Physicochemical Study of Some Thiobarbiturate Derivatives and Their Interaction with DNA in Aqueous Media

Article abstract of DOI:10.1134/S0036024418100023

Abstract: The aim of this study is to investigate the physicochemical behavior of some selected thiobarbituartes and explore their interaction with ds-DNA. To the best of our knowledge limited work has been reported on physicochemical investigation of the

Full text of DOI:10.1134/S0036024418100023

ISSN 0036-0244, Russian Journal of Physical Chemistry A, 2018, Vol. 92, No. 10, pp. 1987–1995. © Pleiades Publishing, Ltd., 2018.
STRUCTURE OF MATTER
AND QUANTUM CHEMISTRY
Physicochemical Study of Some Thiobarbiturate Derivatives
1
and Their Interaction with DNA in Aqueous Media
a,
a
b
c
a
Abbas Khan *, Iltaf Khan , Muhammad Usman , Zahoor H. Farooqi , and Momin Khan
a
Department of Chemistry, Abdul Wali Khan University, Mardan, 23200 Pakistan
Department of Chemistry, Government College University, Faisalabad, Pakistan
b
c
Institute of Chemistry, University of the Punjab, New Campus, Lahore, Pakistan
*
e-mail: abbas053@gmail.com
Received June 4, 2017
Abstract—The aim of this study is to investigate the physicochemical behavior of some selected thiobarbitu-
artes and explore their interaction with ds-DNA. To the best of our knowledge limited work has been reported
on physicochemical investigation of these medicinal compounds and their interaction with ds-DNA. There-
fore, this lack of information on the fundamental physicochemical studies of such medicinal compounds
needs to be addressed. For this purpose five thiobarbiturate derivatives, denoted as: MKA 25, MKA26,
MKA27, MKA28, MKA29, have been synthesized and characterized. Various physicochemical investiga-
tions of these thiobarbiturates are carried out. The thermal decomposition of these medicinal compounds was
also studied by TGA technique. Further the mode of interaction and binding of these newly synthesized com-
pounds with ds-DNA was carried by using UV–Vis spectrometry. It was seen from the overall results that the
physicochemical properties as well as the extent of their interaction with biopolymer not only depend on the
side alkyl groups but also on varying the functional groups of the samples.
Keywords: thiobarbiturates, physicochemical study, TGA, DNA-binding, interaction, UV–Vis spectrometry
DOI: 10.1134/S0036024418100023
INTRODUCTION
Barbiturates have different solubility in various
solvents, which depends on their structure, which
The physicochemical investigation and binding can also affect their in vivo properties. 2,4,6-Pyrimi-
study of small molecules to DNA is important from dinetrione ring is hydrophilic, and 5,5-substituents
both the academic and applied point of view. As the are lipophilic [5]. Barbiturates are the medicinal
binding of conventional molecules to DNA affects compounds that generally depress muscular function
various functions of living organisms, such small mol- [6]. Phenobarbital (5-ethyl-5-phenylbarbituric acid)
ecules have potential as therapeutic agents that func- is an example of a widely used barbiturate drug. Bar-
tion by controlling gene expression. Hence such inves- biturates may also possess some other types of bio-
tigation can provide a key in the chemical and biolog- logical activity [7].
ical drug discovery research [1]. The main cause of
To enhance the biomedical applications of barbitu-
many genetic diseases are DNA mutation. DNA is rates, some derivatives of barbiturates are synthesized.
genetic and heredity material which is responsible for Of the various derivatives, thiobariturates are very
the coding of proteins. The medicinal properties of important from potential biomedical point of view.
thiobarbiturates can be traced from its specificity, Thiobarbiturates have a sulfur atom in the place of the
potency and interaction with DNA. Those com- carbonyl oxygen at C2 position. The replacement of
pounds which containing pyrimidine ring play an the carbonyl oxygen by sulfur at the C2 position favors
important role in many medicinal fields. These rings fat solubility and decrease duration of action. Thio-
have binding sites for many metal ions, so barbiturates barbiturates are more efficient in their toxicity to
are medicinal compounds and used for the treatment micro organism as compared to oxobarbiturates. The
of many such like diseases [2]. Recently barbiturates thiobarbiturates may be used as antiviral, antifertility,
are mainly replaced by benzodiazepines [3]. The gen- and antimalarial agents. The thiobarbiturates have
eral preparation method of barbituric acid is given in antibacterial, antifungal and anti-inflammatory appli-
Fig. 1.
cations, therefore their characterization is very
important. Some thiobarbiturates can be used for the
treatment of malaria and many other diseases. They
1
The article is published in the original.
1987

1988
ABBAS KHAN et al.
O
O
O
O
HN
NH
NaOC2H5
EtO
OEt
H N
3
NH2
O
O
Diethylmalonate
Urea
Barbituric acid
Fig. 1. General preparation method barbituric acid.
may also posess antiallergic, antiviral, and anti tumor rate derivatives denoted as MKA20, MKA21, MKA22,
activity [8]. Thiobarbiturates have sedative and antibi- MKA23, and MKA24, have been synthesized, physi-
otic applications. DNA is a macromolecule and active cochemically characterized and their interaction with
for interaction with thiobarbiturates and other medic- DNA are studied in detail. This research work will
inal compounds. DNA-drug interaction involves non help to understand the physicochemical behavior of
covalent bonds and this non covalent bond can be thiobarbiturates derivatives and explore their interac-
divided into three categories i.e., (i) groove binding, tion with DNA.
(
ii) intercalation, (iii) non specific electrostatic sur-
face binding. The interaction of DNA with potential
medicinal compounds can be affected by the concen-
tration, pH, temperature, and the presence of electro-
lytes.
EXPERIMENTAL
Materials
The reagents used in this research study were of
analytical grade and obtained from Sigma Aldrich.
These reagents include ethanol, ammonium chloride,
potassium hydrogen carbonate, EDTA, and hydro-
chloric acid, which were purified before any experi-
mental use. Thiobarbiturates and their derivatives
were soluble in organic solvents but insoluble in water
The physicochemical investigation of barbiturates,
which is expected to have medicinal properties, is very
important to understand their physicochemical
behavior under the influence of various factors, such
as temperature, pH, and their kinetic studies. The
interaction of such compounds with DNA can be gov-
erned by Van der Waals, hydrophobic, and electro-
static forces, from which the interaction mechanism
can be traced out. The binding strength between
dsDNA and medicinal compounds can be affected by
replacing the different alkyl group. The use of compu-
tational approach can be used to understand the
binding mechanism. The steric effects has also
important role in the binding [9]. The thiobarbitu-
rates and their derivatives have great sites for hydro-
gen bonding, and lastly binding between thiobarbitu-
rates and DNA supposed to be inhibited. Different
mode of interactions, such as surface binding, groove
binding and intercalation between dsDNA and small
molecules can occur [10].
[
13, 14]. Thiobarbiturates and their derivatives showed
good solubility in the ethanol–water mixture (95%
ethanol and 5% water), so this mixed solvent was used
throughout in this project. The double distilled auto-
claved water was also used for DNA experiments. The
thiobarbiturates were prepared by already established
method. The thiobarbiturates used were stable pow-
ders of different colors. All the DNA related stock
solutions were stored below 5°C and used within
5
days.
Preparation of Selected Thiobarbiturates Derivatives
All the selected thiobarbiturates and their deriva-
From the biochemical and clinical point of view, tives were synthesized by the reaction of diethylthio-
the binding of DNA with small molecules is very barbituric acid with different aromatic aldehydes in
important. Cancer is one of the main diseases which water. A typical reaction for a representative sample is
can be prevented by understanding such type interac- given in Fig. 2. Further the diethylthiobarbituric acid
tions. Thiobarbiturates can be used for anesthesia and (1 mmol) was mixed with the aromatic aldehydes
brain disease, they also effect muscular system [11]. (1 mmol) in the presence of 10 mL distilled water, and
Thiobarbiturates are biologically active substances refluxed for about 30 min. Deuterated DMSO was
and they interact with double stranded DNA and this used as solvent in NMR studies [14]. The structures
interaction is mostly of physical type [12]. The inter- and melting points of the prepared compounds are
action between DNA and thiobarbiturates is import- summarized in Table 1.
ant because it give us the response of thiobarbiturates
and its applications. By screening the available litera-
Physicochemical Characterization
ture, it was seen that less work has been reported on
physicochemical study of the thiobarbiturates deriva-
tives and their interactions with DNA. Therefore, by 1800 UV probe 2.43 version. The melting points of the
keeping all these facts in mind, five new thiobarbitu- selected thiobarbiturate derivatives were determined
The UV–Vis spectra were recorded on Shimazdu
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PHYSICOCHEMICAL STUDY OF SOME THIOBARBITURATE DERIVATIVES
1989
Table 1. Main characteristics of the thiobarbiturates deriv- by using Stuart melting point apparatus SMP 10
atives used in this study
(
Bibbay Scientific). FT-IR spectra were recorded on
IRAffinity-1S instrument (Shimadzu). Bomb calo-
rimeter AC 600, Analysis Software v 1.21 (Leco, USA)
was used to investigate the calorific values. Thermo-
gravimetric analyzer (TGA) Shimadzu TGA 50 H was
used to investigate the thermal properties of the sam-
ples. NMR spectra were recorded on Advance Bruker
AM 300 and AM 400 instruments; deuterated DMSO
was used as solvent.
Sample
code
Melting
point, °C
Chemical formula/molecular mass
O
H
2
C
HO
O
N
CH3
H C
3
MKA25
O
N
S
182
H C
2
RESULTS AND DISCUSSIONS
Melting Points of the Compounds Selected
CH3
C H N O S/М = 334.1
The melting points of all samples and their possible
structures are shown in Table 1. The melting points of
these compounds lay in the range of 150–182°C. The
variation in melting points for different sample is due
to the presence of different alkyl groups on one hand
and the functional groups on the other hand. It can be
seen that varying side groups of the basic skeleton
affect the melting points of these medicinal com-
pounds.
16
18
2
4
O
HO
H
2
C
N
CH3
MKA26
O
N
S
172
OMe H C
2
CH3
C H N O S/М = 334.1
16
18
2
4
Calorific Values Investigation
of Thiobarbiturates Derivatives
H C
The calorific values of the studied compounds are
listed in Table 2. As seen from the table, the amount of
sample taken for analysis was fixed for all samples and
also the amount taken was less than a gram. For all
samples the average the calorific values are almost six
thousands calorific value per gram while the amount
of sample used is quite less. From calorific values of
these thiobarbiturate derivatives, we concluded that
the sample having more the number of carbons and
bonds showed greater calorific values. This change in
heat energy in terms of calorimetric values with
change in the molecular and structural nature of the
samples is a step forward toward their better under-
standing from biomedical point of view.
3
O
O
CH2
S
N
N
MKA27
170
CH2
H C
3
C H N O S/М = 388.12
23
20
2
2
O
H
2
C
N
CH3
MKA28
EtO
O
N
S
150
Thermogravimetric Analysis
H C
In order to study the thermo-kinetic behavior of a
solid sample, thermogravimetric analysis (TGA) is
one of the important technique which gives valuable
information. There are two different ways to perform a
TGA experiment. The thiobarbiturates are stable at
room temperature and can be used and stored for
many months without any physical changes [15]. TGA
can be applied in quality controls and new develop-
ments in pharmaceutical industry [16]. Thermogravi-
metric analysis provides valuable information about
the phase transition, stability, polymorphism and
kinetic parameters of thiobarbiturates and their deriv-
atives The aim of TGA analysis was to study the stabil-
ity and decomposition pattern of selected thiobarbitu-
ratic compounds [17]. A representative thermogram
2
CH3
C H N O S/M = 332.12
1
7
20
2
3
O
H
C
2
N
CH3
MKA29 H3C
O
N
H C
2
S
150
CH3
C H N O S/M = 302.11
16
18
2
2
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ABBAS KHAN et al.
Table 2. Calorific values of thiobarbiturates and their the concerned compound is less stable as compared to
derivatives
No.
other samples, however 50% of this compound is
decomposes at final temperature. In case of sample
MKA27 the weight loss started at 32.76°C and com-
pleted at 401.09°C. The loss of weight from 32.76–
Sample code
CV, cal/g
1
2
3
4
5
MKA25
MKA26
MKA27
MKA28
MKA29
5564.4
5751.8
6071.3
5677.5
5471.5
100°C is the indication of loss of water molecules asso-
ciated with this sample. It can also be concluded that
this sample is more hydrophilic as compared to others.
From the thermogram of MKA27, we can conclude
that this sample is more stable till higher temperature
compared to other selected samples. Likewise, the
thermal pattern and decomposition of MKA28 is
almost similar to that of MKA25. The thermal result
for MKA29 obtained showed that the this sample is
thermally stable in the temperature range of 190.44 to
Mass is equal 0.60 g, fuse length is equal 10.0 cm.
3
19.81°C. For this purpose we took about 5 mg of
Table 3. Thermogravimetric analysis results for selected
thiobarbiturates and their derivatives
sample, after completion of analysis 4.604 mg of
weight loss occurred, and 98.397% weight loss was
noted. The decomposition pattern of MKA29 at dif-
ferent stages is shown in Table 3 and Fig. 3.
No.
Sample
Т0, °C Т1, °C Δm, mg Δm, %
1
2
3
4
5
MKA25 205.03 346.38 23.470 100.6
MKA26
MKA27
MKA28
88.63 252.82 48.385
32.76 401.16 88.073
1.273
0.576
DNA-Thiobarbiturates Interaction
and Their Binding Study
Another important part of this project is to study
the interaction of dsDNA with thiobarbiturates deriv-
atives. Looking to the chemical nature of these com-
pounds, it was expected that UV–Vis spectroscopy
may be the more valuable and easier technique to
investigate the DNA–thiobarbiturates interactions.
40.15 350.65
8.00
95.20
MKA29 190.44 319.81
4.406
98.397
Т is starting point, Т is finishing point, Δm is weight loss.
0
1
The maximum absorbance (λ , nm) values of
max
for sample MKA29 is shown in Fig. 3, similar thermo-
grams were also obtained for other samples (which are
not shown here), while the resultant TGA data are
given in Table 3.
selected thiobarbiturates have been studied by UV–Vis
spectrophotometry (Shimadzu 1800 UV probe 2.43
version). All the selected samples showed good solu-
bility in the ethanol water mixture (95% ethanol and
5
% water), so this solvent mixture was used as refer-
In summary, the MKA25 started the weight loss at
05.03°C and finished at 346.38°C. For this analysis
ence. UV–Vis spectra shows that different samples of
thiobarbiturates showed different maxima (peaks) in
the spectra, the maximum absorption wave length
2
we took an amount of about 25 mg of the concerned
sample, and 100 wt % was noted. MKA25 showed
decomposition and loss of various species at different
heating stages. The thermal pattern of MKA26 was
also studied in term of stability, this sample started
weight loss at 88°C, and the weight loss before 100°C
is occurred due to the removal of water molecules. The
weight loss of MKA26 finished at 252.82°C and about
(
λ
) is very important for this study, as it is used as
max
spectral tracer of thiobarbiturates–DNA interactions.
Representative plots for maximum absorbance (λ
)
max
and a typical calibration curve of absorbance for
MKA25 are shown in Fig. 4. Similarly, UV–Vis spec-
tra of all thiobarbiturate samples in the presence of dif-
ferent concentration of DNA are given in Figs. 5–9.
The important spectroscopic parameters extracted
from these measurements are summarized in Table 4.
48.385 wt % loss was recorded. So this data show that
The selected compounds showed different
response and behavior in spectroscopic study. A shift
of an absorption maximum to a longer wave length is
called red shift or bathochromic effect, while a shift to
shorter wavelength is called hypsochromic shift [18].
The present thiobarbiturate derivatives showed both or
one of them upon the addition of solution of DNA,
samples, MKA25, MKA26, MKA27, and MKA29
R
O
O
O
O
O
H2O
N
N
N
N
Reflux, 30 min
R
S
S
R = Substituted aryl group
showed decrease in wave length (λ ) of 2, 6, 2, and
max
5
nm, respectively, while MKA28 show increase in
Fig. 2. Synthesis of 5-Arylidene-N, N-diethylthiobarbi-
turic acid derivatives.
wavelength of 6 nm. Further, MKA27 and MKA28
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PHYSICOCHEMICAL STUDY OF SOME THIOBARBITURATE DERIVATIVES
1991
Table 4. UV–Vis spectroscopy data for free thiobarbiturates and DNA–thiobarbiturates complexes (A
absorbance, ε is molar absorptivity coefficient)
is maximum
max
Free thiobarbiturates
Thiobarbiturates–DNA complex
Sample
ε,
ε,
–
1 –1
λmax, nm
Amax
λmax, nm
Amax
K , (mol L )
mol L ) cm–1
–
1 –1
(mol L ) cm–1
–1 –1
b
(
MKA25
MKA26
MKA27
MKA28
MKA29
432
363
362
411
366
0.012
0.341
0.193
0.136
0.088
6.47 × 101
1.84 × 103
1.042 × 103
7.34 × 102
4.75 × 102
430
369
364
417
361
0.016
0.225
0.239
0.071
0.156
8.63 × 101
1.21 × 103
1.29 × 103
3.83 × 102
8.42 × 102
1.11 × 102
5.1 × 102
4.1 × 102
1.7 × 102
2.6 × 102
showed decrease in maximum absorption (Amax). So
The UV–Visible spectroscopic response of
this blue shift and hypochromic effect is the indication MKA25 showed the maximum absorbance at λmax
=
of penetration of benzyl group occurred, which results 432 nm. When we added the known amount of DNA,
in the formation of H–π bond with the bases of DNA the wave length shifted to 430 nm. The absorbance
and finally the damage of the stands of DNA occurred increased from 0.012 to 0.016. So the free MKA25 has
[19]. MKA26 and MKA29 showed an increase in the
λ
= 432 and absorbance at this point was 0.012.
max
absorbance after the addition of DNA, and the When we added the DNA, the blue shift of 2 nm
increase in the absorbance is known as hyperchromo- occurred and the absorbance increased in this case.
sim. Hence the hyperchromisim indicated that the The compound MKA26 showed the maximum absor-
concerned thiobarbiturates during intercalating bance at 363 nm. The concerned compound has max-
caused the conformational changes in their respective imum absorbance of 0.341 at this wave length. When
rings of DNA. Further the addition of DNA to thio- mixed with a known concentration of DNA, the wave
barbiturates solutions, caused reduction in face to face length (λmax) shifted to 369 nm and the absorbance at
base stacking and extended the DNA strand, and this point was recorded 0.225, which showed the
finally hyperchromisim occurred. The literature study decrease in absorbance. Thus finally this compound
suggested that when the unstaking of base pairs of showed the red shift of 5 nm and decrease in its corre-
DNA occurs, it results hyperchromisim [20]. The sponding absorbance. Similarly, according to the
addition of DNA to thiobarbiturates solutions showed spectroscopic response of MKA27, it has a maximum
different response and behavior which give us the evi- absorbance of 362 nm and the absorbance at this point
dence of interactions. This is systematically and subse- was recorded 0.193. After addition of DNA an increase
quently discussed here.
in both the λmax = 2 nm and Amax = 0.239 was noted.
TGA, mg
T, °C
5
4
3
2
1
0
Start
21.94 min
90.44°C
27.51 min
19.81°C
25.64 min
75.32°C
25.26 min
66.31°C
27.23 min
13.10°C
−4.604 mg
98.397%
1
300
200
End
3
Mid point
2
Onset
2
Endset
3
Weight loss
−
100
0
10
20
30
t, min
Fig. 3. Representative thermogram for sample MKA29.
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1992
ABBAS KHAN et al.
0.12
0.08
0.04
0
0.12
0.08
0.04
0
(
a)
(b)
400
500
600
0
0.1
0.2
0.3
C, mM
λ, nm
Fig. 4. Representative plots of maximum absorbance, λmax (a) and calibration curves of absorbance (b) for MKA25.
0
0
0
.03
.02
.01
0
Isosbestic point
g
Isosbestic point
a
390
400
410
420
430
440
450
460
470
480
λ, nm
Fig. 5. UV-spectra of MKA 25 (0.01 mM dm–3) in the absence and in the presence of different concentration of DNA. Concen-
tration of DNA (1 × 10–6 mol dm ) added in mL: (a) 0, (b) 2, (c) 4, (d) 6, (e) 8, (f) 10, (g) 12.
–3
This special response is again a prominent indication isosbestic points were observed in Figs. 5–9, where an
of the binding of this molecule with DNA. Likewise, isosbestic point is the wavelength at which all the
the DNA free MKA28 compound has a maximum absorbance become/remains constant for the whole
absorbance at 411nm and the absorbance at this wave
length was 0.136. When DNA was added the λ
reactions [21]. Further, the numbers and position of
isosbestic points in the compounds-DNA mixed sys-
tems are changing, which is another physicochemical
evidence of the fruitful interactions. All these results
show that the compound where a red shifting was
observed is the evidence of partial interaction between
DNA and the compound. Due to these interaction the
transition energy of π–π* may be decreased and hence
bathochromic shift occurred. The compounds where
decrease in absorption (hypochromic effect) and blue
max
shifted to 417 nm, which indicated the red shift of
6
nm. However the absorbance decreased to 0.071. So
in this compound the bathochromic shift and hypo-
chromism was observed in DNA–MKA28 mixed sys-
tem. Also the spectroscopic results for DNA free
MKA29 showed that this compound has λ
=
max
366 nm and the absorbance at this point was 0.088.
Upon the addition of DNA the compound showed the
blue shift of 5 nm because the λmax shifted to 361 nm.
The absorbance at this point was 0.156, which reflects
hyperchromic effect or increase in the absorbance.
shift in λ
(decrease in λ ) was observed, reflects
max
max
stronger interaction with DNA. Subsequently this blue
shift and hypochromic effect is the indication of pen-
etration of benzyl group occurred, which results the
From the overall results it is seen that the interac-
tion of these thiobarbiturate derivatives with DNA formation of H–π bond with the bases of DNA and
showed different response and this is evidence of the finally the damage of the stands of DNA may be
interactions of thiobarbiturates with DNA. Also clear occurred.
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PHYSICOCHEMICAL STUDY OF SOME THIOBARBITURATE DERIVATIVES
1993
a
0.012
0.009
0.006
0.003
g
Isosbestic point
Isosbestic point
0
3
35
345
355
365
375
385
395
λ, nm
Fig. 6. UV-spectra of MKA26 (0.01 mM dm–3) in the absence and in the presence of different concentration of DNA. Concen-
tration of DNA (1 × 10–6 mol dm ) added in mL: (a–g) see Fig. 5.
–3
0.04
0.03
0.02
0.01
0
Isosbestic point
Isosbestic point
g
a
340
350
360
370
380
390
400
λ, nm
Fig. 7. UV-spectra of MKA27 (0.01 mM dm–3) in the absence and in the presence of different concentration of DNA. Concen-
tration of DNA (1 × 10–6 mol dm ) added in mL: (a–g) see Fig. 5.
–3
It is expected that the interaction of small mole-
cules such as thiobarbiturate derivatives with a host
with DNA respectively, ε and ε
are the molar
G
H−G
absorption coefficients of the thiobarbiturates and
thiobarbiturates–DNA complex, respectively. The
binding constant of selected thiobarbiturates–DNA
was obtained from the slope of the plot by plotting the
(
macromolecule/DNA) results in a bigger complex,
so, the formation of this complex can be assessed by
the knowledge of binding or formation constant K /K .
f
b
Therefore, the strength and type of interaction of
variables of above straight-line equation and the K
b
DNA with thiobarbiturate derivatives was traced by
values obtained are given in Table 4. The values of Kb
for all thiobarbiturates–DNA complexes are positive
which is an indication of the positive interaction. The
calculating the binding constants (K ) using the fol-
b
lowing Benesi–Hildebrand equation:
sample having lower K value means lesser interaction
A0
A − A0
ε
ε
1
b
G
G
=
+
,
(1)
with DNA while for higher K values the interactions
b
ε
− εG
ε
− ε K[DNA]
H−G
H−G G
are supposed to be stronger. Like other parameters,
where K is binding constant, A and A are the absor- the K values are also changing from sample to sample
b
0
bances of the free thiobarbiturates and its complex which is attributed to the structure effect.
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1994
ABBAS KHAN et al.
0
0
0
.18
Isosbestic point
a
g
.12
.06
0
380
430
480
λ, nm
Fig. 8. UV-spectra of MKA28 (0.01 mM dm–3) in the absence and in the presence of different concentration of DNA; (a–g) see
Fig. 5.
0.070
0.056
0.042
0.028
0.014
0
g
Isosbestic point
a
Isosbestic point
340 360
320
380
400
420
440
λ, nm
Fig. 9. UV-spectra of MKA29 (0.01 mM dm–3) in the absence and in the presence of different concentrations of DNA; (a–g) see
Fig. 7.
CONCLUSION
higher calorific values. It can be seen that varying side
groups of the basic skeleton affect both the melting
In this study we have synthesized several thiobarbi- points and calorific values. TGA results show that the
turates derivatives by the reaction of diethylthiobarbi- thiobarbiturates derivatives are stable in the range of
turic acid with different aromatic aldehydes in distilled 32.76–401°C. The stability of selected thiobarbitu-
water. The physicochemical properties of these newly rates derivatives in decreasing order is MKA27 >
synthesized samples were studied. The prapared thio- MKA25 > MKA29 > MKA26.
barbiturates derivatives have the melting points in the
The interaction of thiobarbiturates with dsDNA
was the main part of this research work. Before study-
ing thiobarbiturates–DNA interaction, maximum
range of 150–182°C. The melting points decrease in
the order MKA25 > MKA29 > MKA26 > MKA27 >
MKA28. The calorific values were in the range of
absorbance (λ , nm) values for selected samples
5
471.5–6071.3 cal/g for these samples. From the calo-
max
rific values it can be concluded that sample having were calculated, and were found in the range of 363–
greater number of carbons and bonds showed the 432 nm. The maximum absorbance (λmax, nm) values
RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A
Vol. 92
No. 10
2018

PHYSICOCHEMICAL STUDY OF SOME THIOBARBITURATE DERIVATIVES
1995
in decreasing order are given as MKA25 > MKA28 >
MKA29 > MKA27 > MKA26. Molar absorptivity coef-
ficient for selected free thiobarbiturates and thiobarbi-
turates–DNA complex were calculated. For free thio-
barbiturates molar absorptivity coefficient occurs in the
5. S. C. Flagg, C. B. Martin, C. Y. Taabazuing,
B. E. Holmes, and M. J. Knapp, J. Inorg. Biochem.
1
13, 25 (2012).
6. S. Spiro, M. Rooker, and M. Blutstein, Anesth. Prog.
22, 78 (1975).
1
3
–1 –1
‒1
range of 6.47 × 10 –1.84 × 10 [(mol L ) cm ],
while for thiobarbiturates–DNA complex it was in the
7. T. Majumder, B. De, B. B. Goswami, and S. Kar, Der.
Pharma. Chem. 3, 268 (2011).
1
3
range of 8.63 × 10 –1.290 × 10 . The change in molar
absorptivity values are the indication of thiobarbitu-
rates–DNA interactions. When we added the DNA
solution of different concentration to solutions of
compound MKA29, it showed decrease in absorbance
as well as in maximum wavelength. Samples MKA27
and MKA28 showed decrease in absorption maxi-
mum. Similarly, MKA25, MKA26, and MKA29
showed hyperchromisim which reflect that the con-
formational changes occurred in rings of DNA. All
this spectroscopic response and behavior reflects that
interactions of selected thiobariturates occurred with
dsDNA. The binding constants and strength of DNA
with thiobarbiturates was find out by using Benesi–
8. M. Usman and M. Siddiq, J. Chem. Thermodyn. 58,
359 (2013).
9. J. M. Mcgrath and M. D. Pluth, J. Org. Chem. 79, 711
(2014).
1
0. M. H. Al-Sayah, R. Mcdonald, and N. R. Branda, Eur.
J. Org. Chem. 2004, 173 (2004).
1
1. R. Kitamura, M. Kakuyama, K. Nakamura, I. Miya-
waki, and K. Mori, Braz. J. Anaesth. 77, 503 (1996).
1
2. G. C. Shaw and A. Fulco, J. Biol. Chem. 268, 2997
1993).
3. J. L. Adcock, P. S. Francis, T. A. Smith, and N. W. Bar-
nett, Analyst 133, 49 (2008).
(
1
1
4. K. M. Khan, M. Khan, A. Ahmad, A. Irshad, S. Kar-
dono, L. Broto, F. Rahim, S. M. Haider, S. Ahmed,
and S. Parveen, J. Chem. Soc. Pakistan 36, 1153 (2014).
Hildebrand equation. The binding constants K was
b
1
calculated, which was in the range of 8.63 × 10 –
1
5. Z. M. Zaki and G. G. Mohamed, Spectrochim. Acta, A
6, 1245 (2000).
6. S. Sadeek and M. Refat, J. Korean Chem. 50, 107
2006).
3
–1 –1
1
.290 × 10 (mol L ) . It is concluded that change in
5
various physicochemical properties and strength of
interaction with DNA of different sample is attributed
to the change in the chemical structure of the com-
pounds.
1
(
1
7. A. F. O. Santos, J. I. Basilio, F. D. Souza, A. Medeiros,
M. F. Pinto, D. De-Santana, and R. Macedo,
J. Therm. Anal. Calorim. 93, 361 (2008).
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RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 92 No. 10 2018