FTIR, 1H NMR, ESR, TGA and DTA analysis of trithiocarbonates of captopril and 6-mercaptopurine as their palladium(II) chloride complexes

Article abstract of DOI:10.1002/jccs.200700202

A simple and sensitive spectrophotometric method has been developed for the determination of the antihypertensive drug captopril and anticancer drug 6-mercaptopurine, in their trithiocarbonate (TTC) form by using Pd(II) chloride as a coloring reagent. Captopril TTC forms a stable dark yellow colored complex with λ_max 383 nm, molar absorption coefficient 1.35 × 10⁵ l/mole/cm and a Beer's law range from 0.084-1.26 ppm. 6-Mercaptopurine TTC forms a stable deep yellow colored complex with λ_max 345 nm, molar absorption coefficient 6.9 × 10 ⁵ l/mole/cm and a Beer's law range from 0.0319 ppm to 3.519 ppm. The M: L ratio of palladium: TTC complexes were confirmed by Job's method of continuous variance and mole ratiomethod and was found to be 1:1 for both captopril TTC as well as 6-mercaptopurine TTC. In addition, on the basis of, FTIR, ¹H NMR, ESR and thermal analysis data a plausible structure of mononuclear Pd(II) complex of Captopril TTC and 6-mercaptopurine TTC has been reported.

Full text of DOI:10.1002/jccs.200700202

Journal of the Chinese Chemical Society, 2007, 54, 1419-1432
1419
FTIR, 1H NMR, ESR, TGA and DTA Analysis of Trithiocarbonates of
Captopril and 6-Mercaptopurine as Their Palladium(II) Chloride Complexes
Mukul Sharma,a* Afraim Koty,a Mamta Srivastavaa and Ashutosh Srivastavab
aGovt. Autonomous Science College, Jabalpur (M.P.)
bDepartment of Chemistry, R.D. University of Jabalpur (M.P.)
A simple and sensitive spectrophotometric method has been developed for the determination of the
antihypertensive drug captopril and anticancer drug 6-mercaptopurine, in their trithiocarbonate (TTC)
form by using Pd(II) chloride as a coloring reagent. Captopril TTC forms a stable dark yellow colored
complex with lmax 383 nm, molar absorption coefficient 1.35 ´ 105 l/mole/cm and a Beer’s law range from
0.084-1.26 ppm. 6-Mercaptopurine TTC forms a stable deep yellow colored complex with lmax 345 nm,
molar absorption coefficient 6.9 ´ 105 l/mole/cm and a Beer’s law range from 0.0319 ppm to 3.519 ppm.
The M: L ratio of palladium: TTC complexes were confirmed by Job’s method of continuous variance and
mole ratio method and was found to be 1:1 for both captopril TTC as well as 6-mercaptopurine TTC. In ad-
dition, on the basis of, FTIR, 1H NMR, ESR and thermal analysis data a plausible structure of mono-
nuclear Pd(II) complex of Captopril TTC and 6-mercaptopurine TTC has been reported.
Keywords: Captopril; 6-Mercaptopurine; Spectrophotometric; Determination.
INTRODUCTION
Trithiocarbonate (TTC) is an important chemical
polarography,10 atomic absorption spectrometry,11 fluoro-
metry,12 and volumetric and spectrophotometric methods.13
Captopril has three different potential donor groups
(S, O and O), which might be involved in thiol acid amide
coordination to metal ions. The direct coordination of the
polymeric gold(I)-captopril (Aucap)n14 is carried out using
viscosity, electronic, mass, and 13C, 15N NMR spectros-
copy.
compound useful in surface colloid science and in the con-
text of nanotechnology.1 Various alkyl TTC forming salts
with copper(I) and zinc(II) are known bird repellents,2 in-
secticides and therapeutic formulations such as Thioquinox,
which is a cyclic trithiocarbonate of quinoxaline dithiol.3
Srivastava, et al.4 reported volumetric determination of tri-
thiocarbonate with N-iodosuccinimide, N-bromosaccha-
rin, N-chlorosaccharin and bromine monochloride. The
stoichiometry was 1:1 with all reagents in aqueous bicar-
bonate, acetic acid and acetonitrile medium.
Complexes of captopril and Zn(II) have been studied
by several authors.15-16 Compounds were precipitated from
aqueous solution at pH 6.0 [Zn (cap)] and in the pH range
6.0-8.2. Similarly to Zn(II), organotin(IV) compounds also
show strong ability to coordinate to the thiolate group.17
6-Mercaptopurine (6MP), a sulfur analogue of adenine, is
one of the oldest anticancer drugs and immunosuppressive
agents.18 It has been established that 6-mercaptopurine and
its metabolites extend their primary cytotoxity through in-
corporation of deoxythioguanosine into DNA and inhibit
the function of RNAse in DNA-RNA heteroduplex mole-
cules.19
Captopril, 1{(2S)-3-mercapto-2-methylpropionyl}-
L-proline, is an angiotensin-converting enzyme (ACE) in-
hibitor, which reduces peripheral resistance and lowers
blood pressure. It is widely used in the hypertensive ail-
ments and in congestive heart failure treatment.5 Due to
such crucial pharmacological importance, development of
simple and accurate methods for the determination of
captopril is desired. Several methods of analysis have been
proposed for the determination of captopril which include
high performance liquid chromatography,6 gas chromatog-
raphy,7 capillary electrophoresis,8 flow injection analyses,9
Various analytical methods have been reported for the
quantitative determination of 6-mercaptopurine including
voltametry,20 1H NMR analysis,21 and high performance
liquid chromatography.22
* Corresponding author. E-mail: mukul_772@yahoo.co.in

1420 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
6-Mercaptopurine is a polydentate heterocycle con-
taining N- or S-donors. It binds with transition metal ions
showing a variety of coordination modes often simulta-
neously with proton (6-H2 mp+) deprotonation (6-mp-,
6-mp-2 ) or intramolecular proton transfer.21 Bariyanga et
al.23 have reported Pt (II) complexes of 6-mercaptopurine
prepared in neutral and acidic media because of their insol-
ubility in organic solvents.
a 0 °C-1000 °C temperature range at a rate of 15 °C /min.
Electronic absorption measurements were carried out
on a Helios delta (Pie Unicam UK) Spectrophotometer us-
ing 1 cm glass cuvettes.
Reagents
All the reagents were of analytical grade and double
distilled water was used throughout the study. Palladium(II)
chloride was purchased from Johnson and Matthey Co.,
and standard stock solution was prepared by dissolving 1 g
of palladium chloride in double distilled water and the vol-
ume is then made up to 1 L. Standardization of the solution
was done gravimetrically by dimethylglyoxime. Solutions
of lower concentration were prepared by approximately di-
luting aliquots of stock solution. Captopril in pure form
was given by Bristol Myers Squibb, Co., New Jersey, USA.
6-Mercaptopurine, Emupurine (50 mg), Dabur India
Ltd, was purchased from a local commercial store; twenty
tablets were weighed and ground into a fine powder. An
amount of powder equivalent to 100 mg of 6-mercapto-
purine was dissolved in a 100 mL volumetric flask using
double distilled water and standardized iodimetrically.
A literature survey shows that no derivatisation in the
form of trithiocarbonates of these drugs has been reported.
The derivatisation of a drug to its trithiocarbonate moiety
plays an important role and becomes more effective as
compared to the parent molecule when coordinated with
metal. The aim of this study is to prepare Pd(II) complexes
of captopril TTC and 6-mercaptopurine TTC in alkaline
medium and characterize them by FTIR, NMR, ESR
thermogravimetry (TGA) and differential thermal analysis
(DTA) in order to verify the coordination sites and estab-
lish the structure of 6-MPTTC and its palladium complex
and captopril TTC and its palladium complex.
C11H18O3S2NK + PdCl2
(Captopril TTC)
®
{Pd[C11H18O3S3N(H2O)4]}×H2O×K+×2Cl
Synthesis of Captopril TTC and 6-Mercaptopurine
TTC
(Captopril TTC: Pd(II) chloride complex)
Trithiocarbonates were prepared by reacting an equi-
molar quantity of captopril and 6-mercaptopurine with an
equimolar mixture of carbon disulphide in the presence of
alkali. The derivatisation with excess of carbon disulphide
in the presence of alkali to the corresponding trithiocar-
bonate proceeds smoothly and quantitatively at room tem-
perature below 10 °C. The alkali drives the reaction to
completion.
C6H4S3N4K + PdCl2
®
(6-Mercaptopurine TTC)
{Pd[C6H4S3N4(H2O)4]}×H2O×K+×2Cl
(6-Mercaptopurine TTC: Pd(II) chloride complex)
EXPERIMENTAL
Instruments
Fourier Transform Infrared measurements using KBr
Procedure
(A) Preparation of Complex
pellets were performed on a Nicolet FTIR spectrometer in
the range 4000-400 cm-1.
The complex is prepared by adding an excess of cap-
topril TTC solution 1.00 ´ 10-3 M) and 6-mercaptopurine
TTC solution to an equimolar solution of Pd(II) (1.00 ´ 10-3
M) taken in a flask and the contents are allowed to react for
a period of 60 minutes at room temperature and 30 minutes
at room temperature. The solid complex is prepared by
evaporating the content of the complex formed. The solid
samples were further purified by crystallization.
(B) Determination of Captopril TTC and
6-Mercaptopurine TTC as Pd(II) Complex
Spectrophotometric studies of Pd(II) chloride com-
Nuclear Magnetic Resonance measurements were
carried out on a Varian 300 MHz spectrometer; samples
were dissolved in D2O as solvent with TMS as internal
reference.
Electron Spin Resonance measurements were carried
out on a Varian ESR spectrometer, using tetracyanoethyl-
ene as marker.
TGA and DTA analyses were carried out on a Dupont
Thermal Analysis system, under nitrogen atmosphere from

Determination of Captopril and 6-Mercaptopurine as its Trithiocarbonate
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1421
Equation 1. Synthesis of captopril TTC and 6-mercaptopurine TTC
plex with captopril TTC and 6-mercaptopurine TTC in-
volves the Io of the spectra, which is obtained by filling
conductivity water in both the reference as well as in the
sample cells.
complex was found to absorb the maximum at 383 nm
(captopril TTC 254 nm) and 345 nm, (6-MPTTC 240 nm)
and were used throughout the determinations. Full color
development was observed after 1 hour in the case of cap-
topril TTC: Pd complex and stable up to 24 hours, whereas
in 6-mercaptopurine TTC: Pd complex full color develop-
ment was observed after 30 minutes and remained un-
changed up to 1 hour at room temperature. The M:L ratio of
the trithiocarbonate complexes was found to be 1:1 con-
firmed by Job’s method of continuous variance and the
Mole ratio method. When the proposed method was ap-
plied to the determination of captopril trithiocarbonate and
6-mercaptopurine trithiocarbonate the % error was found
to be 0.4754%, standard deviation 1.32 ´ 10 –5 - 6.928 ´
10-3 and coefficient of variance was 0.0156 for captopril
and 0.139%, 1.154 ´ 10-4 - 3.160 ´ 10-4 and 0.0482 for
6-mercaptopurine.
A Beer Lambert’s law graph for captopril TTC and
6-mercaptopurine TTC and Pd(II) complex was prepared
by recording and plotting the absorbance value of the con-
centrations of a series of captopril TTC and 6-mercapto-
purine TTC solutions of known concentrations at 383 nm,
and 345 nm which is the lmax of the complex.
Different aliquots containing 0.0319 mg - 3.511 mg
of the drug TTC samples were taken in a 10 mL measuring
flask and then 2.0 mL of Pd(II) chloride (1.00 ´ 10-3 M) so-
lution was added to it and the volume made up to the mark
by adding distilled water. The absorbance values of these
sample aliquots correspond to the unknown concentra-
tions, which were calculated from the standard Beer Lam-
bert’s law graph. The unknown concentrations can also be
calculated from the regression equation derived from
Beer’s law.
Interference of foreign metal ions was also studied; 1
ppm of captopril TTC could sustain copper acetate (1.46
ppm) 0.0001 ppm of nickel sulphate, 0.001 ppm of zinc sul-
phate, 0.007 ppm of cobalt nitrate and 0.2133 ppm of fer-
rous ammonium sulphate, whereas ferric chloride and os-
mium tetra oxide interfere severely. In 6-mercaptopurine
TTC the effect of foreign metal ions show that 1 ppm of
6-MPTTC can bear 0.005 ppm of Cu(II), 0.078 ppm of
Fe(III), 0.12 ppm of Zn(II), whereas Ru(III) and Fe(II) in-
terfere severely. The complexes formed from captopril
TTC and 6-mercaptopurine TTC have been characterized
RESULTS AND DISCUSSION
It was found that the captopril trithiocarbonate and
6-mercaptopurine trithiocarbonate form a dark yellow col-
ored complex with Pd(II), which is stable in alkaline me-
dium, whereas precipitation occurs in acidic medium. The

1422 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
Table 1. Characteristic FTIR spectroscopic bands of captopril and captopril TTC with
palladium(II).{w- weak, m- medium, s- strong, vs.- very strong, b- broad}
Assigned
Captopril
Captopril TTC
Captopril TTC: Pd(II)
1. v (O-H-O)
2. (S-H)
1050 & 1200 cm-1
-
1024 & 1175 cm-1
disappear
2567 cm-1 (m)
disappear
1600 cm-1 (m)
850 cm-1
1400 cm-1
-
3. (O-C-N)
4. C-S
-
1628 cm-1
577 cm-1
631 cm-1
5. v C-N & C=S
6. C=O (str)
-
1300 cm-1
1725 cm-1
1725 cm-1
by the following spectral data.
metal. Moreover, the FTIR spectrum of the captopril mole-
cule shows one band with medium intensity at 2567 cm-1
attributed to the v (S-H) vibration. This band is diminished
in the spectrum of captopril TTC confirming deprotona-
tion. A stretching band at 577 cm-1 in the spectrum of the
drug captopril assigned to the C-S stretch is shifted to 850
cm-1 in its trithiocarbonate group. Furthermore, a band at
631.6 cm-1 appears in the spectrum of captopril TTC: palla-
dium confirming the coordination with palladium(II) as
shown in Table 1.
FTIR studies of Captopril, Captopril TTC and its
Pd(II) Complex
In the solid state, captopril molecules are linked to-
gether as infinite chains by hydrogen bonding involving
the carboxylic OH of one molecule and the carbonyl -CO
of another. Due to the v(O-H-O) system, the FTIR spec-
trum of the free ligand (Fig. 1) exhibits a stretching band at
1050 cm-1 and 1200 cm-1. These bands get shifted to 1024
and 1157 cm-1 upon coordination indicating the breakup of
the hydrogen bond network.
Amedium band at 1600 cm-1 in captopril TTC (Fig. 2)
assigned to the O-C-N band which is shifted to 1628 cm-1
in the spectrum of captopril TTC: Pd complex indicating
the involvement of the carbonyl group in binding with
The coordination of the v C-N and v C-S bands can
be confirmed from the FTIR data, because the band at 1400
cm-1 in the captopril trithiocarbonate is shifted to 1300 cm-1
indicating the binding of sulphur to palladium(II). The
shifting of the band is due to a decrease in the double bond
character of the C-S bond owing to palladium-sulphur
Fig. 1. FTIR spectrum of captopril.

Determination of Captopril and 6-Mercaptopurine as its Trithiocarbonate
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1423
1
bond formation as shown in (Fig. 3). The presence of lattice
water molecules in the complex is confirmed by a broad
band at 3417 cm-1. A stretching band at 1200 cm-1 indicates
the presence of an uncoordinated COOH group. The stretch-
ing frequency of the C=O of -COOH group in captopril at
1725 cm-1 is at the same frequency in Pd(II) complex, but
the intensity of the peak is reduced which is due to the
H-bonded nature of the complex (Table 1).
the expected resonances. In the H NMR spectrum of
trithiocarbonate of captopril the chemical shift at 4.0 ppm
attributed to a-CH has a downfield shift to 4.74 ppm in its
palladium(II) complex, confirming the involvement of a
carbonyl group in bonding with palladium(II).
The 1H NMR spectrum of captopril shows resonance
at 2.60 ppm, which gets shifted to 3.6 ppm in the spectrum
of captopril trithiocarbonate, whereas in the spectrum of
captopril TTC: palladium complex (Fig. 6) this peak is
shifted to 3.85 ppm confirming the binding of sulphur to
palladium.
1H NMR Studies of Captopril, Captopril TTC and its
Pd(II) Complex
The 1H NMR spectrum of captopril (Fig. 4), captopril
The spectrum of captopril TTC complex exhibits sig-
nals at 4.82, 4.85, 4.90 and 5.14 ppm attributed to water
molecules present in the complex (Table 3).
TTC (Fig. 5) and its complex in deuterium oxide display
ESR Data of Captopril, Captopril TTC and its Pd(II)
Complex
The electron spin resonance of the captopril (Fig. 7)
shows no resonance peaks confirming the diamagnetic na-
ture. However conversion of captopril to trithiocarbonate
results in the appearance of the ESR signal.
Calculation of “g” (Lande’s Splitting Factor)
DH
g
Sample = gStandard (1 -
)
H
Fig. 2. FTIR spectrum of captopril TTC.
where
Fig. 3. FTIR spectrum of captopril TTC: Pd(II) complex.

1424 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
Fig. 4. 1H NMR spectrum of captopril.
DH = Width between deflection points on the deriva-
tive absorption
H = Magnetic field
g
Standard = Lande’s factor for free electron
150
= 2.0023 (1-
)
1350
= 2.0023 ´ 0.89 = 1.7820
A lower value of “g” is an indication of the covalent
nature of captopril TTC: Pd(II) (Fig. 8) complex; ESR lines
exhibited by this complex confirm the binding of the sul-
phur atom of trithiocarbonate moiety to the palladium(II).
Fig. 5. 1H NMR spectrum of captopril TTC.
Fig. 6. 1H NMR spectrum of captopril TTC: Pd(II) complex.

Determination of Captopril and 6-Mercaptopurine as its Trithiocarbonate
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1425
Table 2. Characteristic FTIR spectroscopic bands of 6-mercaptopurine and complex of 6-mercaptopurine TTC
with Pd(II)
Assigned
6-Mercaptopurine
6-Mercaptopurine TTC
6-Mercaptopurine TTC: Pd(II)
1. C=S
1050 cm-1
1130 cm-1
873 cm-1
3394 cm-1 (b)
-
disappear
854 cm-1
2. v(C-S)
3. N-H
-
-
-
-
3381 cm
623, 1630, 3381 cm-1
4. OH
5. v (purine)
1229 cm-1 354 cm-1 & 1591 cm-1 1235 cm-1, 1347 cm-1 & 1588 cm-1
Table 3. 1H NMR data of captopril and captopril TTC with palladium(II)
Proton
Captaopril (ppm)
Captopril TTC (ppm)
Captopril TTC: Pd(II) (ppm)
1. S-CH
2. -SH
2.60 (m)
1.53
3.60
-
3.85
absent
4.74
-
3. a-CH
4. -CH
-
4.0
1.17 v
1.20 (w)
Total number of ESR signals for M:L complex
1. Sulphur as donor atom (I1 = 0)
1. Weight loss begins below 200 oC
The thermogram shows that removal of lattice water
molecules begins at 51.89 oC and gets completed at 150 oC.
In this range there is a weight loss of 100% to 97%.
2. Weight loss between 200 oC to 760 oC
(2 ´ n ´ I1 + 1) = (2 ´ 2 ´ 0 + 1) = 1
2. Oxygen as donor atom (I2 = 0)
(2 ´ n ´ I2 + 1) = (2 ´ 2 ´ 0 + 1) = 0 + 1 = 1
Total number of ESR signals is
This range of temperature confirms the removal of
coordinated water molecules and chloride ions from the re-
maining complex. Complete removal of coordinated water
(2 ´ n ´ I1 + 1) + (2 ´ n ´ I2 +1) = 1 ´ 1 =1
Thus only one resonance peak is observed in the ESR
spectrum of captopril TTC: Pd (II) complex confirming the
presence of one captopril molecule in the complex.
o
molecules takes place at 214.28 C. In this range weight
loss of 97% to 73% takes place.
3. Weight loss between 760 oC to 950 oC
Thermogravimetric Analysis of Captopril TTC:
Pd(II) Complex
In this temperature range elimination of captopril
TTC moiety from the remaining complex leaves elemental
carbon, palladium metal and potassium. The derivative
thermogram of the complex shows that the bond between
TGA curves of the captopril trithiocarbonate: Pd(II)
complex (Fig. 9) exhibit the following features.
Fig. 7. ESR spectrum of captopril and captopril TTC.

1426 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
Fig. 8. ESR spectrum of captopril TTC: Pd(II) complex.
palladium and sulphur breaks at 895.98 oC. In this range
weight loss from 73% to 44.5% takes place.
dinated water molecules from the axial position. Removal
of coordinated water molecules from captopril trithiocar-
bonate: palladium(II) complex results in the reduction of
electron density from palladium metal ion and conse-
quently it is oxidized from its coordinated state. As has
been suggested by Wendlendt, the chemical changes lead-
ing to oxidation are exothermic in nature.
Differential Thermal Analysis (DTA) of Captopril
TTC: Pd(II) Complex
DTA curve of captopril TTC: Pd(II) complex (Fig.
10) exhibits the following endotherms and exotherms:
1. Endotherm at 143.38 oC
3. Exotherm at 400 oC to 600 oC
This endotherm confirms the presence of lattice water
molecules in the complex. The DTA curve also confirms
o
that liberation of water molecules starts at 51.89 C and
In this range of temperature, a broad exotherm is ob-
tained which confirmed the removal of two water mole-
cules that are coordinated to palladium(II).
gets completed at 143.38 oC.
4. Endotherm at 600 oC to 1000 oC
2. Exotherm at 160 oC to 400 oC
Endothermic changes are mainly associated with the
decomposition reaction that occurs due to removal of a
whole organic ligand i.e. captopril trithiocarbonate moiety
from the complex. As well, a breakdown of the palladium
sulphur bond in complex may also require energy in the
form of heat.
This exotherm is associated with the removal of coor-
From these studies we hereby propose the most plau-
sible structure of captopril TTC: Pd(II) complex.
FTIR Studies of 6-Mercaptopurine, 6-Mercaptopurine
TTC and its Pd(II) Complex
The FTIR spectrum of 6-mercaptopurine (Fig. 11)
shows that it exists in thione form which is confirmed by
the presence of a band at 1150 cm-1 assigned to C=S. This
band gets shifted to 1130 cm-1 confirming the conversion of
the thione group to trithiocarbonate. Anew band appears in
the mercaptopurine TTC (Fig. 12) at 873 cm-1 attributed to
Fig. 9. TGA spectrum of captopril TTC: Pd(II) com-
plex.

Determination of Captopril and 6-Mercaptopurine as its Trithiocarbonate
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1427
Fig. 10. DTA spectrum of captopril TTC: Pd(II) complex.
Structure of captopril TTC: Pd(II)
the C-S stretch that gets shifted to 854 cm-1 in the spectrum
of complex confirming involvement of the S atom of TTC
for complexation.
Fig. 11. FTIR spectrum of 6-mercaptopurine.
The spectrum of 6-mercaptopurine TTC (Fig. 13)
shows coordination with Pd (II) confirmed by the complete
disappearance of the n C=S band at 1130 cm-1. The coordi-
nation of the v N-H band of 6-MPTTC in the complexation
is confirmed by the shifting of the band at 3394 cm-1 to
3381 cm-1 in the spectrum of Pd (II) complex. This con-
firms the involvement of 6-MPTTC in complexation with
palladium.
The FTIR spectrum of 6-MPTTC exhibits a stretch-
ing band at 623 cm-1, 1630 cm-1 and broad band at 3381
cm-1 assigned to n-OH and bending mode of coordinated

1428 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
water molecules (Table 2).
A chemical shift at 1.2 ppm is assigned to the -SH
group of 6-mercaptopurine which gets shifted to 1.3 and
1.8 ppm showing conversion of -SH to disulfide. This peak
completely disappears in the 6-mercaptopurine TTC: Pd(II)
complex confirming the binding between Pd(II) and S
atom.
1H NMR Studies of 6-Mercaptopurine, 6-Mercapto-
purine TTC and its Pd(II) Complex
In the 1H NMR spectrum of 6-mercaptopurine (Fig.
14), the signal at 7.2 ppm is attributed to aromatic protons
of the purine ring, which gets shifted to 7.8, 8.1 and 8.4
ppm in the spectrum of 6-mercaptopurine TTC (Fig. 15).
These signals remain unaffected in the Pd(II) complex of
6-mercaptopurine TTC (Fig. 16) indicating that the 7th ni-
trogen of purine is not involved in the bond formation with
Pd(II).
A sharp intense peak is seen at 4.95 ppm in the spec-
trum of 6-mercaptopurine TTC: Pd(II) complex assigned to
the co-ordinated water molecules attached to palladium
(Table 4).
ESR Data of 6-Mercaptopurine, 6-Mercaptopurine
TTC and its Pd(II) Complex
Similar to captopril, 6-mercaptopurine (Fig. 17) does
not show any resonance peak in the electron spin spectrum
characterizing its diamagnetic nature. Conversion of 6-
mercaptopurine to its trithiocarbonate derivative results in
Fig. 12. FTIR spectrum of 6-mercaptopurine TTC.
Fig. 14. 1H NMR spectrum of 6-mercaptopurine.
Fig. 13. FTIR spectrum of 6-mercaptopurine TTC:
Pd(II) complex.
1
Fig. 15. H NMR spectrum of 6-mercaptopurine TTC.

Determination of Captopril and 6-Mercaptopurine as its Trithiocarbonate
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1429
Table 4. Characteristic 1H NMR data of 6-mercaptopurine, 6-mercaptopurine TTC and 6-MPTTC: Pd
complex
Proton
6-Mercaptopurine (ppm)
6-Mercaptopurine TTC
6-Mercaptopurine TTC: Pd(II) (ppm)
1. N-H (arom)
2. S-H
7.2
1.2
7.8, 8.1
1.3, 1.8
not affected
-
7.8 (unaffected)
disappears
3. N-H
1.4
not affected
4. O-H
absent
4.95 (coordinated water)
the appearance of an ESR signal at 1600 gauss confirming
the presence of an unpaired electron.
Thermogravimetric Analysis of 6-Mercaptopurine
TTC: Pd(II) Complex
Calculation of Lande’s Splitting Factor (g)
TGA curve of the complex between trithiocarbonate
of 6-mercaptopurine: Pd(II) (Fig. 18) shows the following
features.
DH
g
Sample = gStandard (1 -
)
)
H
1. Weight loss below 100 °C
150
Thermogram of 6-mercaptopurine TTC: Pd(II) com-
plex confirms the removal of one-lattice water molecules
from the complex. In this range weight loss of 100% to
96.98% takes place.
= 2.0023 (1-
1650
= 1.8202
2. Weight loss from 100 °C - 300 °C
The lower value of “g” is an indication of the covalent
nature of 6-MPTTC: Pd complex.
Thermogram of the complex shows the removal of
other two water molecules at 280 °C resulting in the weight
loss from 90.91% to 84.17%.
Total number of ESR signals for M:L complex.
According to (2nI + 1) rule, where I = spin magnetic
quantum number.
3. Weight loss from 400 °C – 800 °C
This temperature range is associated with bond cleav-
age between Pd(II) and chloride ions at 410 °C. Above 410
°C 6-mercaptopurine TTC moiety from the complex starts
breaking. At 510 °C TTC moiety decomposes completely
to give elemental carbon, potassium and palladium in the
form of Pd-S. This thermal decomposition is associated
with the weight loss from 73.45% - 40%.
1. For sulphur donor atom (I =0)
(2 ´ n ´ I1 + 1) = (2 ´ 2 ´ 0 + 1) = 1
2. For oxygen as donor atom (I2 = 0)
(2 ´ n ´ I2 + 1) = (2 ´ 2 ´ 0 + 1) = 0 + 1 = 1
Total number of ESR signals is
(2 ´ n ´ I1 + 1) + (2 ´ n ´ I2 + 1) = 1 ´ 1 =1
Appearance of one resonance peak in the spectrum of
6-MPTTC: Pd(II) complex (Fig. 17) confirms the presence
of one 6-MPTTC molecule in the complex.
4. Weight loss from 800 °C - 1000 °C
Above 800 °C breakage of the Pd(II) and sulphur
bond takes place and the vaporization of potassium. This
Fig. 16. 1H NMR spectrum of 6-mercaptopurine TTC: Pd(II) complex.

1430 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
thermal decomposition is associated with the weight loss
from 40% to 30%.
Differential Thermal Analysis (DTA) of 6-Mercapto-
purine TTC: Pd(II) Complex
The DTA curve of the complex between 6-mercapto-
purine trithiocarbonate (Fig. 19) exhibits the following
endothermal/exothermal changes.
1. Curve from 0 °C - 400 °C
In this temperature range no endothermal changes are
observed in the complex, whereas the derivative thermo-
gram of the complex exhibits change in weight at 40 °C,
Fig. 19. DTA spectrum of 6-mercaptopurine TTC:
Pd(II) complex.
213.89 °C and 280.13 °C, corresponding to removal of lat-
tice water molecules and coordinated water molecules.
2. Exotherm at 520.60 °C
This range is associated with the breaking of bonds
between Pd(II) chloride ions and also decomposition of
6-mercaptopurine TTC moiety starts and gets completed at
850 °C.
3. Endotherm at 900 °C
This temperature is an indication of complete break-
age of the bond between Pd(II) and sulphur.
From these studies we hereby propose the most plau-
sible structure of 6-mercaptopurine trithiocarbonate: palla-
dium(II) complex as follows.
Fig. 17. ESR spectrum of 6-mercaptopurine, 6-mer-
captopurine TTC, and 6-mercaptopurine TTC:
Pd(II) complex.
Fig. 18. TGA spectrum of 6-mercaptopurine TTC:
Pd(II) complex.
Structure of 6-mercaptopurine TTC: Pd(II) complex

Determination of Captopril and 6-Mercaptopurine as its Trithiocarbonate
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1431
Fig. 20. UV-Visible spectrum of captopril.
Fig. 21. UV-Visible spectrum of captopril TTC.
Fig. 22. UV-Visible spectrum of captopril TTC: Pd(II) complex.
Fig. 24. Visible spectrum of 6-mercaptopurine TTC.
Fig. 23. UV-Visible spectrum of 6-mercaptopurine.
an anticancer drug, are not only interesting from medicinal
aspects, but are also versatile ligands, with four potential
donor groups for the formation of trithiocarbonate. Its in-
CONCLUSION
Captopril, an ACE inhibitor, and 6-mercaptopurine,

1432 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sharma et al.
Fig. 25. UV-Visible spectrum of mercaptopurine TTC: Pd.
8. Russell, J.; Rubenstein, D. L. Anal. Biochem. 1996, 242,
136.
teraction towards the transition metal ion have been de-
scribed in detail. Complexes of captopril TTC and 6-mer-
captopurine TTC with Pd(II) chloride were synthesized
and characterized by means of FTIR, 1 H NMR, ESR spec-
troscopy and Thermal Analysis, thus confirming the forma-
tion of a bond between the sulphydryl group of trithiocar-
bonate as well as the carbonyl group of captopril moiety.
9. Siangproh, W.; Nagmukot, P.; Chalapakul, O. Sens. Actua-
tors B: Chem. 2003, 91, 60.
10. Squella, J. A.; Lemus, I.; Borges, Y.; Nunez-Vergara, L. J.
Bol. Soc. Chil. Quim. 1992, 52.
11. Li, Y.; Lang, H.; Tan, F.; Jiao, G. Fenxi Huaxue 2002, 30,
165.
12. Cheviron, N.; Rousseau-Plasse, A.; Lenfant, M. F.; Adeline,
M. T.; Potier, P.; Thierry, J. Anal. Biochem. 2000, 280, 58.
13. Rahman, N.; Singh, M.; Hoda, N. Il Farmaco. 2005, 60, 569.
14. Muhammad, N. A.; Anvarhusein, A. I.; Wazeer, M. I. M. J.
Inorg. Biochem. 1996, 64, 1, 37.
ACKNOWLEDGEMENT
The authors are grateful to the faculty of the Sophisti-
cated Analytical Instrumentation Facility (SAIF), IIT
Mumbai, India and Central Drug Research Institute (CDRI),
Lucknow, India, for providing the instrumentation facility.
15. Aboul-Enein, H.; Dommisse, R. A.; Desseyn, H. O.
Spectrosc. Lett. 1990, 23, 491.
16. Atzei, D.; Filippo, D.; Rossi, A.; Lai, A.; Saba, G.; Bucci, R.
Spectrochim. Acta A. 1992, 48, 911.
17. Jankovics, H.; Nagy, L.; Kele, Z.; Pettinari, C.; Agati, P.;
Mansueto, C.; Pellerito, C.; Pellerito, L. J. Organomet.
Chem. 2003, 668, 129.
Received February 26, 2007.
18. Hwang, Y. N.; Jeong, D. H.; Shin, H. J.; Kim, D.; Jeoung, D.
S.; Han, S. H.; Lee, J. S.; Cho, G. J. Phys. Chem. B. 2002,
106, 7581.
19. Nelson, J.; Carpenter, J. W.; Rose, M. L.; Adamson, D. J.
Cancer Res. 1975, 35, 2872.
REFERENCES
20. Maduen, R.; Sevilla, J. M.; Pineda, T.; Roman, A. J.;
Blazquez, M. Electroanal. Chem. 2001, 506, 92.
21. Lakomskaa, I.; Pazderskia, L.; Sitkowskib, J.; Kozerskib, C.
L.; Peczynskad, M.; Nasulewiczd, A.; Opolskid, A.; Szyk,
E. J. Mol. Struct. 2004, 707, 241.
1. Parrish, J. R. Anal. Sci. 2006, 189.
2. Mailer, T. H. U.S. Patent 1965, 3, 171.
3. Sasse, K.; Wegler, R.; Unterstenhoefer. G.; Grew, F. Angew.
Chem. 1960, 72, 973.
4. Khare, B.; Srivastava, A. Ph. D. thesis. Ranidurgavati Uni-
versity, Jabalpur, Madhya Pradesh, 2000.
22. Erik, C.; Van, A. B.; Jeffrey, A.; McKinney, B.; Bradley, J.;
Zins, A. B.; Dennis, C.; Mays, B. J. Chromatogr., B: Anal.
Technol. Biomed. Life Sci. 1996, 679, 147.
5. Sypniewski, S.; Bald, E. J. Chromatogr. A. 1996, 729, 335.
6. Amini, M.; Zarghi, A.; Vatanpour, H. Pharm. Acta Helv.
1999, 73, 303.
23. Bariyanga, J.; Luyt, A. S. J. Mol. Struct. 2001, 559, 49.
7. Liu, C.; Liu, S.; Chen, H.; Xie, X. Sep u 1998, 16, 82.