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Journal of Modern Medicinal Chemistry, 2014, 2, 1-9 1
Synthesis, Characterization and Microbial Evaluation of Metal
Complexes of Molybdenum with Ofloxacin (Levo (S
-form) and
Dextro (R
-form)) Isomers
Qadeer K. Panhwar1,2 and Shahabuddin Memon2,* 1Dr. M. A. Kazi Institute of Chemistry, University of Sindh, Jamshoro, Pakistan
2National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro 76080, Pakistan

Abstract: The article describes the interaction of molybdenum with dextrofloxacin and levofloxacin (isomers of ofloxacin)
antibiotic drugs. Characterization of compounds was made by UV-Vis, FT–IR, 1H NMR, elemental and thermogravimetric
analyses. The green colored Mo–dextrofloxacin and yellow colored Mo–levofloxacin complexes were isolated. After
complete characterization, the chemical formulae of the complexes were established as [MoO2(R-Oflox)2] or
[MoO2(Dextro)2] and [MoO2(Levo)2] or [MoO2(S-Oflox)2]. The microbial evaluation was made by well diffusion method for
both ligands and their metal complexes against two bacterial strains, S. aureus and E. coli. It was observed that the
antibacterial action of Mo–dextrofloxacin and Mo-levofloxacin was significantly higher than the dextrofloxacin and
levofloxacin alone against S. aureus, while no action was observed against E. coli.
Keywords: Antibacterial, synthesis, levofloxacin, ofloxacin, molybdenum.
bioavailability of ligands or metal ions or both [6]. Fluoroquinolines are substituted quinolines having a In 1945, Selman A. Waksman firstly used the term fluorine atom at position 6. This fluorine atom may ‘‘antibiotic'' in the title of his book. He defined the term increase gyrase inhibition and cell penetration. Main as "….produced by microorganisms and which possess structural importance is that its piperazinyl subtituent is the property of inhibiting the growth and even of active against Gram –ve bacteria while pyrrolidinyl destroying other microorganisms." Antibiotics may be moiety act against Gram +ve cocci. Whereas position 8 synthetic or semi–synthetic. Many antibiotics do not with substituted function may control anaerobe activity require metal ions to show bioactivities, however, a big [4]. In addition to be broad spectrum antimicrobial number may require metal ions for proper functioning agents, fluoroquinolines may also have some other e.g. bacitracin, bleomycin (BLM), and streptonigrin useful characteristics which may increase its (SN) [1]. The chelate formation may increase the bioavailability, penetration into tissues, safety as well lipophilicity of drug, which may increase the drug action as long term serum half-life. These properties may be because of effectual drug permeability into the site of the basis to make them very efficient agents to treat variety of diseases such as respiratory, soft tissue, urinary tract, and bone-joint infections as well as Quinolines are a popular collection of antibiotics sexually transmitted diseases, typhoid fever, used for treating several bacterial diseases. The community acquired pneumonia, prostatitis, sinusitis, significant growth in the quinoline drug family was and acute bronchitis [7, 8]. observed with the discovery of nalidixic acid in 1962. Till to date, this family has been grown to almost 10 Dextrofloxacin and levofloxacin (Figure 1) are two
thousand analogous. Quinolines have ability to pass well–known examples of fluoroquinolines. through cells easily and hence can be utilized for the treatment of intracellular pathogens such as Racemic ofloxacin (50% Dextrofloxacin and 50% Mycoplasma pneumoniae and Legionella pneumophila Levofloxacin) is synthetic [9] broad spectrum [3-5]. It may be proposed that uncharged quinolines antibacterial agents against G (+ve) and G (–ve) may diffuse through cytoplasmic membranes, where bacterial strains [10, 11] and extensively exercised for presence of metal ion may result in higher uptake of clinical purpose [12]. They inhibit bacterial DNA gyrase, quinolines by bacterial cells relative to only drug. and hence DNA replication and transcription [11, 13, Hence, metal complexes' formation may enhance All bacteria may have an essential enzyme known *Address correspondence to this author at the National Center of Excellence in as DNA gyrase and antibiotics may efficiently target it. Analytical Chemistry, University of Sindh, Jamshoro 76080, Pakistan; Tel: +92 (22) 9213429-30; Fax: +92 (22) 9213431; Quinolines work against DNA gyrase and turn its action E-mail: [email protected]

E-ISSN: 2308-8044/14
2014 Synergy Publishers
2 Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1
Panhwar and Memon
Figure 1: Structures of a) ofloxacin (R-form) and b) levofloxacin.
against bacteria as well as block the strand passage for treating a variety of ailments and disorders as and prevent proper DNA replication which ultimately observed in research showing considerable use of cause cell death [15]. Ofloxacin is known as a member such complexes against lymphomas, carcinomas, of second [13] and levofloxacin third generation [15]. infection control, diabetes, anti–inflammatory, and Their structures have oxazine ring with N–1 and C–8 neurological disorders because complexes show a connected through ring structure. The same ring also great diversity in action [2]. The ability of contains methyl group that may exist in two optically fluoroquinolone antibiotics to interact with some cellular active forms i.e., S–isomer and R–isomer. Initially, components is mediated by their complexation with racemic ofloxacin was available as a drug but later it divalent metal cations. While major structural difference was replaced by active S–isomer (Trade name between two kinds of drugs may be responsible for levofloxacin) isolated from the racemic ofloxacin, which their mode of action or mechanism of penetration into a is currently a leader on the quinolone drug market. bacterium [19]. The formation of complexes also Since, the S-isomer has significantly higher increases the bioavailability of metal ion or the ligand antibacterial activity almost two orders of the drug, or both due to increased hydrotropy and liposolubility may enhance the ability of drug molecules magnitude as compared to R-isomer. It is quite in crossing the membrane of a cell, and hence raised surprising that just a methyl group (non-functional) with the biological utilization ratio and activity of the drug respect to the plane of ring may show the different steric configurations (due to structural differences) for two enantiomers [11, 16]. Not only bicyclic Metal coordination to biologically active molecules heteroaromatic pharmacophore may impart the can be used as a strategy to enhance their activity and antibacterial property to the fluoroquinoline drugs, but it overcome resistance [15]. Our strategy is the synthesis may also depend upon nature and the spatial and isolation of new metal complexes of levofloxacin arrangement of tangential substituents. Such and dextrofloxacin with Mo and characterization substituents may influence the antibacterial action in through 1H NMR, UV–Vis, Elemental analysis, IR, order to offer more attraction to bacterial enzymes as conductance measurements and thermal analysis and well as increasing cell penetrations [15]. microbial evaluation against two bacterial species, Staphylococcus aureus and Escherichia coli. Today, In literature, many complexes have been reported little articles have been reported on the coordination with their bioactivities such as ofloxacin complexes of properties of levofloxacin [21]. Cu, Co, Mg, Zn and Ru [10], magnesium complexes of S-form and R-form [16], copper complexes of S-form and R-form [17] and CuII, NiII, MnII, and FeIII complexes of levofloxacin [15]. General Experimental Procedures
Several drugs when administered as metal All the reagents and solvents were of analytical complexes may acquire modified toxicological and grade or chemically pure. Drugs were purchased from pharmacological properties [3]. Chemistry of drug– Alchemy pharmaceuticals (Pakistan), KBr from Aldrich metal coordination compounds is more popular to Chemical (Germany). Sodium molybdate was design drugs of additional bioactivity. Action of many purchased from Fluka (Switzerland). Acetic acid was drugs is affected by metal ions that enhance the obtained from (Spain). All the reagents were weighed efficacy of drugs upon coordination [18]. Many within an accuracy of ± 0.0001 g. transition metal complexes have been used as drugs Synthesis, Characterization and Microbial Evaluation of Metal Complexes
Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1 3
UV–Vis spectra were obtained using a Perkin Elmer colored. The complexes were characterized and their Lambda 35 (USA) UV–Vis double beam formulae and structure was determined by elemental spectrophotometer, using standard 1.00 cm quartz analyses, molar conductivities, FT-IR data, thermal cells. Electrolytic conductance of the complexes was analysis, 1H NMR spectra. From the data of elemental measured by Inolab cond 720 WTW series analysis and molar conductivity, [MoO2(Oflox)2] and conductometer. FT-IR spectra were recorded in the [MoO2(Levo)2] were judged as non–electrolytes with spectral range of 4,000–400 cm–1 on a Thermo values 4.8 and 3.99 S/cm in DMSO, respectively, and Scientific Nicolet iS10 FT–IR (USA) instrument using thus their general chemical formulae were estimated KBr pellets. 1H NMR spectra were recorded on a as[M(L)2]. From spectral analysis like FT-IR and 1H Bruker 500 MHz (Germany) spectrometer in DMSO NMR, we could be in position to identify the ligation using TMS as internal standard. Chemical shifts are sites in the drug ligands. Besides, experimental data given in  relative to TMS. Thermogravimetric– fitted well with the calculated formula, there was no differential thermal analysis (TG–DTA) curves were crystallization water molecules in the complexes, as obtained on a Pyris™ Diamond TG–DTA (Perkin– checked by thermal analysis well as FT-IR. Both Elmer) under a nitrogen atmosphere at a heating rate complexes have been prepared in high yield (72–75%) of 10 °C min–1 from ambient to 600 °C. via the addition of acetic acid solution of ofloxacin (R-form) and levofloxacin to an aqueous solution of the Synthesis of Metal Complexes
metal ion at a ratio 2:1 according to the reactions (1) and (2): 0.0723 g, 0.02 mmol of dextrofloxacin and 0.074 g, 0.02 mmol of levofloxacin was dissloved in 10, 10 mL Na2MoO4 + 2CH3COOH  2NaCH3COO + H2O + of acetic acid, respectively. Subsequently, 0.0421g, 0.01 mmol of molybdenum salt was dissolved in distilled water (10 mL) and mixed metal and ligand MoO3 + 2Oflox  MoO2(Oflox)2 + H2O or solutions to each other. Quickly the precipitates appeared within solutions. Put aside the solutions till to MoO2 + 2Oflox–  MoO2(Oflox)2 settle the precipitates. Filtered the solutions, separated Both the resultant complexes are soluble mainly in the precipitates and washed with distilled water. Both hot DMSO, DMF, ethanol and methanol, while the products were air–dried. After complete drying, the insoluble in all the other solvents. color of precipitates was observed as yellow for Mo–levofloxacin, while initially yellow for Mo–dextrofloxacin The close proximity of keto and carboxyl groups on but after complete drying it turned green. The % yield levofloxacin and ofloxacin (R-form) may impart good was found as 72% and 75% for Mo–dextrofloxacin and chelating properties to both molecules. Hence, Mo–levofloxacin, respectively. The elemental analysis electronic spectra were carried out to characterize their results obtained for [MoO2(R-Oflox)2] complex are: C, metal complexes, in MeOH. Their spectra were almost 50.82; H, 4.7; N, 9.88%, while for [MoO2(S-Oflox)2] are: similar to drug molecules with negligible bathochromic C, 51.02; H, 4.15; N, 9.90%, respectively. shift and ligands retain their structures in complexes. Since bands in metal complexes are observed at Antimicrobial Assay
similar regions because of possessing similar Synthesized drug–metal complexes were applied chromophores. UV bands in 260–340 nm region may for antibacterial assay. The assay was carried out be caused by –* intraligand transitions. Strong using well diffusion method against two bacterial absorption at lower wavelength may be caused by strains i.e., S. aureus (Gram +ve) ATCC 25923 and E. chromophore. The strong absorption peak corresponds coli (Gram –ve) ATCC 25922. The analysis was carried to the chromophore related to nitrogen of position 1 to out at a fixed concentration of 20 g/mL. The solvent carboxyl group, while weak one may arise from DMSO was used as a –ve control. The medium of chromophore of nitrogen from piperazinyl group at 7– Muller Hunton Agar was used for said species. carbon to keto group. No any absorption band is seen in visible region even using higher sample RESULTS AND DISCUSSION
concentrations. In previous literature, no d–d bands are observed for such complexes except few ones. Complexes were formed by usual complex Whereas, using solid–state diffuse reflectance, d–d formation methods. Both the metal–complexes were bands are observed for ofloxacin complexes [7]. 4 Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1
Panhwar and Memon
Figure 2: Electronic spectra of a) Ofloxacin (R-form) and b) Mo–complex in MeOH, bands in ofloxacin (R-form) = 227 nm, 294
nm, 325 nm, and in Mo–complex = 297 nm, 326 nm.
In present case, ofloxacin (R-form) shows two respectively. After complex formation, peak at 1719 maxima at 227, 294 nm, and a shoulder at 325 nm in cm–1 disappeared by showing that carboxyl group has UV region, while in its molybdenum complex studied in been involved in complex formation, while peak at 1623 methanol shows negligible shift to 297 and 326 nm shifted to lower value of wave number 1583 cm–1 (Figure 2), respectively. These both are intraligand
(Figure 3). These variations may suggest that
transitions because they have just shifted little and no levofloxacin is coordinated to molybdenum via pyridone any new peak was formed. Thus, the spectrum is oxygen and one carboxylate oxygen [24]. affected when ofloxacin form complexes with metallic cation MoO 2+ Nakamoto and his co–workers suggested that in leading to a red shift of the strong absorption peak to 297 nm. UV spectra of the carboxylate ion the difference of asymmetric and complexes are practically identical with that of the symmetric stretching vibrations (COO–) may be used ofloxacin (R-form) and levofloxacin ligands but just to indicate its coordination/bong mode [25]. The slightly shifted, indicative of coordination through the separation  (asymm(CO2)–sym(CO2)) of 176–257 cm–1 pyridone oxygen and one carboxylate oxygen [22]. As range may specify the mode of monodentate expected, these complexes are diamagnetic in nature. coordination for carboxylate moiety [26]. Thus, No d–d transitions are observed for these complexes disappearance of peak at 1719 cm–1 in levfloxacin may consistent with d0 configuration. give rise to two strong peaks at 1584 cm–1 and 1408 cm–1 in Mo–levofloxacin complex, with difference of The complexes of levofloxacin and ofloxacin (R- 176 cm–1 indicating monodentate coordination mode of form) characterized by FT-IR show obvious changes in carboxylate ion. their spectra relative to complexes. Levofloxacin and Mo–Levofloxacin Complex
Metal carboxylates show a very strong band due to carboxylic C=O, which may be replaced by two peaks symmetric stretch asymmetric strectch generated from asymmetrical and symmetrical stretchings of COO– group. Because both C–O groups show equal bond orders for carboxylate ion caused by The dioxomolybdenum(VI) complex of levofloxacin electron delocalization. Since, degree of interaction shows two absorptions for (Mo=O) indicating cis between metal centre and coordinated carboxylate arrangement of two oxygen atoms around Mo atom group may affect delocalization as a result stretching [27] for asym(MoO2) and sym(MoO2) stretches to frequencies of carboxylate ions as well [23]. confirm the formation of mononuclear complex [28] with Levofloxacin shows two characteristic absorption peaks a cis–[MoO2]2+ core [29]. Thus, dioxomolybdenum(VI) at 1719 and 1623 cm–1 for C=O of carboxylic acid prefers to form complex of cis arrangement by oxygen and keto oxygen of levofloxacin ring, maximum utilization of d–orbital or d groups for Synthesis, Characterization and Microbial Evaluation of Metal Complexes
Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1 5
Figure 3: IR spectra of a) Levofloxacin and b) Mo–levofloxacin complex.
bonding [30]. The cis arrangement in Mo-levofloxacin for carboxylic proton. In both complexes signal of may be characterized by two IR bands at 941 and 902 carboxylic proton is vanished, which is present in both cm–1 for asym(O=Mo=O) and sym(O=Mo=O) in C2V the ligands before complexation in ofloxacin (R-form) at symmetry, respectively [31]. The trans–MoO 2+ 11.27 ppm and in levofloxacin at 11.15 ppm. But these give rise single strong IR active peak for as(O=Mo=O) signals are absent in molybdenum complexes [21]. [32] but this configuration is rarely exhibited by metal Whereas, aryl protons appeared downfield in dioxo complexes. The peaks at 703 and 665 cm–1 may complexes. In case of levofloxacin complex, there is be attributed to Mo–O bonds for metal and ring downfield shift of aryl protons i.e. from 8.05 to 8.27 for 2H, and 7.51 to 7.75 ppm for 5H. While for ofloxacin (R-form) it is 9.25 to 9.59 and 7.70 to 7.97 ppm, Ofloxacin (R-form) and its Molybdenum Complex
respectively [15]. The negligible shift of hardly 0.2 to 0.3 ppm is taking place in aryl protons [34] perhaps After comparing IR absorptions of ofloxacin (R-form) either due to coordination causing change in with its molybdenum complex, these main conclusions configuration of complexes as compared to ligands. It were obtained: (1) ofloxacin (R-form) shows two strong also indicated that coordination has changed the absorption peaks at 1710 cm–1 for (C=O)c and 1618 magnetic environment of aromatic ring protons [35]. cm–1 (C=O)p; (2) the carboxylic band shifted to 1701 cm–1 in complex spectrum shows the involvement of The piperazine and aliphatic protons remain almost this moity in complexation (3) In addition, techniques unchanged. It is because these protons are lying show no definite conclusion regarding the involvement significantly far from the coordination sites in both of ketone group in complex formation. Band at 1618 ligands. Hence, they are not affected at all. It cm–1 in ofloxacin (R-form) ligand molecule may appear suggested that –COOH group is involved in at 1626 cm–1 is either due to carboxyl or ketone group coordination with metal ion by replacement of its for bonding metal ion [3]. However, suggested changes proton. Hence coordination takes place in molybdenum in the spectrum of complex relative to ofloxacin (R- and drug ligands via vicinal carbonyl and carboxyl form) alone may recommend the coordination of groups. Because almost all the signals observed in ofloxacin (R-form) with metal ion through carboxylate ligand protons are present in complexes at same place and pyridone oxygens. There two strong absorption as in ligand drug molecules expect disappearance of bands for cis arrangement of MoO 2+ may arise at 904 carboxylic protons [36]. Thus, it supports the results and 940 cm–1 for symmetricl and symmetrical vibration obtained from FT-IR spectroscopy that metal ions [27] resulting from the cis–dioxo Mo cores [33]. coordinates to drug molecules through carboxylic and pyridone oxygen atoms. The structure of molybdenum The 1H NMR study was carried out to support the complexes of ofloxacin (R-form) and levofloxacin is coordination of molybdenum to both ligands ofloxacin given in Figure 4.
(R-form) and levofloxacin. But, it was observed that only one major change is observed in the spectra of The thermal analysis (TG, DTA) was performed in complexes relative to their ligands. That change was order to establish the thermal stability of these

6 Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1
Panhwar and Memon
Figure 4: Chemical Structures of a) [MoO2(R-Oflox)2] and b) [MoO2(Levo)2] complexes.
complexes during the pharmaceutical development complex at this stage suffers from loss of some species in its structure. It is likely that some part of the bulky ligand molecule is lost at this stage. The third weight loss occurs between the 350 to 550 ºC being approximately equal to 36.5%. This part of curve In the case of Mo–ofloxacin (Figure 5), the first
reflects slow loss showing no apparent signs of stage shows slow weight loss between ambient to 260 decomposition. The bulky molecule in this region ºC due to the loss of moisture/residual solvents, but the shows good stability and volatility (that does not break TG trace in this region also reflects the decreased rate move as a whole). During this stage weight loss and at which solvent molecules undergo loss. This may volatalisation of degradation product take place rapidly. probably be due to the trapping of solvent molecules in Beyond, 400°C the weight loss is about 6–7%. DTA the molecular network of the ofloxacin (R-form). The shows that it undergoes glass transition, shows melting trace also shows two subsequent small weight losses endotherm, undergoes decomposition and finally of the magnitude less than 6% between 260 to 300 ºC. volatilization endotherm accompanied by swelling of This stage is onset of decomposition and it is likely that bulky organic molecule. DTG shows at first the Figure 5: TG–DTG of Mo–Ofloxacin (R-form) complex.

Synthesis, Characterization and Microbial Evaluation of Metal Complexes
Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1 7
moisture/solvent, then for 1st break Ti at 260, Tmax at overtone concept and Tweedy's chelation theory. 290, Tf at 360 ºC, for 2nd break Ti at 265, Tmax at 355, Overtone concept of cell permeability states that and Tf at 510 º C. However, there is a continuous antibacterial action is controlled by liposolubility decomposition upto 565 ºC. because from lipid membrane (surrounding cells) only lipid soluble materials are allowed to pass through it. Chelation/complexation greatly reduces the metal ion's polarity because ligand orbitals may overlap and may In the case of Mo–levofloxacin, this shows the partly share the +ve charge of metal ion with donor thermal events similar to ofloxacin (R-form) complex, groups. That causes to increase the delecalization of but there is difference of temperatures in both of the /n–electrons over the chelate ring as a whole and endothermic traces. It has degree of glass transition lipophilicity of complexes/coordination compounds may different as well as slow melting along with slow weight increase. Hence higher lipophilicity may increase the penetration of complexes through lipid membranes and thus in microorganisms metal binding sites in enzymes The antibacterial activity of drug molecules and their respective complexes was carried out. From the are blocked. The respiration process of cell has also results, it was observed that the antibacterial action of been disturbed by the complexes that cause the blockage of protein synthesis that inhibits the more all the compounds was higher against s. aureus (Figure growth of organisms [37]. Difference in antibacterial 6) relative to E. Coli and the antibacterial action of both
activity of various complexes against various the complexes is higher than their corresponding microorganisms may either depend upon cells ligands. While the activity of levofloxacin is higher than ofloxacin (R-form). Because former is known to a very impermeability of microbes or ribosomal differences of effective antibacterial agent. Similarly the molybdenum microbial cells. Table 1 indicates the antibacterial
activities results.
complex of levofloxacin has higher activity than ofloxacin (R-form) complex. Table 1: Zone of Inhibition (mm) of Ofloxacin (R-form)
and Levofloxacin and their Molybdenum Metal
Complexes against a Gram +ve and Gram –ve
Bacterial Cultures

Bacterial species
Compounds Concentration
S. aureus
E. coli
Ofloxacin (R-form) 20 Mo-Ofloxacin 20 g mL-1 22 17 Levofloxacin 20 g mL-1 21 18 Mo-Levofloxacin 20 g mL-1 23 18 Control (DMSO) In the case of E.coli, the antibacterial action of both Figure 6: Relative inhibitory action of 2) Mo–ofloxacin (R-
the ligands is comparable with their complexes. In form), 3) ofloxacin (R-form), 4) Mo–levofloxacin, 5) levofloxacin, and c) control (DMSO) against S. aureus in general, position as well as nature of substituents Muller Hunton Agar medium. attached to phenyl rings is decisive for their antimicrobial activities. Hence, the lesser antibacterial The metal complex showing better antimicrobial activities of complexes may account for their lower lipid activity than the parent drug may have potential to be solubility. Thus, it is difficult for metal ion to reach at used as antibacterial and must be explored further [18]. desirable site of action for interfering normal activity of Thus, levofloxacin and its complex have more inhibitory cell. Since, nature of metal ion has key role to action relative to ofloxacin (R-form) and its Mo determine the antimicrobial activities [38]. complex. It shows that antibacterial activity of metal complex is higher than uncomplexed ligand. Anyway, CONCLUSIONS
increased antibacterial action of metal chelate of Mo–levofloxacin relative to uncomplexed drug ligand can be It has been concluded from the study that a explicated on the basis of metal's oxidation state, complex of suitable geometry was formed between 8 Journal of Modern Medicinal Chemistry, 2014 Vol. 2, No. 1
Panhwar and Memon
molybdenum and ofloxacin (R-form and S-form) drug drugs ofloxacin and norfloxacin: structure, DNA– and albumin–binding. J Inorg Biochem 2012; 117: 35-47. molecules. The resulting complexes were characterized by different analytical techniques such as Mohd A, Khan AAP, Bano S, Siddiqi KS. Interaction and UV-Vis, FT-IR and 1H NMR. From the data obtained fluorescence quenching study of levofloxacin with divalent toxic metal ions. Eurasian J Anal Chem 2010; 5: 177-86. through these techniques, the molecular formula of the Azcurra AI, Yudi LM, Baruzzi AM, Kakiuchi T. Interfacial complexes was established as MoO2(L)2, which is behavior of ofloxacin–Fe(III) complex at the water /1,2– consistent with obtained results. The dioxomolybdenum dichloroethane interface: a voltfluorometric and chronofluorometric study. J Electroanal Chem 2001; 506: complexes were of cis configuration in both cases, where the metal ion was coordinated via carboxylate and pyridone oxygens in both cases. Antibacterial De PK, Sahana B, Rakshit S. Enhancement of dissolution results demonstrated that molybdenum complexes of rate and stability study of ofloxacin solid dispersion. Der Pharmacia Sinica 2011; 2: 169-81. ofloxacin (R-form and S-form) were more active than [14] Macıas B, Villa MV, Rubio I, Castineiras A, Borras J. uncomplexed drug against S. Aureus, but they do not Complexes of Ni(II) and Cu(II) with ofloxacin Crystal structure show any effect against E. Coli. of a new Cu(II) ofloxacin complex. J Inorg Biochem 2001; 84: 163-70. Sultana N, Arayne MS, Rizvi SBS, Haroon U, Mesaik MA. Synthesis, spectroscopic, and biological evaluation of some We are thankful to National Centre of Excellence in levofloxacin metal complexes. Med Chem Res 2013; 22: 1371-7. Analytical Chemistry, Department of Microbiology, and Institute of Advanced Studies and Research, University [16] Drevensek P, Kosmrlj J, Giester G, et al. X–Ray of Sindh, Jamshoro/Pakistan for providing necessary crystallographic, NMR and antimicrobial activity studies of facilities to complete this work. magnesium complexes of fluoroquinolones–racemic ofloxacin and its S–form, levofloxacin. J Inorg Biochem 2006; 100: 1755-63. REFERENCES
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Voter Turnout and Fiscal Policy Raphael Godefroy and Emeric Henry Though a large literature on causes of voter turnout has flour- ished, there is scant evidence on consequences of turnout on policiesimplemented in practice. Using data on French municipalities, andinstrumental variables for turnout based on rainfall and influenza in-cidence, we estimate that a 1 percent increase in turnout decreasesthe municipal budget by more than 2 percent. This effect is medi-ated by a decrease in sales and purchases of physical assets. Witha model of electoral competition, we show that a party with a lowbudget platform has a numerical advantage causing its win whenturnout is high.

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21 de Noviembre de 2005 Nota: La siguiente información no representa ninguna posición oficial de la Secretaría de Agricultura Ganadería, Desarrollo Rural, Pesca y Alimentación (SAGARPA), del Departamento de Agricultura de los Estados Unidos (USDA) ni de industrias avícolas de los Estados Unidos o México tales como USAPEEC o la Unión Nacional de Avicultores.