Apr 1, 2015 - Reagent grade Cobalt(II) chloride hexahydrate, Copper(II) chloride ... Manganese(II) acetate tetrahydrate, Zinc(II) sulphate heptahydrate, Iron(II) ...
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International Journal of Applied Medical Sciences Volume 1, Issue 2; 2015: 77-87
Original Article
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY OF SOME MIXED METAL(II) COMPLEXES OF PARACETAMOL AND BENZOIC ACID
ADEROJU A. OSOWOLE 1,*, OLUWATOOSIN B. A. AGBAJE 1,2, SHERIFAT S. WAKIL 3 1Inorganic 2Organic
Chemistry Unit, Department of Chemistry, University of Ibadan, Ibadan, Nigeria
Chemistry Unit, Department of Chemistry, University of Ibadan, Ibadan, Nigeria 3Department
of Microbiology, University of Ibadan, Ibadan, Nigeria Available Online 1st April, 2015
ABSTRACT Mn(II), Fe(II), Ni(II), Cu(II) and Zn(II) mixed ligand complexes of Paracetamol (HL) and Benzoic acid (HL 1) were synthesized and characterized by room temperature magnetic moments, melting points, conductance measurements, infrared and electronic spectroscopies. The molar conductance measurements in DMSO indicated that metal(II) complexes were covalent. The percentage metal analysis showed that the complexes mostly analyzed as [M(L)(HL1)X(H2O)].aH2O where X = Cl or 1/2SO4. Infrared spectra data confirmed that coordination was through enol oxygen and carbonyl oxygen atoms of Paracetamol, whereas, the coordination in Benzoic acid was through the undeprotonated carboxylate oxygen atoms. The room temperature magnetic moment and electronic spectra data indicated that all the metal(II) complexes were octahedral. Furthermore, the Fe(II) complex showed high spin
low
spin octahedral equilibrium, and the Mn(II) complex exhibited antiferromagnetism. The in-vitro antimicrobial studies of these mixed drug metal(II) complexes, Paracetamol and Benzoic acid against E. Coli, Streptococcus spp, Proteus, Candida albicans, Salmonella sp, Bacillus spp, Staphylococcus sp and Pseudomonas spp showed moderate activities with inhibitory zones range of 6.0 – 23.0 mm. Keywords: Antiferromagnetism, benzoic acid, paracetamol, octahedral geometry.
Introduction
*Author for Correspondence
Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 The exploit of transition metal complexes as therapeutic compounds has become more and more pronounced in medicinal therapeutics
[1].
These complexes offer a great diversity in their biological activities such as anti-cancer,
anti-inflammatory, anti-infective, anti-bacterial and anti-diabetic
[2-10].
Furthermore, complexes of Paracetamol with
Co and Fe had good inhibitory effects on E. coli which was absent in Paracetamol alone [11-12]. It is however remarkable that some biologically active compounds may become more carcinostatic and bacteriostatic upon chelation [13]. Benzoic acid, a food additive with considerable sensitizing potential, has been used as a therapeutic agent for reducing ammonium toxicity in patients with enzyme defects in the urea cycle since 1979. It was used as expectorant, analgesic and antiseptic in the early 20th Century [14-15]. Detailed literature search showed that mixed drug metal complexes of benzoic acid and its derivatives have been reported
[16-19].
However, there is no report of metal(II) complexes of
Benzoic acid and Paracetamol. Thus, in view of this and our interest in biologically active transition metal(II) complexes, we present the synthesis, characterization and antimicrobial activities of some novel metal(II) complexes of Benzoic acid and Paracetamol, with the aims of investigating the suitability of these natural ligands in forming high spin /low spin metal complexes, the exhibition of spin-cross over, Ferro- and anti-ferromagnetisms phenomena by the metal complexes, and the potentials of the metal(II) complexes as broad-spectrum antimicrobial agents invitro. This is a continuation of our research
[7-9],
in the search for biologically active metal(II) complexes that could
serve as lead compounds in drug research for pain management. Experimental Materials and reagents Reagent grade Cobalt(II) chloride hexahydrate, Copper(II) chloride dihydrate, Nickel(II) chloride hexahydrate, Manganese(II) acetate tetrahydrate, Zinc(II) sulphate heptahydrate, Iron(II) sulphate heptahydrate and Benzoic acid were obtained from Aldrich and BDH chemicals. Paracetamol was gift from Bentos Pharmaceutical products limited, New Garage Ibadan, Nigeria and was used as received. Solvents were purified by distillation. Synthesis Preparation of [Fe(L)(HL1)1/2SO4].3H2O This complex was prepared by the addition of 1.84 g (6.616 x 10-3 moles) of FeSO4.7H2O to a stirring solution of 6.616 x 10-3 moles (1.00 g, paracetamol, HL) and 6.616 x 10-3 moles (0.81 g, benzoic acid, HL1) in 20 mL of 50% methanol or 100% methanol. The resulting homogeneous solution was then stirred at 32oC for 5 hours during which the products formed. The brown precipitate obtained was filtered, washed with 50% methanol and dried over silica gel. The same method was used for the preparation of the Mn(II), Ni(II), Cu(II) and Zn(II) complexes from their acetate, chloride and sulphate salts respectively. Physical measurement The electronic and infrared spectra (as KBr disc) of the complexes were recorded on a Perkin-Elmer λ25 and PerkinElmer FT-IR spectrum BX spectrometers in the range 4000-400 cm-1. Room temperature magnetic susceptibilities at 300K were measured on Sherwood Susceptibility Balance MSB Mark 1, melting points were determined with MelIJAMS, Volume 1, Issue 1, April 2015
Page 78
Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 Temp electrothermal machine, and molar conductivity measurements of 1 x 10 -3 M solutions in DMSO were obtained using electrochemical analyzer Consort C933. Antimicrobial assay The antimicrobial activities of the synthesized compounds as well as their metal free ligands were studied using the agar diffusion technique. Identified laboratory clinical, food and environmental isolates (microbes) were used in this study, that is, E. Coli(typed strain), Streptococcus sp (clinical), Proteus, Candida albicans, Salmonella sp, Streptococcus sp (clinical), Bacillus sp (food), Staphylococcus sp, Pseudomonas sp (clinical and environmental waste), Bacillus sp (clinical) and E. coli(clinical). The surface of the agar in a Petri dish was uniformly inoculated with 0.2 mL of 18 hour old test bacterial culture. Using a sterile cork borer, 5 mm wells were bored into the agar. Then 0.06 mL of 10 mg/mL concentration of each metal complex in DMSO was introduced into the wells and the plates were allowed to stand on the bench for 30 minutes before incubation at 370C for 24 hours after which inhibitory zones (in mm) were taken as a measure of antimicrobial activity. The experiments were conducted in duplicates and Streptomycin was used as the reference drug. Results and Discussion The reaction of the Paracetamol (HL), Benzoic acid (HL 1) with the metal(II) chlorides (Co, Ni and Cu), acetate (Mn) and metal(II) sulphates (Fe and Zn) gave coloured metal complexes of low yields (20-40%) according to the equations below; Mn(CH3CO2)2.4H2O + 2HL + 2HL1 → [Mn(L)(HL1)(CH3CO2) ].H2O + CH3CO2H + 3H2O (1) MSO4.7H2O + HL + HL1 → [M(L)(HL1)1/2SO4].aH2O + 1/2H2SO4 + bH2O
(2)
(where M = Fe, a = 3, b = 4; M = #Fe, a = 1, b = 6; M = Zn, a = 2, b = 5) MCl2.dH2O + HL + HL1 → [M(L)(HL1)Cl(H2O)].aH2O + HCl + bH2O
(3)
(Where M = Co, a = 4, b= 1, d = 6; M = Ni, a = 0, b = 5, d = 6; M = Cu, a = 1, b= 1, d = 2) The formation of the metal complexes was confirmed by infrared and electronic spectroscopies , distinct decomposition temperature and %metal analysis. The ligands, Paracetamol (HL) and benzoic acid (HL 1) melted at 170-172oC and 121-123oC respectively, whereas all the complexes decomposed in the range 162-210oC confirming coordination. The analytical data, colours, % metal, melting points, molar conductivity and room temperature magnetic moments for the complexes are present in Table 1. Table 1 Analytical data of complexes Compound (Empirical formula) HL
Formula mass
Color
151.15
White
M. pt 170-172
% Yield
%M
-
-
IJAMS, Volume 1, Issue 1, April 2015
µe
^m
-
-
(exp)
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Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 HL1
122.12
White
121-123
-
-
-
-
[Mn(L)(HL1)(CH3CO2)]2.H2O
790.40
Brown
*184
20
13.90 (14.05)
1.00
18.39
[Fe(L)(HL1)(1/2SO4)].3H2O
430.16
Brown
*162
40
12.98 (12.99)
3.82
14.63
#[Fe(L)(HL1)( 1/2SO4)].H2O
394.12
Peach
*164
30
14.17
3.60
11.00
3.39
14.72
3.36
23.90
2.65
18.46
0.59
10.66
(14.28) [Ni(L)(HL1)Cl(H2O)]
384.48
Green
*182
40
15.27 (14.99)
#[Ni(L)(HL1)Cl(H2O)]
384.48
Green
*178
40
15.27 (15.14)
[Cu(L)(HL1)Cl]2.2H2O
707.64
Green
*176
30
17.96 (17.73)
[Zn(L)(HL1)( 1/2SO4)].2H2O
421.68
White
*210
30
15.51 (15.20)
HL = Paracetamol; HL1 = Benzoic acid; * = decomposition temperature; ^m = molar conductance; exp = experimental; µe = Effective magnetic moment; # = prepared in 100% methanol. Solubility and Conductance measurements The complexes were insoluble/slightly soluble in water, methanol, ethanol, nitromethane, and dichloromethane but were soluble in DMSO. Consequently, their molar conductances were measured in DMSO; with values obtain in the range 10.66– 27.40 Ω-1cm2mol-1 indicating their covalent nature [20]. Electronic Spectra and Magnetic moments The electronic spectra data for the ligands and metal complexes are presented in Table 2. The ultraviolet spectra of the compounds were characterized by two strong absorption bands between 29.50 kK and 32.57 – 33.11 kK assigned to nπ* and ππ* transitions respectively. The spectra of the Mn(II) complex showed a strong absorption band at 24.21 kK typical of low spin octahedral geometry and was assigned to 2T2g2A1g transition. An observed room temperature moment of 1.00 B.M was complimentary of a low spin, dimeric octahedral geometry since moments of about 2.0 B.M was reported for monomeric, octahedral low spin Mn(II) [21] . The Fe(II) complex had two absorption bands at 11.88 kK and 24.21 kK typical of 6-coordinate, high spin and low spin octahedral geometry and were assigned to 5T2g5Eg and 1A1g1T2g transitions. A moment of 5.0-5.5 B.M is usually expected for high spin complex and low spin octahedral Fe(II) complexes are expected to be diamagnetic. However, in this study, a moment of 3.82 B.M was observed for this complex, which was intermediate between the
IJAMS, Volume 1, Issue 1, April 2015
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Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 values for the high spin and low spin octahedral geometry, suggestive of a high spin
low spin octahedral
equilibrium[22]. CH3 CH3
O
C
NH
O2CCH3
C O
O
NH
Cu HO O
Mn
O OH
O
Cl
.H2O
CH3
.2H2O
Cl
CH3
C O
C
NH
O
NH O
O
Mn
Cu OH
OH
O
O
CH3CO2
(a)
(b)
Figure 1: Propose structures for the Mn(II) and Cu(II) complexes The Ni(II) complex showed two absorption bands at 14.95 kK and 22.42 kK typical of 6-coordinate octahedral geometry and were attributed to 3A2g 3T1g(F) and 3A2g 3T1g(P) transitions respectively. This complex had a moment of 3.39 B.M corroborating octahedral geometry since room temperature magnetic moments of 2.8-3.4 B.M were reported for high spin octahedral Ni(II) complexes [23-24]. The Cu(II) complex showed two transitions each at 14.03 kK and 24.27 kK respectively. The transitions assigned to 2B1g
→ 2A1g and 2B1g → 2E1g transitions of a distorted octahedral geometry. A moment of 1.9– 2.2 B.M. is usually
observed for mononuclear copper(II) complexes, irrespective of geometry, expectedly higher than the spin only moment due to orbital contribution and spin-orbit coupling. The Cu((II) complex in this study, had a moment 2.65 B.M which is higher than expected [25-27] due to some antiferromagnetic interactions [28] which we are unable to rationalize in the absence of X-ray structural investigation. However, this might indicate that this complex was dimeric (Figure 1) with the Chlorine atoms bridging the metal centers, and each metal centre reinforcing the overall magnetic susceptibility of the complex [29]. The spectra of Zn(II) complex had only charge transfer transition from metal to ligand at 24.15 kK as no d – d transition is expected. The complex was expected to be diamagnetic because of its d 10 configuration. However, a moment of 0.59 B.M was observed due to paramagnetic impurities [30]. Infrared Spectra IJAMS, Volume 1, Issue 1, April 2015
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Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 The relevant bands are presented in Table 2. The strong and broad bands at 3467 cm-1 and 3452 cm-1 in Paracetamol and Benzoic acid were assigned as υOH, and the band at 3382 cm-1 was assigned to υNH of Paracetamol [5]. The 3467 cm-1 band in Paracetamol was absent in all the metal complexes due to deprotonation and coordination of the phenol oxygen atom to the metal ion. In contrast, the vOH band in the Benzoic acid still showed in the metal complexes but shifted to 3434 – 3455 cm-1 due to coordination of the un-deprotonated phenol oxygen atom to the metal(II) ion
[11].
The broad band at 3500 cm-1 in metal(II) complexes of Fe and Zn was assigned to vOH water of crystallization. Furthermore, the v(C=O) band in Paracetamol and Benzoic acid at 1622 cm-1, 1595 cm-1 and 1687 cm-1 shifted significantly to 1549 - 1668 cm-1 in the metal complexes corroborative of coordination , of the carbonyl oxygen atom [12].
In addition, the new bands in the range 596-417 cm-1 and 396-352 cm-1 which were absent in the ligands, were
assigned to v(M-O) and v(M-Cl) respectively, confirming the involvement of oxygen atoms of the carbonyl, phenol and carboxylic acid, and chlorine atom in complexation with the metal atoms [3, 31] . Table 2 Relevant infrared and electronic spectra data of the complexes Compound
υ(C=O)
υ(C-O)
υ(M-O)
υ(M-Cl)
Electronic spectra (kK)
HL
1622s 1595s
-
-
-
32.89
HL1
1687b
1326s
-
-
32.91 29.50
541m
-
24.21 32.97
1292s [Mn(L)(HL1)(CH3CO2]2.H2O
1633b1603w 1563m
1066m
[(Fe(L)(HL1)(1/2SO4)].3H2O
1632b1564m
1177s
481m
-
11.88 24.21 32.79
#[(Fe(L)(HL1)( 1/2SO4)]. H2O
1668w1601s
1306w
478s
-
24.21 20.00 32.79
1566s
1176m
1622w1600s 1559s
1068w
450m
396w
417w
375w
14.95 22.42 24.33 32.57
1660w 1599s
1313w
380w
1558s
1260m
596m 418m
1639b1595w
1125w
[Ni(L)(HL1)Cl(H2O)] #[Ni(L)(HL1)Cl(H2O)] [Cu(L)(HL1)Cl]2.2H2O
422m
1549s [Zn(L)(HL1)( 1/2SO4)].2H2O
1634b1602w 1562m
515w
23.75 32.68
364m 375w
14.03 24.27 32.89
-
24.15 33.11
475m 1315m
478m
HL = Paracetamol, HL1 = Benzoic acid, b = broad, s= strong, m= medium; 1kK = 1000cm-,1 # = prepared in 100% methanol Antimicrobial activities The antimicrobial activities of the Ligands and their metal complexes are presented in Table 3. Paracetamol and while Benzoic acid were active against five and eight organisms with inhibitory zones range of 7.0-13.0 mm and 6.0-13.0 IJAMS, Volume 1, Issue 1, April 2015
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Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 mm respectively. Paracetamol’s lower activity was attributed to its bacteriostatic nature [12]. The Mn(II) complex was active against five organisms with inhibitory zones range of 7.0-15.0 mm, while the Cu(II) complex was active against eight organisms with inhibitory zones range of 7.0-20.0 mm and the Zn(II) complex was active all the organisms with the exceptions of Proteus sp, C. albicans and E. coli(clinical strain) with inhibitory zones range of 6.0-23.0 mm. Interestingly, all the metal complexes and their ligands had activities against Pseudomonas sp (Environmental) with inhibitory zones range of 11.0 – 29.0 mm. Furthermore, Fe(II) and Ni(II) complexes prepared in 50% methanol had better activities against the organisms used than their analogs prepared in 100% methanol due to their good solubility in non-polar solvents better lipophilic nature, favoring permeation through lipid layers of the organism membrane, causing the death of the organisms [32].
Metal Complexes
[Mn(L)(HL1)(CH3CO2]2.H2O
[(Fe(L)(HL1)(1/2SO4)].3H2O
#[(Fe(L)(HL1)( 1/2SO4)]. H2O
[Ni(L)(HL1)Cl(H2O)]
#[Ni(L)(HL1)Cl(H2O)]
[Cu(L)(HL1)Cl]2.2H2O
[Zn(L)(HL1)( 1/2SO4)].2H2O
Paracetamol
Benzoic acid
+ Streptomycin
Table 3 Antibacterial activities of the ligands and their complexes
Bacillus sp F
8.0
7.0
R
7.0
R
R
6.0
7.0
7.0
R
Bacillus E
R
R
R
7.0
9.0
R
11.0
R
7.0
18.0
C. albicans
R
9.0
9.0
7.0
R
7.0
R
9.0
6.0
13.0
E. Coli T
11.0
R
7.0
9.0
7.0
7.0
9.0
R
R
15.0
E. Coli C
R
R
R
13.0
12.0
7.0
R
R
R
27.0
Proteus sp
7.0
R
R
R
R
9.0
R
9.0
9.0
19.0
Salmonella sp
R
R
R
7.0
7.0
R
9.0
R
9.0
11.0
Staphylococcus sp
7.0
R
R
9.0
R
7.0
7.0
R
8.0
R
S. pyogenes
R
R
R
7.0
R
7.0
9.0
7.0
7.0
9.0
Streptococcus sp
R
11.0
R
13.0
R
R
9.0
R
R
25.0
Pseudomonas sp C
R
19.0
11.0
15.0
R
11.0
19.0
R
R
27.0
Pseudomonas sp E
15.0
19.0
19.0
11.0
19.0
20.0
23.0
13.0
13.0
29.0
T= Typed strain, F = food strain, C = clinical isolate, E = Environmental strain R= Resistance, + = positive control, # = Prepared in 100% methanol Its note worthy that Bacillus sp (food strain) was more sensitive to the metal complexes than the environmental strain of Bacillus sp. Similarly, E. coli (type strain) was more sensitive than the environmental strain of E. coli, and IJAMS, Volume 1, Issue 1, April 2015
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Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 Pseudomonas sp (environmental strain) was more sensitive to the metal complexes than the clinical strain of Pseudomonas sp. The general resistance of the clinical and or environmental strains of these bacteria was attributed to antibiotic resistance [33], and development of efflux pump or the breakdown of the metal complexes in anaerobic respiration by these bacteria [34]. Expectedly, Streptomycin was more active against all the tested organisms than the metal complexes and their ligands, with the exceptions of Bacillus sp (Food) and Staphylococcus sp that had no activity, with inhibitory zones range of 9.0 - 29.0 mm . CONCLUSION Mn(II), Fe(II), Co((II), Ni(II), Cu(II), Zn(II) mixed ligand complexes of Paracetamol (HL) and Benzoic acid (HL1) assumed a 6-coordinate octahedral geometry. The molar conductance measurements in DMSO indicated that the metal(II) complexes were covalent. The in-vitro antimicrobial activities of the metal complexes against E. coli, Streptococcus spp, Proteus sp, C. albicans, Salmonella sp, Bacillus spp, Staphylococcus sp and Pseudomonas spp were moderate with inhibitory zones range of 6.0 – 23.0 mm. ACKNOWLEDGEMENT The University of Ibadan, Ibadan, Nigeria is thanked for provision of research chemicals and analyses of the compounds. REFERENCES 1.
Rafique S, Idrees M, Nasim A, Akbar H, Athar A. Transition metal complexes as potential therapeutic agents. Biotech. &Molecular Biol. Reviews, 2010; 5(2): 38-45.
2.
Weder JJE, Dillon CT, Hambley TW et al. Copper complexes of non-steroidal anti-inflammatory drugs: an opportunity yet to be realized. Coordination Chemistry Reviews, 2002; 232: 95-126.
3.
Harminder K, Kanav D, Jaspreet K, Bharti M, Ashish C. Synthesis and evaluation of diorganotin(IV) and triorganotin(IV)derivatives of Aspirin, Paracetamol
and Metronidazole as antimicrobial agents.
American Journal of drugs and development, 2013; 3(1): 13-22. 4.
Lawal A, Obaleye JA. Synthesis, characterization and antibacterial activity of aspirin and paracetamol-metal complexes. Biokemistri, 2007; 19(1): 9-15.
5.
Nejo AA, Kolawole GA, Nejo AO, Muller CJ. Synthesis, characterization
and insulin-mimetic studies of
complexes of Oxovanadium(IV) with Schiff bases. International Journal of Drug Formulation and Research, 2011; 2 (5): 220-241. 6.
Obaleye JA, Orjiekwe CL, Famurewa O. Effects of some novel ascorbic acid
metal complexes on selected
Bacterial and Fungal Species. J. Sci.I.R. of Iran, 1994,5(4): 154-157.
IJAMS, Volume 1, Issue 1, April 2015
Page 84
Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 7.
Osowole AA, Oni AA, Onyegbula K, Hassan AT. Synthesis, spectral, magnetic
and
in-vitro
anticancer
properties of some Metal(II) complexes of 3-[2,4-dihydro-1H-inden -4-ylimino)methyl]napthalen-2-ol. International Research Journal of Pure and Applied Chemistry, 2012; 2(3): 211-20. 8.
Osowole AA, Ekennia AC, Achugbu BO. Synthesis, spectroscopic characterization and antibacterial Properties of some Metal (II) Complexes of 2-(6methoxybenzo thiazol-2-ylimino)methyl)-4-nitrophenol. Research & Reviews: Journal of Pharmaceutical Analysis, 2013; 2(2): 1-5.
9.
Osowole AA, Ekennia AC, Achugbu BO, Etuk GH. Synthesis, spectroscopic characterization and structure related antibacterial activities of some
metal (II) complexes of substituted triflurobutenol. Elixir Appl.
Chem., 2013; 59:15848-15852. 10. Sangita PK, Farhad MA, Sania S, MdZakir S, Mohammad AH, Mohammad SA. Study of Differential Scanning Calorimetry of complex of Magnesium Sulfate with Aspirin, Paracetamol and Naproxen. Bangladesh Pharm Journal, 2012; 15(1):7 - 12. 11. Obaleye JA, Adediji JF, Adebayo MA. Synthesis and biological activities on metal complexes of 2, 5-Diamino-1, 3, 4-thiadiazole derived from semicarbazide hydrochloride. Molecules, 2011; 16: 5861-5874. 12. Choure R, Vaidya N. Polarographic and Pharmacological study of Zn (II) Paracetamol complex. Current Pharma Research, 2011; 1(2):123-126. 13. Raman N, Selvan A, Pothiraj A, Jeyamurugan R. New insights into the antibacterial and antifungal activity study of mixed-ligand metal complexes containing tridentate Schiff base. Journal for Bloomers of Research, 2010; 3(1): 6-12. 14. Sangita PK, Farhad MA, Sania S, MdZakir S, Mohammad AH, Mohammad SA. Study of Differential Scanning Calorimetry of complex of Magnesium Sulfate with Aspirin, Paracetamol and Naproxen. Bangladesh Pharm. J. 2012; 15(1):7-12. 15. Nair B. Final report on the safety Assessment of Benzyl Alcohol, Benzoic acid and sodium benzoate. Int J. Tox., 2001; 20(3): 23-25. 16. Valli G, Gayathri S. Synthesis, characterization, in-vitro and in-silico drug activity of mixed ligand Copper (II) Complexes. Journal of Chemical, Biological and Physical Sciences, 2014; 4(1): 102-109. 17. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology, 2005; 42(6):1364–1372. 18. Selvakumar MS, Bheeter SR. Synthesis and characterization of Benzoic Acid complexes with biologically active metal ions. Mapana Christ University Journal of Sciences, 2005, 4(1):85-89
IJAMS, Volume 1, Issue 1, April 2015
Page 85
Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 19. Arunachalam T, Bhakyaraj R, Sasi AK. Synthesis, Characterization and Biological Activity of Mn2+, Co2+, Ni2+ and Cu2+Complexes of Benzoic Acid Ligand. E-Journal of Chemistry, 2009; 6(3): 743-746. 20. Geary WJ. The use of conductivity measurements in organic solvents for the characterization of coordination compounds. Coordination Chemistry Review, 1971; 7: 81-122. 21. Saha A, Majumdar P, Goswami S. Low-spin manganese(II) and cobalt(III)
complexes of N-aryl 2-pyridyl
azophenylamines: new tridentate N,N,N-donors derived from cobalt mediated aromatic ring amination of 2(phenylazo)pyridine. Crystal structure of a Mn(II) complex. J Chem Soc Dalton Trans., 2000; 11: 1703-8. 22. Olguín J, Brooker S. Spin crossover active iron(II) complexes of selected pyrazole-pyridine/pyrazine ligands. Coordination Chemistry Reviews, 2011; 255(1-2): 203–40. 23. Ajay RP, Donde KJ, Raut SS, Patil V, Lokhande RS. Synthesis, characterization and biological activity of mixed ligand Co(II) complexes of Schiff base with some amino acids. J. Chem. Pharm. Res., 2012, 4(2):
2-amino-4-nitro
phenol-n-salicylidene
1413-1425.
24. Gupta KC, Sutar AK. Polymer supported Schiff base complexes of Fe(III), Co(II) and Ni(II) ions and their catalytic activity in oxidation of phenol and
cyclohexane. J. Macromol. Science A Pure Appl. Chem.,
2007; 44(11): 1171–1185. 25. Osowole AA, Oni TI.Synthesis, spectroscopic characterization and antibacterial activities of mixed ligand metal(II) complexes of 4-amino-6-chloro-2methylthio pyrimidine and 1,10phenanthroline. Scientific Research Reports, 2013; 1(1): 25-31. 26. Beyramabadi SA, Eshtagh-Hosseini H, Housaindokht MR, Morsali A. Synthesis, experimental and theoretical characterization of Cu(II) complex of 2-chloropyrimidine. Sci. Res. Ess., 2011; 6(20): 4341-4346. 27. Ishida T, Mitsubori SI, Nogami T et al. Intra- and inter-molecular ferromagnetic interaction of transition metal complexes containing pyrimidine or pyrazine derivatives. Synthesis Reactivity in Inorganic Metal Organic Chemistry and Nano-Metal Chemistry, 1995; 71: 1791-1792. 28. Osanai K, Okazawa A, Nogami T, Ishida T. Strong ferromagnetic exchange couplings in Cu(II) and Ni(II) complexes with a paramagnetic tridentate chelate ligand, 2,2-bipyridin-6-yl tert-butyl nitroxide. American J Chemical Soc., 2006; 128: 14008-14009. 29. Reddy PR, Reddy AM. Synthesis and characterization of mixed ligand complexes of Ni(II), Cu(II) and Co(II) with pyrimidine nucleoside and amino acid. Indian Academy of Science (Chem. Sci.), 112(6): 593-600. 30. Osowole AA, Kempe R, Schobert R, Effenberger K. Synthesis, spectroscopic, thermal and
in-vitro
anticancer properties of some metal(II) complexes of 3-(-1-(4,6-dimethyl-2-pyrimidinylimino)methyl-2napthol. Synthesis Reactivity in Inorganic Metal Organic
IJAMS, Volume 1, Issue 1, April 2015
Page 86
Osowole et al. Int. J. Applied Medical Sc., Vol. 1, Issue2 Chemistry and Nano-Metal Chemistry, 2011; 41(7): 825-33. 31. Al-Saif FA, Refat MS. Ten metal complexes of vitamin B3/niacin: Spectroscopic, thermal, antibacterial, antifungal, cytotoxicity and antitumor studies of
Mn(II), Fe(III), Co(II), Ni(II),
Cu(II), Zn(II), Pd(II), Cd(II), Pt(IV) and Au(III)
of Molecular Structure, 2012;
complexes. Journal
1021: 40-52. 32. Matangi S, Pragathi J, Bathini U, Gyana K. Synthesis, characterization and antimicrobial activity of transition metal complexes of Schiff base ligand derived from 3-ethoxysalicylaldehyde and 2-(2-Aminophenyl) 1-Hbenzimidazole. E-J Chem., 2012; 9(4):2516-2523. 33. Wang M, Tran J H, Jacoby G A, Zhang Y, Wang F, Hooper DC. , Plasmid-Mediated Quinolone Resistance in Clinical Isolates of Escherichia coli from Shanghai, China, Antimicrobial Agents Chemotherapy., 2003; 47(7): 2242–2248. 34. Gadd GM. In Microbial Mineral Recovery (Ehrlich HL, Brierley CL, Eds.) McGraw Hill, New York., 1990, 249275.
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