these two groups is 160 cm⁻¹ indicating the bidentate nature of the carboxylate group (Fig. 9).

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Figure 9

Structure of the Zn(II) acetate complex,[Zn₂(L)(Ac)₂]·4EtOH (8).

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The ¹³C NMR spectrum of the Zn(II) complex in d₆-DMSO shows several signals at 178, 168, 149, 124-132, 56 and 18.5 ppm, down field of TMS, assigning to the carbon of CO, C⚌N, C⚌S, C⚌C (phenyl), CH₂NH and CH₃, respectively. The existence of these signals as shown in Fig. 10 confirms the proposed for the Zn(II) complex (Fig. 9).

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Figure 10

¹³C NMR spectrum of[Zn₂(L)(Ac)₂]·4EtOH (8).

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The participation of the carboxylic group in coordination in case of the acetate complexes is mainly attributed to the high pH of the solution (6–6.5) during complex formation. On the other hand, the carboxylic remains inert in case of chloride complexes, except the Ni(II) chloride complex, since the pH of the solution is very low (1-1.5) which prevents the ionization and the participation of this group.

Finally, one of our goals is to study the antimicrobial activities of the ligand against B. subtillis and P. aeruginosa. The data suggest that the Gram positive and Gram negative bacteria were affected by the ligand under investigation. Moreover, the effects of the genotoxicity on the DNA for the ligand in comparison to the control sample indicate interesting results. The degradation powers of the tested ligand on calf thymus DNA is high for all complexes supporting the selective action of the ligand against bacteria and the human or related eukaryotic organisms as shown in Fig. 11. The results are promising toward the use the ligand as anti-tumor.

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Figure 11

The degradation powers of the tested ligand on calf thymus DNA.

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