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SOP TRANSACTIONS ON APPLIED CHEMISTRY VOLUME 1, NUMBER 1, March 2014

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Synthesis, Characterization and Biological Activity of Some Ferrocenyl Complexes Containing Antipyrine Moiety Mokhles M. Abd-Elzaher*, Mohamad M. E. Shakdofa, Hanan A. Mousa, Samia A. Moustafa Inorganic Chemistry Department, National Research Center, Dokki, PO 12622, Cairo, Egypt *Corresponding author: [email protected]

Abstract: Manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), mercury(II) and lead(II)complexes of ferrocenyl Schiff base ligand containing antipyrine moiety were prepared in a good yield. They were characterized using IR, 1 H NMR, UV/Vis., mass spectra, magnetic susceptibility and molar conductivity measurements as well as elemental analysis. The analyses showed that the ligand behaved as neutral tetradentate ligand coordinated to the metal ions via the carbonyl oxygen and azomethine nitrogen atoms forming an octahedral geometry around the metal ions. The biological activity of the ligand and its complexes were carried out against fungal strains of Aspergillus niger and bacterial strains of Bacillus subtilis (+ve), Esherichia coli (-ve) using the disk diffusion method. The biological results indicated that the ligand is inactive while its complexes have mild activity. The complexes showed mild antibacterial activity against Bacillus subtilis (+ve), Esherichia coli (-ve) and Aspergillus niger (fungi). The biological results are compared with a standard drugs. Keywords: Diacetylferrocene; 4-amino antipyrine; Complexes; Magnetic Properties Biologica Activity

1. INTRODUCTION In recent years, the field of bioorganometallic chemistry focuses on the synthesis of organometallic compounds that possess novel biological activity. In particular, ferrocenyl compounds have been developed for a wide range of applications in the biological, medicinal, and pharmaceutical disciplines [1–4]. Ferrocene is a neutral, stable organometallic compound that readily undergoes a reversible one electronoxidation to form the ferricenium radical cation [5, 6]. These characteristics led to the synthesis of many ferrocenyl derivatives that have good applications in many fields [7–10]. This area attracted many authors and numerous articles have been published [11–19]. On the other hand antipyrine moiety (2,3-dimethyl- 1-phenyl-1,2-dihydropyrazol-5-one) and its derivatives possess a wide applications including biological [20], clinical [21] and pharamacoloical area [22–25]. They have also antibacterial [26], antimicrobial [27] and antitumor [28] activities. Antipyrines also used as analytical reagents in the determination of metal ions [29–31]. In addition they used in the purification 42

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of penicillin acylase [32], flow-injection and sequential injection spectrophotometric determination of salbutmol [33] and ritodrine hydrochloride [34]. The aim of this work is to prepare and characterize a ferrocenyl ligand derived from condensation of 1,1’-diacetylferrocene with 4-amino-1,5-dimethyl-2-phenyl -1H-pyrazol-3(2H)-one (4-amino antipyrine). The ligand has been well characterized using different spectroscopic techniques. The study was extended to prepare and characterize Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and Pb(II) complexes with the mentioned ligand to obtain the complexes. The prepared compounds have been characterized by IR, 1 H-NMR, mass, UV/V is spectra, elemental analysis as well as magnetic and molar conductivity measurements. Biological activity of the ligand and the prepared complexes was carried out against Bacillus subtilis (+ve), Esherichiacoli(-ve), Aspergillus niger (fungi).The antimicrobial activity of ligand and its complexes were compared with the activity of standard antibacterial drug (tetracycline) and antifungal drug (amphotericin B).

2. EXPERIMENTAL All chemicals and solvents are obtained from Merck. 1,1’-diacetylferrocene was prepared by published method [35]. The yields refer to analytically pure compounds and were not optimized. Melting points were taken on a capillary melting point apparatus and were uncorrected. Elemental analyses were determined at the microanalytical centre, Cairo university. 1 H NMR spectra were recorded on a Bruker DPX 300; δ values are given relative to TMS. Mass spectra were obtained on a Jeol JMS-700 using fast atom bombardment (FAB) with a 3-nitrobenzyl alcohol (NBA) matrix. IR spectra were recorded on a Jasco FT/IR-6100 type A spectrometer from 400 to 4000 cm−1 (resolution 4 cm−1 , Detector TGS) using KBr pellets. Electronic absorptions were recorded on a PG Instruments Ltd. +80+ UV/V is automatic spectrophotometer in DMSO. Magnetic susceptibilities were measured at 25o C by the Gouy method using mercuric tetrathiocyanatocobaltate(II) as the magnetic susceptibility standard. Diamagnetic corrections were estimated from Pascals constant [36]. The magnetic moments were calculated from the equation: p corr µe f f . = 2.84 χM · T . The molar conductance of 10-3 M solution of the complexes in DMSO was o measured at 25 C with a Bibby conductometer type MCl. The resistance measured in ohms and the molar conductivities were calculated according to the equation: ΛM = (V × K × g)/(MW × Ω), where: ΛM = molar conductivity/Ω−1 cm2 mol −1 , V = volume of the complex solution/mL, K = cell constant (0.92/ cm−1 ), MW = molecular weight of the complex, g = weight of the complex/g, Ω = resistance/Ω.

2.1 Synthesis of the ligand I The ligand 1, was prepared by refluxing 1,1’-diacetylferrocene (DAF) (1 mmol, 2.70 gm), dissolved in a small amount of dry ethanol, with 4-amino-1,5- dimethyl-2-phenyl-1H-pyrazol-3(2H)-one(4-aminoantipyrine) (2 mmol, 4.06 gm) with stirring. The brown color of the diacetylferrocene started to change to deep brown within the first hour, but reaction was continued for 4 hours to complete the reaction. The solvent was evaporated at about 50o C. The brown product of the ligand was isolated in good yield.

2.2 General procedure for the synthesis of the complexes 2-9 The complexes of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), mercury(II) and lead(II) ions were prepared easily in a good yield by adding an equimolar ratio of ligand 1(1 mmol. 20 mL absolute ethanol) to the corresponding metal(II) acetate (1mmol. in 20 absolute ethanol). The 43

Synthesis, Characterization and Biological Activity of Some Ferrocenyl Complexes Containing Antipyrine Moiety

reaction mixture was reuxed for two hours. The dark brown product was filtered off, washed with ethanol and dried on anhydrous CaCl2 .

2.3 In-vitro antimicrobial activity The antimicrobial activities of the ligand and its metal complexes were carried out in the Botany Department, Lab. of microbiology, Faculty of Science, El-Menoufia University. They have been studied for their antimicrobial activities by disc diffusion method [37, 38]. The antibacterial activities were done using the following organisms Escherichia coli, Bacillus subtilis while the antifungal activity was done using Fungus (Aspergillus niger), at 20 mg/mL concentrations using DMSO as a solvent, where DMSO poured disc was used as negative control. The bacteria were subcultured in nutrient agar medium which, prepared using (g.L-1 distilled water) NaCl (5 g), peptone (5 g), beef extract (3 g), agar (20 g). while the fungus was subcultured in CzapekDoxs medium which was prepared using (g × L−1 distilled water) yeast extract (1g), sucrose (30 g), NaNO3 , agar (20 g), KCl (0.5 g), KH2 PO4 (1 g), MgSO4 ·7H2 O (0.5 g) and trace of FeCl3 ·6H2 O. This medium was then sterilized by autoclaving at 120 o C for 15 min. After cooling to 45 o C the medium was poured into 90 mm diameter Petri dishes and incubated at 28 o C. After solidify, Petri dishes were stored at 4 o C. Microorganisms were spread over each dish by using sterile bent Loop rod. The test is carried out by placing filter paper disks (3 mm diameter) with a known concentration of the compounds on the surface of agar plates inoculated with a test organism. Standard antibacterial drug (Tetracycline) antifungal drug (Amphotricene B) and solution of metal salts were also screened under similar conditions for comparison. Plates were allowed to stand in a refrigerator for two hours before incubation to allow the tested compounds to diffuse through the agar. The Petri dishes were incubated for 48 h at 28 o C. The growth inhibition zones around the holes were observed, indicating that the examined compound inhibits the growth of microorganism. The inhibition zone was measured in millimeters carefully. All determination was made in duplicate for each of the compounds. An average of the two independent readings for each compound was recorded.

3. RESULTS AND DISCUSSION 3.1 Characterization of the ligand The ligand is brown, stable in air and soluble in common organic solvents. Elemental analysis of the ligand and its complexes is represented in Table 1 . The structure of the ligand (Figure 1 ) was confirmed by IR spectra. The important IR band of the ligand is presented in Table 2 . The IR spectrum of the ligand showed bands at 1669, 1642 cm−1 assigned to the carbonyl group of the antipyine moiety and azomethine group ν(C=N). The characteristic frequencies of the ferrocenyl moiety in the spectra of ligand 1 observed at 3100, 1454, 1114, 1017, 757, 500 cm−1 .The band at 3100 cm−1 was assigned to the CH stretching band. The band at 1454 cm−1 was assigned to the asymmetric CC stretching band. The 1114 cm−1 band was due to asymmetric ring-breathing vibration. The two bands located at 1017 and 757 cm−1 were assigned to parallel and perpendicular CH bands, respectively. The final band at 500 cm−1 was assigned to the Fe-Cp stretching frequency [39, 40]. The 1 H NMR spectrum of the prepared ligand 1 is represented in Table 3 . The 1 H NMR spectrum of the ligand showed that the protons of the ferrocenyl moiety appeared as two multiples at 4.6 and 4.8 ppm. These bands were assigned to the α- and β - protons for the substituted cyclopentadienyl rings [41, 42].The phenyl protons were noticed as new bands at 7.33-7.49 ppm. The signals appeared at 3.33 44

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Figure 1. Structure of ligand 1.

and 2.30 ppm assigned to the two methyl groups (N-CH3 and C-CH3 ) of the antipyrine moiety respectively. These peaks were conrmed from other 1 HNMR spectra of similar antipyrine Schiff bases [43].The signal of the two methyl groups in the diacetylferrocene was observed at 2.09 ppm [41, 42]. The mass spectrum provides a vital clue for elucidating the structure of compound (Table 4 ). The intensity of these peaks reflects the stability and abundance of the ions [44].The formulation of the Schiff base as in Figure 1 is clearly supported from the presence of intense molecular ion peak in the mass spectra of ligand 1 at 640m/z consistent with the molecular weight of the ligand. Moreover, the molecular ion peak splits to numerous fragments having m/z equals 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56 (Table 4 ). These values correspond to C34 H36 FeN6 O2 , C33 H36 FeN6 O2 , C32 H34 FeN6 O2 ,C31 H332 FeN6 O2 ,C29 H32 FeN6 O2 ,C25 H31 FeN6 O2 , C24 H30 FeN6 O2 , C23 H27 FeN6 O2 , C22 H26 FeN6 O2 , C21 H23 FeN6 O2 , C20 H17 FeN6 O2 , C19 H15 FeN6 O2 , C18 H13 FeN6 O2 , C16 H2 0FeN3 O, C5 H4 Fe, C4 H3 N3 O, C6 H5 ,C5 H5 and Fe respectively.

3.2 Characterization of the complexes 2-9 The prepared complexes are deep brown which may be due to conjugation of the ligand with the metal ions; stable in air and insoluble in H2 O, ethanol and non-polar solvents such as benzene. However, they are soluble in polar solvents such as dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). All the complexes are non-electrolytes. The analytical and spectral data (Table 1 ,Table 2 ,Table 3 ,Table 4 ) are compatible with the proposed structures (Figure 2 ). To date, no diffractable crystals have been grown. The elemental analyses data of the ligand and its complexes are consistent with the calculated results from the empirical formula of each compound. They showed that the complexes 2-9 were composed in molar ratio 1:1 L:M. The molar conductivity of 1 × 103 M solution of the metal complexes 2-9 in DMF at room temperature are in the 11.5-27.9 Ω−1 cm2 mol −1 range indicating the non-electrolytic nature of these complexes [45, 46]. 45

Synthesis, Characterization and Biological Activity of Some Ferrocenyl Complexes Containing Antipyrine Moiety

Table 1. ANALYTICAL AND SOME PHYSICAL CHARACTERISTICS FOR THE LIGAND AND ITS COMPLEXES No.

Compound

M. Wt. Calcd.

1 L (C36 H36 FeN6 O2 ) 2 [Cu(L)(OCOCH3 )2 ] (C40 H42 FeCuN6 O6 ) 3 [Ni(L)(OCOCH3 )2 ] (C40 H42 FeNiN6 O6 ) 4 [Co(L)(OCOCH3 )2 ] (C40 H42 FeCoN6 O6 ) 5 [Mn(L)(OCOCH3 )2 ] (C40 H42 FeMnN6 O6 ) 6 [Zn(L)(OCOCH3 )2 ] (C40 H42 FeZnN6 O6 ) 7 [Cd(L)(OCOCH3 )2 ] (C40 H42 FeCdN6 O6 ) 8 [Hg(L)(OCOCH3 )2 ] (C40 H42 FeHgN6 O6 ) 9 [Pb(L)(OCOCH3 )2 ] (C40 H42 FePbN6 O6 ) a

640.57 822.20 817.34 817.58 813.59 824.04 871.06 959.24 966.63

C

ΛaM Yield (%)

Calcd. (Found) % H

67.50 (66.99) 58.43 (57.98) 58.78 (58.45) 58.76 (58.23) 59.05 (58.79) 58.30 (57.98) 55.16 (54.89) 50.09 (50.32) 49.74 (49.56)

5.67 (5.47) 5.15 (4.95) 5.18 (5.01) 5.18 (5.04) 5.20 (5.00) 5.14 (4.95) 4.86 (4.67) 4..41 (4.32) 4.38 (4.11)

N

13.12 (13.13) 10.22 (10.04) 10.28 (10.24) 10.28 (10.23) 10.33 (10.11) 10.20 (9.93) 9.65 (9.49) 8.76 (8.80) 8.69 (8.60)

— 11.5 22.5 17.5 27.9 14.7 7.8 13.6 23.5

85 70 63 65 70 67 73 72 75

Moluar conductivity as 10−3 M solutions (ohm−1 cm2 mol−1 )

Table 2. IR SPECTRAL ASSIGNMENT FOR THE LIGAND AND ITS COMPLEXES No.

Compound

1 L (C36 H36 FeN6 O2 ) 2 [Cu(L)(OCOCH3 )2 ] (C40 H42 FeCuN6 O6 ) 3 [Ni(L)(OCOCH3 )2 ] (C40 H42 FeNiN6 O6 ) 4 [Co(L)(OCOCH3 )2 ] (C40 H42 FeCoN6 O6 ) 5 [Mn(L)(OCOCH3 )2 ] (C40 H42 FeMnN6 O6 ) 6 [Zn(L)(OCOCH3 )2 ] (C40 H42 FeZnN6 O6 ) 7 [Cd(L)(OCOCH3 )2 ] (C40 H42 FeCdN6 O6 ) 8 [Hg(L)(OCOCH3 )2 ] (C40 H42 FeHgN6 O6 ) 9 [Pb(L)(OCOCH3 )2 ] (C40 H42 FePbN6O6)

Table 3.

1 H-NMR

Ferrocene moiety 3100, 1454, 1114, 1017, 757, 500 3096,1451, 1113, 1025, 758, 494 3080, 1450, 1112, 1025, 761, 494 3077, 1450, 1141, 1027, 760, 491 3090, 1451, 1143, 1026, 759, 505 3078, 1453, 1141, 1029, 760, 491 3085, 1452, 1141, 1027, 761, 491 3089, 1453, 1141, 1029, 759, 492 3088, 1411, 1141, 1022, 760, 495

C=O C=N 1669 1652 1659 1659 1658 1657 1657 1655 1648

1642 1627 1629 1630 1629 1633 1621 1625 1617

OCOCH3 () – 1589, 1376 (213) 1584, 1382 (202) 1587, 1418 (169) 1564, 1379 (185) 1570, 1376 (194) 1587, 1380 (207) 1573, 1372 (201) 1567, 1338 (229)

M-O M-N – 538 590 532 533 524 525 505 512

– 470 461 449 482 461 454 446 469

SPECTRAL ASSIGNMENT FOR THE LIGAND AND ITS COMPLEXES

Ligand/complex

1H

L, 1

2.09 (s, 6H, 2CH3), 4.80 (m, 4H, C5H4), 4.60 (m, 4H, C5H4), 7.33-7.49 (m, 10H, ph), 3.33 (s, 6H, 2(N-CH3), 2.30 (s, 6H, 2(C-CH3) 2.08 (s, 6H, 2CH3), 4.80 (m, 4H, C5H4), 4.60 (m, 4H, C5H4), 7.23-7.45 (m, 10H, ph), 3.32 (s, 6H, 2(N-CH3), 2.29 (s, 6H, 2(C-CH3) 2.15 (s, 6H, 2CH3), 4.79 (m, 4H, C5H4), 4.60 (m, 4H, C5H4), 7.09-7.42 (m, 10H, ph), 3.27 (s, 6H, 2(N-CH3), 2.29 (s, 6H, 2(C-CH3) 2.10 (s, 6H, 2CH3), 4.80 (m, 4H, C5H4), 4.61 (m, 4H, C5H4), 6.96-7.49 (m, 10H, ph), 3.33 (s, 6H, 2(N-CH3), 2.29 (s, 6H, 2(C-CH3) 2.10 (s, 6H, 2CH3), 4.80 (m, 4H, C5H4), 4.60 (m, 4H, C5H4), 7.20-7.52 (m, 10H, ph), 2.96 (s, 6H, 2(N-CH3), 2.10 (s, 6H, 2(C-CH3)

[Zn(L)(OCOCH3 )2 ], 6 [Cd(L)(OCOCH3 )2 ], 7 [Hg(L)(OCOCH3 )2 ], 8 [Pb(L)(OCOCH3 )2 ], 9

NMR (DMSO-d6), δ in ppm

Table 4. MASS SPECTRAL DATA FOR THE LIGAND AND ITS COMPLEXES No. Ligand/ Complexes 1 L 2 [Cu(L)(OCOCH3 )2 ] 3 [Ni(L)(OCOCH3 )2 ] 4 [Co(L)(OCOCH3 )2 ] 5 [Mn(L)(OCOCH3 )2 ] 6 [Zn(L)(OCOCH3 )2 ] 46

Mass spectral data (M/Z) 640, 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56 822, 640, 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56 817, 640, 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56 817, 640, 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56 813, 640, 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56 824, 640, 616, 604, 590, 576, 552, 503, 490, 475, 461, 447, 429, 415, 401, 270, 120, 109, 95, 78, 65, 56

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Table 5. BIOLOGICAL ACTIVITY OF THE LIGAND AND ITS COMPLEXES Compounds

1 2 3 4 5 6 7 8 9

DMSO Amphotricene B Tetracyclene L [Cu(L)(OCOCH3 )2 ] [Ni(L)(OCOCH3 )2 ] [Co(L)(OCOCH3 )2 ] [Mn(L)(OCOCH3 )2 ] [Zn(L)(OCOCH3 )2 ] [Cd(L)(OCOCH3 )2 ] [Hg(L)(OCOCH3 )2 ] [Pb(L)(OCOCH3 )2 ]

Inhibation zone /mm Aspergillusniger Escherichia coli Bacillus subtitles 00 15 – 00 10 00 09 00 11 14 17 15

00 – 25 00 18 19 18 00 16 20 13 14

00 – 30 00 24 17 15 00 10 17 12 13

The considerably high values of some complexes may be due to the partial solvolysis by DMSO. The IR spectra of the prepared complexes 2-9 were recorded as KBr pellets and presented in Table 2 . It was found that the characteristic band of the carbonyl and azomethine groups in the free ligand 1 at 1669 and 1642 cm−1 was shifted to frequency of 1659-1648 and 1617-1633 cm−1 in the complexes 2-9 respectively [47]. This shift indicates coordination of the carbonyl oxygen and azomethine nitrogen to the metals in the complexes. In the low-frequency region, two bands were observed for 2-9 in the 446-482 and 505-590 cm−1 range, which were attributed to ν(M-N) and ν(M-O), respectively. These bands were not found in the spectra of 1, suggesting that the coordination of the ligand with the metal ions takes place via the carbonyl oxygen of the antipyrine moiety and azomethine nitrogen atoms [47]. The characteristic frequencies of the ferrocenyl moiety in the spectra of 1 were observed at about 3100, 1454, 1135, 1114, 1017, 757, and 500 cm−1 [48]. The corresponding frequencies of the complexes appeared at nearly the same position in the ligand, which indicates that the cyclopentadienyl ring of the ferrocene is not directly coordinated to the metal ion [48]. The mass spectra of the complexes 2-6 showed molecular ion peaks at 822, 817, 817, 813, 824 corresponding to [Cu(L)(OCOCH3 )2 ], [Ni(L)(OCOCH3 )2 ], [Co(L)(OCOCH3 )2 ],[Mn(L)(OCOCH3 )2 ], [Zn(L)(OCOC -H3 )2 ] stoichiometry respectively (Table 4 ). Peaks correspond to L and fragments of Lare also present in the spectra (Table 4 ). 1 HNMR spectra of complexes 6-9 were recorded in DMSO-d at room temperature using TMS 6 1 as internal standard. The H NMR spectra were represented in Table 3 . The spectra of complexes 6-9 showed that, the protons shifted downfield as expected, due to the increased conjugation during coordination to the metal atoms, but there is no appreciable change in the chemical shifts of the ferrocenyl protons on coordination. DMSO did not have any coordinating effect, either on the spectra of the ligands or on its metal complexes. The spectra showed two multiplets for the α- and β -protons for the substituted cyclopentadienyl rings in the 4.81-4.79 and 4.61-4.59 ppm ranges [41, 42]. The signals of the methyl groups which appeared in the spectrum of ligand at 2.09, were appeared in the 2.07-2.15 ppm range. This signal was slightly shifted in the spectra of complexes, which may be due to complexation of the azomethine nitrogen atom with the metal ion [48] .The other signals of the phenyl and methyl protons of antipyrine moiety in the spectra of complexes 6-9 were appeared in the expected regions [43]. The results of magnetic moments of the complexes 2-9 showed that the complexes 2-5 are paramagnetic. The Cu(II) complex 2 shows magnetic moment value 1.78 BM which are consistent with one unpaired electron system in octahedral or square planar structure [49]. Ni(II) complex 3 shows value 2.95 BM 47

Synthesis, Characterization and Biological Activity of Some Ferrocenyl Complexes Containing Antipyrine Moiety

Figure 2. Structural representation of the complexes 2-9.

which is consistent with two unpaired electrons system of octahedral Ni(II) complex [49]. Co(II) complex 4 shows value 4.15, indicating high spin octahedral Co(II) complex [43]. The magnetic moment values of Mn(II) complex 5 is 5.71 BM. which is compatible with high spin octahedral Mn(II) complex [43]. The important electronic spectral data of the ligand and its complexes were record in DMSO at 10−3 M. The spectrum of Cu(II) complex showed broad band at 590 and 531 nm which can be assigned to the 2 B → 2 B and 2 B →2 E transitions, respectively indicating that the Cu(II) have tetragonal distorted g 1g 2g 1g octahedral geometry [50] (Figure 2 ). The electronic spectra of the Co(II) complex consists of two shoulder bands at 542 and 490 nm. These bands are assigned to the transitions 4 T1g (F) →4 A2g (F) and 4 T (F) →4 T (P) respectively, and they are characteristic for high-spin distorted octahedral geometry for 1g 2g the Co(II) complex [17–19] (Figure 2 ).On the other hand, the Ni(II) complex spectrum showed two bands at 593 and 475 nm. These bands assigned to the b2g → b1g and a1g → b1g transitions, which is compatible with the Ni(II) complex having an distorted octahedral geometry [38, 39]. The electronic absorption spectrum of Mn(II) complex 5 displays weak absorption bands at 600, 530 and 495 nm. These bands may be corresponded to, 6 A1g →4 Eg (4 G), 6 A1g →4 Eg (4 D) and 6 A1g →4 T1g (4 p) transitions respectively. These transitions are characteristic to Mn(II) ion in distorted octahedral geometry [51, 52] (Figure 2 ). It was also observed a weak broad band for every complex at 440-461 nm. This band was assigned to the transition 1 A1g →1 E1g in the iron atom of the ferrocenyl group, which indicates that there is no magnetic interaction between the Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Cd(II), Hg(II) and Pb(II) ions and the Fe(II) ion of the ferrocenyl group [18]. The biological activity of the ligand and its complexes are listed in Table 5 . The results show that most metal complexes exhibit inhibitory effects towards gram-positive bacterium (Bacillus subtilis), gram-negative bacterium (Escherichia Coli) and fungus (Aspergillus niger) in comparison with the parent organic ligand and the solution of metal salts which are biologically inactive. The order of the activity of the compounds against Bacillus subtilisis is, Tetracycline> 2 > 3 = 7 > 4 > 9 > 8 > 6 48

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(Table 5 ). The order of the activity against Escherichia coli is, Tetracycline> 7 > 3 > 2 = 4 > 6 > 9 > 8 (Table 5 ). However, the order of the activity against Fungus (Aspergillusniger) is 8 >Amphotricene B= 9 > 7 > 6 > 2 > 4 (Table 5 ). From the results, the activity of complexes against microorganism tested was increased on coordination. This enhancement in the activity may be rationalized on the basis that their structures mainly possess an additional C=N bond. It is also known that the complexation tends to make the ligands more powerful and potent bactericidal agents, thus killing more of the bacteria than the parent ligand. A possible explanation is that the positive charge of the metal is partially shared with the donor atoms present in the ligands and there is π-electron delocalization over the whole chelated ring. This, in turn, increases the lipophilic character of the metal complex and favors its permeation through the lipoid layers of the microorganism membranes. Furthermore, other factors such as solubility, conductivity and dipole moment (influenced by the presence of metal ions) may also be possible reasons for this activity [17, 18, 39, 42]. On the other hand, the inhibition of the growth of the microorganisms may be due to the inhibition of the glucose uptake, inhibition of RNA and protein synthesis. This result revealed that the complexes induced bacterial cell death [52, 53].

4. CONCLUSION Condensation of 1,1’-diacetylferrocene with 4-amino- 1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (4-amino anti pyrine) has yielded a new ferrocenyl ligand having potential binding sites toward metal ions. It acts as a tetradentate N2 O2 donor ligand by coordinating through the carbonyl group of the antipyine moiety and azomethine group to the metal ions. It forms neutral octahedral complexes with Cu(II), Ni(II), Co(II), Mn(II), Zn(II), Cd(II), Hg(II) and Pb(II) ions. The biological activity of the ligand and its complexes were carried out against fungal strains of Aspergillus niger and bacterial strains of Bacillus subtilis (+ve), Esherichia coli (-ve) using the disk diffusion method. The results showed that most metal complexes exhibit inhibitory effects towards gram-positive bacterium (Bacillus subtilis), gram-negative bacterium (Escherichia Coli) and fungus (Aspergillus niger) in comparison with the parent organic ligand teteracycline and Amphotricene as a standard.

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Synthesis, Characterization and Biological Activity of Some Ferrocenyl Complexes Containing Antipyrine Moiety

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