CHAPTER-5

CYCLIC VOLTAMETRIC STUDIES OF NOVEL INDOLE

ANALOGUES PREPARED IN THE PRESENT STUDY

Page No. 175-187

5.1 Introduction

5.2 Theoretical

5.3 Experimental

5.4 References

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5. 1 Introduction

Electrochemical studies are used to find the structure, oxidation potential and

biological activity of electroactive species. Electrochemical techniques offer

important information about drug molecules and their mode of action in the body,

such as metabolism, which is one of the important steps in drug discovery. Numerous

standard electrochemical methods exist that can be categorized into three general

classes viz., potentiometry, coulometry and voltammetry1,2. This technique consists of

applying a controlled external potential (or current) to the cell and measuring the

resulting flow of current (or potential3). Voltammetry techniques can be divided into

two categories, the potential sweep techniques (e.g. cyclic voltammetry), where the

potential of the working electrode is linearly scanned and the step or pulse techniques

(e.g. chronoamperometry), where the potential is stepped, allowing removal of the

capacitive current. The setup is composed of 3 electrodes; the working electrode,

reference electrode and the counter electrode. The potential is measured between the

reference electrode and the working electrode and current is measured between the

working electrode and counter electrode4-6. Thus cyclic voltammetry (CV) has

become an important and widely used electroanalytical technique that allows studying

redox processes of molecules particularly in organic and metal-organic systems,

electrochemical behaviour of complex chemical and biochemical systems7. Indole

analogues are well-known electro active compounds that are readily oxidized or

reduced at carbon based electrodes, i.e. glassy carbon electrode8-10.

In voltametry, the detection of electroactive species can be carried out at

Glassy carbon electrode. In a voltametric studies many carbon based electrodes have

been used11, 12. These electrodes have a very wide anodic as well as cathodic potential

region both in aqueous and non-aqueous solvents. Carbon paste made of graphite

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powder and mineral solvent was one of the earliest inert electrodes introduced into

the electrochemistry13. Today the most extensively used vitreous or glassy carbon

electrode into electrochemistry14,15. Because of its high mechanical stability, low

porosity, inertness over a wide potential region, good conductivity and reproducibility

are some of its very widespread applications. In this section electrochemical reduction

/ oxidation of indole analogues is studied at glassy carbon electrode As a part of our

continuing effort to understand the mechanism of electro reduction/oxidation of

various novel molecules, we report herewith electrochemical reduction or oxidation

of novel indole analogues in sulphuric acid media.

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5.2 Theoretical

Part-1: Cyclic voltametric studies of 3,5-Disubstituted-N'-(1-(2,5-

dichlorothiophen-3-yl)ethylidene)-1H-indole-2-carbohydrazide.

(80a) (80c)

Cyclicvoltammogram of 5-chloro-N'-(1-(2,5-dichlorothiophen-3-

yl)ethylidene)-3-phenyl-1H-indole-2-carbohydrazide (80a) (Fig. 29) at a glassy

carbon electrode in 25mM sulphuric acid media at scan rates 100 mVs-1. The

compound showed a cathodic peak potential at -0.636 V for the reduction of the C=N

moiety. The quasirreversibility was confirmed by the presence of an anodic peak

between the potential of +1.0 mV to –1.0 mV. The effect of scan rate was studied and

cathodic peak current was proportional to the scan rate and the process is diffusion-

controlled. From the Fig. 29, we can see that the C=N functional groups in the

molecule is easily reduced at the glassy carbon electrode. The reduction potential

value is -0.636V which has chloro substitution at five position of indole. Variation of

scan rate from 50 mVs−1 to 250 mVs−1 is shown in Fig. 30. With the increase of scan

rate, the quasireversibility becomes completely irreversible in nature and the absence

of anodic peak in the reverse direction.

Cyclic voltammogram of (1-(2,5-dichlorothiophen-3-yl)ethylidene)-5-methyl-

3-phenyl-1H-indole-2-carbohydrazide (80c) (Fig. 31) studied at a glassy carbon

electrode in 25mM of sulphuric acid media at a scan rates of 100 mVs-1. The

compound showed a cathodic peak potential at -0.633 V for the reduction of the C=N

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function. The irreversibility was confirmed by the absence of an anodic peak between

the potential of +0.8 mV to –1.0 mV. The effect of the scan rate was studied and the

cathodic peak current was proportional to the scan rate and the process is diffusion-

controlled. From Fig. 31 We can see that the C=N functional groups is easily reduced

at the glassy carbon electrode. The reduction potential value is -0.633 V for methyl

substituted at five position of indole. Variation of scan rate from 50 mVs−1 to 300

mVs−1 there is no change in the nature and remains irreversible as shown in Fig. 32.

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Fig. 29. Cyclic voltammogram of 80a at glassy carbon electrode in 25mM

sulfuric acid at scan rate 100 mVs-1.

Fig. 30. Variation of 80a scan rate from 50 mVs−1 to 250 mVs−1.

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Fig. 31. Cyclic voltammogram of 80c at glassy carbon electrode in 25mM

sulfuric acid at scan rate 100 mVs-1.

Fig. 32. Variation of 80c scan rate from 50 mVs−1 to 300 mVs−1.

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Part-2: Cyclic Voltammetric Studies of 3,5-disubstituted-N-(2-(2,5-

dichlorothiophen -3-yl)-2-methyl-4-oxothiazolidin-3-yl)-1H-indole-2-

carboxamide.

(81a)

The cyclic voltametry of 5-chloro-N-(2-(2,5-dichlorothiophen-3-yl)-2-methyl-

4-oxothiazolidin-3-yl)-3-phenyl-1H-indole-2-carboxamide (81a) (Fig. 33) studied at

glassy carbon electrode in 25mM of sulphuric acid media at different scan rates of 50

to 300 mVs-1 . At the scan rate of 100 mVs-1 compound showed anodic peak potential

at 0.661V for the oxidation of -NH moiety as shown in Fig. 33. The

quasirreversibility was confirmed by the presence of an anodic peak between the

potential of +0.8 mV to –0.8 mV. Variation of scan rate from 50 mVs−1 to 300 mVs−1

as shown in Fig. 34. The cathodic peak current increases with scan rate and the

overall electrode process is diffusion controlled.

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Fig. 33. Cyclic voltammogram of 81a at glassy carbon electrode in

25mM sulfuric acid at scan rate 100 mVs-1.

Fig. 34. Variation of 81a scan rate from 50 mVs−1 to 300 mVs−1.

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Part-3: Cyclic Voltammetric Studies of 3-(2,5-disubstituted-1H-indol-3-yl)-1(4-

substitutedphenyl)prop-2-en-1-one.

(119b)

Cyclic voltammogram of (E)-3-(5-chloro-2-phenyl-1H-indol-3-yl)-1-

phenylprop-2-en-1-one (119b) (Fig. 35). Electrochemical investigation of compound

(119b) was carried out at glassy carbon electrode in a mixture of ethanol and 25mM

sulphuric acid at scan rate 0.1 Vs-1. The potential window was maintained between

+1.0 to -1.0 V. The cyclic voltammogram shows a reduction peak at -0.641 V (Fig.

35) corresponding to the reduction of carbonyl group present in the molecule at the

glassy carbon electrode. In the mixture of ethanol and 25mM sulphuric acid and the

sweep rate was varied from 50 to 200 mVs-1, in all the cases the cathodic peak

current was proportional to the square root of the scan rate. Under these conditions

the currents were diffusion-controlled16. The peak potential was shifted towards more

negative values with an increase in the scan rate, indicating that electrochemical

process was quasirreversible. The presence of peak in reverse scan and the peak

potential shift to higher when the scan rate increased. This means that under these

conditions the electrochemical processes are more irreversible. From the graph, we

can see that the C=O group in the chalcones is easily reduced at the glassy carbon

electrode by cyclic voltammetry. Variation of scan rate from 50 mVs−1 to 200 mVs−1

as shown in Fig. 36.

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Fig. 35. Cyclic voltammogram of 119b at glassy carbon electrode in 25mM

sulfuric acid at scan rate 100 mVs-1.

Fig. 36. Variation of 119b scan rate from 50 mVs−1 to 200 mVs−1.

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5.3 Experimental

Instrumentation

The electrochemical experiments were carried out using a model-660

Electrochemical Workstation (CHI660c). All experiments were carried out in a

conventional three-electrode system. The electrode system contains a working Glassy

Carbon electrode, a platinum wire as counter electrode and saturated calomel

electrode as reference electrode (a reference electrode, typically Ag/AgCl) as shown

in Fig. 37. Experimentally, the potential of a working electrode is linearly scanned Vs

a reference electrode from an initial value to a final value and back. Thus, forward

and backwards electrochemical reactions can be studied. This in a typical cyclic

voltammetric experiment of substrate (indole derivative), reaction mixture consisted

of indole derivative solution, ethyl alcohol and sulphuric acid media was used for the

electrolytic reduction. The three electrodes were connected to a computer controlled

potentiostat and required potential scan rate, current sensitivity, initial potential and

final potential were fixed and the resulting current measured as a function of applied

potential.

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Fig. 37. Electrochemical cell used in cyclic voltammetry experiments.

Pre-treatment of glassy carbon electrode

Before each measurement, Glassy-carbon electrode is generally pre-treated

either electrochemically or mechanically to obtain a reproducible electrode surface.

Electrochemical pre-treatment is usually performed by cyclic scanning over a wide

potential range. Mechanical polishing is generally performed by polishing the glassy-

carbon electrode with alfa alumina powder (0.3µ) on rubbing pad and then rinsed

with purified water until there were no visible markings or scratches. This procedure

was repeated after each set of experiment.

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5.4 References

1. J. G. Teixeira, C. B. Dias, D. M. Teixeira, Electroanalysis., 21, 2345 (2009).

2. B. Bozal, B. Uslu, S. A. Ozkan, Int. J. Electrochem., 1 (2011).

3. P. Protti Introduction to Modern Voltammetry and Polarographic Analysis

Techniques; fourth ed.; Amel electrochemistry, (2001).

4. J. Wang, Analytical Electrochemistry, second edition, (2001).

5. Z. Galus, Fundamentals of electrochemical analysis, second edition, (1994).

6. H. H. Willard, L. L. Merritt, J. A. Dean, F. A. Settle, Instrumental methods

of analysis, 7th edition,1988.

7. Heinze, J. Angew. Chem., Int. Ed. 23, 831 (1984).

8. S. Yilmaz, B. Uslu, S.A. Ozkan, Talanta., 54, 351 (2001).

9. J. M. P. Carrazon, A. J. R. Garcia, L. M. P. Diez, J. Electroanal. Chem., 234,

175 (1987).

10. J. M. P. Carrazon, A. J. R. Garcia, L. M. P. Diez, Analyst 115, 869 (1990).

11. R. E. Panzer, P. J. Elving, Electroclzemi. Acta., 20, 635 (1975).

12. J. P. Randin, Encyclopedia Electrochem. Elements., 5, 1 (1976).

13. R. N. Adams, Electrochemistry at Solid Electrodes, (Marcel Dekker, New

York) 1969.

14. H. E. Zittel, F. J. Miller, Anal. Clrem., 37, 200 (1965).

15. W. E. VanDer Linden, J. W. Dieker, Anal. Clrem. Acta., 119, 1 (1980).

16. B. Eshwarappa, B. S. Sherigara, B. E. Kumaraswamy, Bull. Electroclzem.,

20, 1 (2004).