Synthesis, characterization, coordination chemistry and biological activity of some pyrimidine complexes

Article abstract of DOI:10.1016/j.molstruc.2020.128612

A group of biologically active ligands: 5-(2hydroxyphenylide) barbituric acid (L¹), 5-(phenyl azo) thiobarbituric acid (L²) and 5-(phenyl azo) barbituric acid (L³) and its complexes with Os(VIII), Ru(III),Zr(IV) and V(III)

Full text of DOI:10.1016/j.molstruc.2020.128612

Journal Pre-proof
Synthesis, characterization, coordination chemistry and biological activity of some
pyrimidine complexes
Mamdouh Saad Masoud, Amr Mohamed Sweyllam, Mahmoud Moursy Ahmed
PII:
S0022-2860(20)30937-6
DOI:
https://doi.org/10.1016/j.molstruc.2020.128612
MOLSTR 128612
Reference:
To appear in: Journal of Molecular Structure
Received Date: 3 April 2020
Revised Date: 16 May 2020
Accepted Date: 3 June 2020
Please cite this article as: M.S. Masoud, A.M. Sweyllam, M.M. Ahmed, Synthesis, characterization,
coordination chemistry and biological activity of some pyrimidine complexes, Journal of Molecular
Structure (2020), doi: https://doi.org/10.1016/j.molstruc.2020.128612.
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Author Agreement Statement
We the undersigned declare that this manuscript is original, has not been published before and is not
currently being considered for publication elsewhere.
We confirm that the manuscript has been read and approved by all named authors and that there are
no other persons who satisfied the criteria for authorship but are not listed.
We further confirm that the order of authors listed in the manuscript has been approved by all of us. We
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the manuscript.
Role of the authors:
1
-Prof/ Mamdouh Saad Masoud (drmsmasoud@yahoo.com): Conceptualization, Methodology ,
Writing - Review & Editing ,Resources and supervision .
2
-prof/ Amr Mohamed Sweyllam(Sweyllam1@yahoo.fr): Conceptualization, Methodology , Data
Curation, Validation, Writing - Review & Editing,Software and supervision
3
-Mr/Mahmoud Moursy Ahmed(mmoursy2017@yahoo.com)
Formal analysis , Validation, Writing - Review & Editing, Writing - Original Draft and
Visualization.

SYNTHESIS, CHARACTERIZATION
,
COORDINATION CHEMISTRY AND BIOLOGICAL
ACTIVITY OF SOME PYRIMIDINE COMPLEXES.
a
b
Mamdouh Saad Masoud , Amr Mohamed Sweyllam and
Mahmoud Moursy Ahmed *
a
a
: Chemistry Department ,Faculty of Science, Alexandria University, Alexandria, Egypt.
b : Physics Department ,Faculty of Science, Alexandria University, Alexandria, Egypt.
corresponding author :mmoursy2017@yahoo.com
*
Keywords : PYRIMIDINES;COORDINATION CHEMISTRY,ANTICANCER:ANTIMICROBIAL:ANTIOXIDANTS
Abstract
1
A group of biologically active ligands: 5-(2hydroxyphenylide) barbituric acid (L ) , 5-(
2
3
phenyl azo) thiobarbituric acid (L ) and 5-( phenyl azo) barbituric acid (L ) and its
complexes with Os(VIII) , Ru(III) ,Zr(IV) and V(III) ions were synthesized .The chemical
1
structures of these compounds were fully identified using MALDI-TOF , FT-IR , H-NMR
,
TGA and DSC techniques , magnetic susceptibility measurements helped to determine the
exact geometry of the complexes under study. The dissociation constants of the ligands
were evaluated by analyzing their electronic absorption spectra at different pH’s. All the
compounds were tested for its anticancer, antimicrobial and antioxidant activities .The
collected data showed that some of the compounds can be used as drugs for the treatment
of breast cancer (MCF-7 cancer cells) and as potent antibiotics for both gram-positive and
gram –negative bacterial species including : Staphelococcus Epidermisis , Escherishia Coli
,
Staphyllococcus Auresis and Salmonilla and the fungal species: Candida Albicans . The
DPPH Radical Scavenging Activity of the compounds showed that most of the compounds
can be used as good antioxidant agents.
1-Introduction
Heterocyclic compounds containing nitrogen and/or sulphur including pyrimidines
represent a major component of many natural products and biologically active
(1)
molecules .These compounds have been widely used as agrochemicals ,flavors and stains
(2)
but they were mainly applied as drugs in medicinal chemistry . The pyrimidine nucleus is
a 1,3-diazine containing two nitrogens at 1 and 3 positions. As a response to the great
importance of pyrimidines in many aspects, a large number of synthetic procedures have
been designed for the efficient synthesis of pure pyrimidine derivatives. The barbituric acid
and thiobarbituric acid derivatives exhibited a wide range of biological activities and
(3)
consequently, they are considered one the most important examined drugs .
Cancer is one of the most serious diseases that eventually lead to death .It involves
uncontrolled cell growth forming injurious tumers that may spread in body organs .

Pyrimidine derivatives have been greatly involved in the cancer therapy and showed
(4)
excellent antoxidant and antimicrobial activity .Breast cancer is one of the most common
diseases in women and dramatic rise in its incidences occurred globally .So, it is important
to develop new drugs that act against this disease. According to literature, many
pyrimidine derivatives and thieir transition metal complexes are reported to exhibit potent
(
4-12)
anticancer activity against MCF-7 breast carcinoma and many other cancers
research group “Masoud et al
. Our
(13-44)
” published a large number of papers concerning the
chemistry of pyrimidines. In continuation of our research , the present work aimed to
synthesize and fully characterize some biological active ligands derived from barbituric
and thiobarbituric acids and their complexes using :
1
•
•
H NMR spectra to confirm the proposed structure of the ligands and to support the
tautomeric behavior of the ligands.
MALDI-TOF mass spectroscopy to determine the exact molecular weight of the
compounds.
•
•
FT-IR spectra to discuss the mode of binding in their metal complexes.
Electronic spectra and magnetic measurements to determine the geometry of the
transition metal complexes derived from Os(VIII) , Ru(III) ,Zr(IV) and V(III) salts.
Thermal methods (TGA and DSC) of some compounds to propose the mechanism
of their decomposition and their heat capacities.
•
•
Spectrophotometric methods to evaluate the Pka values of the ligands.
2-Experimental:
2
.1.Synthesis of the ligands
The prepared ligands are azo and ylide derivatives of barbituric and thio barbituric
acids which are purchased from Alpha –chemika company.
1
2
.1.1.Synthesis of 5-(2hydroxyphenylide) barbituric acid (L )
Barbituric acid (0.01 mol) was dissolved in 50 ml of 0.1 M HCl. A bout 15 ml of
salisaldehyde slowly added to the solution with continuous stirring. The nitrogen content,
colour, m. p. ºc and formula are given in Table (1).
2
2
.1.2.Synthesis of 5-( phenyl azo) thiobarbituric acid (L )
Aniline (0.01 mol) was dissolved in HCl (0.2 mol ) and 25 ml distilled water. The
hydrochloride compound was diazotized below 5 ºc with a solution of NaNO (0.1 mol)
2
and 20 ml distilled water. The diazonium chloride was coupled with an alkaline solution
of 0.1 mol thiobarbituric acid / 30 ml distilled water. The solid products where filtered off
and allowed to dry under suction. Table (1) collects the nitrogen content, colour, m. p. ºc
and formula of the ligands.
3
2
.1.3.Synthesis of 5-( phenyl azo) barbituric acid (L )
0
. 01 mol of aniline acid was dissolved in 0. 2 mol HCl and 25 mi distilled water.
The hydrochloride compound was diazotized below 5 ºc with a solution of NaNO (0. 1
2

mol) and 20 ml distilled water. The diazonium chloride was coupled with an alkaline
solution of 0. 1 mol barbituric acid / 30 ml distilled water. The observed molecular weight,
colour, m. p. ºc and formula are given in Table (1).
The ligands used during this work are given as follows [Figure(1)]:
1
2
5
-(Salicylidene) barbituric acid (L )
5-( phenyl azo) thiobarbituric acid (L )
3
5
-( phenyl azo) barbituric acid (L )
Figure (1) : The synthesized ligands
2
.2.Sythesis of transition metal complexes
All complexes where prepared in the same way. The inorganic salts of RuCl ,VCl ,
3
3
ZrOCl and OsO ) are dissolved in distilled water, while the ligands where dissolved in
2
4
ethanol. The complexes where prepared using (1:1) mole ratio of metal to ligand.
In all preparations, the reaction takes place at room temperature. Filtration of the
solid products is done through suction system and then dried in a vaccum desictor over
anhydrous CaCl . The analytical results are given in Table (2).
2
2
.3.Elemental analysis
The complexes were digested and decomposed with aqua regia and the metal
(45)
contents were determined either complexometrically using published procedures and by
means of atomic absorption spectroscopy. The chloride content in certain comolexes were
determined by the usual Volhard method.

Table (1): Colour, m.p (◦c) and analytical data for the prepared ligands
Compound
m. p(c◦) M. wt(g/mol)
Formula
Colour
[Calculated/(Found)%]
C
H
N
S
-
5
-(2hydroxyphenylide) barbituric
281-282
232. 20
C H O N
2
Red-
orange
1
1
8
4
1
56.9
3.47
12.06
acid(L )
(
56.53) (3.87) (12.56)
5
-(2 phenyl azo) thiobarbituric acid 294-295
248. 26
232. 20
C H O N S Brown
48.38 3.25 22.57
12.91
10
8
2
4
(
L )
(47.99) (3.71) (22.86) (12.78)
51.73 3.47 24.13
52.03) (3.35) (24.33)
5
-(3 phenyl azo) barbituric acid
288-289
C H O N
4
Dark
1
0
8
3
-
(
L )
violet
(

Table (2):Elemental analysis and physical properties of the complexes (All the complexes are with “1:1”stoichiometry)
M. wt
Complex
Calculated Colour
Found)
Formula
Calculated (Found) %
(
C
H
N
M
X
1
438. 61
Dark
Brown
23.04
(23. 88)
19. 83
(19. 36)
Ru. L . Cl .
C H Cl N O Ru
30.12
1. 61
6.39
3
11
7
3
2
4
(441.23)
3
OsO . L .
490.45
(491.192)
Dark
grey
38.79
(38. 15)
2
C H N O Os
24.49
2.47
1.82
11.42
14.42
-
10
12
4
7
2OH
3
388.48
389.107)
13.11
(13. 53)
27.38
(27.82)
V. L . Cl
Black
C H Cl N O V
30. 92
3
10
7
3
4
3
(
2
425.38
426.285)
21.45
(21.56) (16.89)
16.67
ZrO. L .Cl
Brown
C H Cl N O SZr
28.24
1.66
13.17
2
10
7
2
4
3
(
3
409.31
408.125)
Dark
Brown
22.29
(22.59) (17.96)
17.32
ZrO. L . Cl
C H Cl N O Zr
29.34
24.46
1.72
1.64
13.69
11.41
2
10
7
2
4
4
(
2
491.13
492.723)
Dark
Brown
20.58
(20.86)
28.67
(29.01)
Ru. L . Cl
C H Cl N O RuS
10 10 4 4 2
4
(
-

2
.4.Instrumental analysis:
2
.4.1.NMR spectroscopy
NMR measurements were done using an Avance Bruker (300 MHz) instrument.
2
.4.2.Infra-red spectroscopy
The IR spectra of the ligands and their complexes were recorded using Perkin-Elmer
-
1
spectrophotometer model 1430 covering the frequency range 4000-200 cm , by the KBr disc
method. The analytical procedure were done at the central laboratory, Faculty of science,
Alexandria university.
2
.4.3.UV-VIS Specroscopy
The spectral data in the visible and ultraviolet spectral regions were recorded using Perkin-
Elmer spectrophotometer model 4B Lambada scanning the wavelength range 190-900 nm at the
central laboratory, Faculty of science, Alexandria university. The complexes were measured in
(46)
nujol mull, following the method described by Lee, Griswold and Kleinberg
.
2
.4.4.Magnetic susceptibility measurements
Molar magnetic susceptibility measurements were carried out on a Sherwood scientific
magnetic balance. The calculations were evaluated by applying the following equations (1, 2
(47)
and 3)
.
◦
3
x
x
µ
g
= C x L (R -R ) / 10 x m
m = g
x x M.wt
(1)
(2)
(3)
1/2
m
eff =2. 84 (x x T)
xg= the mass susceptibility per gram sample.
C =the calibration constant of the instrument.
L = the sample length in cm.
R = the balance reading for the sample and tube.
◦
R = the balance reading for the empty tube.
m=the mass of the sample in gm.
T =absolute temperature.
2
.4.5.Thermal analysis
Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were
carried out for the prepared ligands and their complexes. The rate of heating was 5º c / min. The
cell used was platinium, the atmospheric nitrogen rate flow was 20 ml/min. The instrument is
located at the central laboratory, Faculty of Science, Alexandria university.

2
.4.6. Matrix Assisted Laser Desorption Ionization Time-of-flight (MALDI-
TOF) mass spectroscopy
The instrument used for the analysis of the prepared compounds is MALDI Ultraflextreme
for Bruker Daltonics company of software flex analysis at the Faculty of Medicine , proteomic
department, Alexandria University.
2
2
.5.Biological activity
.5.1.Disc diffusion method
(
48)
Disc diffusion method was determined by Kirby-Bauer’s
disc diffusion method as
.
National Committee for Clinical Laboratory Standards (NCCLS) recommendations Nutrient agar
media plates were cultured with inoculums of each bacterium isolate using sterile cotton swabs.
The discs of the prepared compounds placed on the inoculated plates. The compounds were
(49)
dissolved in DMSO which was used as control . Different concentrations of each compound
were prepared (in DMSO).The bacterial and fungal growth were examined in absence and
◦
presence of the compounds at 37 C for 2 days and later, applied to bacteria grown on agar
plates. Inoculation was performed with the help of a platinum wire loop,which was made red-
hot in flame and used for the application of bacterial strains after cooling. Sterilized forceps
were used to apply paper disc on inoculated agar plates. The inhibition zone diameters were
measured and recorded for the investigation of both antibacterial and antifungal activity of the
prepared compounds.
2
.5.2.Antioxidant Assay:
The antioxidant activity of extract was determined at the Regional Center for Mycology
and Biotechnology (RCMB) at Al- Azhar University by the DPPH free radical scavenging assay
in triplicate and average values were considered.
DPPH Radical Scavenging Activity:
Freshly prepared (0.004%w/v) methanol solution of 2,2-diphenyl-1-picrylhydrazyl
(DPPH) radical was prepared and stored at 10C in the dark. A methanol solution of the test
compound was prepared. A 40 µL aliquot of the methanol solution was added to 3ml of DPPH
solution. Absorbance measurements were recorded immediately with a UV-visible
spectrophotometer (Milton Roy, Spectronic 1201). The decrease in absorbance at 515 nm was
determined continuously, with data being recorded at 1 min intervals until the absorbance
stabilized (16 min). The absorbance of the DPPH radical without antioxidant (control) and the
reference compound ascorbic acid were also measured. All the determinations were performed in

three replicates and averaged. The percentage inhibition (PI) of the DPPH radical was calculated
according to the formula:
PI = [{(AC- AT)/ AC} x 100] (4)
Where AC = Absorbance of the control at t = 0 min and AT = absorbance of the sample+DPPH at
(
50)
t = 16 min
.
2
.5.3.Anticancer activity:
Cell culture:
All the prepared compounds were tested for their anticancer activity against human breast
adrenocarcinoma MCF-7 cells which are obtained from VACSERA company, Alexandria, Egypt
.Cells were cultured in complete culture medium: DMEM (Dulbecco's Modified Eagle Medium)
purchased from LONZA company, U.S.A, supplemented with 10%fetal bovine serum (SIGMA-
ALDRICH, U.S.A) at 37 ºC in a humidified incubator (NUAIRE, U.S.A) with 5% CO
atmosphere.
2
Cell viability examination using MTT test
The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used for
the evaluation of the antiproliferative and /or cytostatic effect of the tested compounds on cancer
cells. In this procedure. Trypsinized cells were suspended in complete culture medium before
seeding in 96-well plates (3000 cells per well). Incubation proceeded for 24 hours at 37 ºC in 5%
CO atmosphere. Maximum concentarion of 100 µg/ml was applied followed by two-fold serial
2
dillutions. Different concentrations of the tested compounds were added to the MCF-7 cells and
then the plates were incubated at 37 ºC with 5% CO atmosphere for 48 hours after which old
2
medium was removed followed by washing with saline solution (0.89%) and the addition of 100
µL of MTT solution (0.5mg/ml). After a period of 4 hours of incubation, the supernatants were
carefully separated and the precipitates of formazan crystals were dissolved 100 µL of dimethyl
sulfoxide (DMSO). At last, the absorbances at 490 nm were measured using a 96-well plate
(
51)
reader spectrophotometer . A dose response curve was constructed, to conclude the IC , using
5
0
the concentration as x-axis and the % viability as Y axis.
3
3
.Results and discussion :
1
.1. HNMR Spectra in d6-DMSO:
1
1
2
3
HNMR spectrum of the ligands (L , L and L ) showed the following peaks : δ(6.8-8.0
ppm) assigned for the(4H) in the phenyl group, δ(2.4-4.0 ppm) are due to –CH protons,
1
2
δ(3.47 ppm-1H) of –OH group in L and δ(2.47 ppm-1H) of –SH group in L . The absence of

2
3
the signals assigned for O–H in L and L is an evidence for the keto rather than the
(52)
2
enolform. The singlet band of the proton of C-H group appeared at (6.9 ppm) for L , and
also the proton of the OH group of thiobarbituric acid (TBA) appeared at δ(12.0 ppm), are
(53)
due to denote keto-enol forms
.
3
.2. MALDI-TOF spectroscopy
All the prepared compounds were analyzed using MALDI-TOF technique. The
experimental and calculated molecular weights of the compounds are collected in Table (3)
Based on the obtained data , it is obvious that the experimentally determined molecular weights
.
are either equal or matching with the theoretically calculated ones which give a clear evidence
for the accuracy of the proposed structures of the prepared compounds.
Table (3):Summary of the experimentally observed molecular weights and the theoretical
ones for the prepared compounds.
Compound (Chemical formula)
Calculated Molecular
weight(g/mol)
Observed Molecular
weight(g/mol)
1
L (C11
H
8
8
O
4
2
N
2
4
)
232.20
248.26
232.20
490.45
438.61
491.13
388.48
425.38
409.31
236.35
248.70
234.80
491.19
441.23
492.72
389.10
426.28
408.12
2
L (C10
H
O
N
S)
3
L (C H O N )
10
8
3
3
4
OsO . L . 2OH(C H N O Os)
2
10 12
4
7
1
Ru. L . Cl (C H Cl N O Ru)
3
11
7
3
2
4
2
Ru. L . Cl (C H Cl N O RuS)
4
10 10
4
4
2
3
V. L . Cl (C H Cl N O V)
3
10
7
3
4
3
2
ZrO. L .Cl
2
2
(C10
H
H
7
7
Cl
2
2
N
4
O
O
3
4
SZr)
Zr)
3
ZrO. L .Cl
(C10
Cl
N
4
3
.3.FT-IR spectra :
1
2
3
-1
The ligands (L ,L and L ) showed spectral bands at 3398,3325 and 3331 (cm )
-1
respectively due to νO-H. The bands showed at 3212,3086 and 3112 (cm ) respectively are due
to νN-H stretching overlapped with hydrogen bonds of the type N–H· · · O, O· · ·H–O and O–H
· ·N. The bands at 1620–1700 cm region are assigned to νC=O, and those at 1588–1595 cm
are due to νC=N.The bands due to νO–H · · ·N are shown in the region(2500-2850 cm .The
ligand containing sulphur (L ) exhibited the four thioamide bands at : 1535,1392,1149 and 824
cm . The presence of νOH and νC=O denoting keto↔ enol tautomerism, beside the presence of
thioamide bands and νS–H indicating thiol↔ thione tautomerism.
detected at 1232, 1297 and 1260 for L ,L and L respectively. C–N stretching bands appeared
357, 1392 and 1333 respectively. The Ligands (L and L ) show bands due to stetching
−
1
−1
·
-1)
2
-1
(
54,55)
The νC-O bands are
1
2
3
2
3
1
-
1
(56)
vibration of the azo group (νN=N) at 1441 and 1470 (cm ) respectively.
The bands due to both νN-H and ν C=O stretching disappeared in the IR spectra of the
-
1
complexes and the appearance of new spectral bands in the regions (2400-2600 cm ),(1594-
-1
1
650 cm ) and (1350-1402) are assigned for νO-Himinol, ν C=N and νC-O respectively provide a
strong evidence that tautomerization of the NH group with the adjacent carbonyl and
thiocarbonyl groups takes place before complexation.The psudo aromaticity of the iminol

structure can stabilize the enol form as compared to the keto form.The spectra of the azo
complexes do not show any shift in the frequencies of νN=N indicating that N=N do not
participate in the coordination with the metal ions.The broad bands appeared at
-
1
3
3
1
2
3
405,3433,3401,3440,3436 and 3451 (cm ) in , Zr.L .H O, V.L . H O, Ru.L . H O, Ru.L . H O
2 2 2 2
3
(57)
and Os.L .H O respectively are due to the the existence of a coordinated water molecule. The
four thioamide bands in -azothiobarbituric acid complexes: Zr.L . H O and Ru.L . H O are
affected on complexation with different degrees to give a proof for the M–S bonding.
2
2
2
2
2
(
58)
From the previous findings, together with the elemental analysis data, Table (2), the
following structures are suggested for the prepared complexes[Figure(2)]:

Figure (2) : The prepared complexes
3
.4. Magnetism and electronic spectral studies:
The electronic absorption spectra of diamagnetic complexes Zr(IV)O.L .CL2
,
2
Zr(IV)O.L .CL and Os(VIII)O .L .(OH) showed the bands due to π-π* at 289 ,289 and 252 nm
3
2
2
3
2
respectively .The bands assigned to n-π* for these complexes appeared at 349 ,366 and 363 nm
(
59)
respectively
.
1
The room temperature magnetic susceptibility measurements of the Ru(III)L .CL
3
and Ru
III)L .Cl complexes showed that these complexes are paramagnetic with one unpaired electron
2
(
4
with effective dipole moments (µeff): 1.39 and 1.74 B.M respectively. Such values of µeff gave
a strong evidence for the existence of these complexes in the octahedral geometry and their
(
60)
trivalent nature .The bands showed at (327-335 nm) ,(369-375 nm) and (586-593 nm)
2
2
2
4
respectively in the spectrum of Ru(III) complexes are assigned for T g→ A g , T g→ T g and
2
2
2
2
2
4
(61)
T g→ T g electronic transitions
.
2
1
The effective dipole moment value (µeff=2.82 BM) of the paramagnetic complex
V.L .Cl ) agreed with the conclusion that the complex exists in an octahedral geometry .The
3
3
(62)
(
electronic absorption spectrum of this complex shows an absorption band at 247 nm which is
assigned for π-π* transitions. On the other hand , the absorption peaks at 402 nm and 600 nm are
3
3
(63)
due to n-π* and d-d( T
1
g→ T
2
g) transitions in an octahedral ligand field respectively
.
3
.5.Thermal analysis:
3
.5.1. Thermogravimetry (TG)
The thermal stability of the ligands was studied by heating the sample at a control rate of 10
3
k/minute under air atmosphere except for 5-( phenyl azo) barbituric acid (L ) the rate was 10
o
C/minute under nitrogen atmosphere . All the prepared ligands were stable up to (187.5-
o
(64)
2
36.5 C) giving a strong evidence for the absence of lattice water . Typically in TGA, the loss
o
of lattice water occurs at low temperature in the range 60–120 C, whereas coordinated water
requires a temperature in the range 120–230 C .Accordingly, all the prepared ligand do not
contain lattice water. L begins to undergo thermal decomposition at 236.2 C and its thermogram
shows Three distinct decomposition stages. The first stage started at 236.2 C with a loss of
o
1
o
o

weight (Obs.; 7.34%,Calc.;7.32%) could be due to loss of one hydroxyl radical. The second
o
fragmentation between 236.4 and 342.4 C shows the weight loss (Obs.; 19.46%, Calc.;
2
•
2
0.0%)due to loss of the organic fragment (CHNO ) in the form of gaseous radical product
3
•
leaving carbon residue. The final stage involved the loss of another organic moiety (C H NO )
Obs.; 34.87%,Calc.; 39.53%) as a gaseous radical between 342.4 and 499.8 C.The second
ligand (L ) starts decomposing at 187.5 C in three distinct stages, the first stage started at 187.5
C with weight loss (Obs.; 24.63%,Calc.; 23.75%) where the radical (CHNS ) was lost.The
second stage started at 340.7 C with weight loss(Obs.; 25.34%,Calc.; 22.75%) giving out a
small organic moiety (CHNO ) as a gaseous product. In the third stage a larger organic moiety
was given out (C H ) (Obs.; 50.11%,Calc.; 52.74%)leaving a carbon residue between 340.70
and 499.10 C .For (L ), the thermal decomposition took place in three stages of thermal
3
2
o
(
2
o
o
2.
o
2
.
.
6
5
o
3
.
degradation ; the first gave out (C H N ) (Obs.; 48.14%,Calc.; 45.24%) in the temperature range
193.91-220.04 c), the second stage started between (302.54-324.01 c) giving out the
radical(O ) (Clac; 12.58%,Obs.; 12.81%),the third stage occurs between (324.01-400.00 c) with
6
5
2
o
o
(
2
.
o
•
weight loss (Clac; 35. 71%,Obs.; 35.446%) due to loss of an organic moiety (C
7
H
5
O ) as a
gaseous radical, in the final stage (338.08-432.06 c) another organic moiety is lost (Clac;
3.95%,Obs.; 62.25%) leaving a carbon residue.
o
6
3
The TGA curve of the complexes gives a three-stage decomposition pattern for V.L .Cl
3
2
3
3
,
ZrO.L .Cl and ZrO.L .Cl complexes. In case of the thermograms of OsO .L .(OH) and
2 2 2 2
2
1
Ru.L .Cl complexes four-stage thermal degradation stages are observed. The complex Ru.L .Cl
showed a five stage decomposition pattern .The complex V.L .Cl started to decopose in
temperature range (39.9-119.1 C) with weight loss (Clac; 23.16%,Obs.; 23.37%) is due to the
loss of an organic moiety (C H N ) as a gaseous product. The second stage gave out another
4
3
3
3
o
2
•
6
5
2
•
o
organic moiety (C H N O ) (Clac; 24.00%,Obs.; 24.44%) at 329.5 C , finally the third stage
2
4
2
o
occurred at 498.4 C to give out the rest of the molecule leaving a metal oxide residue. For
2
o
2
ZrO.L .Cl the first stage occurs in the temperature range (23.6-190.3 C) with weight loss(Clac;
2
•
2•
1
4
2.85%,Obs.; 13.16%) due to loss of (CHNO ), the second stage gave out (CHNO ) at (190.3-
o
3•
o
2
07.5 C),the final one gave out (CH S ) at 691.5 C and a residual metal oxide is obtained. The
3
o
2•
ZrO.L .Cl
2 7 6 2
complex starts decomposition at 189.7 C indicating the loss of ( C H N ), the
3
•
second decomposition stage gave out an organic moiety (C HNO ) Clac; 28.84 %,Obs.;
9.28%) at 295.5 C.The final decomposition stage occurs in the range (295.5-669.4 C) to
complete the loss of the rest of the complex yielding the metal oxide residue. The OsO .L .(OH)
complex strated the first stage at 140.1 C giving out (C H )(Clac; 13.65%,Obs.; 13.69%), the
second stage also gave an organic fragment(C H N O ) (Clac; 30.20%,Obs.; 32.30%) at
25.6 C, at 392.5 C the third stage occurs with the loss of (CH NO ) (Clac; 27.10%,Obs.;
8.64%) .The fourth stage occurred at 499.5 C leaving the residue. The Ru.L .Cl complex lost
a (SH ) gaseous radical(Clac; 6.68%,Obs.; 6.08%) in the first decomposition stage at 116.85 C ,
the second stage involved the loss of (C H N O ) radical at 292.18 C,the third stage is
accompanied with the loss of ( C H NO ) (Clac; 18.84%,Obs.; 19.61%) at 382.57 C,finally the
last decomposition stage gave out the rest of the molecule at 457.85 C leaving the metal oxide
residue. For the complex Ru.L .Cl
2
2
o
o
2
3
2
2
o
3•
5
5
5
•
4
4
3
2
o
o
3•
2
2
3
o
2
4
.
o
2
•
o
8
7
3
5
•.
o
2
2
o
1
.
3•
5•
3
3•
3
gave out ( Cl , C
3
H
3
O , C
4
H
and C
2
H
2
NO ) leaving the
o
metal residue at 600 C.
3
.5.2. Differential scanning calorimetery (DSC)

1
2
1
Typical DSC method was applied for the ligands (L and L ) and the complexes (Ru.L .Cl
3
2
3
,
ZrO.L .Cl and ZrO.L .Cl ), which are done under air at heating rate10 °C /min in the temperature
range 25-700 C. The heat capacity can be determined by dividing the heat flow by the heating rate.
The variation of Cp versus T can be represented using Debye model as the following relations .
3 3
0
(65)
CP
3
2
C =
α
T +
γT
,
=
α
T +
γ
, Cp ≃ Cv
P
T
Where, α is the slope of the line and γ is the intersection of the line with y-axis (Cp axis),
C
p
is the specific heat at constant pressure ,C
v
is the heat capacity at constant volume, γ is
-4
constant equals10 cal/gram.mole.
2
34R
234R
(
66)
According to Debye model
,
α
=
,
θD = 3
(5)
3
θ D
α
o
R is the universal gas constant equals 8.3 J/mole/ K and θ is Debye temperature, which
D
defined as the temperature separate between the high temperature range and the low temperature
2
range. By plotting C /T as y-axis and T as x-axis(Figure(3)), a straight line is obtained with a
p
slope equals α, also the intersection with y-axis gives the coefficient (γ), Table (4).
(
67)
The entropy change (ΔS) for any phase change can be obtained from the relation
ΔS = ΔH /T (6)
Where , ΔH the enthalpy change at any peak temperature (T ).
:
m
:
m
The studied compounds showed exothermic peaks at lower temperatures with negative ΔS values
(
68)
which give an indication that the activated transition states are ordered
.
2
Figure(3): Typical C
p
/T against T plot.
C P
T
γ
0
2
T
Table (4): Slopes and intercepts for DSC curves of some compounds.

3
.5. Effect of pH on the electronic absorption spectra and determination of
dissociation constants
(
69,70)
The pKa values of the ligands were evaluated using Half – height method
limiting absorption method and Colleter method
Table(5).
, Modified
(
71)
(72,73)
.The data obtained is collected in
Table (5): pK’s values of the ligands
Number
of
ionized
protons
Modified
limiting
λma
x
Half height
Colleter
Average
Isobestic
points
Compound
(nm
(n)
(nm)
)
pk
pk1
2
pk1 pk2 n
1
n
2
pk1 pk2
pk1 pk2
1
L
420, 400.7,242
41 .1
6.4
10.
7
6.1
10.
2
1
1
6.42 10.33 6.3± 10.41±0.3
0.2
2
2
L
344. 344.8,283
,28
.4
Heat range
7.0
11.
0
6.8
10.
9
1
1
1
7.3 11.23 7.03 11.04±0.3
±0.4
8
T
°
m
ΔH
J/g
5
CP
2
ΔS
C
1
a
p
= aT + b
=
α
T +
γ
C
°
C
Co
3
mpound
T
L
407, 388,282
5.5
9.1 6.00
9
J
.
/
2
g.°C
6.23 9.26 5.91 9.18±0.02
B
α
γ
2
85
25.1-341.1
69.4-611.6
22.0-341.1
±0.3
1
-8
-8
-7
-7
-7
L
82.3
-1206.462
3340.854
-14.66
.67
0.0033 -0.8842 6.0 x 10
-0.0023
5
589.2
96.4
5
2
L
-4307.51
4833.435
-44.68
10.52
0.0364 -8.4113 9.0 x 10
0.0015
-0.0089
-0.0311
-0.0383
5
19.0-581.8 459.3
22.6-393.5 80.5
53.0-488.9 465.0
ZrO. L .Cl 23.2-352.8 95.0
94.5-593.7 550.1
33.7-147.0 95.8
15.0-507.6 466.2
1
Ru.L .Cl
-4542.956 -47.82
-58.9281 -0.127
-3333.924 -35.09
1515.701 2.76
-889.2633 -9.28
4369.964 9.37
0.038
0.0846 -24.157 4.0 x 10
0.105 -30.559 5.0 x 10
-11.085 1.0 x 10
3
4
2
3
4
3
ZrO. L .Cl
3
2

3
.6.Biological activity
3
.6.1.Antimicrobial activity
The in vitro antibacterial activity of compounds was evaluated against both gram positive
and
gram
negative
bacteria
including
two
gram-positive
species
:
Staphylococcus aureus “ATCC 6538” and Staphylococcus Epidermidis”ATCC12228” and two
gram-negative species :Escherichia coli”ATCC 25922” and Salmonella”ATCC 25566” .In
addition, all the compounds were tested for their antifungal activity against the species: Candida
albicans”ATCC 10231”. Nutrient agar plates were inoculated with the test strains and the results
were expressed by measuring the diameter of the zone of inhibition (in mm) around the disc and
collected in Table (6).
2
According to the data given in Table (6) it can be concluded that, The ligand (L ) showed
great inhibitory effect on the bacterial cell growth of both gram positive and gram negative
strains under study with inhibition diameters: 12,13,13 and 12mm for the species Staphylococcus
2
aureus, Staphylococcus Epidermidis, Escherichia coli and Salmonella respectively . Also, L
exhibit good antifungal activity against Candida albicans with inhibition zone diameter of 15
3
mm. A moderate antimicrobial activity was shown by (L ) as it affects only the gram-positive
strains: Staphylococcus Aureus and Staphylococcus Epidermidis with inhibitory zone of
3
diameters 17 and 24 mm respectively. However, L have the greatest antifungal effect with
1
inhibition diameter of 23 mm against Candida albicans. On the other hand,(L ) showed the least
activity as it cause an inhibition diameter of 15 mm against the fungal species under study.
The species : Escherichia coli , Salmonella and Candida albicans showed complete
resistance against all the prepared transition metal complexes .However , the collected data
clarified that all the complexes exhibited a moderate to good antibacterial activity against the
gram-positive species :Staphylococcus aureus and Staphylococcus epidermidis. Among these
3
complexes, “OsO
2
.L .(OH)
2
” gave the highest bacterial cell growth inhibitory action with
1
3
diameters 16.5 and 20 mm followed by ” Ru.L .Cl ” with 13.5 and 20 mm , “ZrO.L .Cl ” with
1.5 and 16 mm , “V.L .Cl ” with 11 and 15 mm,” Ru.L .Cl ” with 11.5 and 15 and the complex
3
2
2
1
3 3 4
“
ZrO.L .Cl ” with the smallest diameters 10 and 14 mm against Staphylococcus Aureus and
2 2
Staphylococcus Epidermidis respectively.
2
3
The antimicrobial action of the tested ligands follows the descending order : L > L >
1
2
L >.Such variation in activity may be attributed to the presence of sulfur atom in L that improve
(
74)
the antimicrobial effect of this compound which is a thiobarbituric acid deravative
The cell
(75)
wall of bacteria contains lipids which are non-polar materials ,so a successful anti-microbial
agent should have some lipophilic groups. Since, the nature of the tested ligands are mainly
lipophilic,they showed good antimicrobial activity.
3
The antibacterial activity of the tested complexes increases in the order : OsO .L .(OH) >
2
2
1
3
3
2
Ru.L .Cl > ZrO.L .Cl > V.L .Cl > Ru.L .Cl > ZrO.L .Cl , these variations in antibacterial
3
2
3
4
2
2
activity cannot be clearly explained. The gram negative bacteria show higher resistance than
gram positive ones, this is attributed to intrinsic resistance of the gram negative bacteria. The
membrane of the gram negative bacteria functions as a barrier and prevents penetration of the
drug molecules, that’s why the gram-negative strains under investigation exhibited full resistance
(76)
against the tested complexes . In general all the metal(II) complexes possess higher anti-

bacterial action against gram-positive species than ligands and this may be due to the change in
structure due to coordination and chelating tends to make metal complexes act as more powerful
and potent bactereostatic agents, thus inhibiting the growth of the microorganisms. Moreover,
coordination reduces the polarity of the metal ion mainly because of the partial sharing of its
positive charge with the donor groups within the chelate ring system formed during the
(68)
coordination .This process, in turn, increases the lipophilic nature of the central metal atom,
which favors its permeation more efficiently through the lipid layer of the microorganism, thus
destroying them more aggressively. Increased activity of the metal chelates is due to the
(
77)
lipophilic nature of the metal ion in complexes . Furthermore,The metal ion interaction is
preferred with the lipidsand polysaccharides which are the important constituents of the cell wall
and membranes. Other components of cell wall, many phosphates, carbonyl and cysteinyl
ligands which maintain the integrity of the membrane by acting as a diffusion barrier also
(76)
provide suitable sites for binding .This would suggest that the chelation could facilitate the
ability of a complex to cross a cell membrane and can be explained by Tweedy’s chelation
(
78)
theory .The pathogens secreting various enzymes, which are involved in the breakdown of
activities, appear to be especially susceptible to inactivation by the ion of complexes. The metal
complexes facilitate their diffusion through the lipid layer of spore membrane to the site of
action and ultimately killing them by combining with the OH and C=N groups of certain cell
(79)
enzymes.
Table (6):
Species
In vitro Antibacterial activity of the complexes against some reference strains
Inhibition Zone (mm)
1
2
3
3
2
3
1
2
3
L
L
L
OsO .L .(OH) . ZrO.L .Cl2 ZrO.L .Cl2 Ru.L .Cl3 Ru.L .Cl4 V.L .Cl3
2 2
Staphylococcus
Aureus.(S.A)(ATCC 6538)
-
-
-
-
12 17
13 24
16.5
10
14
-
11.5
16
-
13.5
20
-
10.5
15
-
11
16
-
Streptococcus
Epidermidis.(S.E)(ATCC 12228)
20
-
Eschirichia Coli.(E.C)(ATCC
13
-
25922)
Salmonilla.(S)(ATCC25566)
Candida Albicans.(C.A)(ATCC
12
-
-
-
-
-
-
-
-
-
-
-
-
-
15 15 23
10231)
3
.6.2.Antioxidant activity
The in vitro antioxidant activity of the tested compounds was evaluated using 1,1-
(
80)
diphenylpicrylhydrazyl (DPPH) radical scavenging method
at eight different
concentrations(640,320,160,80,40,20,10 and 5 µg/mL) . By analyzing the collected data in table
7),it was found that the parent ligands showed a weak to moderate antioxidant activity as
(
1
2
3
indicated from the IC values:118, 49.5 and 53.6 µg/mL for L ,L and L respectively compared
5
0

to the IC50 =14.2 µg/mL of the reference drug: Ascorbic acid.On the other hand, the complexes :
1
3
Ru.L .Cl
3 2 2
and OsO .L .(OH) exhibited a great antioxidant effect as compared to the reference
compound with IC values:9.2 and 19.4 µg/mL respectively. The other tested complexes:
5
0
2
3
3
Ru.L .Cl ,V.L .Cl and ZrO.L .Cl gave rise to very high IC values:268.7 ,258.7 and 118.2
4
3
2
50
µg/mL respectively, which is an evidence for the very weak antioxidant activity of these
complexes.
(81)
The anti-oxidant activity depend on the presence of the active groups (OH- and NH2)
Since phenolic compounds are good electron donors, they may accelerate the conversion of H O
.
2
2
to H O. Phenolic compounds are known as powerful chain breaking antioxidants. This indicated
2
1
2
3
that the parent ligands (L ,L and L ) had fair inhibitory effect on the oxidation process since
they can generate free radicals.This may be related to their structure since they exist mainly in
1
the enol or thiol forms as proved by FT-IR analysis .On the other hand, the complexes: Ru.L .Cl
3
3
and OsO
2 2
.L .(OH) have electron donating groups and atoms (OH- and Cl-) which enhance their
antioxidant activity and consequently these complexes exhibited significant antioxidant activity
(82)
at all examined concentrations
.
Table (7):The in vitro antioxidant activity(DPPH scavenging %) of tested compounds using
DPPH method.
Compound
Concentrations(µg/mL)
6
40
320
160
80
40
20
10
5
IC50
118.00
49.50
53.60
9.20
1
2
3
L
L
L
92.10 88.70 64.30
92.40 91.10 89.60
91.20 90.40 84.70
95.00 94.80 94.50
37.00
78.60
72.20
93.90
89.80
17.30
41.10
38.50
92.30
81.10
8.60
4.50
5.70
4.90
56.30
14.10
1.30
1.90
1.40
18.10
4.40
14.40
12.70
88.40
52.20
1
Ru.L .Cl
3
3
OsO .L .(OH) 93.50 93.10 92.20
19.40
2
2
2
Ru.L .Cl
4
81.40 55.90 37.50
85.30 56.40 39.70
90.50 82.20 68.70
20.20
21.40
32.90
-
11.30
12.30
13.10
92.84
5.60
5.90
2.80
3.00
0.70
0.80
268.70
258.70
118.20
14.20
3
V.L .Cl
3
3
ZrO.L .Cl
2
6.10
3.10
0.90
Ascorbic acid
-
-
-
70.94
17.49
11.78
3
.6.2.Anticancer activity
The synthesized compounds were tested for their invitro cytotoxic activity against the human
breast cancer (MCF-7) cell line using the MTT assay technique. Different concentrations
ranging from 3.9 to 500 µg/ml) of the compounds were applied to the cancer cells as doses of
(
treatment. The values of the half maximal inhibitory concentration (IC50) of the compounds were
2
listed in table (8).Based on the data collected in table (8) ,it is clear that L exhibited the greatest

3
2
-
activity with IC50 : 22 µg/ml followed by L (IC50 : 28.98 µg/ml) and [Ru.L .Cl
µg/ml) respectively. According to the structure-activity relationship (SAR) investigations
was concluded that thiooxy pyrimidine derivatives have exhibited a more potent anticancer
action than the oxy pyrimidines and this may account for the excellent activity of the compounds
4
] (IC50 : 37.8
(
83)
, it
1
3
3
containing sulfur. The compounds : L , ZrO.L .Cl and V.L .Cl showed moderate anticancer
2
3
activity against the tested cells giving IC values:52.53 , 59.70 and 72.05 µg/ml respectively.
5
0
On the other hand the rest of the tested drugs have a little effect on the the human breast cancer
MCF-7) cells .
(
Table (8):Cytotoxic activity of the compounds against MCF-7 cell line expressed as IC50.
Compound
IC (µg/ml)
50
1
L
52.53±2.6
22 ± 0.9
2
L
3
L
28.98±3.1
203 ± 5.3
37.8 ± 1.3
237± 7.4
72.05±5.3
222 ± 6.8
59.7 ± 3.4
1
Ru.L .Cl
3
2
-
[
Ru.L .Cl ]
4
3
OsO .L .(OH)
2
2
3
V.L .Cl
3
2
ZrO.L .Cl
2
2
3
ZrO.L .Cl
4
.conclusion:
1
2
3
In conclusion, our research group synthesized three biologically active ligands (L ,L and L )
derived from barbituric and thiobarbituric acid and six of their transition metal
1
2
-
3
3
2
3
complexes(Ru.L .Cl ,[Ru.L .Cl ] ,OsO .L .(OH) , V.L .Cl , ZrO.L .Cl , ZrO.L .Cl ) .All the
3
4
2
2
3
2
2
prepared compounds were fully characterized and tested for their antimicrobial, antioxidant and
2
anticancer activities. The collected data showed that L is the most effective anticancer agent as
2
compared to the other compounds against MCF-7 cells with “IC50=22 µg/ml” .The ligands (L
3
and L ) exhibited great antimicrobial action against both gram positive and gram negative
species and the fungal species under study.Moreover, the complex: Ru.L .Cl is recommended to
1
3
be used as excellent antioxidant as seen from the DPPH radical scavenging technique.

References:
1
2
3
4
5
6
.
.
.
.
.
.
M.Mastalir, M.Glatz, E.Pittenauer, G.Allmaier, and K.Kirchner,J.of the American
Society,136,15543-15546(2016).
E.M.H.Ali and M.S.Abdel-Maksoud , Recent advances, Bioorganic & Medicinal
Chemistry,44,1014-1018(2019).
J.Figueiredo, J.L. Serrano, M.Soares and S.Ferreira, European Journal of Pharmaceutical
Sciences,137,928-987(2019).
A.Misra, D.Kishore, V.P.Verma, S.Dube, S.Chander, N.Gupta, S.Bhagyawant, J.Dwivedi,
Z.A.Alothman, S.M.Wabidur and S.Sharma, J.of King Saud Univ.Sci.,32,1486-1495(2020).
S.K.Prajapti, A.Nagarsenkar, S.D.Guggilapu, k.k.Gupta, L.Allakonda, M.K.Jeengar,
V.G.M.Naidu and B.N. Babua, Bio.Org. and Med.Chem.Letters,26,3024-3028(2016).
A.Kamal, S.Faazil, S. M. A.Hussaini, M. J.Ramaiah and M. Balakrishna, Bio.Org. and
Med.Chem.Letters,26,2077-2083(2016).
7
8
.
.
S.A.Elmetwally, A.K.Khalil and W.M.Elsayed, Bio.Org.Chem.,94,103492-103496(2020).
M.Sankarganesh,J.D.Raja, N.Revasi, R.V.Solomon and R.S.Kumar, J.of
Molec.Liq.,294,111655-111661(2019).
9
.
N.Patel, S. N. Pushpavalli, M.Bhadra, S.M.Roopan and R.Sompalle, J.of Synthetic
Communications,46,645-676(2016).
1
1
0. I.Lakomaska and M.Fandzloch, Coord.Chem.Rev.,327,221-241(2016).
1. M.Sankarganesh, J.Rajesh, G.G.Vinoth Kumara,M.Vadivel, L.Mitu, R.S. Kumar and
J.D.Raja, J.of Saudi Chem.Soc.,22,416-426(2018).
1
1
2. G.Luo, Z.Tang, K.Lao, X.Li, Q.You and H.Xiang, Euro.J.of Med.Chem,150,783-795(2019).
3. M.S. Masoud, G.B. Mohamed, Y.H. Abdul-Razek, A.E .Ali and F.N. Khairy. Spectrosc
Lett,35,377-380(2002).
1
1
1
4. M.S. Masoud, A.M. Heiba and F.M. Ashmawy, Transition Met. Chem. 8 (2) ,124–126
(
1983).
5. N. Z. Shaban, M. S. Masoud, M. A.Mawlawi , D. Awad and O. M. Sadek. Physiol Biochem
68,475–484 (2012).
6. M. S. Masoud, A. El-Marghany, A. Orabi and A. E. Ali, R. Sayed, Spectrochimica Acta ,
07 ,179–187(2013).
,
1

1
1
7. M.S. Masoud, N.A. Ibrahim, S.A. Abou Ali, G.Y. Ali and I.M. Abed, J. Indian.. Chem. 25,
89-291 (1986).
8. M.A. El-Dessouky, M.S. Masoud, F. Ali and S.A. Abou El-Enien, Afinidad, 416, 321-
25(1988).
2
3
1
2
9. M.S. Masoud and Z.M. Zaki, Trans. Met. Chem., 13, 321-323 (1988).
0. M.S.Masoud, E.A.Khalil and A.R.Youssef, Synth.React.Inorg. and Met.Org.Chem. 20,
7
93-795 (1990).
2
2
1. M.S.Masoud, S.A.Abou El-Enein and H.M.Kamel, Indian J.Chem. 41, 297-301 (2002).
2. M.S. Masoud, S.A. Abou El-Enein, M.E. Ayad and A.S. Gohar, Spectrochim. Acta, 60A,
7
0-75 (2004).
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
3. M.S.Masoud, E.A.Khalil, A.M.Hindawy and A.M.Ramadan, J.of Analytical Science and
Spectroscopy, 50(4), 207-220 (2005).
4. M.S. Masoud, A.E.Ali, M.A. Shaker and G.S. Elasal, Spectrochim.Acta, A, Molecular and
Biomolecular Spectroscopy, 90, 93-108 (2012).
5. M. S. Masoud, A. M. Ramadan and G. M. El-Ashry, Thermochimica Acta, 551, 164–174
(2013).
6. M.S. Masoud, A.M. Hindawey, E.A. Khalil and A.M. Ramadan, Bull. Fac. Sci., Assuit
Univ. 32 ,140-143 (2004).
7. M.S. Masoud, M.Y. Abd El-Kaway, A.M. Hindawy and A.A. Soayed, SpectrochimicaActa
Part A: Molecular and Biomolecular Spectroscopy, 92, 256-282, (2012).
8. M.S. Masoud, A.A. Soayed and A.S. El-Kholany, J. of Radioanalytical and Nuclear
Chemistry,108, 1-8 (2011).
9. M.S. Masoud, M.Y. Abd El-Kaway, A.M. Hindawy and A.A. Soayed. Research
Conference for Egyption Faculties of Science, Alexandria University, 6, 11 18-19, (2011).
0. M.S. Masoud, A.M. Hindawy, Amina A. Soayed and M.Y. Abd El-Kaway. J. Fluid Phase
Equilibria, 312, 37-59 (2011).
1. M.S. Masoud, M.K. Awad, M.A. Shaker and M. M. T. El-Tahawy, Corrosion Science, 52,
2
387–2396 (2010).
2. M.S. Masoud, A. El-Merghany, A.M. Ramadan and M.Y. Abd El-Kaway, J. Therm Anal
Calorim. 101, 839–847 (2010)
3. M.T. Zaworotko, H.H.Hammud, G.Mc- Manus, A.M. Ghannoum, A.Kabbani and
M.S.Masoud, J. Of Chemical Crystallography, 39, 853-863 (2009).
4. M.S. Masoud, S.A. Abou El-Enein and A.M. Ramadan and A.S. Goher. J. Anal. App.
pyrolysis, 81, 45-51 (2008).
5. H.H. Hammud, K.H. Bouhadir, M.S. Masoud, A.M. Ghannoum and S.A. Assi, Journal of
Solution Chemistry, 37, 895-917 (2008).
6. M.S. Masoud, M.F. Amira, A.M. Ramadan and Gh.M El Ashry, Spectrochim.Acta, 69,
2
30-238 (2008).
7. M.S. Masoud, S.S. Haggag and E.A. Khalil. Nucleosides, Nucleotides and Nucleic Acids
5, 73-87 (2006).
8. M.S. Masoud, T.S. Kasem, M.A. Shaker and A.A. Ali, J.Thermal Analysis and Calorimetry,
4, 549-555 (2006).
2
8
9. M.S. Masoud, M.F. Amira, S.A. El-Moneim. G.M. Moghazy, A.A. Abou-Hagar and Gh.M.
El-Ashry, The Egyptian Science Magazine 2, 88-92 (2005).
0. M.S. Masoud, E.A Khalil, A.M. Hindawy and A.M .Ramadan, Canadian J.of Analytical
Sciences and Spectroscopy 50, 297-310 (2005).

4
4
4
1. M.S. Masoud, A.A. Elewa, A.E. Ali and E.A. Mohamed, Bultetin of the Chemists and
Technologists of Macedonia, 24, 21-34 (2005).
2. M.S. Masoud, E.A. Khalil, A.M. Hafez and A.F. El-Husseiny, Spectrochim.Acta, A, 61,
9
89-993 (2005).
3. M.S. Masoud, A.E. Ali, M.A. Shaker and M. Abdul Ghani, Spectrochim. Acta 60, 3155-
159 (2004).
3
4
4
4. M.S. Masoud and N.N. Maximous, Mikrochim. Acta 147, 111-115 (2004).
5. A. Vogel, “Textbook of Quantitative Chemical Analysis”, 4th Indian Reprint (2004).
4
4
6. R.H.Lee ,E.Griswold and J.Kleinberg,J.of Inorganic Chemistry,3(9),1278-1283(1964).
7. M.S.Refat, S.A.El-Korashy and A.S.Ahmed ,Spectrochemica Acta part(A),71(3),1084-
1
094(2008).
4
4
8. X.S.L.lorens and G.H.McCracken, Clinical Pharmacology of Antibacterial Agents, 1223-
1
267 (2006).
9. P.Zeng, Y.Zhang, ChenPan, QiJiaa, FujiangGuo, YimingLi, Weiliang Zhu, KaixianChen.
Acta PharmaceuticaSinicaB,3(3),154–162(2013).
5
5
0. G.C.Yen and P.C.Duh,J.of Agric.Food,42,629-632 (1994).
1. M.Chonghui,W.Yunyun,D.Fuhao,Z.Yuxun,Y.Shan,G.Wen and W.Shifa,J.of Chinese
Academy of Sciences,210037,13522-13528(2019).
5
5
5
5
5
2. M. S. Masoud, A.M. Ramadan and G.M. El-Ashry, Thermochimica ActaVolume 551, 164–
1
74 (2013).
3. M.S. Masoud and M.Y. Abd El-Kaway,Spectrochimica Acta Part A: Molecular and
Biomolecular SpectroscopyVolume 102, 175–185(2013).
4. X.S.L.lorens and G.H.McCracken, Clinical Pharmacology of Antibacterial Agents, 1223-
1
267 (2006).
5. P.Zeng, Y.Zhang, ChenPan, QiJiaa, FujiangGuo, YimingLi, Weiliang Zhu, KaixianChen.
Acta Pharmaceutica SinicaB;3(3):154–162(2013).
6. M.S. Masoud, A.A. Hasanein, A.K. Ghonaim, E.A. Khalil and A.A. Mahmoud, Z. Fur.
Phys. Chem. 209 ,223-231(1999).
5
5
7. M.Banyay, M.Sarkar, A.Graslund, Biophysical Chemistry 104, 477–488 (2003).
8. A. Sadeek, Walaa H. El-Shwiniy, Wael A. Zordok and Essam Kotb. Journal of Molecular
Structure, 1006 ,192–209 (2011).
5
6
9. S.S. Mohite, A.B. Patil-Deshmukh and S.S. Chavan, J.of Molecular Structure,10,1016-
1
025(2018).
0. V. K.Sharma, A.Srivastava and S.Srivastava, J.of the Serbian Chemical Society, 71(8-9),
17–928 (2006).
9
6
6
1. D. J. Machin and K. S. Murray, J. Chem. Soc. (A), 1500-1503(1967).
2. P. S.Prasad, S. Praveen Kumar, K. Bharathi and V. Narayanan, Materials Today:
Proceedings 5 , 9026–9032,(2018).

6
6
3. M.S. Masoud, M.Y. Abd El-Kaway, A.M. Hindawy and A.A. Soayed, SpectrochimicaActa
Part A: Molecular and Biomolecular Spectroscopy, 92, 15, 256-282 (2012).
4. M. S. Masoud, A. E. Ali and M. Y. Abd El-Kaway, J. Therm. Anal. Calorim.,
1
16(1), 183-189 (2014).
6
6
6
5. M.S.Masoud, S.A. Abou El-Enien and O.F.Hafez, J.Thermal Anal. 38, 1365 (1992)
6. K. Traore, J. Therm. Anal., 4, 135(1972).
7. M. S. Masoud, A. M. Ramadan and Gh. M. El-Ashry, Thermochim. Acta, 551,
1
64-169(2013).
6
6
7
8. M.S. Masoud, M.A. Shaker and A.E. Ali, Spectrochim. Acta 65A, 127-131 (2006).
9. Z.M.Zaki, Spectrochemica Acta part A 56,1245-1250 (2000).
0. A.B.P. Lever, Inorganic Electronic Spectroscopy, Elsevier Publishing Company,
Amsterdam, 312-314(1968)
7
1. R. Bau and M. Sabat, B. Lippert (Ed.), Cisplatin: Chemistry and Biochemistry of a Leading
Anticancer Drug, VHCA Zürich and Wiley-VCH Weinheim, 318 (1999).
7
7
2. A. Terzis. Inorg. Chem. 15, 793-801 (1976).
3. G.Rajitha1,V.Ravibabu1, G.Ramesh and B. Rajitha, J.of Research on Chemical
Intermediates,42,1989-1998(2015).
7
4. H.C. Wong, R. Coogan, F.P. Intini, G. Natile and L.G. Marzilli, Inorg.Chem. 38, 777-
7
91(1999).
7
7
7
7
5. S. Yao, J.P. Plastaras and L.G. Marzilli, Inorg.Chem, 33, 6061-6073(1994).
6. E.Yuriev and J.D. Orbell, Inorg. Chem 37, 6269-6278 (1998).
7. T.W. Hambley, Inorg. Chem. 27, 1073 -1086(1988).
8. M.S. Ali, S. Rounaa, A. Khan, H.O Jima, I.Y. Guzman, K.H. Whitmire, Z.H. Siddik and
A.R. Khokhar, J. Inorg. Biochem. 99, 795-803 (2005).
7
8
9. M. Burits and F. Bucar, Phytother. Res., 14 ,323-328(2000).
0. I.A. Efimenko, A.P. Kurbakova, Z.D.Matovic and G. Ponticelli, Trans. Met.Chem. 19, 640-
6
51(1994).
8
1. M. Garijo Aňorbe, M.S. Lüth, M. Roitzsch, M. Morell Cerdá, P. Lax, G. Kampf, H. Sigel,
and B. Lippert, Chem. Eur. J. 10, 1046-1058 (2004).
8
8
2. R.N.M.Kalla,R.S.Karuna,M.Balaji and LL.Kim,J.of Chemistry select,4,644-649(2019).
3. S.V.Laxmi, G.Rajitha, B.Rajitha and A.J.Rao,J.of.Chem.Biology,9(2),57-63(2015).

•
•
The research paper focused on bioinorganic chemistry of barbiturates and thiobarbiturates.
IR,NMR, MALDI-TOF ,UV-VISIBLE spectral methods are used to identify the prepared
compounds.
•
•
•
The compounds were tested for their anticancer, antimicrobial and antioxidant activities.
2
The compound L exhibited the greatest anticancer activity (IC =22µg/ml).
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0
Some of the compounds exhibited excellent antioxidant, antimicrobial(against both gram
positive and negative species) and anticancer (against breast cancer) activity.

Declaration of Interests
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
Mr. Mahmoud Moursy