R

SHa

b

c

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a

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K4aEQRHc

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cmnddapaq

0h

Electrochimica Acta 88 (2013) 858– 864

Contents lists available at SciVerse ScienceDirect

Electrochimica Acta

jou rn al h om epa ge: www.elsev ier .com/ locate /e lec tac ta

edox behavior of a novel menadiol derivative at glassy carbon electrode

hamsa Munira , Afzal Shaha,∗ , Abdur Raufa , Amin Badshaha , Suzanne K. Lunsfordb , Zia-ur-Rehmana ,idayat Hussainc, Gul Shahzada Khand

Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, PakistanWright State University, 466 Oelman Hall, Dayton, OH 45435, United StatesDepartment of Biological Sciences and Chemistry, University of Nizwa, 616, Birkat Al Mauz, Nizwa, OmanDepartment of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan

r t i c l e i n f o

rticle history:eceived 24 October 2012ccepted 28 October 2012vailable online xxx

eywords:-Hydroxy-5-methoxynaphthalene-1-yl

a b s t r a c t

The redox behavior of a menadiol derivative, 4-hydroxy-5-methoxynaphthalene-1-yl acetate (HMNA)was investigated in a wide pH range by using modern electrochemical techniques. The techniques utilizedin this study were cyclic voltammetry, square wave voltammetry and differential pulse voltammetry(CV, SWV and DPV). A sharp anodic signal in the forward scan followed by a cathodic peak (associatedwith the reduction of the oxidation product of HMNA) in the reverse scan produced a counter oxidationsignal in the positive realm of glassy carbon electrode. Physical parameters like diffusion coefficient

cetatelectro-oxidationuasi-reversibilityedox mechanismeterogeneous electron transfer rate

and heterogeneous electron transfer rate constant were determined from scan rate and concentrationeffects. Square wave voltammetry evidenced the quasi-reversible nature of the electrochemical process.The involvement of protons in the redox mechanism was determined from the peak potential shift asa function of pH. The redox mechanism of HMNA proposed on the basis of CV, SWV and DPV resultswas supported by theoretical calculations. Moreover, a detailed UV–vis spectroscopy was carried out in

cteri

onstant a wide pH range for chara

. Introduction

Menadiol diphosphate is a synthetic water-soluble form of vita-in K. It is given as a supplement to prevent bleeding caused by

itamin K deficiency. Vitamins of K group are involved in manyiological and physiological processes due to their ability of trans-orting electrons and protons. Literature survey has revealed the

nvolvement of such compounds in photosynthetic mechanism,ellular respiration and oxidative phosphorylation [1] The antiemorrhagic properties of menadiol based compounds depend onheir reduction potential that is modulated with the electron donat-ng and withdrawing nature of the attached substituents [2–4].

Naphthoquinones and their reduced forms are considered as theomponents of biological electron transfer chains located in theembranes of mitochondria, bacteria and chloroplast [5]. Some

aphthoquinone derivatives like menadiols are used as vitaminsepending upon their molecular structure [5]. Two importanterivatives of naphthoquinones, menadione and � lapachon havechieved clinical status as anti-tumor drugs. These type of com-

ounds are gaining mounting attention of chemists, biologistsnd pharmacologists because many anticancerous drugs containuinone functionality [6–9]. However, these large numbers of

∗ Corresponding author. Tel.: +92 5190642110; fax: +92 5190642241.E-mail address: afzals qau@yahoo.com (A. Shah).

013-4686/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.ttp://dx.doi.org/10.1016/j.electacta.2012.10.141

zation and pKa determination of HMNA.© 2012 Elsevier Ltd. All rights reserved.

quinones with diverse structures available are difficult to gen-eralize the overall biological action mechanism [10]. The abilityof accepting electrons to form radical anion or dianion makesthese naphthoquinoes quite significant biologically. Therefore,their redox properties are governed by the electron donating orwithdrawing substituents attached to their basic framework [11].

Vitamin K3 is a naturally occurring naphthoquinone associatedwith the production of prothrombin, a blood clotting protein. Vita-min K includes K1 and K2 which are formed from provitamin K3.These vitamins play an integral part in bone calcification. Defi-ciency of these can lead to serious health problems like excessivebleeding and hemorrhage. Plumbagin and other structural analogsof vitamin K have been reported to have anticancerous properties[12].

Electro-reduction of menadione to menadiol has been pre-viously studied at a gold electrode in aprotic media wheresemiquinone anion and dianion radicals are not protonated in thetime scale of the voltammetric experiments [5]. Due to the narrowpotential range of the gold electrode and the lack of reported liter-ature on the redox mechanism of menadione/menadiol in proticsolvent our research group has focused attention on the reac-tion mechanism of a novel structural derivative of Vitamin K4,

4-hydroxy-5-methoxynaphthalene-1-yl acetate (HMNA). HMNAshown in Scheme 1 was investigated at a glassy carbon electrode(having wide potential window) in different pH media using mod-ern voltammetric techniques. This present work was performed

S. Munir et al. / Electrochimica Acta 88 (2013) 858– 864 859

OCH3

O

OH

C

O

CH3

OCH3

O

O

C

O

CH3

-e

-H+

OCH3

O

O

C

O

CH3

OCH3

O

O

C

O

CH3

CH3 C

O

OCH3

O

O

+

OCH3

OH

OH

2H+

2e

Butan-2,3-dione

dimerization

Sa

wiK

2

2

S2aapi1WCe(

2

rga

Table 1Supporting electrolytes of 0.1 M ionic strength.

pH Composition

1.22 HCl + KCl2.0 HCl + KCl3.0 HAcO + NaAcO4.0 HAcO + NaAcO4.9 HAcO + NaAcO6.0 NaH2PO4 + Na2HPO4

7.0 NaH2PO4 + Na2HPO4

8.07 NaH2PO4 + Na2HPO4

10.05 NaHCO + NaOH

cheme 1. Proposed redox mechanism of HMNA in slightly acidic, neutral andlkaline conditions.

ith the objective of providing useful insights into the understand-ng of unexplored pathways by which the derived form of vitamin

exerts its biochemical actions.

. Experimental

.1. Materials and reagents

4-Hydroxy-5-methoxynaphthalene-1-yl acetate (HMNA) fromigma was used without further purification. A stock solution of.5 mM HMNA was prepared in analytical grade ethanol and storedt 25 ◦C. Working solutions of HMNA were prepared in 20% ethanolnd 80% aqueous supporting electrolytes. The composition of sup-orting electrolytes prepared in doubly distilled water is given

n Table 1. Microvolumes were measured using EP-10 and EP-00 Plus Motorized Microliter Pipettes (Rainin Instrument Co. Inc.,oburn, USA). The pH measurements were carried out with a

rison micropH 2001 pH-meter with an Ingold combined glasslectrode. All experiments were carried out at room temperature25 ± 1 ◦C).

.2. Equipment and measurements

Voltammetric experiments were performed using �Autolabunning with GPES 4.9 software, Eco-Chemie, The Netherlands. Alassy carbon (GC) with electroactive area of 0.07 cm2 was useds working electrode. A Pt wire and saturated calomel electrode

3

12.93 NaOH + KCl

(SCE) were employed as counter and reference electrodes. Beforeeach experiment, the surface of GCE was polished with aluminapowder followed by thorough rinsing with distilled water. Forreproducible experimental results, the clean GC electrode wasplaced in supporting electrolyte solution and various cyclic voltam-mograms were recorded until the achievement of steady statebaseline voltammogram. All the voltammetric experiments wereconducted in a high purity argon atmosphere. Differential pulse vol-tammetry (DPV) was carried out at 10 mV s−1 scan rate. For squarewave voltammetry (SWV) the experimental conditions were 20 Hzfrequency and 5 mV potential increment corresponding to aneffective scan rate of 100 mV s−1. The high performance liquid chro-matography (HPLC) of HMNA was performed on reversed-phaseLiChrosorber RP-18 column, (5 �m particle size, 150 mm × 4.6 mminternal diameter, Agilent Technologies, Wilmington, DE, USA)using a 90:10 (v/v) mixture of water–acetonitrile with 0.1% tri-fluoroacetic acid and methanol as eluent. Flow rate was adjustedto 0.5 mL min−1. Absorption spectra were recorded on Shimadzu1601 spectrophotometer and the pH measurements were carriedout with a Crison micro pH 2001 pH-meter with an Ingold combinedglass electrode. For Density Functional Theory (DFT) optimizationand energy calculations GAUSSIAN 03W software package wasused. An internal default criterion of GAUSSIAN 03W was used. Thecomputations were carried out on P-4 computer.

3. Results and discussion

3.1. Cyclic voltammetry

Cyclic voltammetry of 4-hydroxy-5-methoxynaphthalene-1-ylacetate (HMNA) was carried out using 0.2 mM solution (80% aque-ous ethanol), at pH 4.0 using 0.1 M acetate buffer at a clean GCEbetween the limits ±1.5. On proceeding from 0 to +1.5 V, a singleoxidation signal was observed at +0.367 V. On reversing the scandirection, a reduction peak was observed at a potential correspond-ing to −0.193 V with a counter oxidation signal. Therefore, furthercyclic voltammetric experiments were carried out between +0.6and −0.5 V using 0 V as a starting potential.

Number of scans ranging from 1 to 5 determined the extent ofadsorption of HMNA on the electrode surface. Fig. 1 demonstratesthe effect of subsequent scans. There is a considerable decrease ofpeak current on the 2nd scan showing adsorption of HMNA on GCEsurface but peak current becomes constant after 5th scan and asteady state is eventually reached. Furthermore, the second scan isaccompanied with the appearance of another oxidation peak at apotential less positive to the first oxidation signal. Interdependencyof peaks was ensured using peak clipping experiments. The cyclicvoltammograms (Fig. S-1) obtained in the potential range of 0.0 to

+0.6 V established that peak c in Fig. 1 is related to peak a1 whilepeak a2 is the result of the oxidation of reduction product obtainedfrom peak c.

860 S. Munir et al. / Electrochimica

F4

ritmt

F�a

ig. 1. CVs (scan 1–5) of 0.2 mM HMNA obtained at 100 mV s−1 in a solution of pH.0, using 0.1 M acetate buffer.

CVs of 0.2 mM HMNA obtained in different electrolytes of pHanging from 1.22 to 12.93 at 100 mV s−1 scan rate have been shown

n Fig. 2A and B. The effect of pH of the media was used to establishhe redox mechanism of the analyte. With increase in pH of the

edium, both peaks a1 and c were shifted cathodically indicatinghe involvement of proton during electron transfer. The peaks were

ig. 2. (A) CVs obtained at a GCE in Ar saturated solution of 0.2 mM HMNA at = 100 mV s−1 in different supporting electrolytes of pH ranging from 1.22 to 7.0nd (B) 8.07 to 12.93.

Acta 88 (2013) 858– 864

not resolved at pH 12.93 showing non-feasibility of HMNA oxida-tion process in strongly alkaline conditions. Epa vs. pH plot with aslope of 51 mV pH−1 according to the equation: Epa = 0.5 + 0.051 VpH suggested the oxidation of HMNA to occur by the same numberof electrons and protons [13,14].

Effect of increasing scan rate was also studied to evaluate thediffusion coefficient of HMNA at pH 4.0 and 7.0. Peak currentincreased with increasing scan rate with no significant peak poten-tial shift (Fig. S-2A and B). At pH 4.0 two distinct straight linesegments were obtained when Ipa was plotted vs. the square rootof scan rate (see Fig. S-3A), one being at lower scan rates (up to100 mV s−1) and other at higher scan rates (up to 400 mV s−1).Therefore, the diffusion coefficient (D0) was calculated separatelyfor each linear segment. The slope values at lower and higherscan rates were 19.82 × 10−6 and 48.8 × 10−6 A/(V s−1)1/2 respec-tively. From experimentally obtained Epa − Epa/2 values of 32 and71 mV at pH 4.0 and 7.0, ˛an was calculated using equation:Epa − Epa/2 = 47.7/(�an). Considering n = 1 (from DPV) the diffusioncoefficient with values 1.46 × 10−6 and 8.85 × 10−5 cm2 s−1 wasdetermined at pH 4.0 using Ipa = 2.99 × 105n (˛an)1/2AC0 × D0

1/2v1/2

for scan rates below and above 100 mV s−1 [15–17]. Using the slopevalue (26.8 × 10−6 A/(V s−1)1/2) of Ipa vs. �1/2 at pH 7.0 (Fig. S-3B),diffusion coefficient was calculated as 1.1 × 10−5 cm2 s−1.

In order to find out the diffusion-controlled nature of the pro-cess, log Ipa was plotted vs. log � as shown in Fig. 3A and B. The slopevalues of 0.83 and 1.3 indicated the adsorption controlled processat pH 4.0 while the slope value of 0.57 at pH 7.0 showed interme-

diate (diffusion cum adsorption controlled) nature of the process[18–20]. Adsorption controlled nature of the process is also indi-cated by the sharp peaks of CVs (Fig. S-2A) obtained at pH 4.0 [16].The reason for their sharpness is related to the fact that during an

Fig. 3. (A) Plots of log Ipa (�A) vs. log � (V s−1) at pH 4.0 and (B) pH 7.0.

S. Munir et al. / Electrochimica

Fm

atep

aopaIab

3

b9ermuc

Fo

ig. 4. CVs of different concentration of HMNA obtained at � = 100 mV s−1 in aedium buffered at pH 4.0 using 0.1 M acetate buffer.

dsorption-controlled process, electron transfer takes place afterhe analyte is being adsorbed and it does not have to travel to thelectrode surface. The broad shape of cyclic voltammetric peaks atH 7.0 shown in Fig. S-2B demonstrate mixed mode of transport.

Heterogeneous electron transfer rate constant (k0) was evalu-ted at pH 4.0 from CVs obtained at different concentrations. Effectf varying concentrations has been shown in Fig. 4. By plottingeak current vs. concentration, a straight line was obtained with

slope of 26.7 × 10−6 A/mol m−3 (Fig. S-4). Reinmuth’s expression:p = nFACk0 was employed for the determination of k0. The k0 with

value of 3.89 × 10−3cm s−1 characterized the oxidation process toe quasi-reversible in nature.

.2. Differential pulse voltammetry of HMNA

DPVs of 0.2 mM HMNA obtained in different pH media haveeen depicted in Fig. 5. The width at half peak height (W/2) of8 mV (close to the theoretical value of 90.4 mV) evidenced onelectron oxidation process [21]. The shift of peak potential withise in pH showed similar trends as obtained from cyclic voltam-

etry. Epa was plotted against pH and a slope of 53 mV per pH

nit (close to the theoretical value of 59 mV per pH unit) authenti-ated the CV results of one electron–one proton oxidation process. A

ig. 5. DPVs of 0.2 mM HMNA obtained at � = 10 mV s−1 in supporting electrolytesf pH 1.22–12.93.

Acta 88 (2013) 858– 864 861

dramatically different situation from cyclic voltammetry, whereoxidation peak related to the first oxidation product appeared inthe second scan was the appearance of that peak in the first scanof DPVs under strongly acidic conditions. The appearance of thispeak suggests the presence of a small amount of the oxidized formof HMNA that is detected by DPV due to its more sensitivity ascompared to CV. This attribution is supported by the fact that acidcatalyzed hydrolysis of HMNA can lead to the formation of oxi-dized product which undergoes two electron–two proton oxidationprocess as witnessed by the W1/2 value of 50 mV.

3.3. Square wave voltammetry of HMNA

The square wave voltammetry (SWV) has an edge over otherelectrochemical techniques because of greater speed of analysis,little consumption of the electroactive species in comparison toDPV and reduced problems with poisoning of the electrode sur-face. Another advantage of SWV is that the reversibility of electrontransfer process can be checked during one scan only. Since thecurrent is sampled simultaneously in both positive and negative-going pulses so peaks corresponding to oxidation and reduction ofthe electroactive species at the electrode surface can be obtainedin the same experiment. The main objective of SWV is to ensurethe reversibility, irreversibility or quasi-reversibility of the redoxprocess of the analyte.

SWV of 0.2 mM HMNA was performed at GCE which endorsedthe quasi-reversible nature of the oxidation process (Fig. 6A andB). SW voltammogram at pH 4.24 is shown along with the effectof number of scans at pH 7.4. In cyclic voltammetry another oxi-dation peak related to the first oxidation appeared in second scansimilar to DPV. In SWV this peak was observable in the first scanunder acidic conditions as well, owing to the much more sensitiv-ity of SWV in comparison to CV and DPV [22]. Appearance of thisoxidation peak in the first scan suggests that a small amount ofthe oxidized form corresponding to this potential already existedin solution as a result of acid catalyzed hydrolysis of HMNA lead-ing to the oxidized product which could undergo two electron–twoproton oxidation as depicted by the W1/2 value of 50 mV from DPVobtained in supporting electrolytes of pH 1.22. Moreover, the samepeak disappeared from the first scan square wave voltammogramrecorded in a medium buffered at pH 7.4 and observed only inthe second scan like CV indicating the inability of HMNA to gethydrolysed under these conditions.

3.4. Redox mechanism of HMNA

The oxidation of 4-hydroxy-5-methoxynaphthalene-1-ylacetate was found to occur by the transfer of a single electron asdetermined from the average W1/2 value of 98 mV. Epa vs. pH plotwith a slope of 53 mV pH−1 slope indicated the oxidation to occurby one electron one proton process. Based upon these values it wasproposed that hydroxyl moiety of HMNA after the loss of one elec-tron and proton results in the formation of oxygen radical, whichcan exist in three resonance forms. The canonical form in whichelectron is residing on carbon atom having attached acetate groupgets converted to dione (5-methoxynaphthalene-1,4-dione) andacetyl radical by the cleavage of C O bond as shown in Scheme 1.The acetyl radical thus formed can dimerize to the simplest dike-tone, butane-2,3-dione. The cathodic peak in the reverse scan ofCV suggested the reduction of 5-methoxynaphthalene-1,4-dioneto its corresponding diol form by two electrons and two protonsinvolvement (Scheme 1). Appearance of another anodic peak in

the second scan of CV can be corresponded to the oxidation of diolback to dione by the loss of two electrons and protons in a quasi-reversible manner. The oxidation of diol occurs at lower potentialas compared to 4-hydroxy-5-methoxynaphthalene-1-yl acetate

862 S. Munir et al. / Electrochimica Acta 88 (2013) 858– 864

Fig. 6. SW voltammograms obtained in solution of 0.2 mM HMNA in pH 4.24 (A)1st scan showing total current (It), forward current (If) and backward current (Ib);ft

bgmss5rs

rDsh(vtebpfnottur

OCH3

O

OH

C

O

CH3

OCH3

OH

OH

H+

H2O+ CH3COOH

OCH3

O

O

C

O

CH3

H+ -e 2H+ -2e

OCH3

O

O

of 9.6 was estimated from the plot of absorbance vs. pH at 300 nm

= 20 Hz, �Es = 5 mV, �eff = 100 mV s−1 and pulse amplitude = 50 mV (B) SWVs of firsthree scans of 0.2 mM HMNA recorded at �eff = 100 mV s−1 in pH 7.4.

ecause in the latter case acetate being the electron-withdrawingroup makes the oxidation process difficult thus resulting inore positive oxidation potential of HMNA. This attribution was

upported by performing DFT calculation using B3LYP, 6-31G basiset for the optimization and energy calculation of HMNA and-methoxynaphthalene-1,4-diol thus authenticating our proposededox mechanism of HMNA as explained later in the computationaltudy of the compounds.

The peak (which is recorded in the second scan of CV) cor-esponding to the oxidation of diol is observed in the first scanP voltammograms obtained in low pH media. Its appearance in

trongly acidic conditions can be related to the reversible acidicydrolysis of the acetate group that results in the formation of diolScheme 2). The absence of second anodic peak in the first scan of DPoltammograms recorded in media buffered at pH ∼ 7.0 ruled outhe possibility of HMNA hydrolysis under these conditions. How-ver, the broadness of the DPV peak in high pH conditions maye due to the merging of the signals of HMNA and its hydrolyticroduct. For further confirmation of HMNA hydrolysis its high per-ormance liquid chromatography (HPLC) was carried out in acidic,eutral and alkaline conditions. Only one signal at 4.283 min wasbserved in neutral medium indicating the purity of HMNA whilewo peaks in acidic and alkaline conditions were noticed indicating

he presence of the starting compound and its hydrolytic prod-ct (see Fig. S-5). The hydrolysis in acidic medium supports theesults obtained from differential pulse voltammetry. However,

Scheme 2. Proposed redox mechanism of HMNA and its hydrolyzed product understrongly acidic conditions.

the hydrolysis in basic medium is a dramatically different behav-ior from that observed in DP voltammograms. The anomaly can beresolved by considering the broadness of the DPV peak in high pHconditions to be due to the merging of the signals of HMNA and itshydrolytic product.

5-Methoxynaphthalene-1,4-dione is structurally related tomenadione but its cathodic potential is much less negative as com-pared to that reported for menadione thus demonstrating its facilereduction. Moreover, its easy reduction in biological systems ascompared to menadione may result in the generation of reactiveoxygen species (ROS). This is because if the reduction potentialis more positive than −0.5 V, the species fall in the electrochem-ical range that may sustain electron transfer reactions in vivo withpossible generation of ROS [23].

3.5. Electronic absorption spectroscopy of HMNA

Electronic absorption spectroscopy of 25 �M HMNA was carriedout in different pH media to determine the pKa of phenolic groupattached to HMNA molecule. The spectra showed an intense bandat 223 nm and a broad band with overlapping peaks in the range of275–350 nm. Absorption maxima at 223 nm are thought to be dueto benzene moiety [24]. The fine structure consists of overlappingpeaks including n → �* transitions may be due to acetate groupattached to HMNA. Absorption spectra of naphthalene show a sim-ilar maxima and fine structure but at a shorter wavelength [25].The shift of peaks to longer wavelengths in case of HMNA (substi-tuted naphthalene) is due to the electron releasing nature of OCH3and OH groups. Fig. S-6 and Fig. 7 demonstrate the effect of pHon UV–vis absorption spectra of HMNA. An increase in pH resultedin slight bathochromic shift of the absorption maxima at 223 nmwhile no shift was observed for the peaks of fine structure until pH9.2. The shift in peak position is attributed to the removal of OHproton in basic media with the negative charge on oxygen atom,thus making the transitions energetically more favorable as repre-sented by the bathochromic shift. The pKa of HMNA with a value

owing to the pronounced change in absorbance and bathochromiceffect at this wavelength (see Fig. 8). For this purpose absorptionspectra were taken with minor increment of pH from 9.2 to 10.2 for

S. Munir et al. / Electrochimica Acta 88 (2013) 858– 864 863

Fa

tsmfo

3

1e6cE1dntng

iLdtimt

Fig. 9. (A) Charge distribution of HMNA and (B) 5-methoxynaphthalene-1,4-diol.

ig. 7. Absorption spectra of 25 �M HMNA obtained in pH 4.0–9.2 using 20% ethanolnd 80% aqueous supporting electrolytes.

he evaluation of more accurate value of pKa. The pH 9.6 thus corre-ponds to the deprotonation of phenolic proton of the naphthaleneoiety of HMNA. The pKa of the analyte was not observable in dif-

erential pulse voltammetry because of the probable overlappingf the peaks of HMNA and its hydrolytic product.

.6. Computational studies

Computational studies of HMNA and 5-methoxynaphthalene-,4-diol were carried out to obtain Mulliken charge distribution andnergies of HOMO and LUMO. Molecules were first optimized using-31G basis set. Calculations of the optimized structures were thenarried out to obtain the charge densities and values of EHOMO andLUMO. Charges distribution of HMNA and 5-methoxynaphthalene-,4-diol are shown in Fig. 9. In the case of HMNA, Mulliken chargeistribution shows negative charge on oxygen atoms with the mostegative charge on oxygen of OH group indicating its facile oxida-ion. Similarly in case of 5-methoxynaphthalene-1,4-diol, the mostegative charge can be seen on the oxygen atoms of the two OHroups.

DFT calculations were performed using 6-31G basis set to ver-fy the proposed mechanism (see Fig. 10). Energies of HOMO andUMO were calculated for HMNA and 5-methoxynaphthalene-1,4-iol. The DFT calculations showed 5-methoxynaphthalene-1,4-diol

o have less negative value of EHOMO than HMNA. This findings in good agreement with the experimental anodic peak of 5-

ethoxynaphthalene-1,4-diol located at less positive potentialhan HMNA. Less negative EHOMO value is a manifestation of facile

Fig. 8. Plot of absorbance of HMNA vs. pH at 300 nm.

Fig. 10. (A) Graphical representation of EHOMO of HMNA and (B) 5-methoxynaphthalene-1,4-diol.

864 S. Munir et al. / Electrochimica

Table 2EHOMO and ELUMO values of compounds.

Compound EHOMO ELUMO

olms

4

dcamrdgiwapypbtmmHmotTmw

A

Qts

A

i2

R

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[

[son, Relationship between the ionization and oxidation potentials of molecular

HMNA (4-hydroxy-5-methoxynaphthalene-1-ylacetate)

−0.19813 −0.03838

5-Methoxynaphthalene-1,4-diol −0.18028 −0.01635

xidation of the species [26–29]. An examination of EHOMO valuesisted in Table 2 reveals that the difference in the EHOMO values

atch well with the variation of oxidation potentials of the twopecies.

. Conclusion

4-Hydroxy-5-methoxynaphthalene-1-yl acetate (HMNA), aerivative of menadiol was found to have robust electrochemi-al signature on glassy carbon electrode. Cyclic voltammetry (CV)nd pulse techniques were successfully used for the establish-ent of electrode reaction mechanism of HMNA. The CV results

evealed that HMNA undergoes one electron and one proton oxi-ation resulting in the formation of an electroactive product thatives reduction signal with a counter oxidation peak. The result-ng reduced product was quite similar to menadione (vitamin K3)

hose reversible reduction has been investigated previously inprotic media using gold electrode. DPV and SWV supported theroposed mechanism and established that acid catalyzed hydrol-sis of HMNA could lead to the formation of the same diol asroduced from the reduction of dione in the 2nd scan of CVy one electron-one proton oxidation of HMNA. It was foundhrough HPLC that HMNA gets hydrolyzed in both acidic and basic

edia. Computational studies also supported the formation of 5-ethoxynaphthalene-1,4-dione as a result of electro-oxidation ofMNA. The appearance of two anodic peaks in the DP voltam-ograms obtained in solutions of low pH revealed the oxidation

f HMNA and its hydrolyzed product. Furthermore, UV–vis spec-roscopy was employed to determine the pKa of the compound.hese detailed investigations enabled the prediction of redoxechanism of HMNA and thus predicted the possible pathway byhich it can exert its biochemical actions.

cknowledgements

The authors gratefully acknowledge the funds provided byuaid-i-Azam University, Islamabad, Wright State University, Day-

on, OH and Higher Education Commission, Islamabad, Pakistan, forupporting this work.

ppendix A. Supplementary data

Supplementary data associated with this article can be found,n the online version, at http://dx.doi.org/10.1016/j.electacta.012.10.141.

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