http://informahealthcare.com/dct ISSN: 0148-0545 (print), 1525-6014 (electronic) Drug Chem Toxicol, Early Online: 1–7 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/01480545.2015.1017882

RESEARCH ARTICLE

Synthesis, characterization and biological activity of some unsymmetrical Schiff base transition metal complexes

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Fatima T. Esmadi1, Omar F. Khabour2,3, Khamis Abbas1, Abdel Elah Mohammad1, Ra’ad T. Obeidat2, and Doa’a Mfady2 1

Department of Chemistry, Yarmouk University, Irbid, Jordan, 2Department of Biology, Faculty of Science, Taibah University, Medina, Saudi Arabia, and 3Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan

Abstract

Keywords

In this study, several unsymmetrical Schiff bases and their cobalt and manganese complexes have been synthesized and characterized. The unsymmetrical Schiff bases were prepared from reaction of o-phenylendiamine derivatives with 1-hydroxy-2-acetonaphthone and then the product was reacted with the following aldehydes: salicyaldehyde, 2-hydroxynaphthaldehyde, 2-pyridinecarboxaldehyde and 2-qinolinecarboxaldehyde to produce the desired tetradentate unsymmetrical Schiff base ligands H2SL, H2NL, HPYL and HQN, respectively. Reaction of these ligands with cobalt and manganese salts produced complexes of the general formula [M(SL)], [(NL)], [M(PYL)] and [M(QL)]. All the complexes were characterized by elemental analysis, infrared spectroscopy, UV-visible spectroscopy, electrical conductivity and magnetic susceptibility measurements. The prepared complexes were examined for their anti-bacterial activity using gram-positive and gram-negative pathogens. The following complexes showed strong antibacterial activity against Staphylococcus aureus: MnSL1, MnSL2 and MnSL3. The genotoxic activity of four complexes, which are MnNL1, MnSL1, CoNL1 and CoSL1, were examined using 8-hydroxy-2-deoxy guanosine (8-OHdG) assay in cultured human blood lymphocytes. All examined complexes were found to be genotoxic at examined concentrations (0.1–100 mg/mL), but with variable magnitudes (p50.05). The levels of 8-OHdG induced by MnNL1 and MnSL1 were significantly higher than that induced by CoNL1 and CoSL1 ones. In general, the order of mutagenicity of the compounds is MnSL14MnNL14CoSL14CoNL1. In conclusion, some of the prepared complexes showed some biological activities that might be of interest for future research.

8-OHdG, anti-bacterial activity, Co(II) complexes, genotoxicity, Mn(II) complexes, unsymmetrical Schiff bases

Introduction Schiff base complexes are considered to be among the most important stereo-chemical models in main group and transition metal coordination chemistry due to their preparative accessibility and structural variety. They have played a key role in the development of coordination chemistry, resulting in an enormous number of publications, ranging from pure synthetic to modern applied studies of these complexes. Many Schiff bases have been used for analytical purpose in the determination of metal ions (Grabaric et al., 1994; Koprivanac et al., 1992), and some Schiff base derivatives have been used for solvent extraction of metal ions (De et al., 1970). Schiff base complexes of Co(II) and Mn(II) were found to have anti-bacterial (Alghool et al., 2010; Kumar et al., 2010), anti-fungal (Mandala et al., 2011) and anti-tumor activities (Shahabadi et al., 2010). Co(II). Schiff base complexes have been extensively used as biologically active

Address for correspondence: Dr. Omar F. Khabour, Department of Biology, Faculty of Science, Taibah University, Madena, Saudi Arabia. Tel: 00966-557-306-579. E-mail: [email protected]

History Received 5 July 2014 Revised 23 January 2015 Accepted 8 February 2015 Published online 20 March 2015

complexes and as catalyst in chemical reaction, such as oxidative carbonylation of aniline (Chen et al., 2008). We have reported reaction of several Schiff bases with a variety of transition metal as Cu(II), Ni(II), Fe(II), Rh(III), Ir(III), Ru(II), Pt(II), Pd(II) and reaction of some of the prepared Schiff base complexes with different amines, where transamination reaction occurred (Esmadi & Irshaidat, 2000, 2001; Esmadi et al., 2010). In addition, mixed Schiff base complexes (Mostafa, 2010), thiocarbohydrazone and semithiocarbazone. Schiff base transition metal complexes (Esmadi et al., 2013) have been prepared and characterized. Moreover, the biological activity of some of the prepared complexes had been studied earlier (Khabour et al., 2013; Saleh et al., 2011). In continuation of our work on the synthesis and structural studies of transition metal Schiff base complexes and due to the high activity found for several cobalt and manganese complexes (Alghool et al., 2010; Kumar et al., 2010; Mandala et al., 2011), synthesis, characterization and the biological activity of some unsymmetrical tetradentate Schiff bases derived from substituted o-phenylendiamine and their Co(II) and Mn(II) complexes are described in this work.

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Figure 1. Structure of the mono-condensation products.

Unsymmetrical tetradentate Schiff bases were prepared by the reaction of 1-hydroxy-2-acetonaphthone with substituted o-phenylenediamine to get the mono-condensation product (half unit). Reaction of the half units with another aldehyde, such as salicylaldehyde and 2-hydroxynaphthaldehyde produced unsymmetrical tetradentate Schiff bases, which were reacted with Co(II) and Mn(II) salts. However, reaction of the half units with 2-pyridinecarboxaldehyde and 2-qinolinecarboxaldehyde failed to produce the desired unsymmetrical Schiff bases and therefore their complexes were obtained from reaction of the half unit with the corresponding aldehyde in the presence of the metal ion. The structure of the mono-condensation products (half units), HL, are shown in Figure 1, whereas the structures of the unsymmetrical Schiff bases; H2SL, H2NL, HPY and HQL are shown in Figure 2. The anti-bacterial activity and the oxidative DNA damage potential of the complexes were examined. The anti-bacterial activity of the complexes was studied against some gram-positive and gram-negative pathogens using the disc diffusion method. The oxidative DNA damage potential of the complexes was investigated using 8-hydroxy deoxyguanosine (8-OHdG) assay.

Materials and methods Instrumental

Figure 2. Structures of the unsymmetrical Schiff bases.

Preparation of Schiff bases Schiff bases were prepared according to the reported method for similar compounds (Boghaei & Lashanizadegan, 2000). The mono-condensation products (half unit) were first prepared and then reacted with an aldehyde to produce the desired unsymmetrical Schiff base.

The elemental analysis (C, H and N) for the isolated complexes was carried out on SP2-PYE-UNICAM atomic absorption spectrometer (Pye Unicam, Cambridge, UK). The infrared spectra were recorded over the range 4000–600 cm1 on FT-IR spectrometer (Bruker FT/IR-4100, Billerica, MA). Conductivity measurements were carried out on a Cyber Scan 510 conductivity meter (Thermo Scientific, Vernon Hills, IL) at 25  C using 1  103 M solution in DMF. Electronic absorption spectra were recorded on a Shimadzu UV-1800 spectrophotometer (Columbia, MD) in DMF using 8  105 M solution. Melting points were measured on an electrothermal melting point apparatus (Staffordshire, UK). Magnetic susceptibility measurements were done using an instrument obtained from Sherwood Scientific Ltd (Cambridge, UK).

Preparation of the mono-condensation compounds (half units)

Chemicals

Preparation of salicylaldehyde (H2SL) and naphthaldehyde (H2NL) Schiff bases

Chemicals were purchased from commercial sources. All solvents were of analytical grade and were used as purchased. Organic solids were recrystallized before use.

The mono-condensation compounds (half units: HL1, HL2 and HL3) are products of reaction of the diamine derivatives with 1-hydroxy-2-acetonaphthone. Equimolar quantities of the substituted o-phenylenediamine (3,4-diaminotolune, 4,5dimethylphenylenediamine, and 4-chlorophenylenediamine) and 1-hydroxy-2-acetonaphthone were mixed in absolute ethanol (20 mL) and left to reflux for 6.5, 7.5 and 9 h, respectively. The resulting precipitate in each reaction was isolated after cooling the solution at 0  C, washed with ethanol, then with ether and left to dry at 45  C overnight. In all cases, the yields were around 75%.

Preparation of H2SL1, H2SL2, H2SL3, H2NL1, H2NL2 and H2NL3 was done according to the following general

Unsymmetrical Schiff base complexes

DOI: 10.3109/01480545.2015.1017882

procedure: salicylaldehyde or 2-hydroxy-1-naphthaldehyde (1 mmol) dissolved in ethanol (10 mL) was added to a solution (25 mL) of the mono-condensation product (1 mmol) (HL1, HL2 and HL3) and then few drops of piperidine was added. The mixture was left stirring for 1 h at room temperature until precipitation was complete. The product was collected, washed with ethanol, petroleum ether and dried at 45  C for 24 h. Yields were around 80% in all cases.

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Preparation of [M(SL)] and [M(NL)] complexes where M ¼ Co, Mn; SL ¼ SL1, SL2 and SL3 and NL ¼ NL1, NL2 and NL3 In each preparation, an ethanolic solution (10 mL) of cobalt(II) acetate or manganese(II) acetate (1 mmol) was added to an ethanolic solution (15 mL) of the corresponding ligand (1 mmol), and the mixture was refluxed for 3 h. The resulted precipitate was washed with ethanol, petroleum ether and then dried at 45  C for 24 h. Preparation of unsymmetrical Schiff base complexes derived from 2-quinolinecarboxaldehyde and 2-pyridinecarboxaldehyde In each preparation, an ethanolic solution (5 mL) of the metal(II) perchlorate (1 mmol) was added to an ethanolic solution (1 mmol) of 2-pyridinecarboxaldehde (1 mmol) or 2-quinolinecarboxaldehyde and the corresponding monocondensation product (HL1, HL2 and HL3) (1 mmol). The mixture was refluxed for 3 h, the resulting solution was left to cool at room temperature to allow for complete precipitation. The precipitate was filtered and washed with ethanol then with petroleum ether and left to dry at 45  C for 24 h. Genotoxicity study using 8-hydroxy-2-deoxy guanosine (8-OHdG) assay The ability of [M(SL1)] and [M(NL1)] complexes to induce oxidative DNA damage in cultured human lymphocytes was examined using 8-OHdG assay. Here, M ¼ Co and Mn while SL1 is the deprotonated form of 2-(1-{2-[(2-hydroxybenzylidine)amino]-4-methylphenylimino}-ethyl)-1-naphthol, H2SL1 and NL1 is the deprotonated form of the ligand 2-(1-{2-[(2hydroxynaphthylmethylene)amino]-4-methylphenylimino}ethyl)-1-naphthol, H2NL1. Blood samples were obtained from healthy donors in sterile heparin tubes. Blood was immediately cultured by inoculating 1 mL of blood into 60 mL tissue-culture flasks containing 9 mL of PB-Max medium (Gibco–Invitrogen, Paisley, UK). Cultures were then incubated for 72 h at 37  C. Cultures were then centrifuged at 1000g and washed three times with RBMI medium (Gibco–Invitrogen, Paisley, UK). Cells were resuspended in 10 mL of RBMI medium and were treated with compounds dissolved in DMSO (final concentrations in cultures: 0.1, 1, 10 and 100 mg/mL) for 6 h at 37  C. After treatments, cultures were centrifuged at 1000g. Levels of 8-OHdG in the supernatant was determined using ELISA assays (Stress Marq, s 8-OHdG EIA kit; Biosciences, Mississauga, Canada) according to manufacturer’s instructions. Samples were assayed in duplicates using 100 mL of supernatant in each. The experiment was repeated four times.

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Plates were read at 405 nm using an automated ELISA reader (ELx 800/Universal Microplate Reader, Bio-TEK instrument, Winooski, VT). Antibacterial activity of the complexes using disc diffusion Disc diffusion assay was applied to study activity of the prepared drugs against the gram negatives Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922), and the gram positives Staphylococcus aureus (ATCC 29213) and Streptococcus pneumonia bacterial strains as previously described (Esmadi et al., 2013). All bacterial strains were obtained from American Type Culture Collection (Manassas, VA) except St. pneumonia was obtained from King Abdullah University Hospital Diagnostic Laboratories. Isolated pure colonies were transferred from the cultured plates into sterile NaCl (0.9%) solution to form bacterial suspensions. After the bacterial density was adjusted to 0.5 McFarland standard units, the suspension was then spread over Mueller–Hinton agar plates. Sterile filter paper discs (diameter: 6 mm) were placed over these plates and then 15 mL of the test drug (10 mg/mL dissolved in DMSO) was applied on each disk. The plates were then incubated at 37  C for 24 h. The inhibition zones were calculated from two replicates of each drug (n ¼ 4/replicate). Polymyxin-B (10 mg/mL, Sigma Aldrich, Milan, Italy) was used as a positive control for E. coli, P. aeruginosa and S. aureus, while tetracyclin (10 mg/mL, Sigma Aldrich, Milan, Italy) was used as a positive control for St. pneumonia. DMSO alone was used as a negative control. Statistical analysis All statistics were carried out using the GraphPad Prism (4.0) computer program (La Jolla, CA). Comparisons of the 8OHdG values were made using one-way ANOVA for each concentration; followed by Bonferroni’s post-test. p50.05 was considered significant. All values are represented as mean ± standard error means (SEM).

Results The results of the elemental analysis of the isolated complexes are listed in Table 1. Color, molar absorptivity coefficient (") and lmax of the isolated complexes are listed in Table 2. The obtained molar conductivity values, decomposition points, magnetic moments and important IR bands of the isolated complexes are listed in Table 3. With respect to biological activity, the antibacterial effect of the complexes was examined against E. coli, P. aeruginosa, S. aureus, St. pneumonia using the disc diffusion assay. Nine complexes out of 14 showed some antibacterial activity (Table 4). Notably, [Mn(SL1)].0.5H2O, [Mn(SL2)].0.5H2O and [Mn(SL3)].0.5H2O showed strong antibacterial activity against S. aureus with inhibition zones comparable to that of the positive control. The gram negative P. aeruginosa strain showed weak susceptibility to [Mn(SL1)].0.5H2O, [Co(SL1)].0.5H2O and [Mn(NL1)].H2O with inhibition zones range of 7–8 mm. However, the gram negative E. coli and the gram positive St. pneumonia were resistant to all compounds. In addition, the gram positive S. aureus

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Table 1. Elemental analysis of the isolated Schiff base complexes. Analysis:Calculated (found)

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Metal complex [Co(SL1)]H2O [Mn(SL1)]0.5H2O [Co(NL1)]0.5H2O [Mn(NL1)]H2O [Co(SL2)]0.5H2O [Mn(SL2)]0.5H2O [Co(NL2)]0.5H2O [Mn(NL2)] [Co(SL3)] [Mn(SL3)]0.5H2O [Co(NL3)]0.5H2O [Co(PYL2)]ClO4 [Mn(PYL2)]ClO4 [Mn(QL2)]ClO4

Empirical formula (F.W*) CoC26H22O3N2 (469.40) MnC26H21O25N2 (456.40) CoC30H23O25N2 (510.45)) MnC30H24O3N2 (515.45) CoC27H23O25N2 (474.42) MnC27H23O25N2 (470.42) CoC31H25O25N2 (524.48) MnC31H25O25N2 (520.48) CoC25H17O2N2Cl (471.80) MnC25H18O25N2Cl (476.80) CoC29H20O25N2Cl (530.87) CoC26H22O5N3Cl (550.86) MnC26H22O5N3Cl )546.86) MnC30H22O5N3Cl (596.92)

%C 66.52 68.42 70.58 69.90 68.35 68.93 70.99 71.53 63.64 62.97 65.61 56.69 57.10 60.36

(66.96) (68.88) (70.85) (69.34) (68.52) (68.59) (71.23) (71.29) (63.37) (63.32) (65.22) (56.41) (57.60) (60.13)

%H 4.76 4.63 4.54 4.69 4.88 4.92 4.80 4.84 3.63 3.80 3.79 4.02 4.05 4.05

%N

(5.22) (5.14) (5.00) (5.23) (5.39) (5.25) (5.29) (5.36) (4.16) (4.18) (4.18) (4.51) (4.53) (4.08)

5.97 6.13 5.48 6.43 5.90 5.95 5.34 5.38 5.93 5.87 5.27 7.62 7.68 7.04

6.37)) (5.84) (5.24) (6.13) (6.24) (5.77) (5.86) (5.83) (6.24) (6.32) (5.85) (8.14) (6.24) (7.22)

%M 12.55 12.03 11.54 11.04 12.42 11.67 11.23 10.55 12.49 11.52 11.10 10.69 10.04 9.20

(12.23) (12.45) (11.21) (11.60) (12.92) (11.15) (11.82) (10.12) (12.94) (11.93) (11.56) (10.90) (10.48) (8.85)

*F.W: Formula Weight.

Table 2. Color and UV-visible spectral data for Schiff base complexes. Metal complex [Co(SL1)]H2O [Mn(SL1)]0.5H2O [Co(NL1)]0.5H2O [Mn(NL1)]H2O [Co(SL2)]0.5H2O [Mn(SL2)]0.5H2O [Co(NL2)]0.5H2O [Mn(NL2)] [Co(SL3)] [Mn(SL3)]0.5H2O [Co(NL3)]0.5H2O [Co (PYL2)]ClO4 [Mn(PYL2)]ClO4 [Mn(QL2)]ClO4

Color

max (nm)

" (L mol1 cm1)  104

Deep brown Brown Deep brown Brown Deep brown Brown Deep brown Deep brown Deep brown Brown Brown Deep brown Brown Brown

411 412 421 410 409 389 420 412 401 408 416 410 395 404

1.63 1.70 1.65 1.69 1.84 1.90 1.84 1.92 1.23 1.62 1.58 2.21 3.66 2.41

showed resistance only to [Mn(NL2)], [Co(SL3)] and [Mn(PYL2)]ClO4. Figure 3 shows the levels of 8-OHdG induced by [M(NL1)], where NL1 is the deprotonated form of the ligand 2-(1-{2-[(2-hydroxynaphthylmethylene)amino]-4methylphenylimino}-ethyl)-1-naphthol, H2NL1 and [M(SL1)], where SL1 is the deprotonated form of 2-(1{2-[(2-hydroxybenzylidine)amino]-4-methylphenylimino}ethyl)-1-naphthol, H2SL1 (Figure 2). Levels of 8-OHdG induced by MnNL1 and MnSL1 compounds were significantly higher than that induced by CoNL1 and CoSL1 (p50.05). At low concentrations of compounds (0.1 and 1 mg/mL), the order of mutagenicity induced by the different compounds were: MnSL14MnNL14CoSL14CoNL1. The mutagenicity of MnNL1 and CoNL1 increases in a dosedependent manner. However, the mutagenicity of MnSL1 and CoSL1 decreases at higher concentrations.

Discussion This study describes synthesis and characterization of new Schiff base complexes. Some of these Schiff bases were found to be effective against S. aureus pathogen. In addition, four of the prepared complexes were examined for their genotoxic



max(nm)

310 309 313 307 311 300 305 306 312 300 302 302 315 312

" (L mol1 cm1)  104 3.22 2.15 4.67 3.06 3.37 2.34 4.46 2.67 2.74 2.50 4.09 3.50 3.74 3.56

potential using 8-OHdG assay. The results showed significant genotoxicity of the assayed Schiff base complexes with notable variations in the magnitude. All Schiff bases used in this work contain relatively acidic protons which can be abstracted by acetate or perchlorate anions of the metal salt. Complexes of the three unsymmetrical Schiff base H2SL1, H2SL2 and H2SL3 were obtained upon reaction of the Schiff base with cobalt(II) acetate or manganese(II) acetate. They are formulated as [Co(SL1)]H2O, [Co(SL2)]0.5H2O, [Co(SL3)] and [Mn(SL)]0.5H2O where SL ¼ SL1, SL2 and SL3. In all the complexes, the Schiff bases are proposed to act as tetradentate dibasic ligands. Infrared spectra of the complexes show the azomethine stretching frequency appearing in 1603–1609 and 1606– 1616 cm1 range in cobalt and manganese complexes, respectively. The corresponding band appears at higher frequencies in free Schiff bases (at 1621 cm1 in H2SL1 and H2SL2 and at 1614 cm1 in H2SL3), which is an indication of the imine bond involvement in bonding to metal (Bagherzadeh et al., 2009). In the IR spectra of [Co(SL1)]H2O, [Co(SL2)]0.5H2O and [Mn(SL)]0.5H2O, a broad band appears in the range 3346– 3462 cm1, which is assigned to O–H stretching of the water of hydration (Boghaei et al., 2008).

Unsymmetrical Schiff base complexes

DOI: 10.3109/01480545.2015.1017882

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Table 3. Decomposition points, molar conductivity (^m ), magnetic moment values (m) and important IR bands for Schiff base complexes. Metal complex

m (Bohr Magneton)

^m a (ohm1cm2mol1)

Decomposition point ( C)

IR Peak cm1

[Co(SL1)]H2O

2.12

2.1

377

[Mn(SL1)]0.5H2O

2.05

3.2

300

[Co(NL1)]0.5H2O

2.11

2.5

303

[Mn(NL1)]H2O

1.95

3.1

265

[Co(SL2)]0.5H2O

2.09

3.1

327

[Mn(SL2)]0.5H2O

1.95

2.6

283

[Co(NL2)]0.5H2O

2.13

4.3

319

[Mn(NL2)] [Co(SL3)] [Mn(SL3)]0.5H2O

2.08 2.14 1.82

3.7 2.8 3.1

225 305 259

[Co(NL3)]0.5H2O

2.06

4.2

314

[Co (PYL2)]ClO4

1.87

90

215

[Mn(PYL2)]ClO4

2.12

98

213

[Mn(QL2)]ClO4

1.92

85

267

1603 3446 1608 3447 1616 3446 1618 3461 1607 3462 1616 3462 1615 3462 1617 1609 1606 3462 1615 3442 1602 1092 1592 1090 1627 1102

^m stands for the molar conductivity of 1  103 M solution at 25  C in DMF.

a

Table 4. The antibacterial activity of the prepared compounds.

Compound (10 mg/mL) [Co(SL1)]H2O [Mn(SL1)]0.5H2O [Co(NL1)]0.5H2O [Mn(NL1)]H2O [Co(SL2)]0.5H2O [Mn(SL2)]0.5H2O [Co(NL2)]0.5H2O [Mn(NL2)] [Co(SL3)] [Mn(SL3)]0.5H2O [Co(NL3)]0.5H2O [Co (PYL2)]ClO4 [Mn(PYL2)]ClO4 [Mn(QL2)]ClO4 Positive controla Negative controlb

P. aeruginosa Inhibition zone (mm)

E. coli Inhibition zone (mm)

S. aureus Inhibition zone (mm)

St. pneumonia Inhibition zone (mm)

0 8 8 7 0 0 0 0 0 0 0 0 0 0 17 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 19 0

0 19 6 9 8 19 6 0 0 16 8 8 0 0 18 0

0 8 8 7 0 0 0 0 0 0 0 0 0 0 18 0

a

Polymyxin-B for E. coli, P. aeruginosa and S. aureus; and tetracycline for St. pneumonia. DMSO alone. mm (millimeter).

b

The measured values of the effective magnetic moments for the cobalt and manganese complexes range from 2.09– 2.14 and 1.82–2.05 B.M. for cobalt and manganese complexes, respectively, which indicate the presence of one unpaired electron. Tetracoordinate Co(II) and Mn(II) complexes with one unpaired electron are expected to have square planar geometry (Cotton & Wilkinson, 1999). The molar conductivity values in DMF solvent are low (2.1–3.1 and 2.6–3.2 ohm1 cm2 mol1 range for Co and Mn complexes, respectively), which support the formulation of the complexes as neutral.

Cobalt complexes of the formula [Co(NL)].0.5H2O, where NL ¼ NL1, NL2 and NL3 and [Mn(NL], where NL ¼ NL1 or NL2 were obtained from reaction of the cobalt(II) acetate or manganese (II) acetate with the corresponding Schiff base. These complexes have brown to deep brown colors and stable at room temperature. Manganese complexes decompose above 225  C, whereas, cobalt complexes decompose above 303  C. Infrared spectra of the [Co(NL)]0.5H2O complexes, show the azomethine stretching frequency band around 1615 cm1 and in 1613–1618 cm1 range. For [Mn(NL)] complexes, the

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Figure 3. Genotoxicity of [M(NL1)] and [M(SL1)] Schiff base complexes, where M ¼ Mn and Co as examined by 8-OHdG assay. Genotoxicity was examined using human cultured lymphocytes. The levels of 8-OHdG induced by MnNL1 and MnSL1 were significantly higher than that induced by CoNL1 and CoSL1 ones. The order of mutagenicity of the compounds was MnSL14MnNL14 CoSL14CoNL1. Data are expressed as mean ± SEM.

imine bond stretching frequency appears at higher values in spectra of the free ligands (1620, 1630 and 1626 cm1 in H2NL1, H2NL2 and H2NL3, respectively), which is an indication of bond formation through the nitrogen atom. In addition, a broad band appears in 3446–3462 cm1 range in spectra of the cobalt complexes, which is assigned to O–H stretching of the water of hydration. Conductivity measurements for solution of the complexes fall in 3.1–4.3 ohm1 cm2 mol1 range indicating that they are non-conducting, which support their formulation as non-ionic compounds. Magnetic susceptibility measurements revealed that the complexes are paramagnetic (for Co complexes they are in 2.06–2.13 B.M. range and for Mn complexes they are in 1.95– 2.08 B.M. range). These values indicate the presence of one unpaired electron. Tetracoordinate Mn(II) and Co(II) with one unpaired electron are expected to have square planar geometry (Cotton & Wilkinson, 1999). Attempts to isolate products from reaction of the monocondensation compounds (half units) with the aldehydes 2pyridinecarboxaldehyde and 2-quinolinecarboxaldehyde in order to obtain unsymmetrical Schiff bases were unsuccessful. Therefore, preparation of their complexes was carried out by the reaction of mono-condensation compound (half unit) with the second aldehyde in the presence of the metal ion. Reaction of each of the three half units with each of both aldehydes in the presence of cobalt ion or manganese ion was carried out. However, it was possible to characterize correctly only three of the obtained, one cobalt and two manganese complexes products. These complexes were obtained from the reaction of Co(II) perchlorate or Mn(II) perchlorate with a mixture of 2-pyridinecarboxaldehyde or 2-quinolinecarboxaldehyde and HL2 compound. The complexes were brown colored and decomposed at a temperature of above 213  C. IR spectra of the complexes show the characteristic imine bond frequency for [Co(PYL2)], [Mn(PYL2)] and [Mn(QL2)] complexes appearing at 1602, 1592 and 1627 cm1, respectively. The corresponding band appears at 1635 cm1 in IR spectrum of the half unit. This shifts to lower values supporting the coordination of the imine group through the nitrogen. The spectrum also shows a broad band, which

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is assigned to Cl–O of the perchlorate group at 1092, 1090 and 1102 cm1 for Co(PYL2), Mn(PYL2) and Mn(QL2), respectively (Nakamoto, 2009). The shift in the position of C–O stretching frequency which appears at 1387 cm1 in the spectrum of the complex compared to that in the corresponding half unit (1365 cm1) indicates the formation of M–O bond (Nakamoto, 2009). Conductivity measurement in DMF solvent indicates that the complexes are ionic (1:1 electrolytes). The molar conductivity values were ^m ¼ 90, 98 and 85 ohm1 cm2 mol1 for Co(PYL2), Mn(PYL2) and Mn(QL2) complexes, respectively. Measurement of the magnetic moment of the complexes indicated that the complexes are paramagnetic with one unpaired electron (meff ¼ 1.87, 2.12 and 1.92 B.M for Co(PYL2), Mn(PYL2) and Mn(QL2), respectively). This suggests that the geometry around both manganese and cobalt atoms is square planar (Cotton & Wilkinson, 1999). The spectra of the each complexes shows two absorption bands in 300–315 nm and 355–385 nm range, which are assigned as intraligand absorption,  ! * and n ! * of both conjugated and azomethine group, respectively (Thaker et al., 2007). Schiff bases used in this work are conjugated such that intraligand absorption bands can appear in the visible region. The absorption band that appears in 395– 421 nm range is assigned as charge transfer transition (LMCT). In most cases, d–d transition cannot be detected since they are obscured by the broad charge transfer transition tailing into the visible spectrum (Thaker et al., 2007). The activity of the prepared complexes against bacterial strains was examined using the disc diffusion assay. Three complexes, [Mn(SL1)]0.5H2O, [Mn(SL2)]0.5H2O and [Mn(SL3)]0.5H2O, showed strong antibacterial activity against the gram positive S. aureus with inhibition zones comparable to that of Polymyxin-B antibiotic. This effect is specific as no inhibition was observed for these complexes against St. pneumonia and E. coli. Staphylococcus aureus has long been recognized as an important pathogen in human disease (Lucet & Regnier, 2010). It is associated with skin, respirator and food poisoning. It is considered as one of the serious infectious agents in hospitals due to its acquired resistance to antibiotics (Lepelletier & Lucet, 2013). Thus, the reported complexes that showed strong activity against S. aureus are promising and might represent good candidates for agents against infection caused by this bacterium. The result also showed that manganese complexes had relatively higher antibacterial activity than cobalt complexes. More studies are required to investigate the mechanisms behind such differences in bioactivity of the prepared complexes. Four of the presented complexes were examined for their genotoxic potential using 8-OHdG, which is potent in detecting agents that cause oxidative DNA damage (Valavanidis et al., 2009). While all complexes were found to cause genotoxicity, significant variations were observed. In general, levels of 8-OHdG induced by MnNL1 and MnSL1 compounds were significantly higher than that induced by CoNL1 and CoSL1. The antibacterial experiments also showed that Mn complexes were more bioactive than their Co counterparts. It is possible that Mn complexes might cause

DOI: 10.3109/01480545.2015.1017882

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more oxidative stress inside cells compared to Co complexes and the subsequent release of more 8-OHdG into the media by the cells. Alternatively, Mn complexes might interact more strongly to DNA than Co ones. On the one hand, it is unlikely that the observed variation in the genotoxicity could be attributed to the type of metal in the complexes, since Mn ion is present inside cells and is required for the activity of several enzymes (Avila et al., 2013). The results that the mutagenicity of MnSL1 and CoSL1 decreases at higher concentrations might indicate that these complexes are cytotoxic to cells at high doses. More studies are required to explore the mechanisms and the differences in genotoxic profile of the examined complexes.

Conclusion Several Mn and Co Schiff base complexes were prepared and characterized in this study. Three complexes showed strong activity against S. aureus and might be used to control infection caused by this pathogen. The complexes also possess activity against DNA as measured by 8-OHdG assay.

Declaration of interest The authors are very grateful to Yarmouk University for supporting this work (project no. 9/2011).

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Synthesis, characterization and biological activity of some unsymmetrical Schiff base transition metal complexes.

In this study, several unsymmetrical Schiff bases and their cobalt and manganese complexes have been synthesized and characterized. The unsymmetrical ...
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