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*Corresponding author e-mail: liqaa.aljailawi@uokufa.edu.iq , sci.abbas.abid@uobabylon.edu.iq
Receive Date: 29 May 2021, Accept Date: 05 June 2021
DOI: 10.21608/EJCHEM.2021.78206.3820
©2021 National Information and Documentation Center (NIDOC)
Egypt. J. Chem. Vol. 64, No. 10, pp. 5607 – 5612 (2021)

Chemical reactivity study of anew suggested Chemotherapy agent using
DFT
Lekaa Husina Khdaima and Abbas Abd Ali Dreab
a Al-Kufa University , College of Education forWomen, Al-Najafe,54001, b University of Babylon , College of
Science , Babil-Al Hashimiyah,51012, a,b Department of Chemistry
Abstract
Cisplatin is ([PtCl2(NH3)2] ( CDDP) or its antitumor properties, including the treatment of various solid tumor s). Clinical use
of CDDP confirmed for different kind of cancer have been treated, including usage of complexes as Sb (antiprotozoal), Bi
(antiulcer), Au (antiarthritic), Fe (antimalarial), Ag (antimicrobial) and Pt (anticancer) in the treatment of different drugs.
Materials and methods: This study was involve Our new suggested chemotherapy agent is
diaminobis((methylthio)oxy)platinum(VI)chloride (DMOP) complex. The agent has been described to be as effective anticancer
therapy, the investigation is carried by a method of DFT based on B3LYP and LANL2DZ basis set. Suggested transition states
formation of DMOP (II) complex(square planer) with purine bases(guanine and adenine) are studied by DFT/B3LYP method.
Results:The energy gap 0.02632 kCal.Mol-1
is small value of indicate of high chemical reactivity for DMOP complex. Gibbs
free energy of DMOP (IV) conversion into DMOP (II) is -14.92823 kCal.Mol-1
. The reaction is most probable of the complex
with guanine bases than adenine bases by total energy value equal to -792.613k Cal mol-1
. The compounds formation of guanine
bases with a platinum complex is the most probably than other suggested states by ZPE value equal to113.326 kCal mol-1
.
Keywords: Chemotherapy, Cis-platinum, Geometry optimization, transition state, DFT.
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Introduction
Cisplatin ([PtCl2(NH3)2] or CDDP) is strong
chemotherapy drugs widely with observance to its
antitumor properties, including the treatment of
various solid tumor s) "[1], Clinical use of CDDP
confirmed for different kind of cancer have been
treated, including use of compounds as Sb, Bi , Au,
Fe , Ag and Pt in the treatment of different drugs. The
wide range of compounds for activity of antitumor[2].
Cisplatin is square planar d8 PtII complexes that death
of cancer cell by binding to nuclear DNA, distorting
its structure1. The PtII complexes readily react with
N7 of guanine in DNA strand. The process is well
known by conversion of Pt(IV) complex to Pt(II) is
Metabolic proceed. The global reactivity descriptors
of molecule such an (IP), (EA), (A), (µ) and (?) is very
important for the appreciation of anticarcinogenic
activities. "A lot of theoretical methods have emerged
to estimate these global reactivity factors"[3].
Molecular modelling of the drug can be discovery and
synthesis new useful optimizing structures candidate
[4]. Computational chemistry plays an important rule
in drug discovery and modification of discovered
drugs for that are used in chemotherapy."As Pt(II) and
Pt(IV) complexes are widely used complexes with
cytotoxic activity", although Pt(IV)"complexes are
more inert than Pt(II) complexes". Because their
containing axial ligands that are reduced in the lived
tissues and converted into Pt(II) species, and therefore
are more resistant to unwanted side-reactions [5,6].
This interaction displays the stability of the Pt(II)
complex has been used The "DFT for calculating the
electronic properties, HOMO and LUMO energies,
Mulliken charge of atoms"[7], "The one of the
quantum mechanics which is used to investigate the
electronic structure of atoms, molecules is DFT "and
it can also be applied to large molecules [8,9].
The aim of the paper is to suggest of DMOP (IV)
complex and the combination of DMOP (II) complex
with nucleobase in DNA and molecular geometry,
optimized parameters and vibrational frequencies of
DMOP (IV) complex and complex with nucleobase
Egyptian Journal of Chemistry
http://ejchem.journals.ekb.eg/
531
L. H. Khdaim and A. A. Drea
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Egypt. J. Chem. 64, No. 10 (2021)
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by DFT/B3LYP with LANL2DZ using the Gaussian
09 package of programs[10-12].
Methods
The DMOP complex is theoretically prepared in
vacuum by one molecule of PtCl4 with ex NH3, ex
H2O2 and add of axial ligand (HOSCH3) as
follows[18]:
Scheme 1. The chemical reaction of complex formation.
Computational details
In the present work, All geometry optimization of
a ground state was calculated and performed using
Gaussian 09 program package[13] by using
DFT/B3LYP method. The calculations were based on
LANL2DZ (5d,7f) basis set. The imaginary
frequencies indicate that the energy minima are best
optimized geometries . The HOMO, LUMO, and
energy gap are indicated for the reactivity of DMOP
complex towered reactions. The different reactivity
and selectivity descriptors such as chemical hardness,
chemical potential, nucleophilicity, and
electrophilicity were calculated as well as total
density, dipole moment, electrostatic and Mulliken
charge. The electronic transitions and vibrational
transitions and NMR (C13, H1) spectra of DMOP
(IV)complex . The chemical structures of the suggest
DMOP (IV)complex is represented in Fig. 1 by using
ChemDraw professional 15.0.”
Diaminobis((methylthio)oxy)platinum(VI)
chloride(DMOP).
Fig.1. Name and chemical structure of
Pt(IV)complex.
Results and discussions
Geometrical parameters
The geometry optimized structure of DMOP
complex is represented in Fig. 2. "The geometry
optimization process stops when the force resultant on
atoms equal to zero". The local symmetry around the
metal centre. Table 1. Shows the structural properties
of DMOP complex, some of the bond lengths, bond
selected. They found agreement between the
experimental values of X-ray diffraction
measurments[14] and different computational values
for bond lengths of DMOP (IV) complex such as Pt1-
Cl2, Pt1-O6, Pt1-N5 are equal to 2.290, 1.940, 1.976
? respectively. Bond angles such as N5-Pt1-N3, Pt1-
N3-O6, and Pt1-Cl2-N3 are equal to 82.2°,90.0°,180°
respectively. The dihedral angle in the molecule (S7-
O6-Pt1-Cl2), ( C8-S7-O6-Pt1) and (S10-O9-Pt1-Cl2)
are (180°,-180°,180°) respectively. The bond length
between Pt atom and O, N, Cl atoms in DMOP
complex are very important in a load of charge transfer
between donor and acceptor. From the dipole moment
value of DMOP complex less than 15 value, therefore,
is indicate quite a polar complex[15].
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Egypt. J. Chem. 64, No. 10 (2021)
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Fig.2. Geometry optimized Structure of DMOP
comple
Atomic charges and electron density
Milliken analysis of DMOP complex, Atomic
charges are calculated, since the charge distribution is
shown in Fig. 3. It may be noted that the oxygen atom
has a negative charge and the carbon atom has the
highest positive charge. The Chlorine atoms have
slightly negative more than other atoms. "All nitrogen
atoms in DMOP (IV) complex have a negative charge
and the nitrogen N5 atom has more negative than
nitrogen N2, also the hydrogen atoms for the amino
group have large net positive charge (H3, H6, H7, H8,
H9) atoms. "The presence of a large number of
negative charges on carbons (C16, C20) atoms and the
positive charge on hydrogen in methyl group (H17,
H18, H19, H21, H22, H23) atoms easy formation of
quite a large number of intra and intermolecular
hydrogen bonding in the complex[16]. "
The electron density is typically shown a
comparison of the identified electron density with that
predictable by spherical models of the atoms and that
is called distortion electron density. The electron
density was calculated of ESP with SCF density
matrix. Figures. 3, and 4 represented Mulliken charge,
electron density respectively
Fig.3. Mulliken charge of Pt(IV)complex.
Fig.4. The total density of Pt(IV)complex.
The energy of Molecular Orbitals
HOMO and LUMO are the important orbitals to
describe the chemical reactivity[17,18], "optical
properties[19] and biological activity[20]. The energy
gap value of 0.02632 kCal.Mol-1 between HOMO and
LUMO is the small bandgap of DMOP complex lead
to the easy electrons transfer. Decreasing of the
energy gap leads to the increase of the intramolecular
charge transfer and is indicated of more reactivity for
a reaction of DMOP complex characters[21], Fig. 5.
Shows different view of molecular orbitals of DMOP.
A- two-dimensional view of Wireframe molecular
orbitals.
L. H. Khdaim and A. A. Drea
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Egypt. J. Chem. 64, No. 10 (2021)
5610
B- three-dimensional view of molecular orbital s.
Fig. 5. Frontier molecular orbitals of 3D for DMOP complex.
Energetic parameters and global reactivity
Thermodynamic parameters are calculated at
DFT/B3LYP level using a LANL2DZ basis set as
shown in Table 2, the stability of DMOP complex is
determined by the total energy, according to its low
value is most stable complex. Zero-point energy has
the lowest power possible in a quantum mechanical
system from the low value of the zero-point energy can
be known as a stable complex, calculated standard
enthalpy and entropy for DMOP complex is given in
Table 2. Also, the global reactivity of complex is the
values of chemical hardness softness shows that the
decrease in the hardness and softness leads to an
increase in the complex activity [22]. The high value
of electrophilic which have the highest capability to
the good donor of electrons[23].
3.5. Reactivity toward Purine Bases
Cisplatin ([PtCl2(NH3)2] or CDDP) is a square
planar d8 contain two cis chloride ligands and two
ammine ligands. The Pt-N bonds are kinetically inert
and thermodynamically stable, but Pt-Cl bonds are
unstable and Pt-OH2 are more reactive. The chloride
ligands can be slowly exchanged with water (aquatint)
or by other nucleophiles. The non-ammine ligands are
replaced by two N7 atoms of two adjacent guanines
and adenine on the same DNA strand as shown in
Scheme 2.
Scheme 2. The competitive reaction of DMOP complex with Purine Bases at DNA strand
Gibbs free energy of prodrug DMOP (IV) conversion
into drug DMOP (II) is -14.92823 kCal.Mol-1, the
reaction is forward into drug formation. The
combination reaction with Guanine is exothermic, the
value of -792.613 a.u. is more probable than a
combination with Adenine value of -773.479 a.u. .
Also is indicate a spontaneous reaction towards
guanine than adenine. Different transition states are
proposed for DMOP complex with Guanine and
Adnene, Table 2. shows energetic values of different
transition states that are conversion interaction within
the Cis-Platinum complex. According to the total
energy value of geometry optimization, we found
TS4-Guanine is the most optimized state with a value
of -792.613 kCal mol-1 than all other proposed
transition states. At the same time, ZPE value of TS4
is equal to 113.326k Cal Mol-1 while the ZPE of TS4-
Adenine is equal to 121.68Cal Mol-1, that’s mean
another proofing is present about TS4-Guanine is the
most probable by a factor of 7.354 kCal.Mol-1, it’s
more stable and has a long lifetime. So Platinum
complex is binding to N7 in Guanine base of DNA
strand.

EHOMO = -0.01949 ?Egap =0.02632 ELUMO =0.00683
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Table 2. Configuration interaction energetic values of Cis-Pt complexes at different suggested probabilities of
transition states formations.
Energies Configuration interaction of Guanine Configuration interaction of Adenine
TS1 TS2 TS3 TS4 TS1 TS2 TS3 TS4
Total energy
(a. u.)
-644.288 -792.29 -792.58 -792.613 -774.106 -773.42 -773.42 -773.479
G(kCal.Mol-1 91.177 78.313 69.591 68.606 94.565 94.440 85.090 82.925
S(kCal.Mol-1 119.96 123.75 121.861 124.932 124.175 124.94 121.02 127.86
H(kCal.Mol-1 126.945 115.21 105.924 104.662 131.588 131.652 121.172 121.047
ZPE(kCal.Mol-1 94.91 96.23 105.63 113.63 110.64 111.61 121.66 121.68
The molecular modelling of adenine and guanine
contains four main negative regions corresponding to
the four N lone electron pairs on the nitrogen
atoms(N1, N3, N7, and N9). the results are showed
that the best site for platinum complex binding from
less total energy by a.u in the N7 position of guanine
than adenine, in Table 5, Fig.7 & 8. The results are
showed guanine are contained the oxo group at the C6
position allows for the formation of a hydrogen bond
with ammine or water in [Pt(NH3)2(H2O)2]2[27],
also the amino group at the C6 position in adenine.
Whereas the oxo and amino groups at the C6 position
of the guanine and adenine respectively, are hydrogenbond acceptors. The oxo group in guanine is better
hydrogen-bond acceptor than the amino group in
adenine, therefore, the guanine the best stable than
adenine as well as the energy values are the lowest in
the quinine compared with the adenine[28-29]
Conclusion
The bond length between Pt atom and O, N, Cl
atoms in DMOP complex are very important in a load
of charge transfer between donor and acceptor. The
small value of the energy gap implies low electronic
stability and high reactivity of complexes toward
binding with nitrogen bases. The dissociation value is
exothermic (-14.92823 kCal.Mol-1) of prodrug IV
converted into drug II. The DOP complex is more
reactive with guanine than adenine.
Acknowledgement
The authors would like to thank the management of
Babylon University, College of Science, for doing this
research in our theoretical lap. of the chemistry
department.
Funding
This study did not supported by any one or any
university.
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