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Hindawi Publishing CorporationJournal of ChemistryVolume 2013 Article ID 517420 8 pageshttpdxdoiorg1011552013517420

Research ArticleSynthesis and In Vitro Antioxidant Evaluation of New135-Tri-2-methoxy-4-[(45-dihydro-1119867119867-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Benzene Derivatives

H Yuksek O Akyildirim and O Gursoy Kol

Department of Chemistry Kaas University 36100 Kars Turkey

Correspondence should be addressed to O Gursoy Kol gursoyozlemyahoocom

Received 18 February 2012 Revised 3 May 2012 Accepted 12 June 2012

Academic Editor Brijesh Tiwari

Copyright copy 2013 H Yuksek et al is 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

Nine new 45-dihydro-1H-124-triazol-5-one derivatives were synthesized and characterized by elemental analyses and IR 1H-NMR 13C-NMR and UV spectral data e synthesized compounds were analyzed for their in vitro potential antioxidantactivities in three different methods ose antioxidant activities were compared to standard antioxidants such as BHA BHTand 120572120572-tocopherol Compounds 4e 5a and 5d showed best activity for iron binding In addition the compounds 4 were titratedpotentiometrically with tetrabutylammonium hydroxide (TBAH) in four non-aqueous solvents (isopropyl alcohol tert-butylalcohol acetone and NN-dimethyl formamide) us the half-neutralization potential values and the corresponding p119870119870a valueswere determined in all cases

1 Introduction

124-Triazole and 45-dihydro-1H-124-triazol-5-one deriv-atives are reported to possess a broad spectrum of biologicalactivities such as antibacterial antifungal anti-inammatoryantioxidant and anticancer [1ndash9] In addition several arti-cles reporting the synthesis of some N-arylidenamino-45-dihydro-1H-124-triazol-5-one derivatives have been pub-lished [7 8 10ndash13]e acetylation of 45-dihydro-1H-124-triazol-5-one derivatives have also been reported [12ndash14]

Furthermore antioxidants have extensively been stud-ied for their capacity to protect organism and cell fromdamage that are induced by oxidative stress Scientists havebecome more interested in new compounds they haveeither synthesized or obtained from natural sources thatcould provide active components to prevent or reduce theimpact of oxidative stress on cell [15] Exogenous chemicalsand endogenous metabolic processes in human body or infood system might produce highly reactive free radicalsespecially oxygen-derived radicals which are capable ofoxidizing biomolecules resulting in cell death and issuedamage Oxidative damages signicantly play a pathologi-cal role in human diseases Cancer emphysema cirrhosisatherosclerosis and arthritis have all been correlated with

oxidative damage Also excessive generation of ROS inducedby various stimuli which exceeds the antioxidant capacityof the organism leads to a variety of pathophysiologicalprocesses such as inammation diabetes genotoxicity andcancer [16] In the present study due to a wide range ofapplications to nd their the possible radical scavenging andantioxidant activity the newly synthesized compounds wereinvestigated using different antioxidant methodologies 11-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavengingreducing power and metal chelating activities

Besides it is known that 124-triazole and 45-dihydro-1H-124-triazol-5-one rings have weak acidic properties sothat some 124-triazole and 45-dihydro-1H-124-triazol-5-one derivatives were titrated potentiometrically with tetra-butylammoniumhydroxide (TBAH) in nonaqueous solventsand the p119870119870a values of the compounds were determined [7 810 12 13 17 18]

2 Experimental

Chemical reagents used in this study were purchased fromMerck AG Aldrich and Fluka e starting materials 3andashgwere prepared from the reactions of the corresponding ester

2 Journal of Chemistry

ethoxycarbonylhydrazones 2andashg with an aqueous solutionof hydrazine hydrate as described in the literature [14 19]Melting points were determined in open glass capillariesusing an electrothermal digital melting point apparatus andare uncorrected e IR spectra were recorded on a Perkin-Elmer Instruments Spectrum One FT-IR spectrometer 1Hand 13C NMR spectra were recorded in deuterated dimethylsulfoxide with TMS as internal standard using a VarianMercury spectrometer at 200MHz and 50MHz respectivelyUV absorption spectra were measured in 10mm quartz cellsbetween 200 and 400 nm using a Schimadzu-1201 UVVISspectrometer Extinction coefficients (120576120576) are expressed in L sdotmolminus1 sdot cmminus1 Elemental analyses were carried out on an Leco932 Elemental Combustion System (CHNS-O) for C H andN

21 General Procedure for the Synthesis of Compounds 43-Methoxy-4-hydroxybenzaldehyde (003mol) dissolved inethyl acetate (100mL) was treated with 135-benzenetri-carbonyl chloride (001mol) and to this solution was slowlyadded triethylamine (003mol) with stirring at 0ndash5∘CStirring was continued for 2 h and then the mixture wasreuxed for 3 h and ltered e ltrate was evaporatedin vacuo and the crude product was washed with waterand recrystallized from ethanol to afford compound 1 mp137∘C IR (KBr) (120592120592 cmminus1) 2850 and 2739 (CHO) 1748 1700(C=O) 1274 (COO) 1H NMR (DMSO-d6) 120575120575 387 (s 9H3OCH3) 756ndash764 (m 9H ArH) 901 (s 3H ArH) 999 (s3H CHO) 13CNMR (DMSO-d6) 120575120575 5606 (3OCH3) [11190(2C) 12352 (3C) 12363 (3C) 13021 (4C) 13546 (4C)14357 (4C) 15126 (4C)] (Ar-C) 16163 (3COO) 19198(3CHO) UV 120582120582max (120576120576) 304 (9298) 256 (26386) 222 (39042)212 (35722) nme corresponding compound 3 (0003mol)was dissolved in acetic acid (15mL) and treated with 135-tri-(2-methoxy-4-formylphenoxycarbonyl)-benzene 1(0001mol) e mixture was reuxed for 15 h and thenevaporated at 50ndash55∘C in vacuo Several recrystallizations ofthe residue from AcOH-H2O (1 3) gave pure compounds135-tri-2-methoxy-4-[(3-alkylaryl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-benzene4 as colorless crystals

211 135-Tri-2-methoxy-4-[(3-methyl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Benzene(4a) Yield 067 g (74) mp 174∘C IR (KBr) 3223 (NH)1751 1715 1705 (C=O) 1602 (C=N) 1271 (COO) cmminus11H NMR (DMSO-d6) 120575120575 229 (s 9H 3CH3) 386 (s 9H3OCH3) 745ndash768 (m 9H Ar-H) 902 (s 3H Ar-H) 975(s 3H 3N=CH) 1186 (s 3H 3NH) UV 120582120582max (120576120576) 310(41762) 262 (37725) 222 (64713) nm

212 135-Tri-2-methoxy-4-[(3-ethyl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Benzene(4b) Yield 072 g (76) mp 319∘C IR (KBr) 3220 (NH)1750 1703 (C=O) 1600 (C=N) 1271 (COO) cmminus1 1HNMR(DMSO-d6) 120575120575 118 (t 9H 3CH3119869119869 119869 1198691198691198692Hz) 270 (q 6H3CH2119869119869 119869 1198691198691198692Hz) 388 (s 9H 3OCH3) 734ndash769 (m 9H

Ar-H) 902 (s 3H Ar-H) 975 (s 3H 3N=CH) 1189 (s 3H3NH) UV 120582120582max (120576120576) 310 (22888) 260 (27033) 224 (55717)nm

213 135-Tri-2-methoxy-4-[(3-n-propyl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Ben-zene (4c) Yield 076 g (77) mp 168∘C IR (KBr) 3216(NH) 1751 1707 (C=O) 1598 (C=N) 1271 (COO) cmminus11HNMR (DMSO-d6) 120575120575 094 (t 9H 3CH3119869119869 119869 1198691198691198692Hz) 168(sext 6H 3CH2119869119869 119869 1198691198691198692Hz) 384 (s 9H 3OCH3) 264 (q6H 3CH2119869119869 119869 1198691198691198692Hz) 741ndash766 (m 9H Ar-H) 900 (s3H Ar-H) 974 (s 3H 3N=CH) 1189 (s 3H 3NH) UV120582120582max (120576120576) 310 (23732) 260 (26373) 218 (52676) nm

214 135-Tri-2-methoxy-4-[(3-benzyl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Ben-zene (4d) Yield 103 g (91) mp 161∘C IR (KBr) 3214(NH) 1750 1718 (C=O) 1599 (C=N) 1272 (COO) 760and 706 (monosubstituted benzenoid ring) cmminus1 1H NMR(DMSO-d6) 120575120575 385 (s 9H 3OCH3) 407 (s 6H 3CH2)720ndash768 (m 24H Ar-H) 902 (s 3H Ar-H) 970 (s 3H3N=CH) 1203 (s 3H 3NH) UV 120582120582max (120576120576) 310 (13919) 258(17758) 216 (45657) nm

215 135-Tri-2-methoxy-4-[(3-p-methylbenzyl-45- dihy-dro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycar-bonyl-Benzene (4e) Yield 115 g (98) mp 216∘C IR(KBr) 3219 (NH) 1751 1705 (C=O) 1600 (C=N) 1272(COO) 829 (14-disubstituted benzenoid ring) cmminus1 1HNMR(DMSO-d6) 120575120575 221 (s 9H 3CH3) 384 (s 9H 3OCH3)400 (s 6H 3CH2) 706ndash765 (m 21H Ar-H) 902 (s3H Ar-H) 969 (s 3H 3N=CH) 1204 (s 3H 3NH) 13CNMR (DMSO-d6) 120575120575 2054 (3PhCH3) 3083 (3CH2Ph) 5607(3OCH3) 11193 12094 (arom-C) 12350 (2C) 12359 (2C)12857 (6C) 12899 (6C) 13035 (arom-C) 13070 (3C)13268 13303 (arom-C) 13546 (3C) 13579 (3C) 14113(3C) 14360 (3C) 14636 (3C) 15119 (3C) 15095 (3triazoleC3) 15131 (N=CH) 15191 (3triazole C119869) 16169 (3COO)UV 120582120582max (120576120576) 300 (10113) 258 (13837) 226 (66208) 216(61806) nm Anal Calcd for C63H1198694N12O12 (117119) C6461 H 465 N 1435 Found C 6485 H 622 N 1329

216 135-Tri-2-methoxy-4-[(3-p-chlorobenzyl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Benzene (4f) Yield 089 g (72) mp 230∘C IR (KBr)3210 (NH) 1750 1717 (C=O) 1598 (C=N) 1271 (COO)824 (14-disubstituted benzenoid ring) cmminus1 1H NMR(DMSO-d6) 120575120575 388 (s 9H 3OCH3) 409 (s 6H 3CH2)735ndash756 (m 24H Ar-H) 902 (s 3H Ar-H) 971 (s 3H3N=CH) 1204 (s 3H 3NH) UV 120582120582max (120576120576) 310 (30831) 258(47779) 222 (73777) 208 (58290) nm

217 135-Tri-2-methoxy-4-[(3-phenyl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-Benzene(4g) Yield 106 g (98) mp 243∘C IR (KBr) 3210 (NH)1750 1716 (C=O) 1602 1585 (C=N) 1268 (COO) 768and 693 (monosubstituted benzenoid ring) cmminus1 1H NMR

Journal of Chemistry 3

(DMSO-d6) 120575120575 384 (s 9H 3OCH3) 750ndash764 (m 18HAr-H) 790ndash794 (m 6H Ar-H) 902 (s 3H Ar-H) 972 (s3H 3N=CH) 1241 (s 3H 3NH) UV 120582120582max (120576120576) 308 (24520)258 (44728) 234 (67930) 216 (64853) nm

22 General Procedure for the Synthesis of Compound 5 ecorresponding compound 4 (0001mol) was reuxed withacetic anhydride (20mL) for 05 h Aer the addition ofabsolute ethanol (100mL) the mixture was reuxed for 1 hEvaporation of the resulting solution at 40ndash45∘C in vacuo andseveral recrystallizations of the residue from EtOH gave purecompounds 5 as colorless needles

221 135-Tri-2-methoxy-4-[(1-acetyl-3-methyl-45-dihy-dro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycar-bonyl-Benzene (5a) Yield 066 g (64) mp 207∘C IR(KBr) 1728 (C=O) 1623 1582 (C=N) 1268 (COO) cmminus11H NMR (DMSO-d6) 120575120575 236 (s 9H 3CH3) 250 (s 9H3COCH3) 385 (s 9H 3OCH3) 750ndash764 (m 9H Ar-H)885 (s 3H Ar-H) 959 (s 3H 3N=CH) UV 120582120582max (120576120576) 310(20060) 258 (20237) 220 (63380) 216 (58300) nm

222 135-Tri-2-methoxy-4-[(1-acetyl-3-benzyl-45-dihy-dro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycar-bonyl-Benzene (5d) Yield 088 g (71) mp 182∘C IR(KBr) 1746 (C=O) 1602 1590 (C=N) 1217 (COO) 746and 710 (monosubstituted benzenoid ring) cmminus1 1H NMR(DMSO-d6) 120575120575 250 (s 9H 3COCH3) 385 (s 9H 3OCH3)416 (s 6H 3CH2) 723ndash758 (m 24H Ar-H) 901 (s 3HAr-H) 958 (s 3H 3N=CH) UV 120582120582max (120576120576) 310 (45812) 296(45995) 258 (47147) 230 (83429) 224 (81387) nm

23 Antioxidant Activity Chemicals Butylated hydroxy-toluene (BHT) was obtained from E Merck (Merck KGaADarmstadt Germany) Ferrous chloride 120572120572-tocopherol11-diphenyl-2-picryl-hydrazyl (DPPHbull) 3-(2-pyridyl)-56-bis(phenylsulfonic acid)-124-triazine (ferrozine) butylatedhydroxyanisole (BHA) and trichloroacetic acid (TCA) wereobtained from Sigma (Sigma-Aldrich GmbH SteinheimGermany)

24 Reducing Power e reducing power of the synthe-sized compounds was determined according to the methodof Oyaizu [20] Different concentrations of the samples(50ndash250 120583120583gmL) in DMSO (1mL) were mixed with phos-phate buffer (25mL 02M pH = 66) and potassium ferri-cyanide (25mL 1) e mixture was incubated at 50∘C for20min aer which a portion (25mL) of trichloroacetic acid(10) was added to the mixture which was then centrifugedfor 10min at 1000 timesg e upper layer of solution (25mL)was mixed with distilled water (25mL) and FeCl3 (05mL01) and then the absorbance at 700 nm was measured in aspectrophometer Higher absorbance of the reaction mixtureindicated greater reducing power

25 Free Radical Scavenging Activity Free radical scavengingactivity of compounds was measured by DPPHbull using the

method of Blois [21] Briey 01mM solution of DPPHbull inethanol was preparedand this solution (1mL) was added tosample solutions in DMSO (3mL) at different concentrations(50ndash250 120583120583gmL) e mixture was shaken vigorously andallowed to stand at room temperature for 30min en theabsorbance was measured at 517 nm in a spectrophometerLower absorbance of the reaction mixture indicated higherfree radical scavenging activity e DPPHbull concentration(mM) in the reaction medium was calculated from the fol-lowing calibration curve and determined by linear regression(R 0997)

Absorbance = 00003 times DPPHbull minus 00174 (1)

e capability to scavenge the DPPH radical was calculatedusing the following equation

DPPHbull scavenging effect () = 100765310076531198601198600 minus1198601198601119860119860010076691007669 times 100 (2)

where 1198601198600 is the absorbance of the control reaction and 1198601198601 isthe absorbance in the presence of the samples or standards

26 Metal Chelating Activity e chelation of ferrous ionsby the synthesized compounds and standards were estimatedby the method of Dinis et al [22] Briey the synthesizedcompounds (50ndash250 120583120583gmL) were added to a 2mM solutionof FeCl2 (005mL)e reaction was initiated by the additionof 5mM ferrozine (02mL) and then themixture was shakenvigorously and le standing at the room temperature for10min Aer the mixture had reached equilibrium theabsorbance of the solution wasmeasured at 562 nm in a spec-trophotometer All tests and analyses were run in triplicateand averaged e percentage of inhibition of ferrozine-Fe2+complex formation was given by the formula Inhibition =(1198601198600 minus 11986011986011198601198600) times 100 where 1198601198600 is the absorbance of thecontrol and 1198601198601 is the absorbance in the presence of thesamples or standardse control did not contain compoundor standard

27 Potentiometric Titrations A Jenco model ion analyzerand an Ingold pH electrode were used for potentiometrictitrations For each compound that was titrated the 0001Msolution was separately prepared in each non-aqueous sol-vent e 005M solution of TBAH in isopropyl alcoholwhich is widely used in the titration of acids was usedas titrant e mV values that were obtained in pH-meterwere recorded Finally the HNP values were determined bydrawing the mL (TBAH)-mV graph

3 Results and Discussion

e 135-tri-2-methoxy-4-[(3-alkylaryl-45-dihydro-1H-124-triazol-5-on-4-yl)-azo-methine]-phenoxycarbonyl-benzene 4andashg were prepared e starting compounds3-alkyl(aryl)-4-amino-45-dihydro-1H-124-triazol-5-ones2andashg were prepared from the reactions of the correspondingester of ethoxycarbonylhydrazones 1andashg with an aqueoussolution of hydrazine hydrate as described in the literature

4 Journal of Chemistry

[14 19 23] Compounds 4 were obtained from thereactions of compounds 3 with 135-tri-(2-methoxy-4-formylphenoxycarbonyl)-benzene 1 which were synthesizedby the reactions of 3-methoxy-4-hydroxybenzaldehyde with135-benzenetricarbonyl chloride by using triethylamineen the reactions of compounds 4a and 4d with aceticanhydride were investigated and compounds 5a and 5dwere prepared (Scheme 1)

e structures of seven new 135-tri-2-methoxy-4-[(3-alkylaryl-45-dihydro-1H-124-triazol-5-on-4-yl)-azome-thine]-phenoxycarbonyl-benzenes 4andashg and two new 135-tri-2-methoxy-4-[(1-acetyl-3-alkylaryl-45-dihydro-1H-124-triazol-5-on-4-yl)-azomethine]-phenoxycarbonyl-benzenes 5a and 5d were characterized using IR 1H NMR13C NMR UV and elemental analyses data

31 Antioxidant Activity e antioxidant activities of 9 newcompounds 4andashg 5a and 5d were determined Severalmethods have been used to determine antioxidant activitiesand the methods used in the study are given below

311 Total Reductive Capability Using the Potassium Fer-ricyanide Reduction Method e reductive capabilities ofcompounds were assessed by the extent of conversion of theFe3+ferricyanide complex to the Fe2+ferrous form usingthe method of Oyaizu [20] e reducing powers of thecompounds were observed at different concentrations andresults were compared with BHA BHT and 120572120572-tocopherol Ithas been observed that the reducing capacity of a compoundmay serve as a signicant indicator of its potential antioxidantactivity [24] e antioxidant activity of putative antioxi-dant has been attributed to various mechanisms amongwhich are prevention chain initiation binding of transitionmetal ion catalyst decomposition of peroxides preventionof continued hydrogen abstraction reductive capacity andradical scavenging [25] In this study all the amount of thecompounds showed lower absorbance than blank Hence noactivities were observed to reduce metal ions complexes totheir lower oxidation state or to take part in any electrontransfer reaction In other words compounds did not showthe reductive activities

312 DPPH Radical Scavenging Activity emodel of scav-enging the stable DPPH radical model is a widely usedmethod to evaluate antioxidant activities in a relatively shorttime comparedwith othermethodse effect of antioxidantson DPPH radical scavenging was thought to be due to theirhydrogen donating ability [26] DPPH is a stable free radicaland accepts an electron or hydrogen radical to become astable diamagnetic molecule [27]e reduction capability ofDPPH radicals was determined by decrease in its absorbanceat 517 nm induced by antioxidants e absorption maxi-mum of a stable DPPH radical in ethanol was at 517 nme decrease in absorbance of DPPH radical was causedby antioxidants because of reaction between antioxidantmolecules and radical progresses which resulted in thescavenging of the radical by hydrogen donation It is visuallynoticeable as a discoloration from purple to yellow Hence

DPPHbull is usually used as a substrate to evaluate antioxidativeactivity of antioxidants [28] In the study antiradical activitiesof compounds and standard antioxidants such as BHA and120572120572-tocopherol were determined by using DPPHbull methodScavenging effect values of compounds 4a 4c 4e 4f BHAand 120572120572-tocopherol at different concentrations are given inFigure 1 e newly synthesized compounds showed noactivity as a radical scavenger

313 Ferrous Ion Chelating Activity e chelating effecttowards ferrous ions by the compounds and standards wasdetermined according to the method of Dinis [22] Ferrozinecan quantitatively form complexes with Fe2+ In the presenceof chelating agents the complex formation is disrupted withthe result that the red colour of the complex is decreasedMeasurement of colour reduction therefore allows estima-tion of the chelating activity of the coexisting chelator [29]Transition metals have pivotal role in the generation oxygenfree radicals in living organism e ferric iron (Fe3+) isthe relatively biologically inactive form of iron However itcan be reduced to the active Fe2+ depending on conditionparticularly pH [30] and oxidized back through Fenton-type reactions with the production of hydroxyl radical orHaber-Weiss reactions with superoxide anions e pro-duction of these radicals may lead to lipid peroxidationprotein modication and DNA damage Chelating agentsmay not activate metal ions and potentially inhibit the metal-dependent processes [31] Also the production of highlyactive ROS such as O2

bullminus H2O2 and OHbull is also catalyzed byfree iron though Haber-Weiss reactions

O2bullminus +H2O2 ⟶ O2 +OH

minus +OHbull (3)

Among the transition metals iron is known as the mostimportant lipid oxidation pro-oxidant due to its high reac-tivity e ferrous state of iron accelerates lipid oxidation bybreaking down the hydrogen and lipid peroxides to reactivefree radicals via the Fenton reactions

Fe2+ +H2O2 ⟶ Fe3+ +OHminus +OHbull (4)

Fe3+ ion also produces radicals from peroxides eventhough the rate is tenfold less than that of Fe2+ ion whichis the most powerful pro-oxidant among the various typesof metal ions [32] Ferrous ion chelating activities of thecompounds 4 5 BHT and BHA are shown in Figures 2 and3 respectively In this study metal chelating capacity wassignicant since it reduced the concentrations of the catalyz-ing transition metal It was reported that chelating agentsthat form 120590120590-bonds with a metal are effective as secondaryantioxidants because they reduce the redox potential therebystabilizing the oxidized form of metal ion [33] e dataobtained from Figures 2 and 3 reveal that the compoundsespecially 4e 5a and 5d demonstrate a marked capacity foriron binding suggesting that their action as peroxidationprotectors may be related to their iron binding capacity Onthe other hand free iron is known to have low solubilityand a chelated iron complex has greater solubility in solutionwhich can be contributed solely by the ligand Furthermore

Journal of Chemistry 5

R

N

N

NH

OR

31AcOH

C

CC

O

O

O

O

O

CH N

O

O

CH N

N CH

N

N

NH

OR

N NH

NR

N

N

NH

OR

C

CC

O

O

O

O

O

CH N

O

O

CH N

N CH

N

N

N

OR

N N

NR

N

N

N

OR

C

CC

ClO

Cl

O

O

Cl

C

CC

O

O

O

O

CHO

O

O

CHO

HOC

+OH3HOC

OCH3

C

R

NH2

CH3

Et3N OCH3

OCH3

OCH3

CH3O

CH3O

CH3O

CH3O

CH3O

CH3O

NNHCO2C2H5+H2NNH2minus2C2H5OH minus3H2O

+3(CH3CO)2Ominus3CH3CO2H

COCH3

COCH3

COCH3

CH2CH3CH2CH2CH3CH2C6H5

C6H5

1

2 3 4

5

2ndash5

a

b

c

d

e

f

g

CH2C6H4sdotCH3 (p-)CH2C6H4sdotCl (p-)

OC2H6

S 1

the compound-iron complex may also be active since it canparticipate in iron-catalyzed reactions

314 Potentiometric Titrations In order to determine thep119870119870a values of the compounds 4andashg they were titratedpotentiometrically with TBAH in four non-aqueous solventsisopropyl alcohol tert-butyl alcohol acetone and DMFe mV values read in each titration were plotted against005M TBAH volumes (mL) added and potentiometrictitration curves were obtained for all the cases From thetitration curves the HNP values were measured and thecorresponding p119870119870a values were calculatede data obtainedfrom the potentiometric titrations was interpreted and the

effect of the C-3 substituent in 45-dihydro-1H-124-triazol-5-one ring as well as solvent effects was studied [7 8 10 1213 17 18]

As an example for the potentiometric titration curvesfor 0001M solutions of compounds 4b titrated with 005MTBAH in isopropyl alcohol tert-butyl alcohol DMF andacetone are shown in Figure 4

When the dielectric permittivity of solvents is taken intoconsideration the acidity order can be given as follows DMF(120576120576 120576 120576120576120576120576120576 120576 acetone (120576120576 120576 120576120576120576 120576 isopropyl alcohol (120576120576 120576191205764120576 120576tert-butyl alcohol (120576120576 120576 1120576120576 As seen in Table 1the acidity order for compound 4a is tert-butyl alcohol 120576acetone for compound 4b it is acetone 120576 DMF 120576 tert-butyl

6 Journal of Chemistry

T 1 e HNP and the corresponding p119870119870a values of compounds 4a-g in isopropyl alcohol tert-butyl alcohol DMF and acetone

Comp Isopropyl alcohol tert-Butyl alcohol DMF AcetoneHNP (mV) p119870119870a HNP (mV) p119870119870a HNP (mV) p119870119870a HNP (mV) p119870119870a

4a mdash mdash minus142 1000 mdash mdash minus214 10074b minus377 1480 minus343 1417 minus336 1406 minus146 9814c minus172 973 mdash mdash minus400 1520 mdash mdash4d minus253 1147 mdash mdash minus364 1467 mdash mdash4e minus432 1608 minus195 1045 minus398 1534 mdash mdash4f minus244 1175 mdash mdash minus467 1566 minus609 mdash4g mdash mdash mdash mdash minus730 mdash minus160 987

0

10

20

30

40

50

60

70

80

0 10 20 30 40

Scav

engi

ng

effec

t (

)

BHA

4a

4c

4e

4f

F 1 Scavenging effect of compounds 4a 4c 4e 4f BHA and120572120572-tocopherol at different concentrations (125ndash25ndash375 120583120583gmL)

alcohol gt isopropyl alcohol for compounds 4c and 4d itis isopropyl alcohol gt DMF for compound 4e it is tert-butyl alcohol gt DMF gt isopropyl alcohol for compound 4fit is isopropyl alcohol gt DMF gt acetone while the orderfor compound 4 g is acetone gt DMF Moreover as seen inTable 1 for compounds 4a and 4 g in isopropyl alcohol forcompound 4a in DMF for compounds 4c 4d 4f and 4 gin tert-butyl alcohol and for compounds 4c 4d and 4e inacetone the HNP values and the corresponding p119870119870a valueswere not obtained

As it is well known the acidity of a compound dependson some factors e two most important factors are thesolvent effect and molecular structure [7 8 10 12 13 1718 34] Table 1 and Figure 4 show that the HNP values andcorresponding p119870119870a values obtained from the potentiometrictitrations depend on the non-aqueous solvents used and thesubstituents at C-3 in 45-dihydro-1H-124-triazol-5-onering

4 Conclusion

e synthesis and in vitro antioxidant evaluation of new 45-dihydro-1H-124-triazol-5-one derivatives are described Allof the compounds demonstrate a marked capacity for iron

0

10

20

30

40

50

60

70

80

90

0 10 20 30 40

Ch

elat

ing

effec

t (

)

BHT

BHA

4a

4b

4c

4d

4e

4f

4g

F 2 Metal chelating effect of different amount of the com-pounds 4andashg BHT and BHA on ferrous ions

0

10

20

30

40

50

60

70

80

90

0 10 20 30 40

Ch

elat

ing

effec

t (

)

BHT

BHA

5a

5d

F 3 Metal chelating effect of different amount of the com-pounds 5a and 5d BHT and BHA on ferrous ions

binding e data reported with regard to the observedradical scavenging and metal chelating activities of thestudied compounds could prevent redox cycling Design andsynthesis of novel small molecules can play specically aprotective role in biological systems and inmodernmedicinal

Journal of Chemistry 7

0 02 04 06 08

(mV

)

(mL)

DMF Acetone

Isopropyl alcohol

minus795

minus695

minus595

minus495

minus395

minus295

minus195

minus95

5

Tert-butyl alcohol

F 4 Potentiometric titration curves of 0001M solutions ofcompound 4b titrated with 005M TBAH in isopropyl alcohol tert-butyl alcohol DMF and acetone at 25∘C

chemistry ese results may also provide some guidance forthe development of novel triazole-based therapeutic target

Acknowledgments

is work was supported by the Turkish Scientic andTechnological Council (Project no TBAG 108T984) eauthors thankDr ZaferOcak for determination of p119870119870a valuesand Dr Mustafa Calapoglu for antioxidant activities

References

[1] H Yuumlksek A Demirbaş A Ikizler C B Johansson CCcedilelik and A A Ikizler ldquoSynthesis and antibacterial activitiesof some 45-dihydro-1H-124-triazol-5-onesrdquo Arzneimittel-ForschungDrug Research vol 47 no 4 pp 405ndash409 1997

[2] G Turan-Zitouni Z A Kaplancikli M T Yildiz PChevallet and D Kaya ldquoSynthesis and antimicrobialactivity of 4-phenylcyclohexyl-5-(1- phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-124-triazole derivativesrdquoEuropean Journal of Medicinal Chemistry vol 40 no 6 pp607ndash613 2005

[3] S Papakonstantinou-Garoufalias N Pouli P Marakos andA Chytyroglou-Ladas ldquoSynthesis antimicrobial and antifun-gal activity of some new 3-substituted derivatives of 4-(24-dichlorophenyl)-5-adamantyl-1H-124-triazolerdquo Farmaco vol57 no 12 pp 973ndash977 2002

[4] A A Ikizler F Ucar H Yuskek A Aytin I Yasa and T GezerldquoSynthesis and antifungal activity of some new arylidenaminocompoundsrdquo Acta Poloniae Pharmaceutica vol 54 no 2 pp135ndash140 1997

[5] H Bayrak A Demirbas S A Karaoglu and N DemirbasldquoSynthesis of some new 124-triazoles their Mannich andSchiff bases and evaluation of their antimicrobial activitiesrdquoEuropean Journal of Medicinal Chemistry vol 44 no 3 pp1057ndash1066 2009

[6] M Amir M S Y Khan and M S Zanan Indian Journal ofChemistry vol 43 p 2189 2004

[7] M Alkan H Yuumlksek O Gursoy-Kol and M CalapogluldquoSynthesis acidity and antioxidant properties of somenovel 34-disubstituted-45-dihydro-1H-124-triazol-5-one derivativesrdquoMolecules vol 13 no 1 pp 107ndash121 2008

[8] O Gursoy Kol and H Yuumlksek ldquoSynthesis and in vitro antioxi-dant evaluation of some novel 4 5-dihydro-1H-1 2 4-triazol-5-one derivativesrdquo E-Journal of Chemistry vol 7 no 1 pp123ndash136 2010

[9] O Bekircan B Kahveci and M Kucuk ldquoSynthesis and anti-cancer evaluation of some new unsymmetrical 35-diaryl-4H-124-triazole derivativesrdquo Turkish Journal of Chemistry vol 30pp 29ndash40 2006

[10] H Yuumlksek and O Gursoy-Kol ldquoPreparation characterizationand potentiometric titrations of some new di-[3-(3-alkylaryl-45-dihydro-1H-124-triazol-5-one-4-yl)-azomethinphenyl]isophthalateterephthalate derivativesrdquo Turkish Journal ofChemistry vol 32 pp 773ndash784 2008

[11] H Yuumlksek O Gursoy-Kol G Kemer Z Ocak and B AnilldquoSynthesis and in-vitro antioxidant evaluation of some novel4-(4-substituted)benzylidenamino-45-dihydro-1H-124-triazol-5-onesrdquo Indian Journal of Heterocyclic Chemistry vol20 no 4 pp 325ndash330 2011

[12] S Bahceci H Yuumlksek Z Ocak A Azaklı M Alkanand M Ozdemir ldquoSynthesis and potentiometric titrationsof some new 4-(Benzylideneamino)-45-dihydro-1H-124-triazol-5-one derivatives in non-aqueous mediardquo Collection ofCzechoslovak Chemical Communications vol 67 no 8 pp1215ndash1222 2002

[13] Ş Bahccedileci H Yuumlksek Z Ocak C Koumlksal and M OumlzdemirldquoSynthesis and non-aqueous medium titrations of some new45-dihydro-1H-124-triazol-5-one derivativesrdquo Acta ChimicaSlovenica vol 49 no 4 pp 783ndash794 2002

[14] A A Ikizler and H Yuumlksek ldquoacetylation of 4-amino-44-dihydro-1H-124-triazol-5-onesrdquo Organic Preparations andProcedures International vol 25 no 1 pp 99ndash105 1993

[15] H H Hussain G Babic T Durst et al ldquoDevelopment ofnovel antioxidants design synthesis and reactivityrdquo Journal ofOrganic Chemistry vol 68 no 18 pp 7023ndash7032 2003

[16] D J McClements and E A Decker ldquoLipid oxidation in oil-in-water emulsions impact ofmolecular environment on chemicalreactions in heterogeneous food systemsrdquo Journal of FoodScience vol 65 no 8 pp 1270ndash1282 2000

[17] H Yuumlksek Z Ocak M Alkan Ş Bahccedileci and M OumlzdemirldquoSynthesis and determination of pKa values of some new 34-disubstituted-45-dihydro-1H-124-triazol-5-one derivativesin non-aqueous solventsrdquoMolecules vol 9 no 4 pp 232ndash2402004

[18] H Yuumlksek F İslamoglu O Gursoy-Kol Bahccedileci Ş M Bekarand M Aksoy ldquoIn virto antioxidant activities of new 45-Dihydro-1H24-triazol-5-ones having thiophene ring withtheir acidic propertiesrdquo E-Journal of Chemistry vol 8 no 4 pp1734ndash1746 2011

[19] A A Ikizler and R Un ldquoReactions of ester ethoxycarbonyl-hydrazones with some amine type compoundsrdquo Chimica Acta

8 Journal of Chemistry

Turcica vol 7 pp 269ndash290 1979 Chemical Abstracts 1991 9415645d

[20] M Oyaizu ldquoAntioxidative activities of products of browningreaction prepared from glucosaminerdquo e Japanese Journal ofNutrition and Dietetics vol 44 no 6 pp 307ndash315 1986

[21] M S Blois ldquoAntioxidant determinations by the use of a stablefree radicalrdquo Nature vol 181 no 4617 pp 1199ndash1200 1958

[22] T C P Dinis V M C Madeira and L M Almeida ldquoActionof phenolic derivatives (acetaminophen salicylate and 5-aminosalicylate) as inhibitors of membrane lipid peroxidationand as peroxyl radical scavengersrdquo Archives of Biochemistry andBiophysics vol 315 no 1 pp 161ndash169 1994

[23] A A Ikizler A Ikizler H Yuumlksek S Bahccedileci and K SancakldquoSynthesis of some tert-buthoxyhydrazones and related 4 5-dihydro-1H-1 2 4-triazol-5-onesrdquo Turkish Journal of Chem-istry vol 18 no 9 pp 51ndash56 1994

[24] S Meir J Kanner B Akiri and S Philosoph-Hadas ldquoDeter-mination and involvement of aqueous reducing compounds inoxidative defense systems of various senescing leavesrdquo Journal ofAgricultural and Food Chemistry vol 43 no 7 pp 1813ndash18191995

[25] A Yildirim A Mavi and A A Kara ldquoDetermination ofantioxidant and antimicrobial activities of Rumex crispus Lextractsrdquo Journal of Agricultural and Food Chemistry vol 49no 8 pp 4083ndash4089 2001

[26] J Baumann G Wurn and V Bruchlausen ldquoNaunyn-Schmiedebergrsquos Prostaglandin synthetase inhibitingO2radical scavenging properties of some avonoids andrelated phenolic compoundsrdquo Naunyn-Schmiedebergrsquos Archivesof Pharmacology vol 308 article R27 1979

[27] J R Soares T C P Dinis A P Cunha and L M AmeidaldquoAntioxidant activities of some extracts of ymus zygisrdquo FreeRadical Research vol 26 no 5 pp 469ndash478 1997

[28] P-D Duh Y-Y Tu and G-C Yen ldquoAntioxidant activityof water extract of harng jyur (Chrysanthemum morifoliumRamat)rdquo LWTmdashFood Science and Technology vol 32 no 5 pp269ndash277 1999

[29] F Yamaguchi T Ariga Y Yoshimira and H NakazawaldquoAntioxidative and anti-glycation activity of garcinol fromgarcinia indica fruit rindrdquo Journal of Agricultural and FoodChemistry vol 48 no 2 pp 180ndash185 2000

[30] M Strlič T Radovič J Kolar and B Pihlar ldquoAnti- andprooxidative properties of gallic acid in fenton-type systemsrdquoJournal of Agricultural and Food Chemistry vol 50 no 22 pp6313ndash6317 2002

[31] A E Finefrock A I Bush and P M Doraiswamy ldquoCurrentstatus of metals as therapeutic targets in Alzheimerrsquos diseaserdquoJournal of the American Geriatrics Society vol 51 no 8 pp1143ndash1148 2003

[32] I Ccedilaliş M Hosny T Khalifa and S Nishibe ldquoSecoiridoidsfrom Fraxinus angustifoliardquo Phytochemistry vol 33 no 6 pp1453ndash1456 1993

[33] M H Gordon Food Antioxidants Elsevier 1990[34] T Guumlnduumlz Susuz Ortam Reaksiyonlar120484120484 Gazi Buumlro Kitabevi Tic

Ltd Şti Ankara Turkey 1998

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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