Research Article Synthesis, Physicochemical Properties

Research ArticleSynthesis Physicochemical Properties andAntimicrobial Studies of Iron (III) Complexes ofCiprofloxacin Cloxacillin and Amoxicillin

Fabian I Eze1 Uzoechi Ajali1 and Pius O Ukoha2

1 Department of Pharmaceutical and Medicinal Chemistry University of Nigeria Nsukka 410001 Nigeria2 Department of Pure and Industrial Chemistry University of Nigeria Nsukka 410001 Nigeria

Correspondence should be addressed to Fabian I Eze ezeifeanyifabyahoocom

Received 23 August 2014 Revised 30 October 2014 Accepted 30 October 2014 Published 19 November 2014

Academic Editor Hussein El-Subbagh

Copyright copy 2014 Fabian I Eze et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Iron (III) complexes of ciprofloxacin amoxicillin and cloxacillin were synthesized and their aqueous solubility profiles relativestabilities and antimicrobial properties were evaluatedThe complexes showed improved aqueous solubility when compared to thecorresponding ligands Relative thermal and acid stabilities were determined spectrophotometrically and the results showed thatthe complexes have enhanced thermal and acid stabilities when compared to the pure ligands Antimicrobial studies showed thatthe complexes have decreased activities againstmost of the testedmicroorganisms Ciprofloxacin complex however showed almostthe same activity as the corresponding ligand Jobrsquos method of continuous variation suggested 1 2 metals to ligand stoichiometryfor ciprofloxacin complex but 1 1 for cloxacillin complex

1 Introduction

Manydrugs possessmodified pharmacological toxicologicaland physicochemical properties when administered in theform of metal complexes [1] Physicochemical properties ofdrugs are very pertinent to dosage forms and drug deliveryand complex formation affects these properties sometimesto advantage and sometimes adversely Among the propertiesthat may be altered upon complex formation are solubil-ity energy absorption stability partitioning behaviour andchemical reactivity [2ndash4] For many systems it has beenshown that the complex provides faster dissolution andgreater bioavailability than the physicalmixtureThe process-ing characteristics (physical state stability flow ability etc) ofthe complexes may also be better than those of the free drugs[5] In some cases complexation has been found to improvebiological activity [6ndash11]

Quinolones are complexing agents for a variety of metalions including alkaline earth and transition metal ionsReports indicate that the coordination of quinolones tometalions such as Cu (II) Mg (II) and Ca (II) appears to beimportant for the activity of the quinolone antibiotics [11ndash13] Coordination compoundsmay also release valuable trace

elements needed for maintenance of life when they areadministered as drugs

The structure-activity relationship of drugs could bepredicted by complexation If a particular biological activityof a drug is lost or diminished on complexation with metalions it would be reasonable to suggest that one ormore of thegroups bonded to themetal is necessary for the activity Drugcomplexation experiments can also help medicinal chemiststo predict some dosage form incompatibilities explain themode of action of some drugs and devise new methods ofdrug analysis

2 Materials and Methods

21 Chemicals and Equipment All chemicals and solventsused were AnalaR grade All melting points were takenon a melting point apparatus (Electrothermal England)Magnetic stirrer (Gallenkamp England) UV-visible spec-trometer (Jenway 6305 Barlowood Sci Ltd Dunmow) pHmeter (Jenway Dunmou) and electronic weighing balance(Adventurer OHAUS Corp China) were used

Hindawi Publishing CorporationInternational Journal of Medicinal ChemistryVolume 2014 Article ID 735602 6 pageshttpdxdoiorg1011552014735602

2 International Journal of Medicinal Chemistry

22 Microorganisms Clinical isolates of the following mi-croorganisms Staphylococcus aureus Pseudomonas aerug-inosa Bacillus subtilis Escherichia coli Salmonella typhiShigella spp Aspergillus niger and Candida albicans wereused They were maintained in the Department of Pharma-ceutics University of Nigeria Nsukka Nigeria

23 Synthesis of Iron (III) Complex of Ciprofloxacin Cipro-floxacinHCl (1mmole) was dissolved in aminimumquantityof distilled water To this solution FeCl

3(05mmole) dis-

solved in absolute ethanol was addedThemixturewas stirredcontinuously with magnetic stirrer at room temperature for3 hours The resulting red solution was transferred into anevaporating dish and allowed to evaporate slowly at roomtemperature for one week The red crystals formed werepurified by recrystallizing in a minimum quantity of ethanoland weighed

24 Synthesis of Iron (III) Complex of Cloxacillin Cloxacillinpowder (1mmole) was dissolved in dioxane (100mL) Tothis solution an ethanolic FeCl

3solution containing 1625mg

of FeCl3in ethanol (10mL) was added The mixture was

stirred continuously for 4 hours at room temperature atthe end of which clay-brown crystals separated from thesolution The mixture was filtered and the crystals werewashed thoroughly with dioxane dried in a desiccator andweighed

25 Synthesis of Iron (III) Complex of Amoxicillin Amoxi-cillin powder (1mmole) was dissolved in methanol (100mL)in a beaker FeCl

3(1mmole) was put in another beaker

containing ethanol (10mL) The two solutions were put in around bottom flask and stirred with a magnetic stirrer underreflux maintained at 40∘C for 4 hours The resulting greensolution which was foaming was transferred into an openbeaker and allowed to stand for 1 week The green crystalsobtained were washed thoroughly with small quantity ofethanol dried and weighed

26 Determination of Stoichiometry of the Complexes Jobrsquosmethod of continuous variation [14 15] was followed Amixture of each ligand and ferric chloride solutionwas stirredfor 3 hours and allowed to equilibrate The absorbances wereread at the 120582-max of each complex

27 Determination of Aqueous Solubility Saturated solution(10mL) of each of the complexes and ligands at ambient tem-perature (28∘C) was evaporated to dryness in an evaporatingdish The mass of the solid left in each case was determinedThe solubilities were calculated using the relation [16]

119878 =massvolume

times 1000 (1)

The solubilities of the complexes were compared with thoseof the ligands

28 Thermal and Acid Stabilities The relative thermal andacid stabilities of the complexes were determined spectro-metrically Dilute solutions (01mgmL) were prepared their

absorption spectra were generated and the 120582-max in eachcase was noted The solution of each complex was dividedinto seven equal portions and the temperature regulated to20∘C 30∘C 40∘C 50∘C 60∘C 70∘C and 80∘C respectivelyfor a period of 24 hours The absorbance in each case wasthen measured Similarly the same concentration of thesesolutions was prepared at the pH range of 1ndash6 and theabsorbance was measuredThese changes in absorbance withtemperature and pH assuming that Beer-Lambertrsquos law isobeyed are a measure of the stability of the complexes

29 Antimicrobial Studies on the Complexes The ligands andcomplexes were assayed for antimicrobial activity by the agarwell diffusion [17 18] and dilution methods respectively[19ndash21] The culture media employed were nutrient agarfor bacteria and Sabouraudrsquos dextrose agar for fungi Themicroorganisms had been maintained by weekly subcul-turing and incubation A 24-hour old culture of each testorganism was employed A constant cell population sizeof 106CFUmL was used throughout the studies The cellsize was established by dilution and standardization throughcomparison with MacFalan optical density

Solution of the complexes and pure ciprofloxacin HClwere made in distilled water and those of other ligands inDMSO Each sample was tested at the same concentrationlevel of 5mgmL The plates were incubated at 32∘C for 24hours (for bacteria) and at 25∘C for 48 hours (for fungi)Double determination was made for each sample and meanvalues of clear inhibition zone diameter (IZD)weremeasuredand recorded Six dilutions of each of the solutions of ligandsand complexes weremade and the IZDof eachwasmeasuredA linear plot of IZD2 against logarithm of concentrationwas obtained for each organism and test sample and theminimum inhibitory concentration (MIC) was determined

3 Results and Discussions

31 Yield and Physical Properties The percentage yield andsome physical properties of the iron (III) complexes ofciprofloxacin (CPF-Fe3+) cloxacillin (Clox-Fe3+) and amox-icillin (Amox-Fe3+) are given inTables 1 and 2The solubilitieswere determined at 28∘C

32 Relative Thermal Stability The absorbance of 01mgmLsolutions of each of the ligands and their iron (III) complexesat different temperatures is given in Tables 3 and 4 Thesechanges in absorbance with temperature are a measure of thethermal stability of the drugs

33 Relative Acid Stability The absorbance of 01mgmLsolution of each of the ligands and their iron (III) complexesat different pHs is given in Tables 5 and 6 The changes inabsorbance with pH are a measure of the acid stability of thecompounds

Complexation offers a useful means of manipulation ofthe redox potentials of drug molecules which determinesreactivity and hence the stability of the molecules [4] Thehigher the redox potential of a substance the more the

International Journal of Medicinal Chemistry 3

Table 1 Yield and physical properties of the iron (III) complexes

Percentage yield () Melting point (∘C) 120582-max (nm) Metal-ligand stoichiometry Estimated molecular weight (gmolminus1)CPF-Fe3+ 80 172 443 1 2 891Clox-Fe3+ 95 150 385 1 1 586Amox-Fe3+ 635 142 440 mdash mdash

Table 2 Aqueous solubility

Compound Solubility (gdmminus3)Pure ligand Fe3+ complex

Ciprofloxacin ≪1 gt5Cloxacillin Negligible 18Amoxicillin Negligible 20

reactivity and hence lower stability and vice versa Fromthe results of absorbance of the complexes and ligands atdifferent temperatures and pH the differences in absorbancewere very significant in the ligands but not very significantin the complexes even at very drastic conditions (80∘C andpH 1) This shows that the concentration of these complexeswas still high at such adverse conditions This may be as aresult of the greater ability of the complexes to withstandacidmedium (less ease of acid hydrolysis) Pure ciprofloxacinand penicillins are not appreciably stable in aqueous and acidmedia Therefore we can conclude that these complexes aremore stable than the pure ligands and hence have advantageover the ligands as drugs

34 Results of Antimicrobial Studies The inhibition zonediameter (IZD) and minimum inhibitory concentration(MIC) of the ligands and complexes are given in Tables 7 and8 respectively

Ciprofloxacin complex shows improved antibacterialactivity against Staphylococcus aureus and Bacillus subtiliswhen compared to that of the ligand It had almost thesame activity against Pseudomonas aeruginosa Escherichiacoli and Shigella spp as the ligand and lower activityagainst Salmonella typhi when compared to that of theligand as shown in the MIC result Iron (III) complexes ofcloxacillin and amoxicillin showed decreased antibacterialand antifungal activities when compared to those of thecorresponding ligands This could be attributed to loss ofsome essential pharmacophoric moieties due to coordinationwith the metal ionThe sites used for dative bonding with thecentral metal ion are no longer available for binding with thebiological receptors in themicroorganismsThis could also beexplained on the basis of action of some antibiotics Severalantibiotics have the property of forming chelates with metalsions needed for normal functioning of enzyme system inthemicroorganisms rendering them inactiveThe complexedform of the drug is not capable of such chelation sincethe chelation sites are already occupied A deviation fromthe optimal lipophilicity due to increased aqueous solubilitycan also account for the activity

0010203040506070809

1

0 01 02 03 04 05 06 07 08 09 1

Abso

rban

ce

Mole fraction of iron (III)

Figure 1 Jobrsquos plot for ciprofloxacin complex The mole fractionof iron (III) at the intersection of the two straight lines is 032The mole ratio is 32 68 which corresponds to 1 2 metal-ligandstoichiometry

0

005

01

015

02

025

03

035

04

045

0 01 02 03 04 05 06 07 08 09 1

Abso

rban

ce


Figure 2 Jobrsquos plot for cloxacillin complex The mole fractionof iron (III) at the intersection of the two straight lines is 048The mole ratio is 48 52 which corresponds to 1 1 metal-ligandstoichiometry

35 Results of Stoichiometry by Jobrsquos Method of ContinuousVariation Jobrsquos plot for ciprofloxacin and cloxacillin is givenin Figures 1 and 2 respectively while the raw results are givenin Tables 9 and 10 respectively These suggest 1 2 and 1 1metal-ligand stoichiometry respectively

4 Conclusion

Complexation improves the aqueous solubility and ther-mal and acid stabilities of ciprofloxacin cloxacillin andamoxicillin The improvement in solubility can be appliedin parenteral administration of these drugs Loss of these


Table 3 Absorbance of the complexes at different temperatures

Temperature 20∘C 30∘C 40∘C 50∘C 60∘C 70∘C 80∘C 120582-max (nm)ComplexCPF-Fe3+ 0609 0686 0689 0686 0665 0635 0629 443Clox-Fe3+ 0114 0122 0122 0120 0109 0102 0083 385Amox-Fe3+ 0095 0109 0128 0133 0126 0122 0105 440

Table 4 Absorbance of the pure ligands at different temperatures

Temperature 20∘C 30∘C 40∘C 50∘C 60∘C 70∘C 80∘C 120582-max (nm)LigandCiprofloxacin 0348 0362 0311 0240 0170 0104 0081 315Cloxacillin 0721 0727 0683 0455 0337 0190 0184 290Amoxicillin 0661 0664 0643 0428 0369 0312 0126 254

Table 5 Absorbance of the complexes at different pHs

Complex pH 1 pH 2 pH 3 pH 4 pH 5 pH 6 pH 7 120582-max (nm)CPF-Fe3+ 0216 0246 0256 0291 0360 0362 0368 443Clox-Fe3+ 0008 0013 0053 0055 0072 0110 0122 385Amox-Fe3+ 0645 0511 0452 0360 0124 0118 0109 440

Table 6 Absorbance of the ligands at different pHs

Ligand pH 1 pH 2 pH 3 pH 4 pH 5 pH 6 pH 7 120582-max (nm)Ciprofloxacin 0150 0152 0171 0220 0300 0315 0360 315Cloxacillin 0437 0449 0550 0554 0696 0704 0722 290Amoxicillin 0387 0404 0499 0511 0603 0620 0664 254

Table 7 Inhibition zone diameter (in mm)

Ciprofloxacin Cloxacillin AmoxicillinLigand CPF-Fe3+ Ligand Clox-Fe3+ Ligand Amox-Fe3+

S aureus 440 480 315 mdash 300 mdashB subtilis 450 460 320 mdash 300 mdashP aeruginosa 485 480 200 mdash 280 mdashE coli 400 450 280 mdash 330 mdashS typhi 485 110 270 mdash 355 mdashShigella spp 300 270 300 mdash 300 mdashA niger mdash 300 mdash 350 mdashC albicans mdash mdash mdash mdash mdash

Table 8 Minimum inhibitory concentration (MIC) in 120583gmL


S aureus 120 79 125 mdash 125 mdashB subtilis 63 50 125 mdash 125 mdashP aeruginosa 32 32 220 mdash 140 mdashE coli 28 28 145 mdash 125 mdashS typhi 018 177 145 mdash 110 mdashShigella spp 14 125 125 mdash 110 mdashA niger mdash mdash 145 mdash 150 mdashC albicans mdash mdash mdash mdash mdash mdash


Table 9 Absorbance of ciprofloxacin complex at different molefractions of iron (III)

Metal-ligand ratio Mole fraction of Fe3+ Absorbance1 9 01 03372 8 02 06923 7 03 09434 6 04 08825 5 05 07426 4 06 06007 3 07 04538 2 08 02809 1 09 0157

Table 10 Absorbance of cloxacillin complex at different molefractions of iron (III)


drugs to deterioration during storage may be minimized ifthey are stored in the form of their coordination complexesComplexes of these drugs therefore have advantage over thepure drugs due to this inherent stability Oral administrationof these drugs in their complex forms may reduce absorptionin the lipid layers This is because the increased aqueoussolubility would result in lower partition coefficient Coad-ministration of these drugswith iron supplements is thereforediscouraged because complexation may occur in vivo

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors are grateful to Juhel Pharmaceuticals NigeriaLimited Enugu for donating pure analytical samples ofciprofloxacin cloxacillin and amoxicillin

References

[1] GWuGWang X Fu and L Zhu ldquoSynthesis crystal structurestacking effect and antibacterial studies of a novel quaternarycopper (II) complex with quinolonerdquo Molecules vol 8 no 2pp 287ndash296 2003

[2] J J N Silva W R Pavanelli F R Salazar Gutierrez et alldquoComplexation of the anti-Trypanosoma cruzi drug benznida-zole improves solubility and efficacyrdquo Journal of MedicinalChemistry vol 51 no 14 pp 4104ndash4114 2008

[3] A A A De Queiroz E J Franca G A Abraham and J SRoman ldquoDrug complexation and physicochemical propertiesof vinylpyrrolidone-N N1015840-dimethylacrylamide copolymersrdquoJournal of Applied Polymer Science vol 93 no 3 pp 1337ndash13472004

[4] K A Connors ldquoComplex formationrdquo inRemingtonThe Scienceand Practice of Pharmacy R G Alphonso Ed vol 2 pp 183ndash197 University of the Science in Philadelphia 2000

[5] V A Marcolino G M Zanin L R Durrant M D T Benassiand G Matioli ldquoInteraction of curcumin and bixin with 120573-cyclodextrin complexation methods stability and applicationsin foodrdquo Journal of Agricultural and Food Chemistry vol 59 no7 pp 3348ndash3357 2011

[6] S S Konstantinovic B C Radovanovic Z Cakic and V VasicldquoSynthesis and characterization of Co(II) Ni(II) Cu(II) andZn(II) complexes with 3-salicylidenehydrazono-2-indolinonerdquoJournal of the Serbian Chemical Society vol 68 no 8-9 pp 641ndash647 2003

[7] R Kaushal and S Thakur ldquoSyntheses and biological screeningof schiff base complexes of titanium(IV)rdquoChemical EngineeringTransactions vol 32 pp 1801ndash1806 2013

[8] S Arayne N Sultana U Haroon andM AMesaik ldquoSynthesischaracterization antibacterial and anti-inflammatory activitiesof enoxacin metal complexesrdquo Bioinorganic Chemistry andApplications vol 2009 Article ID 914105 6 pages 2009

[9] R Joseyphus and M Nair ldquoAntibacterial and antifungal studieson some schiff base complexes of zinc (II)rdquoMycobiology vol 36no 2 pp 93ndash98 2008

[10] A A Osowole I Ott and O M Ogunlana ldquoSynthesisspectroscopic anticancer and antimicrobial properties of somemetal(II) complexes of (substituted) nitrophenol Schiff baserdquoInternational Journal of Inorganic Chemistry vol 2012 ArticleID 206417 6 pages 2012

[11] E K Efthimiadou G Psomas Y Sanakis N Katsaros and AKaraliota ldquoMetal complexes with the quinolone antibacterialagent N-propyl-norfloxacin synthesis structure and bioactiv-ityrdquo Journal of Inorganic Biochemistry vol 101 no 3 pp 525ndash535 2007

[12] J H Paton and D S Reeves ldquoFluoroquinolone antibioticsMicrobiology pharmacokinetics and clinical userdquo Drugs vol36 no 2 pp 193ndash228 1988

[13] A A Olaniyi EssentialMedicinal Chemistry pp 483ndash526 HopePublications Ibadan Nigeria 3rd edition 2005

[14] C MacKinnon ldquoSpectroscopic determination of a complexionrsquos stoichiometry by Jobrsquos methodrdquo in Inorganic ChemistryLaboratory Manual Lakehead University 2012

[15] C Y Huang ldquoDetermination of binding stoichiometry bythe continuous variation method the job plotrdquo Methods inEnzymology vol 87 pp 509ndash525 1982

[16] J A Ibemesi Physical Chemistry for Tertiary Institutions SnaapPress Enugu Nigeria 1994

[17] U Ajali and F B C Okoye ldquoAntimicrobial and anti-inflammatory activities of Olax viridis root bark extracts andfractionsrdquo International Journal of Applied Research in NaturalProducts vol 2 no 1 pp 27ndash32 2009

[18] C Valgas S M de Souza E F A Smania and A SmaniaJr ldquoScreening methods to determine antibacterial activity of


natural productsrdquo Brazilian Journal of Microbiology vol 38 no2 pp 369ndash380 2007

[19] D A Vanden Berghe and A J Vlietinck ldquoScreening methodsfor antibacterial and antiviral agents from higher plantsrdquo inMethods in Plant Biochemistry P M Dey and J D HarboneEds pp 47ndash69 Academic Press London UK 1991

[20] A Smania F D Monache E F A Smania and R SCuneo ldquoAntibacterial activity of steroidal compounds iso-lated from Ganoderma applanatum (Pers) Pat (Aphyllophoro-mycetideae) Fruit bodyrdquo International Journal of MedicinalMushrooms vol 1 no 4 pp 325ndash330 1999

[21] V Lovian Antibiotics in Laboratory Medicines vol 7 Williamsand Williams Baltimore Md USA 1980

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

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Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


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Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


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Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


22 Microorganisms Clinical isolates of the following mi-croorganisms Staphylococcus aureus Pseudomonas aerug-inosa Bacillus subtilis Escherichia coli Salmonella typhiShigella spp Aspergillus niger and Candida albicans wereused They were maintained in the Department of Pharma-ceutics University of Nigeria Nsukka Nigeria

23 Synthesis of Iron (III) Complex of Ciprofloxacin Cipro-floxacinHCl (1mmole) was dissolved in aminimumquantityof distilled water To this solution FeCl

3(05mmole) dis-

solved in absolute ethanol was addedThemixturewas stirredcontinuously with magnetic stirrer at room temperature for3 hours The resulting red solution was transferred into anevaporating dish and allowed to evaporate slowly at roomtemperature for one week The red crystals formed werepurified by recrystallizing in a minimum quantity of ethanoland weighed

24 Synthesis of Iron (III) Complex of Cloxacillin Cloxacillinpowder (1mmole) was dissolved in dioxane (100mL) Tothis solution an ethanolic FeCl

3solution containing 1625mg

of FeCl3in ethanol (10mL) was added The mixture was

stirred continuously for 4 hours at room temperature atthe end of which clay-brown crystals separated from thesolution The mixture was filtered and the crystals werewashed thoroughly with dioxane dried in a desiccator andweighed

25 Synthesis of Iron (III) Complex of Amoxicillin Amoxi-cillin powder (1mmole) was dissolved in methanol (100mL)in a beaker FeCl

3(1mmole) was put in another beaker

containing ethanol (10mL) The two solutions were put in around bottom flask and stirred with a magnetic stirrer underreflux maintained at 40∘C for 4 hours The resulting greensolution which was foaming was transferred into an openbeaker and allowed to stand for 1 week The green crystalsobtained were washed thoroughly with small quantity ofethanol dried and weighed

26 Determination of Stoichiometry of the Complexes Jobrsquosmethod of continuous variation [14 15] was followed Amixture of each ligand and ferric chloride solutionwas stirredfor 3 hours and allowed to equilibrate The absorbances wereread at the 120582-max of each complex

27 Determination of Aqueous Solubility Saturated solution(10mL) of each of the complexes and ligands at ambient tem-perature (28∘C) was evaporated to dryness in an evaporatingdish The mass of the solid left in each case was determinedThe solubilities were calculated using the relation [16]

119878 =massvolume

times 1000 (1)

The solubilities of the complexes were compared with thoseof the ligands

28 Thermal and Acid Stabilities The relative thermal andacid stabilities of the complexes were determined spectro-metrically Dilute solutions (01mgmL) were prepared their

absorption spectra were generated and the 120582-max in eachcase was noted The solution of each complex was dividedinto seven equal portions and the temperature regulated to20∘C 30∘C 40∘C 50∘C 60∘C 70∘C and 80∘C respectivelyfor a period of 24 hours The absorbance in each case wasthen measured Similarly the same concentration of thesesolutions was prepared at the pH range of 1ndash6 and theabsorbance was measuredThese changes in absorbance withtemperature and pH assuming that Beer-Lambertrsquos law isobeyed are a measure of the stability of the complexes

29 Antimicrobial Studies on the Complexes The ligands andcomplexes were assayed for antimicrobial activity by the agarwell diffusion [17 18] and dilution methods respectively[19ndash21] The culture media employed were nutrient agarfor bacteria and Sabouraudrsquos dextrose agar for fungi Themicroorganisms had been maintained by weekly subcul-turing and incubation A 24-hour old culture of each testorganism was employed A constant cell population sizeof 106CFUmL was used throughout the studies The cellsize was established by dilution and standardization throughcomparison with MacFalan optical density

Solution of the complexes and pure ciprofloxacin HClwere made in distilled water and those of other ligands inDMSO Each sample was tested at the same concentrationlevel of 5mgmL The plates were incubated at 32∘C for 24hours (for bacteria) and at 25∘C for 48 hours (for fungi)Double determination was made for each sample and meanvalues of clear inhibition zone diameter (IZD)weremeasuredand recorded Six dilutions of each of the solutions of ligandsand complexes weremade and the IZDof eachwasmeasuredA linear plot of IZD2 against logarithm of concentrationwas obtained for each organism and test sample and theminimum inhibitory concentration (MIC) was determined

3 Results and Discussions

31 Yield and Physical Properties The percentage yield andsome physical properties of the iron (III) complexes ofciprofloxacin (CPF-Fe3+) cloxacillin (Clox-Fe3+) and amox-icillin (Amox-Fe3+) are given inTables 1 and 2The solubilitieswere determined at 28∘C

32 Relative Thermal Stability The absorbance of 01mgmLsolutions of each of the ligands and their iron (III) complexesat different temperatures is given in Tables 3 and 4 Thesechanges in absorbance with temperature are a measure of thethermal stability of the drugs

33 Relative Acid Stability The absorbance of 01mgmLsolution of each of the ligands and their iron (III) complexesat different pHs is given in Tables 5 and 6 The changes inabsorbance with pH are a measure of the acid stability of thecompounds

Complexation offers a useful means of manipulation ofthe redox potentials of drug molecules which determinesreactivity and hence the stability of the molecules [4] Thehigher the redox potential of a substance the more the










0010203040506070809

1

0 01 02 03 04 05 06 07 08 09 1

Abso

rban

ce



0

005

01

015

02

025

03

035

04

045

0 01 02 03 04 05 06 07 08 09 1

Abso

rban

ce




4 Conclusion

























Acknowledgment


References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of










0010203040506070809

1

0 01 02 03 04 05 06 07 08 09 1

Abso

rban

ce



0

005

01

015

02

025

03

035

04

045

0 01 02 03 04 05 06 07 08 09 1

Abso

rban

ce




4 Conclusion

























Acknowledgment


References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of
























Acknowledgment


References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of









Acknowledgment


References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of










Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

Documents

Research Article Synthesis, Physicochemical Properties