Synthesis, Characterization and Antifungal Activity of Some Metal Complexes Derived From Quinoxaloyl...

Ahmed Mahal, Rajab Abu-El-Halawa, Sami A. Zabin, Mohammad Ibrahim, Mahmoud Al-Refai, Tawfeq Kaimari

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Synthesis, Characterization and Antifungal Activity of Some Metal Complexes Derived From Quinoxaloylhydrazone

Ahmed Mahal1, 2,, Rajab Abu-El-Halawa3, 4,, Sami A. Zabin5, Mohammad Ibrahim3, Mahmoud Al-Refai3, Tawfeq Kaimari6

1Department of Chemistry, Sultan Qaboos University, Muscat, Sultanate of Oman

2Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, Napoli, Italy

3Department of Chemistry, Al al-Bayt University, Mafraq, Jordan

4Clinical Pharmacy, Al-Baha University, Al Baha, Saudi Arabia

5Department of Chemistry, Al-Baha University, Al Baha, Saudi Arabia

6Faculty of Pharmacy & Medical Science, Hebron University, Hebron, Palestine


New Complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and Tin(II) with 3-methyl-2-(pyridine-2-yl-methylene-hydrazinocarbonyl)quinoxaline-4-oxide (LHP) and 2-(2-hydroxy benzylidene-hydrazinocarbonyl)-3-methylquinoxaline-4-oxide (LHS) were prepared. The new complexes were characterized by elemental analysis, conductivity, magnetic measurements, IR and UV-Vis spectroscopic measurements. The results indicate 1:1 [M:L] chelates with the general formula [M(LHP)Cl2].nH2O where: M = Mn(II), n=4, Co(II), n=1/2, Cu(II), n=1, Hg(II), n=1, and 1:2 [M:L] in case of [M(LHS)2](OAc)2.nH2O when M = Zn(II), n= 3, Cd(II), n= 1, Hg(II), n= 1/2. The tin complex structure is suggested to be [Sn(LHP)2]Cl2.2H2O, while copper produces [Cu2(LHS)2SO4].H2O complexes. Also, the formula for mercuric complex found to be [Hg(LHS)2Cl2].2H2O. The magnetic moment measurements and electronic spectra suggest octahedral geometry for the prepared complexes. The antifungal investigation reveals that the activity was enhanced by chelation. The Cu(II) complexes has the highest inhibition zone against A. niger. But, the antifungal activity was weaker than the standard drug used.

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Cite this article:

  • Mahal, Ahmed, et al. "Synthesis, Characterization and Antifungal Activity of Some Metal Complexes Derived From Quinoxaloylhydrazone." World Journal of Organic Chemistry 3.1 (2015): 1-8.
  • Mahal, A. , Abu-El-Halawa, R. , Zabin, S. A. , Ibrahim, M. , Al-Refai, M. , & Kaimari, T. (2015). Synthesis, Characterization and Antifungal Activity of Some Metal Complexes Derived From Quinoxaloylhydrazone. World Journal of Organic Chemistry, 3(1), 1-8.
  • Mahal, Ahmed, Rajab Abu-El-Halawa, Sami A. Zabin, Mohammad Ibrahim, Mahmoud Al-Refai, and Tawfeq Kaimari. "Synthesis, Characterization and Antifungal Activity of Some Metal Complexes Derived From Quinoxaloylhydrazone." World Journal of Organic Chemistry 3, no. 1 (2015): 1-8.

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1. Introduction

The development of bioinorganic chemistry field has increased the interest in Schiff base complexes, as they may serve as models for biologically important compounds and bioinorganic processes [1, 2, 3]. Biological activity of complexes derived from hydrazones has been widely studied and found to have numerous biological activities: antibacterial, antitumor, antimalarial and antituberculosis effects [4, 5, 6, 7, 8]. The acid hydrazides, RCONHNH2 and their corresponding aroylhydrazones, RCONHN=CHR', have been widely investigated and have aroused interest due to their effective tridentate chelation with transition metal ions, and their ability to bind with the transition metal ions present in the living systems and possible biomimetic applications [9, 10].

Metal complexes of substituted hydrazones have been reported to hold therapeutic activity and have pharmacological applications [11, 12]. The complexes could bind and cleave the DNA strands via different mechanisms under different physiological conditions [13]. Aroyl hydrazone complexes of transition metals are used as models for elucidation the mechanism of enzyme inhibition [14].

Many reported research work shows that metal chelates are more biologically active than free ligands; this may be due to chelation which reduces the polarity of metal ions. This increases the hydrophobic character of the metal chelate and favors the penetration through liploid layers of microorganism membrane [15].

The Schiff bases having hydrazone moiety have proved to be strong chelating agents for transition metals and are attractive ligands from the structural point of view [16]. Aroyl hydrazones have donor properties in coordinating metals and prsent a combination of donor sites, such as protonaed/deprotonated amide oxygen and the imine nitrogen of hydrazone moiety. These ligands capable of undergoing keto-enol tautomerism [17]. Aroyl hydrazone ligands very often have additional donor site (usually N or O) which is provided by the aldehyde or ketone forming the Schiff base [16].

N-Aroylhydrazones as tridentate chelators derived from heterocyclic aldehydes and ketones and of methyl pyruvate forming selectively 2:1 (L:M) complexes and show considerable chelating ability towards metal ions [18, 19] and can be used in analytical chemistry to recover and selectively determine transition metals as hydrazone complexes [19, 20]. Also, The use of potentially tridentate ligands in the synthesis of organometallic compounds has received much more attention because tridentate metal complexes are expected to exhibit interesting catalytic properties, such as better stereoselective or chemoselective control of the reactions [21, 22, 23]. The present study deals with the synthesis and characterization of Schiff bases derived from quinoxaline-4-oxide hydrazide derivative 3, i.e. 3-methyl-2-(pyridine-2-yl-methylene-hydrazinocarbonyl)quinoxaline-4-oxide (6, LHP) and 2-(2-hydroxybenzylidene-hydrazinocarbonyl)-3-methylquinoxaline-4-oxide (7, LHS) and their complexation with Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and Sn(II). Synthesis of LHP and LHS ligands and their complexes are shown in Scheme 1, 2 and 3.

Scheme 1. Synthesis of LHP and LHS ligands

2. Procedure and Expermintal Section

2.1. Material

All the starting chemicals and solvents were of analytical grade and used without further purification. The hydrated metal salts were obtained from Sigma-Aldrich and Luba.

2.2. Physical Measurenment

C, H, and N analysis for Ligands and complexes were determined using a Parkin-Elmer 2400 series (II) elemental analyzer. Metal analysis was performed on a Unicam 929 Atomic Absorption Spectrometer. Conductivity measurements were recorded on Conductivity Meter LF 538 at 25°C using 10-3 M solutions in dimethylsulfoxide (DMSO). Magnetic measurements were carried out in the solid state at room temperature on Johnson Matthy Magnetic Susceptibility susceptometer using Hg[Co(SCN)4] as calibrant. The IR spectra (KBr pellets) were recorded on Thermo Nicolet NEXUS 670 FT-IR spectrophotometer. Electronic absorption spectra were measured using a Unicam UV-Vis spectrometer for 10-3 M solution in DMSO. Melting Points were recorded on an Electrothermal 9001 apparatus.

1H-NMR spectra and 13C-NMR of the ligands were measured in d6-DMSO using TMS as internal standard on a Burker AV-300 spectrometer. Mass spectra of the ligands were recorded on shimadzo GC-MS-QP 1000 Ex at 70 ev mass spectrometer.

2.3. Synthesis of LHP and LHS

The ligands LHP 6 and LHS 7 were prepared according to the reported procedure [24, 26]. A solution of 11.0 mmol pyridine-2-carboxyaldehyde (4) or 2-hydroxy benzlaldehyde (5) with 10.0 mmol (2.18 g) of 3-methyl-quinoxaline-2-carboxylic acid hydrazide 4-oxide (3) in 30 mL ethanol and 5 mL acetic acid was boiled under reflux for 20 min with stirring. The reaction mixture was concentrated by evaporation of the solvent. The solid was filtered and recrystallized from chloroform and petroleum ether (1:1) [24].

LHP (6): Yield 78%, colour : whitish, m.p. 194-196 °C, (CHCl3 / Pet. Ether), elemental analysis calculated for C16H13N5O2 (307.31): C, 62.53, H, 4.26, N, 22.79, Found: C, 62.76, H, 4.34, N, 22.57, Mass, 307 (M+), IR (KBr disc, cm-1) 3200 (NH), 1679 (C=O), 1570 (C=N), 1300 (amide), 927 (N-N), 1H NMR (DMSO-d6): δ 11.28 (s, 1H, NH), 8.52 (s, 1H, N=CH), 8.34 (m,1H, H5), 8.32 (m,1H, H6’), 8.07 (m, 1H, H8), 7.95 (m,1H, H3’), 7.82 (m,2H, H6+H7), 7.39 (m,1H, H4’), 6.91 (m,1H, H5’), 3.08 (s, 3H, CH3), 13C NMR (DMSO-d6 δ): 148.6 (C=N), 162.8 (C=O), 134.2 (C2), 138.5 (C3), 119.7 (C5), 132.8 (C6), 131.7 (C7), 119.7 (C8), 136.3 (C9), 137.6 (C10), 152.5 (C2’), 127.6 (C3’), 147.8 (C4’), 124.6 (C5’), 149.8 (C6’), 29.2 (C, CH3).

LHS (7): Yield 72%, colour: yellow, m.p. 185-187 °C, (CHCl3 / Pet. Ether), elemental analysis calculated for C17H14N4O3 (322.32), C, 63.35, H, 4.38, N, 17.38, Found: C, 63.56, H, 4.58, N, 17.18, Mass 322 (M+), IR (KBr disc, cm-1): 3200 (NH), 1660 (C=O), 1570 (C=N), 1300 (amide), 959 (N-N), 1H NMR (DMSO-d6 δ): 12.22 (s, 1H, OH), 11.42 (s, 1H, NH), 8.61 (s, 1H, N=CH), 7.52 (m,1H, H6’), 8.34 (m,1H, H5), 8.07 (m, 1H, H8), 7.91 (m,1H, H3’), 7.82 (m,2H, H6+H7), 7.25 (m,2H, H4’+ H5’), 3.08 (s, 3H, CH3), 13C NMR (DMSO-d6 δ): 157.6 (C2), 148.3 (C=N), 162.9 (C=O), 138.4 (C3), 137.7 (C4a), 119.7 (C5), 132.8 (C6), 131.7 (C7), 119.6 (C8), 136.2 (C8a), 156.7 (C2’), 136.92 (C4), 132.73 (6’), 120.72 (1’), 119.84 (5’), 117.55 (3’), 29.1 (C, CH3).

2.4. Synthesis of Metal Complexes

All complexes prepared were dried under vacuum at 25 °C and were prepared according to the following general procedures:

i) For preparation of [M(LHP)Cl2)].nH2O (1:1 metal to ligand reaction ratio), M= Mn(II), n= 4, Co(II), n= 1/2, Cu(II), n=1, Hg(II), n= 1] 17-20, the following procedure was followed:

To a stirred solution of 1.0 mmol (0.307 gm) of the ligand LHP 6 in 10 mL THF was added to a solution of the corresponding 1.0 mmol of metal (II) chloride 8-11 in 10 mL THF. The reaction mixture was stirred at room temperature (or heated at 50 °C in the case of Cu(II), and Mn(II)) for 1 h, then the reaction mixture was concentrated by the evaporation of THF. The solid was filtered and thoroughly washed with water and ethanol. {[Cu(LHP)Cl2].H2O Yield = 74%, m.p. = 254 °C, colour = light green, [Hg(LHP)Cl2].H2O Yield = 82%, m.p. =267 °C, colour = Yellow, [Mn(LHP)Cl]Cl.4H2O Yield = 75%, m.p. =220 °C, colour = orange, [Co(LHP)Cl2]. 0.5H2O Yield = 73%, m.p. = 256 °C, colour = dark green}.

The [Sn(LHP)2]Cl2.2H2O, 21 (1:2 metal to ligand reaction ratio), was prepared as in the above procedure using 2.0 mmol of the ligand LHP 6 with 1.0 mmol of tin(II) chloride and heating the mixture at 50 °C for half an hour. The precipitate obtained was washed with ethanol and then with distilled water. The complex obtained was 77% yield, yellow in colour and its m.p. = 313 °C. ii) For preparation of [M(LHS)2] (OAc)2.nH2O (1: 2 metal to ligand reaction ratio), [M = Zn(II), n= 3, Cd(II), n= 1, Hg(II), n= 0.5, 22-24, the following procedure was followed:

To a stirred solution of 2.0 mmol of the ligand LHS (7) in 10 mL water was added to a solution of the corresponding 1.0 mmole of hydrated metal acetate 14-16 in 10 mL water. The reaction mixture was stirred at room temperature for 1 h then the reaction mixture was concentrated. The solid obtained was filtered and thoroughly washed with water and acetone. {[Zn(LHS)2](OAC)2.3H2O Yield = 80%, m.p. =277-280°C, colour = brown, [Hg(LHS)2](OAC)2.0.5H2O Yield = 84%, m.p. =242 °C, colour = orange, [Cd(LHS)2](OAC)2.H2O Yield = 69%, m.p. = 280 °C, colour = orange}.

Under the same conditions, hydrated copper (II) sulfate (13) and Hg(II) chloride (9) form complexes of the structure [Cu2(LHS)2SO4].H2O, 25, and [Hg(LHS)2]Cl2.2H2O, 26, respectively. {[Cu2(LHS)2SO4].H2O Yield = 80%, m.p. =225 °C, colour = yellow, [Hg(LHS)2]Cl2.2H2O Yield = 78%, m.p. =340 °C, colour = brown}.

2.5. Antifungal Activity Studies

The antifungal activity of the ligands and their complexes were tested by Well Diffusion Assay method [27, 29]. The antifungal activities were tested for their in vitro growth inhibitory activity against the pathogenic fungal strains Aspergillus niger (A. niger) cultured on potato dextrose agar. The stock solution (10-2 mol. L-1) of the compounds was prepared by dissolving the compounds in DMSO as solvent. The concentration was diluted and the concentration used in this study was 200 ppm.

The solvent (DMSO) was used as a control in a similar manner to the prepared solutions of the tested compounds. Also, standard antifungal drug (Amphotricene B) was used for comparison.

Solutions of the ligands and its complexes in DMSO were plated onto the cultured agar medium and incubated for a period of 72 h at 30°C. After the incubation period, the plates were observed for zones of inhibition (in cm). Each sample was repeated three times, and statistical analysis were performed with SPSS 16.0 for windows. The limit of statistical analysis was set at p < 0.05. Data were presented as mean ± standard deviation (SD).

3. Result and Discussion

3.1. Preparation and Elemental Analysis

Quinoxalinoyl hydrazone ligands LHP 6, and LHS 7, were prepared by the condensation of pyridine-2-caroxyaldehyde (4) or 2-hydroxy benzlaldehyde (5) with 3-methyl-quinoxaline-2-carboxylic acid hydrazide 4-oxide (3) in ethanol and acetic acid. The latter hydrazide 3 was prepared by the hydrazinolysis of the 2-ethoxycarbonyl-3-methylquinoxaline 1,4-dioxide (1) in MeOH at 0-15 °C for 2 hours as reported [24] and shown in Scheme 1.

When solutions of the hydrazone derivative, LHP 6 was stirred with THF solution of the hydrated metal chloride salts 8-11 using 1:1 [M : L] molar ratio, colored air-stable mononuclear complexes of the formula [M(LHP)Cl2].nH2O 17-20, where [M= Cu(II), n= 1, Hg(II), n= 1, Mn(II), n=4, Co(II), n= 0.5] were formed. Under the same conditions using 1:2 [M: L], the [Sn(LHP)2]Cl2.2H2O 21 was formed in case of tin(II) chloride (12).

The [M(LHS)2](OAc)2.nH2O complexes, 22-24, where: M = Zn(II), n= 4, Cd(II), n= 1, Hg(II), n= 1/2, were formed with 1:2 (metal: ligand) molar ratio in case of hydrazone derivative, LHS 7. Under the same conditions, copper sulfate 13 and Hg(II) chloride 9 form complexes of the formula [Cu2(LHS)2SO4].H2O, 25, and [Hg(LHS)2]Cl2.2H2O, 26, respectively. The elemental analysis and physical properties of the ligands are given in section (2.3.), while the elemental analysis for the prepared complexes is shown in Table 1.

3.1.1. Conductivity

The molar conductivities for the complexes 17-20 were measured in DMSO solutions and are shown in Table 1, indicate that most of the complexes are consistent with their non-electrolyte nature. This is in accordance with the fact that conductivity values for a nonelectrolytes are below 50 Ω-1 cm2 mol-1 in DMSO solution. The presence of two chloride ions in the coordination sphere confirms that the ligands are neutral and supports the low conductance values of the complexes. This is in good agreement with those reported for similar complexes [6, 30]. The complexes [Sn(LHP)2]Cl2.2H2O, 21, [Zn(LHS)2](OAc)2.3H2O, 22, and [Hg(LHS)2]Cl2.2H2O, 26, are found to be 1:1 electrolytes.

Table 1. The analytical and physical data for the complexes

The molar conductance measurement agreed with the molecular formulae arrived from the analytical data. The conductivities of other prepared complexes were not measured because of their insolubility in common solvents.

3.1.2. Infrared Spectra

The infrared spectra of the ligands (LHP and LHS) exhibit bands characteristic of the stretching vibrations of N-H, N-N, C=N, C=O and OH (Table 2). The stretching vibrations of N-H at about 3200 cm–1, whereas the C=O group gives rise to a strong band at about 1679 cm–1 for LHP and 1660 cm–1 for LHS. The hydrazonic chain is represented by two intense bands centered at about 1570 cm–1 and 1300 cm–1, assigned to the amide systems. The N-N is represented by the band at 927 cm–1 for LHP and 959 cm–1 for LHS. It was expected the presence of two tautomeric structures of keto and enol forms for both ligands (LHP & LHS). The keto form was supported by the presence of the bands due to N-H and C=O in the IR spectrum. The presence of these bands suggests that these compounds predominantly exist in ‘keto’ form (Scheme 4) [18, 31, 33]. The significant bands observed in the IR spectra of the free ligands and their complexes are listed in Table 2. The main points are discussed below.

i) Free ligands characteristic band of the carbonyl group υ(C=O) at 1679 cm-1 for LHP and 1660 cm-1 for LHS are shifted to higher bands (4-30 to 24-52 cm-1) respectively (Table 2) indicating complexation with metal ions. This is in agreement with other reported research work [32, 33].

Table 2. Important IR frequencies for the ligands and complxes (cm-1)

ii) In the Infrared spectra of the complexes there were bands in the range of 3160-3200 and 1595-1610 of the characteristic υ(N-H) and υ(C=O) stretching vibrations with a slight shift from the bands of the free ligands. This indicates the ligands are coordinated to the metal centers in the keto form [31].

iii) The bands at 1570 cm-1 and 927 cm-1 are assigned to azomethine group υ(C=N) and υ(N-N) of the free ligand respectively. The band of the azomethine group was reduced in intensity and shifted to lower frequency on complex formation by 10-30 cm-1 (Table 2), suggesting the participation of nitrogen atom of azomethine group in coordination in all metal complexes under investigation. Also, the shift of the band assigned to υ(N-N) to higher frequency can be taken as an additional evidence for participation of azomethine group in bonding. This is in agreement with what has been reported for such complexes before [8].

iv) The characteristic free ligand LHS broad band of hydroxyl group υ(O-H) at 3398 cm-1 has shifted to higher frequency by (10-22 cm-1) in all of its complexes (Table 2). This indicates deprotonation with the involvement of the oxygen atom in bonding on complexation.

v) The bands at 1588, 1050, 777 and 480 cm-1 assigned to υ(C=N) py ring skeletal, and in-plan ring deformation mode and out-of-plan ring deformation mode of the free ligand respectively. These bands changes upon complexation and shifted slightly to higher frequencies indicating the participation of pyridyl nitrogen in coordination [34].

vi) The appearance of new weak broad bands in the region 425-530 and 550-570 cm-1 can be assigned to υ(M-N) and υ(M-O) respectively [6-36][6].

vii) The appearance of a medium, broad band in the range 3400-3430 cm-1, due to υ(OH) indicate the presence of an H2O molecules in the crystal of hydrated complexes [37, 38]. These bands are absent in the free ligand LHP.

viii) The coordinated chloro atom in the complexes shows a far-IR absorption peak in the range 332-392 cm-1, which may be attributed to υ(M-Cl) [6, 30].

ix) The bridging SO4-2 group in [Cu2(LHS)2SO4] 25 was characterized by the medium band at 683 and 1092-1125 cm-1 in the IR spectra [8, 37].

x) The spectra of the complexes [M(LHS)2](OAc)2.nH2O (M = Zn (II), Hg(II) and Cd(II)) show a band in the range 1500 -1510 cm-1 which can be assigned to υ(C-O) asymmetric stretching of acetate group and a band at 1415-1420 cm-1 which can be assigned to υ(C-O) symmetric stretching vibration of acetate group [37]. These results predict that the acetate ions were coordinated outside the coordination sphere.

3.1.3. 1H-NMR and 13C-NMR Spectra Data of the Ligands

The 1H-NMR Spectral data of the ligands LHP and LHS in DMSO-d6 shows a singlet signal at 11.28 ppm and 11.42 ppm at both ligands and were assigned for the NH proton.

The presence of the NH proton singlet indicates the presence of the ligands in the keto form. The singlet at 12.22 ppm in LHS ligand assigned for the hydroxyl proton (OH). The singlet at 8.52 and 8.61 in the spectrum of LHP and LHS respectively were assigned to azomethine proton (H-C=N) [39, 40]. The presence of multiplet signals at the range 6.91-8.34 are assigned to the protons of pyridyl and phenyl rings. Also the singlet at 3.08 in both ligands spectra assigned to the proton of the CH3 [35].

13C-NMR Spectra shows Peaks at δ 148.6 and δ 162.8 in the spectra of LHP ligand and at δ 148.3 and δ 162.9 in the spectra of the ligand LHS were assigned for the groups (C=N) and (C=O) respectively [17]. The 13C-NMR spectra of LHP and LHS display signals in the range 117.55-156.7 ppm which have been assigned to the aromatic (phenyl and pyridyl) carbon atoms [28]. The peaks at 29.2 in the spectra of LHP and LHS respectively were assigned to the carbon atom of CH3.

3.1.4. Magnetic Measurements

Magnetic moments susceptibility (µeff) for the complexes [Mn(LHP)Cl2].4H2O 19 and [Co(LHP)Cl2].1/2H2O, 20, were performed at room temperature and found to be 6.66 and 4.34 BM respectively.

The magnetic moment measurement for Mn(II) complex 19 under consideration has the value 6.66 BM which is higher than the spin-only magnetic moment of 5.9 BM, supporting the octahedral geometry around the metal ion [41]. Further the values indicate no antiferromagnetic interaction. The observed room temperature magnetic moment value of 4.34 BM for Co(II) complex 20 (higher than the spin-only value of 3.87 BM.) demonstrate paramagnetic behavior and consistent with their high-spin octahedral geometry around metal ion [8-42][8].

The Cu(II) complex ([Cu(LHP)Cl2].H2O), 17, show magnetic moment 1.87BM which is slightly higher than the spin-only value (1.73BM) expected for one unpaired electron, which offers possibility of an octahedral geometry [42, 43]. The magnetic moment value of 1.87 BM is consistent with d9 configuration and in the range suggested for monomeric copper complexes [40].

3.1.5. Electronic Absorption Spectrum

The electronic absorption spectral data for some complexes are summarized in Table 3. Insufficient solubility of other complexes has hindered their study.

A comparison of the electronic spectra of the free ligands with those of their corresponding metal complexes show some shifts that can be considered as evidence for the complex formation [44]. Upon complexation the Ligand-centered (LC) bands (n →π*, π →π*, σ →π*) undergo an intensity increase with a slight shift relative to the ligand. The spectra exhibit, in addition to LC bands, broad bands which are assigned to metal-ligand charge transfer (MLCT) transitions and d-d transitions, which are responsible for the characteristic colors of these complexes.

The electronic spectra (Table 3) show two bands at 40983 cm-1 and 31250 cm-1 for LHP ligand and two bands at 34246 cm-1 and 30487 for the ligand LHS due to the benzene and heterocyclic ring and to the π π* transition of the chromophore (-C=N-NH-CO-). These bands shifted in the electronic spectra of the complexes [7]. Complexes in general display weak absorption bands at around : 22522 cm-1, 29069 cm-1, 29411 cm-1, 31746 cm-1, 37593 cm-1 in most complexes assigned to ligand-centered (LC), metal-ligand charge transfer (MLCT) and d-d transitions, which are characteristic for octahedral geometry [37, 44, 45].

The electronic spectra of the Cu(II) complex display a broad band at 25125 cm-1 were assigned to d-d transitions and the appearance of two bands at 27247 cm-1 and 29069 cm-1 assigned to charge transfer bands assuming an octahedral geometry environment around the metal ion [46]. This was supported by magnetic moment measurements.

Mn(II) complexes show three bands at 20833 cm-1, 22522 cm-1, 22935 cm-1 assigned to d-d transitions and another two bands at 29069 and 34246 cm-1 assigned to charge transfer. The band exhibited at 22935 cm-1 is assigned to 6A1g→ 4T1g (p) transition. This is the same range as reported for octahedral coordinated Mn(II) ion [46]. The high spin d5 configuration for Mn(II) gives high-spin magnetic moment of 6.66 BM is an additional evidence for the octahedral geometry around the metal ion.

The µeff value of 4.34 BM for Co(II) complex is indicative of a high-spin octahedral geometry for the ion. Two bands of medium intensity observed at 20491 cm-1 29411 cm-1 for Co(II) complex were assigned 4T1g → 4T1g(P), 4T1g → 4A2g(F) transitions, respectively. Therefore these bands together with the magnetic moment are attributable to an octahedral environment around the Co(II) ion [41].

On the basis of the previous observations, it is tentatively suggested that all of the complexes show an octahedral geometries in which the ligands act as tridentate.

Table 3. Important UV-Visible spectra of Ligands LHP & LHS and their complexes

The weight loss shown by the complexes on heating in the 120–160 oC temperature range corresponds to the presence of half mole of water molecule in Co(II) 20 and Hg(II) 24 one mole of water molecule in Cu(II) 17, Hg(II) 18 and Cd(II) 23 complexes, two moles of water molecules in Hg(II) 26, three water molecules in Zn(II) complexes, four moles of water molecules in Mn(II) 19 and six moles of water molecules in Cu(II) 25.

The following are the proposed tentative structures of the complexes.

Structure I. [M(LHP)Cl2].nH2O, M= Mn(II), Co(II), Cu(II) or Hg(II)

In structure I the ligand LHP functions as a neutral tridentate in case of Mn(II), Co(II), Cu(II) and Hg(II) chloride complexes via the azomethine group, carbonyl group in the keto-form and the pyridine ring nitrogen. Similarly in case of Sn (structure II).

Structure III. M= Hg(II), Zn(II), Cd(II), Hg (II), X= AcO, Cl

In case of LHS it coordinates through azomethine group, carbonyl group in the keto-form and the OH group of the phenyl ring (structure III, IV, and V).

3.1.6. Antifungal activity

The synthesized Schiff base ligands (LHP and LHS) and some of their soluble complexes were evaluated for their antifungal activities against fungal strains named A. niger. The ligands and their complexes showed variable antifungal activities (Table 4) against the fungal strains.

By careful study of the results obtained we can see that the ligands showed an inhibitory week effect against the tested organism with diameter of inhibition zones range of 0.90-. The activity of the ligand LHP was a little more effective than LHS. The ligands antifungal activity becomes more pronounced on coordination with the metal ions under the same experimental conditions. A synergistic effect involving the metal ion and the aroylhydrazone might be responsible for this enhancement. The metal complexes were found to be little more toxic than the parent ligands with inhibition zones range of of 1.3 – 1.5 cm for A. niger. The increase in antifungal activity of the metal chelate may be due to the effect of the metal ion on the normal cell process.

Table 4. Antifungal activity data for the ligands and their some metal complexes

Chelation considerably reduces the polarity of the metal ion because of partial sharing of its positive charge with the donor group and possible π-electron delocalization within the entire chelate ring system that is formed during coordination [47]. Such chelation could enhance the lipophilic character of the central metal atom and hence increase the hydrophobic character and liposolubilty of the complex favoring its permeation through the lipid layers of the cell membrane [28].

In addition to this, the mode of action of the compounds may involve the formation of a hydrogen bond through the azomethine nitrogen atom (>C=N) with the active centers of cell constituents, resulting in interference with the normal cell process [48]. The results show that the Cu(II) complexes exhibit higher activity against the fungus compared with other analogous complexes containing M(II) ions. The activity of Cu(II) complexes may be attributed to its higher stability constant [6, 7].

Since the complexes have the different donating atoms (N,N,O) and (O,N,O), and containing metals with the same oxidation state M(II), therefore the more effective factors that influence the antifungal activity are the donating atoms and the nature of the central atoms [6, 7].

On comparison with the standard antifungal drug Amphotricene B (inhibition zone ), the results indicate that, the tested complexes exhibited moderate activity against the fungal strains and weaker than the standard Amphotericin B.

4. Conclusion

In this study we have reported the synthesis and structural characterization of the tridentate quinoxaloylhydrazones Schiff bases ligands (LHP and LHS) and their complexes with transition metals (Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and Tin(II)). The ligand to metal stoichiometry and the nature of bonding were ascertained on the basis elemental analysis, IR spectra, electronic absorption spectra, magnetic moment measurements and conductivity data. The results show that the ligands behave as tridentate with NON donor sequence. The complexes were characterized by physico-chemical measurements which led to the proposal of octahedral geometry for Mn(II), Co(II) and Cu(II) complexes. The biological activity tests for the ligands and their complexes show enhancement of the ligands activity against the tested organism on chelation with metals. But, it is still weak to be compared with standard drug.


Most of the work presented in this paper is part of the first Author’s Master thesis submitted to Al al-Bayt University in Jordan, supported by Al al-Bayt University. Financial support from Deutsche Forschungsgemeinschaft DFG (Germany) is gratefully acknowledged. The authors are indebted to Prof. Maas (University of Ulm) for his kind encouragement, support, advice and criticism. Dedicated to the memory of Professor K. Al-Obaidi, who was the co-supervisor (University of Al al-Bayt).


[1]  A. Golcu, M. Tumer, H. Demirelli, and R.A. Wheatley, Cd(II) and Cu(II) complexes of polydentate Schiff base ligands: synthesis, characterization, properties and biological activity. Inorg. Chim. Acta, 358, 1797, (2005).
In article      CrossRef
[2]  W. Rehman, F. Saman, and I. Ahmad, Synthesis, characterization, and biological study of some biologically potent Schiff Base transition metal complexes. Russ. J. Coord. Chem., 34(9), 678-682, (2008).
In article      CrossRef
[3]  P.K. Panchal, P.B. Pansuriya, and M.N. Patel, In-vitro biological evaluation of some ONS and NS donor Schiff’s bases and their metal complexes. J. Enzy. Inhib. Med. Ch., 21(4), 453-458, (2006).
In article      CrossRefPubMed
[4]  R. Abu-El-halawah, B.A. Fares, S.K. Fares, H. Baker, M. Qandil, M. Al-Refai, M. Ibrahim, Z. Juddeh, and K. Al-Obaidi, J. Coord. Chem., 57(13), 1139-1149, (2004).
In article      CrossRef
[5]  R. Abu-El-Halawa, M. Al-Nuri, and F. Mahmoud. Asian J. Chem., 19(3), 1658-1666, (2007).
In article      
[6]  A.A. El-Sherif, Shoukry M.M., and Mohamed M.A. Abd-Elgawad, Synthesis, characterization, biological activity and equilibrium studies of metal(II) ion complexes with tridentate hydrazone ligand derived from hydralazine. Spectrochim. Acta A., 98, 307-321, (2012).
In article      CrossRefPubMed
[7]  M.V. Angelusiu, S.F. Barbuceanu, C. Draghici, and G.L. Almajan, New Cu(II), Co(II), Ni(II) complexes with aroyl-hydrazone based ligand. Synthesis, spectroscopic characterization and in vitro antibacterial evaluation. Eur. J. Med. Chem., 45 2055-2062, (2010).
In article      CrossRefPubMed
[8]  N.M. Hosney, M.A. Mahmoud, and M.R.E. Aly, 2-ydroxybenzaldehyde-(4,6-Dimethylquinolin-2-yl)-Hydrazone (HBDH), Synthesis, Characterization, andLigational Behavior Towards Some Metals. Synth. React. Inorg. Me., 40, 439-446, (2010).
In article      
[9]  S. Vogel, D. Kaufmanna, M. Pojarováa, C. Müller, T. Pfaller, S. Kühne, P. J. Bednarski, and E.V. Angerer, Aroyl hydrazones M.of 2-phenylindole-3-carbaldehydes as novel antimitotic agents. Bioorgan. Med. Chem., 16, 6436-6447, (2008).
In article      CrossRefPubMed
[10]  F. Grande, F. Aiello, O. De Grazia, A. Brizzi, A. Garofalo, and N. Neamati, Synthesis and antitumor activities of a series of novel quinoxalinehydrazides. Bioorg. Med. Chem., 15, 288-294, (2007).
In article      CrossRefPubMed
[11]  D.S. Kalinowski, P.C. Sharpe, P.V. Bernhardt, and D.R. Richardson, Structure–Activity Relationships of Novel Iron Chelators for the Treatment of Iron Overload Disease: The Methyl Pyrazinylketone Isonicotinoyl Hydrazone Series. J. Med. Chem., 51, 331-344, (2008).
In article      CrossRefPubMed
[12]  A.M. Stadler, and J.Harrowfield, Bis-acyl-/aroyl-hydrazones as multidentate ligands. Inorg. Chim. Acta, 362, 4298-4314, (2009).
In article      CrossRef
[13]  W. Jing-lin, Z Ya-qin., Y.Bin-sheng, Transition metal complexes of asymmetrical aroyl-hydrazone ligand: Syntheses, structures, DNA binding and cleavage studies. Inorg. Chim. Acta, 409 484–496, (2014).
In article      CrossRef
[14]  D.R. Richardson, and P.V. Bernhardt, Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity J. Biol. Inorg. Chem. 4 266-273, (1999).
In article      CrossRefPubMed
[15]  L. Ronconi, and P.J. Sadler, Using coordination chemistry to design new medicines. Coordin. Chem. Rev., 251, 1633-1648, (2007).
In article      CrossRef
[16]  S. Naskar, S. Naskar, S. Mondal, P.K. Majhi, M.G.B. Drew, and S.K.Chattopadhyay, Synthesis and Spectroscopic Properties of Cobalt(III) Complexes of some Aroyl Hydrazones: X-ray Crystal Structures of one Cobalt(III) Complex and Two Aroyl Hydrazone Ligands. Inorg. Chim. Acta, 371 100-106, (2011).
In article      CrossRef
[17]  S. Sinha, A.K. Srivastava, S.K. Sengupta, and O.P. Pandey, Microwave Assisted Synthesis, Spectroscopic and Antibacterial Studies of Bis(cyclopentadienyl)hafnium (IV) Derivatives with Bezil Bis(aroyl hydrazones). Transit. Met. Chem., 33, 563-568, (2008).
In article      CrossRef
[18]  H.H. Monfareda,, N.A. Lalami, A. Pazio, K. Wozniak, and C. Janiakc, Dinuclear Vanadium, Copper, Manganese And Titanium Complexes Containing O,O,N-Dichelating Ligands: Synthesis, Crystal Structure And Catalytic Activity. Inorg. Chim. Acta. 406, 241-250, (2013).
In article      CrossRef
[19]  E. Macková, K. Hrušková, P. Bendová, A. Vávrová, H. Jansová, P. Hašková, P. Kovarˇíková, K. Vávrová, and T.Šimu˚nek, Methyl And Ethyl Ketone Analogs of Salicylaldehyde Isonicotinoyl Hydrazone: Novel Iron Chelators With Selective Antiproliferative Action. Chem-Biol. Interact.197, 69-79, (2012).
In article      CrossRefPubMed
[20]  A. Casoli, A. Mangia, G. Mori, and G. Predieri, Liquid-Liquid Extraction And Determination Of Uranium (VI) With 2,6-Diacetylpyridine Bis(Benzoylhydrazone). Anal. Chim. Acta, 186, 283-287, (1986).
In article      CrossRef
[21]  K.K. Rajac, N.I. Gandhi, L. Lekha, D. Easwaramoorthye, and G. Rajagopal, Synthesis, Spectral, Electrochemical And Catalytic Properties Of Ru(III) Schiff Base Complexes Containing N, O Donors. J. Mol. Struct., 1060 49-57, (2014).
In article      CrossRef
[22]  M. Turkyilmaz, M. Kacan, and Y. Barana, Structure, Spectroscopic, Thermal Properties And Catalytic Activity of Iron(III)-Schiff Base Complexes. Inorg Chim Acta, 395, 255-259, (2013).
In article      CrossRef
[23]  Z. Li, L. Lianga, L. Yanga, H. Chena, and X. Zhoua, Asymmetric Epoxidation Catalyzed By Cr(III)-Binaphthyl Schiff Base Complexes. J. Mol. Catal. A-Chem., 235, 108-113, (2005).
In article      CrossRef
[24]  M.F. Ibrahim, Synthesis Of Some Quinoxaline Derivatives, M. Sc. Thesis, Al al-Bayt University, Mafraq, Jordan, (2002).
In article      
[25]  S. Mondal, S. Naskar, A.K. Dey, E. Sinn, C. Eribal, S.R. Herron, and S.K. Chattopadhyay, Mononuclear And Binuclear Cu(II) Complexes Of Some Tridentate Aroyl Hydrazones. X-Ray Crystal Structures of A Mononuclear And A Binuclear Complex. Inorg. Chim. Acta, 398, 98-105, (2013).
In article      CrossRef
[26]  A.A.R. Despaigne, L.F.Vieira, I.C. Mendes, F.B. Costa, N.L. Speziali, and H. Beraldo, Organotin(IV) Complexes With 2-Acetylpyridine Benzoyl Hydrazones: Antimicrobial Activity. J. Braz. Chem. Soc., 21(7), 1247-1257, (2010).
In article      CrossRef
[27]  A. Rahman, M.I. Choudry, W.J. Thomsen, Bioassay Techniques for Drug Development, Harwood Academic Publishers, Netherlands, (2001).
In article      CrossRef
[28]  N.N. Emmanuel, A. Husian, F. Majoumo-Mbe, I.N. Njah, O.E. Offiong, and S. A. Bourne, Synthesis, Crystal Structure And Antifungal Activity Of A Ni(II) Complex Of A New Hydrazone Derived From Antihypertensive Drug Hydralazine Hydrochloride. Polyhedron, 63, 207-213, (2013).
In article      CrossRef
[29]  R.K. Mohapatra, U.K. Mishra, S.K. Mishra, A. Mahapatra, and D.C. Dash, Synthesis And Characterization Of Transition Metal Complexes With Benzimidazolyl-2-Hydrazones Of O-Anisaldehyde And Furfural. Journal of the Korean Chem. Soc., 55(6), 926-931, (2011).
In article      
[30]  S. Biswas, T. Kar, S. Sarkar, and K. Dey, Synthesis, Characterization, And Density Functional Study Of Some Manganese(III) Schiff-Base Complexes. J. Coord. Chem., 65(6), 980-993, (2012).
In article      CrossRef
[31]  C.M. Armstrong, P.V. Bernhardt, P. Chin, and D.R. Richardson, Structural Variations And Formation Constants Of First-Row Transition Metal Complexes Of Biologically Active Aroylhydrazones. Eur. J. Inorg. Chem., 1145-1156, (2003).
In article      CrossRef
[32]  B. Mondal, M.G.B. Drew, and T. Ghosha, Synthesis, Structure And Solution Chemistry of Dioxidovanadium(V) Complexes With A Family Of Hydrazone Ligands. Evidence of Formation of Centrosymmetric Dimers via H-Bonds in the Solid State. Inorg. Chim. Acta, 363, 2296-2306, (2010).
In article      CrossRef
[33]  H. Hosseini-Monfared, R. Bikas, and P. Mayer, Homogeneous Green Catalysts For Olefin Oxidation By Mono Oxovanadium(V) Complexes Of Hydrazone Schiff Base Ligands. Inorg. Chim. Acta, 363, 2574-2583, (2010).
In article      
[34]  N.M. Hosny, N.M. (E)-N-(1-Phenylethylidene) Nicotinohydrazide (PNH) And Some Of Its Metal Complexes. J. Mol. Struct., 923, 98-102, (2009).
In article      CrossRef
[35]  N. M. Hosny, Synthesis and Charcterization of Transition Metal Complexes Derived from (E)-(N)-(1-(Pyridine-2-yl)ethylidiene)benzohydrazide (PEBH).Synth. React. Inorg. Me., 41, 736-742, (2011).
In article      CrossRef
[36]  G.G. Mohamed, M.M. Omar, A.A. Ibrahim, Biological Activity Studies on Metal Complexes of Novel Tridentate Schiff base Ligand. Spectroscopic and Thermal Characterization. Eur. J. Med. Chem., 44, 4801-4812, (2009).
In article      CrossRefPubMed
[37]  K. Nakamoto. In Infrared and Raman Spectra of Inorganic and Coordination Compounds, Part B, 6th ed., John Wiley and Sons, Inc., USA, (2009).
In article      
[38]  S. Chattopadhyay, M.G.B. Drew, and A. Ghosh, Methylene Spacer-Regulated Structural Variation in Cobalt(II/III) Complexes with Bridging Acetate and Salen- or Salpn-Type Schiff-Base Ligands. Eur. J. Inorg. Chem., 1693-1701, (2008).
In article      CrossRef
[39]  A.S. El-Tabl, F.A. Aly, M.M.E. Shakdofa, and A.M.E. Shakdofa, Synthesis, Characterization, and Biological Activity Of Metal Complexes Of Azohydrazone Ligand, J. Coord. Chem., 63(4), 700-712, (2010).
In article      CrossRef
[40]  N. Nawar, and N.M. Hosny, Transitionmetal Complexes of 2-Acetylpyridine O-Hydroxybenzoylhydrazone (Apo-OHBH): Their Preparation, Characterization and Antimicrobial Activity. Chem. Pharm. Bull., 47, 944, (1999).
In article      CrossRef
[41]  E. Soleimani, Novel Complexes of Mn(II), Co(II), and Cu(II) with Ligand Derived from Dibromobenziloxime. Journal of the Chinese Chemical Society, 57, 653-658, (2010).
In article      
[42]  G.B. Bagihalli, P.S. Badami, and S.A. Patil, Synthesis, Spectral Characterization And In Vitro Biological Studies Of Co(II), Ni(II) And Cu(II) Complexes With A,2,4-Triazole Schiff Bases. J. Enzy. Inhib. Med. Ch., 24(2), 381-394, (2009).
In article      CrossRefPubMed
[43]  F.A. Cotton, C. Murillo, G. Wilkinson, and M. Bochmann, “Advanced Inorganic Chemistry”, Wiley and Sons, New York, 6th ed. (1999).
In article      
[44]  M.S. Refat, and N.M. El-Metwaly, Spectral, Thermal And Biological Studies Of Mn(II) And Cu(II) Complexes With Two Thiosemicarbazide Derivatives. Spectrochim. Acta A., 92 336-346, (2012).
In article      
[45]  A.B.P. Lever, Crystal Field Spectra Inorganic Electronic Spectroscopy, 1st ed., Elsevier, Amsterdam, p. 249, (1968).
In article      
[46]  J. Singh, Anu, and N. Singh, Synthesis and Spectral Studies of Copper (II) and Manganese (II) Complexes Using 2-Hydroxybenzyl-(pyridine-2-carbo)Iminohydrazone and 2-Furyl(pyridine-2- carbo)Iminohydrazone: Evaluation of Their Magnetic, and Antimicrobial Properties. Journal of Spectroscopy, 2013, 1-8, (2013).
In article      CrossRef
[47]  M. Tumer, D. Ekinci, F. Tumer, and A. Bulut, Synthesis, Characterization And Properties Of Some Divalent Metal(II) Complexes: Their Electrochemical, Catalytic, Thermal And Antimicrobial Activity Studies. Spectrochim. Acta A., 67, 916-929, (2007).
In article      CrossRefPubMed
[48]  N. Dharmaraj, P. Viswanathamurthi, and K. Natarajan, Ruthenium(II) Complexes Containing Bidentate Schiff€ Bases And Their Antifungal Activity. Transit. Metal Chem., 26, 105-109, (2001).
In article      CrossRef
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