Research Journal of Recent Sciences ________________________________________________ ISSN 2277 - 2502
Vol. 1(ISC-2011), 341-344 (2012)
Res.J.Recent.Sci.

Short Communication

A Study of Transition Metal Complex of Diuretic Drug and study of its
Physico-chemical properties as Potential Therapeutic Agent
Nair Smita
Prestige Institute of Engineering and Science, Indore, M.P. INDIA

Available online at: www.isca.in
(Received 30th December 2011, revised 1st January 2012, accepted 24th January 2012)

Abstract
It has been found that biologically active compounds become more effective and bacterio-static upon chelation with metal ions1.
The biological activity of many drugs has been shown to be enhanced on complexing with metal ions, hence promoting their use in
Pharmacology5. The pharmaceutical action of such ‘drug complexes’ are henceforth studied. In the context of present research
work, drugs are used as ligands or chelating agents that contain atoms or groups like N, O, P etc that can attach with metals or
metal ions by coordinate linkages to form complexes. . Although a large number of therapeutic agents are known, the literature
survey reveals that very little work has been done on the metal complexes of diuretic drugs. The present work deals with the
synthesis of metal complexes derived from diuretic drugs and their physio-chemical analysis to find out ligand- metal ratio of these
complexes in solution. The complexes of Mn salts are prepared. For the structure elucidation of these complexes “Monovariation
method” has been used to ascertain the ligand-metal ratio in the complex. The stability constant of the formed complex was
calculated by molar conductance measurement using Modified Job’s method. The analysis has been carried out using
conductometry and pHmetry. To confirm metal-ligand ratio, conductometric titrations were carried out at room temperature using
analytical grade metal salts. Titrations were carried out with “systronics conductivity-meter” using dip type conductivity cell
having cell constant 1 at room temperature. These findings might be useful in the optimization of Amyloride as lead for future
development of diuretic drugs for hypertension.
Keywords: Diuretic drugs, transition metals, complexes, ligand, conductometry.

Introduction

Material and Methods

Diuretics, according to modern pharmacology, are described
as medicines or substances that help to reduce the amount of
water in body and promote formation of urine by kidney.
They are used to treat the buildup of excess fluid in body i.e.
edema. But their application to the management of
hypertension has outstripped their use in edema. They are
among the most widely used prescribed drugs for the
treatment of high blood pressure. In this paper I have
attempted to prepare transition metal complexes of the
diuretic drug Amyloride and to study their compositions.
Amyloride is a direct acting potassium sparing diuretic, used
in the management of hypertension and congestive heart
failure. It promotes the loss of sodium and water from the
body but without depleting potassium.

Conductometric titrations for detection of Metal-Ligand
ratio (Monovariant method)4: Solution of drug having
strength 0.01m was prepared using methanol: water mixture
(3:2) of 100ml. Similarly, 0.02M of metal salt was prepared
and these stock solutions were suitably diluted as and when
required.

Amyloride is 3,5-diamino-N- (aminoiminomethyl)-6–
chloropyrazine carboxamide monohydrochloride dihydrate.
Its molecular formula is C6H8ClN7O.HCl.2H2O. The
molecular weight of monohydrochloride is 266.09

Conductance= {(V+v)/V}*(Observed Conductance)
Where, V=initial volume of ligand solution, v=volume of
metal solution added, Titration results are recorded in table 1.
Results were plotted in the form of a graph between
corrected conductance and volume of metal salt. From the
equivalence point in the graph, ratio between metal and
ligand was noted to be 1:17.

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5ml of drug solution (0.01M) was diluted to 50ml in a beaker
and kept at thermostatic bath at 25◦C (ligand solution). This
was titrated conductometrically against 0.02M metal salt
solution taken in a burette. Conductance was recorded after
every addition of 0.5ml of metal salt solution with constant
stirring at constant temperature. Volume corrections were
applied as

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Research Journal of Recent Sciences ____________________________________________________________ ISSN 2277 - 2502
Vol. 1(ISC-2011), 341-344 (2012)
Res.J.Recent.Sci

S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.

Table 1
Conductometric titration between Amyloride drug solution and MnCl2.4H2O
Volume of metal salt added
Observed Conductance
Corrected Conductance
(ml)
(mS)
(mS)
0
0
0
0.5
0.10
0.102
1.0
0.15
0.153
1.5
0.17
0.175
2.0
0.19
0.197
2.5
0.22
0.231
3.0
0.24
0.276
3.5
0.27
0.288
4.0
0.30
0.324
4.5
0.31
0.337
5.0
0.32
0.350
5.5
0.34
0.370
6.0
0.36
0.400
6.5
0.38
0.420
7.0
0.40
0.450
7.5
0.41
0.470
8.0
0.43
0.498
8.5
0.45
0.526
9.0
0.47
0.550
9.5
0.48
0.570
10.0
0.50
0.600
Corrected conductance (mS)

0.7

0.6
0.5
0.4
0.3
0.2
0.1
0
0

1

2

3

4

5

6

7

8

9

10

Volume of metal solution added (mL)

Graph - 1
Conductometric titration between Amyloride drug and MnCl2.4H2O
12.0ml and ligand solution from 12.0ml to 0.0ml.
Conductance was recorded for each solution. ∆ Conductance
Modified Job’s Method of continuous variation3 for
determining composition and stability constant of
complex: Equimolar solutions of ligand and metal solutions
Was calculated as “C1+C2-C3” 10.Graphs were plotted
were prepared and three series C1, C2, C3 of solutions were
between corrected conductance and mole metal-ligand ratio.
made. In set C1 metal salt solution was filled with volume
The composition and stability constants were determined
0.0ml to 12.0ml and total volume was made to 12.0ml in
from the equivalence point in the graph8. The study was
each. Similarly, in C2 ligand solution was filled and set C3
carried out using Amyloride drug as ligand and Mn (II) as
was prepared by mixing metal salt solution from 0.0ml to
metal salt. The results are recorded in table 2a and 2b. Table
2a and 2bThe results of the tables are plotted in the form of

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342

Research Journal of Recent Sciences ____________________________________________________________ ISSN 2277 - 2502
Vol. 1(ISC-2011), 341-344 (2012)
Res.J.Recent.Sci
graph 2. The peak in the graph coincides with the ratio of
metal and drug in solution9, which comes out to be 1:1.
Table 2 (a)
Conductance of Amyloride drug and MnCl2.2H2O (Modified Job’s Method)
Concentration of metal= 0.01M, Concentration of ligand=0.01M
Corrected.
S.No Ratio
M:S
S:L
M:L
∆conductance
Conductance
(C1)
(C2)
(C3)
(C1+C2-C3) (mS)
(mS)
1
0:12
0.082
0.102
0.120
0.06
0
2
1:11
0.120
0.105
0.135
0.09
0.030
3
2:10
0.131
0.109
0.130
0.11
0.050
4
3:9
0.150
0.110
0.136
0.124
0.064
5
4:8
0.180
0.130
0.150
0.16
0.100
6
5:7
0.201
0.150
0.159
0.192
0.132
7
6:6
0.209
0.180
0.177
0.212
0.152
8
7:5
0.211
0.187
0.199
0.199
0.139
9
8:4
0.213
0.191
0.220
0.184
0.124
10
9:3
0.215
0.195
0.230
0.180
0.120
11
10:2
0.218
0.200
0.268
0.150
0.090
12
11:1
0.220
0.206
0.286
0.140
0.080
13
12:0
0.230
0.208
0.313
0.115
0.055
Table 2(b)
Concentration of metal= 0.005M, Concentration of ligand=0.005M
S.No

Ratio

M:S

S:L

M:L

∆conductance

1
2
3
4
5
6
7
8
9
10
11
12
13

0:12
1:11
2:10
3:9
4:8
5:7
6:6
7:5
8:4
9:3
10:2
11:1
12:0

(C1)
0.04
0.054
0.078
0.097
0.107
0.132
0.151
0.159
0.164
0.168
0.171
0.175
0.178

(C2)
0.089
0.090
0.087
0.087
0.086
0.086
0.086
0.084
0.083
0.081
0.080
0.075
0.068

(C3)
0.091
0.093
0.095
0.096
0.097
0.098
0.099
0.122
0.137
0.153
0.165
0.185
0.190

(C1+C2-C3) (mS)
0.038
0.051
0.070
0.088
0.096
0.120
0.138
0.121
0.110
0.096
0.086
0.065
0.056

Corrected
conductance (mS)

0.3
0.25
0.2
0.15
0.1
0.05
0

Corrected
Conductance
(mS)
0
0.013
0.032
0.050
0.058
0.082
0.100
0.083
0.072
0.058
0.048
0.027
0.018

0.01M
0.005M

Metal-ligand ratio
Graph - 2
Conduct metric estimation of composition of complex of Amyloidal and Mn

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Research Journal of Recent Sciences ____________________________________________________________ ISSN 2277 - 2502
Vol. 1(ISC-2011), 341-344 (2012)
Res.J.Recent.Sci
Synthesis of complex of Amyloride with Mn(II): For the
synthesis of complex, 0.005M solutions of Amyloride drug
and Manganese chloride (MnCl2) were prepared. On mixing
both the solutions the pH was adjusted to 8.2 using freshly
prepared NaOH solution. This solution was refluxed for 4
hours and kept undisturbed for 7 days. Brown coloured
product was obtained. The product was washed, filtered,
dried and weighed. % yield -8%

Results and discussion
Turner and Anderson2 have modified Job’s method for the
determination of stability constants. If the initial
concentration of metallic ions and ligands are “a” and “b”
respectively then stability constant “K” is given by the
equation
K=

………… (1)

Where “x” is the concentration of the complex.ⁿ
If two solutions on the two curves have the same
conductance then a1, a2 and b1, b2 represent the concentration
of the metal and the ligand respectively for 1:1 complex.
Thus, following equation can be derived from equation (1)
……… (2)
From graph 2,
= (0.01*2)/12= 0.00166, b1= (0.01*10)/12=0.00833
a2= (0.005*3)/12=0.00125, b2= (0.005*9)/12=0.00375.
From equation 2, value of x comes out to be x= 0.00145
Thus, from equation 1 K= 1.003599 x 103 or log K= 3.00156
Free energy change
∆G= -2.303 RT log K Or ∆G= -4.134 Kcal/mol
Through this analysis, it has been observed that the formation
of complex of Amyloride with bivalent metal cations like
Mn(II) takes place in the ratio 1:1. The modified Job’s
method of continuous variation was used to calculate the
stability constant of the complex and the free energy change.
The value of free energy change is negative showing the
feasibility of complex formation. The results are recorded in
table 3. After determining the metal-ligand ratio, the stability
constant and free energy changes, the complex was
synthesized. These findings might be useful in the
optimization of Amyloride as lead for future development of
diuretic drugs for hypertension.

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Conclusion
Through this work it has been ascertained that the drug
Amyloride forms a complex in solution with bivalent cations
like Mn (II) in the ratio of 1:1. The stability constant of the
complex and the free energy change values show the
feasibility and stability of the formed complex. These
findings might be useful in the optimization of Amyloride as
lead for future development of diuretic drugs for
hypertension.

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1.

Weisman M.H. and Albert. D, American Journal of
Medicine 75, 157-164 (1983)

2.

Anderson W.F., Inorganic Chemistry in Biology and
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3.

Carradona J.P. and Lippard S.J., Inorganic Chemistry
(1988)

4.

Sengupta N.R., Indian Journal of Chemistry 29, 33
(1966)

5.

Raman N, Antonysamy Transition metal chemistry, 1-2,
26 (2001)

6.

Iqbal S.A., Qureshi R. and Siddiqui S., Orient Journal
of Chemistry , 3(3), 276-277 (1987)

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Iqbal S.A. and Kaushal R., Journal of Science and
Research, 2, 223 (1980)

8.

Qualitative Inorganic Analysis, Longmann Green and
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Wilkins R.G, Kinetics and Mechanism of Reactions of
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