International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 1 ISSN: 2319-1058
Molecular modeling of platinum (IV) complex
as new drugs for anticancer chemotherapy
Abbas A-Ali Drea
Department of Chemistry- College of Science
University of Babylon, Hilla, Babylon, Iraq
Lekaa Hussain Khdaim
Department of Chemistry- College of Science
University of Babylon, Hilla, Babylon, Iraq
Abstract- Molecular modeling through theoretical calculation have been done to synthesis a new drugs for anticancer
chemotherapy. Complex of (bis((4- methoxy -4- oxobutanoyl) oxy) bis methoxy amine )platinum (IV) chloride have been
modeled synthesis as Prodrug molecule theoretically using density functional theory, DFT, B3LYP/LanL2DZ at level of
theory. Geometry optimization have been calculated for all chemical species that’s participate in the modulation.
Energetic properties and all other characteristics properties have been calculated to estimate the general features of
complex reactivity and stability toward the biochemical reactions.
They found that total energy value of geometry optimized structure equal to -1482.398 a.u. The reactivity
measurement by energy gap value 0.01141 kCal mol-1. Prodrug molecule have positive value of imaginary frequency,
evidence for their stable complex is achieved through calculus of vibrational transition spectrum. Electronic transition
calculation gave a clear view about the nature of chemical bonding and back donation of ligands.
Keywords – Molecular modeling, platinum (IV) complex, anticancer chemotherapy DFT, Theoretical calculation,
Geometry optimization, Surface potential energy, and transition state.
I. INTRODUCTION
A lot of chemical compounds have been fabricated for medical uses, epically for Cancer diseases treatments. One of
the famous chemical compounds as anticancer chemotherapy are Cis-platinum complexes and its derivatives of
carboplatin [1, 2] .Also oxaliplatin [3], nedaplatin[4] have been used widely in anticancer chemotherapy [5-6].
Square planer platinum(II)complex are acting as prodrugs containing two carrier ligands and two leaving groups, the
two leaving group are exchanged in the cell platinum complex(IV) are possess ant malignant properties and can act
as prodrugs. Novel platinum complex is large group in both Cis and Trans form with different donor ligand
[7].Cisplatin is treatment small cell lung, ovarian, testicular, head, and neck tumors [8].The primary target of
cisplatin is genomic DNA, specifically the N7 position of guanine bases [9]. Higher level of theory basis set into
DFT calculation, that’s implemented in package programs like Hyperchem program and Gaussian program been
used to achieve a new model of drags or to proposed mechanism respect complex acting as prodrug for anticancer
chemotherapy [10-14].
In the present work, modulation anew prodrug anticancer of platinum complex (IV) based on theoretical
calculation that’s will be done depending on DFT calculations. Geometry optimization process are proceed to get on
physiochemical properties such as Mullikan charge ,EHOMO,ELUMO ,energy gap ?E ,dipole moment (?),total
density, electrostatic potential ,Absolut electronegativity (X) ionization potential(I) chemical hardness (?) ,chemical
softness(S) and electron affinity(A) [15-17].
II. COMPUTATIONAL DTAIL
Different theoretical MO method have been used, that’s implemented onto G09W [18] running on windows
XP work station with core i7 .The geometry optimization of platinum complexes at DFT /B3Lyp [Becke’s three
parameter exchange functional along with the Lee-Yang-Parr nonlocal correlation functional [19-20]. Frequencies of
vibration and electronic transitions have been calculated for platinum (IV) complexes using B3Lyp /LanL2DZ
method. Calculus are done using restricted and unrestricted Hartree Fock respectively [21]. All characteristic
properties of complexes, like ionization potential, Electron affinity, and others labeling phenomena have been
calculated using Koopmans s theorem [22, 23].
International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 2 ISSN: 2319-1058
III. EXPERIMENT AND RESULT
Geometry optimized structure of complexes have been calculated using DFT based on B3Lyp /LanL2DZ at
level of theory in vacuumed. Figure 1. Represent the geometry optimized structure of complex A. Table 1.
Represent the theoretical parameters of optimize geometry as bond length and bond angle of Pt(IV)complex.
Figure 1. Geometry optimized for Pt (IV) complex by DFT/ B3Lyp/LanL2DZ (5d, 7f) at Level of theory.
Table 1. Theoretical parameter of bond length and bond angle Pt (IV) complex by using DFT/B3Lyp/LanL2DZ at level of theory.
Bond type Length bond
nm
Angle type Bond angle ? Dihedral Type Dihedral
Pt1-N21 1.97 Pt1-N21-O22 120 Pt1-N21-O22-C23 -180
Pt1-Cl17 2.29 Pt1-N18-O19 120 Pt1-N18-O19-C20 -180
Pt1-O3 1.94 N21-Pt1-N18 90 Pt1-O3-C5-C7 90
N21-Pt1-O3 90 Pt1-O2-C11-O12 -90
Cl4-Pt1-N18 180 Pt1-O2-C11-C13 90
Cl4-Pt1-O3 90 Pt1-O3-C5-O6 -90
The symmetry of complex A form is C1 refer to asymmetrical distribution in the Pt(IV)complex .The output of
this complex A gave C1 symmetry which is wrong symmetry [24].The dipole moment (?) vary from 3 to 15 due to
complex A is quite polar complex [5],the dipole moment values of complex for I.R and UV-Vis spectra is different
8.0922,6.2402 respectively. The imaginary frequencies is positive and the energy values is negative ,therefore stable
complex A .The physical an thermodynamic properties of complex A were calculated such as energy (kCal mol-1),
heat of formation ?H, Gibbs free energy ?G, entropy ?S, thermal energy .
Table 2. Thermodynamic calculation of Pt(IV)complex by using DFT/B3Lyp/Lan2DZ at 298.150K at levels of theory
Total energy -1482.398 a.u
Enthalpy ?H 268.8867 Kcal/Mol
Gibbs free energy 202.4278 Kcal/Mol
Entropy 222.9042 Kcal/Mol
Zaro point energy 237.0818 Kcal/Mol
Imaginary frequencies +
Time of calculation IR=1h:17m:27s and UV=8h:46m:8s
Degree of freedom 147
Kinetic energy 1.375159960421D+03
E-N energy -9.549360577589D+03
International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 3 ISSN: 2319-1058
N-N energy 3.059532181679D+03
High electron density distribution on oxygen in carbonyl groups and nitrogen in amine group because the high
value of electronegativity [25].The electrostatic potential in Figure 2,3, the negative charge are remarked by red
color are distribution on the oxygen atoms in carbonyl groups and the nitrogen in amine group due to high value of
electronegativity .The positive charge are remarked by green color are distribution on Carbone atoms[26].The
Mullikan atomic charges give a positive value for C and H and negative values for O, N, S, Cl atoms .Figure 4.
Figure 2. Total charge density for Pt(IV)complex by using DFT/B3Lyp/Lan2DZ at levels of theory.
Figure 3. Electrostatic potential (ESP) for Pt (IV) complex by using DFT/B3Lyp/LanL2DZ at levels of theory.
International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 4 ISSN: 2319-1058
Figure 4. Mullikan atomic charge for Pt(IV)complex by using DFT/B3Lyp/LanL2DZ at levels of theory
C-HOMO-LUMO Calculation
Geometry optimization form for platinum (IV) complex described the frontal orbital’s is useful to explore the
interaction of surface metal’s atoms and adsorption centers of the inhibitor molecule [27].The value of HOMO
energy is often associated with electron donating ability of complex ,but the energy of LUMO is ability to acceptor
electron [28].The energy of HOMO =-0.00239,while the of LUMO =0.00902, low energy gap candidates this
complex to be a good semiconductor and solar material .The reason behind this small gap is the extended of the
metallic element platinum due to their availability in the HOMO energy level[29] , table 2 .Figure5 .
Table 2. Physical properties for Pt (IV) complex at DFT/B3LYP/LanL2DZ (5D, 7F) at levels of theory.
Type of calculation
Value of properties calculation
HOMO energy -0.00239 Kcal/Mol
LUMO energy 0.00902 Kcal/Mol
Energy gap 0.01141 Kcal/Mol
ionization potential 0.26692
Electron affinity 0.12087
electronegativity 0.193895
chemical hardness 0.073025
chemical softness 13.69394
International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 5 ISSN: 2319-1058
Figure 5. HOMO-LUMO of the geometry optimized Pt(IV)complex by DFT/B3LYP/LanL2DZ at levels of theory.
D-Infrared spectroscopy study
The theoretical I.R data for platinum (IV) complex was calculation by using DFT/B3LYP/LanL2DZ , table
3show vibrational frequencies for complex A ,the limited refer to high intensity in IR spectra also description of type
frequencies in complex A .The spectrum of complex shows band 2850-3000cm-1 which due to (C-H) aliphatic ,the
spectrum of complex show band 3300-3500cm-1 which due to (N-H)stretching, the band in IR of complex at 1705-
1725cm-1 which due to (C=O) ,the band at 1000-1300cm-1which due to(C-O)stretching , the two band 1515-1560 &
1345-1385 which due to (N-O)stretching . New bands have been occurred around (Pt-O) ,(Pt-Cl) (Pt-N)at 710cm-1 ,
320cm-1 , 568cm-1 respectively as shown at Figure 6.
Figure 6. I.R.- frequencies calculated for Pt (IV) complex at DFT/B3LYP/LanL2DZ at levels of theory.
E-Ultra –violet spectra
The UV-Vis spectra of the complex A showed abroad band in visible region at 10000cm-1 table1 show transition
state for complex A was characterized by different beak at high oscillator strength in select cell at (293 and 306) nm
refer to (n-?*) from O4Px,y,z to 1Pt 7d,1Pt7d+2 ,transition state other from Cl 4p x,y,z to 1Pt 7d,1Pt7d+2 , Figure7 ,and
can be assignable to [30].
LUMO 0.00902
?Egap 0.01141
HOMO -0.00239
International Journal of Innovations in Engineering and Technology (IJIET)
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Volume 8 Issue 4 August 2017 6 ISSN: 2319-1058
Figure 7. U.V-Vis spectra calculated for Pt(IV) complex at DFT/B3LYP/LanL2DZ at levels of theory
Table 1. Theoretical calculation for UV-Visible transition state for Pt(IV) complex at levels of theory
F-NMR spectra
Theoretical calculation
Excitation
energy (ev)
Wavelength
(nm)
Oscillator
strength
Occ MO Unocc
MO
Coefficient Explanation
3.1939
388.19
0.0039
108
110
111
113
112
113
0.57435
0.11820
0.10744
n-?*
2Cl4px 1 pt7d+2
3Cl4px 1 pt7d0
35O4px 1 pt7d+2
3.2895
376.91
0.0031
106
107
109
109
110
111
112
113
112
113
112
112
0.25360
0.27824
0.10880
0.22106
0.29981
0.36509
n-?*
35O4px 1 pt7d0
3Cl4py 1 pt7d+2
2Cl3pz 1 pt7d0
2Cl3pz 1 pt7d+2
2Cl3px 1 pt7d0
35O4px 1 pt7d0
3.3308
372
0.0033
107
107
110
111
112
113
113
113
0.12380
0.55124
0.16756
0.16750
n-?*
3Cl4py 1 pt7d0
3Cl4py 1 pt7d+2
3Cl4px 1 pt7d+2
35O4px 1 pt7d+2
3.8906
318.67
0.0069
100
102
103
106
113
112
113
112
0.10286
0.11850
0.27107
0.38060
n-?*
43O4py 1 pt7d+2
20O4py 1 pt7d0
21O4pz 1 pt7d+2
35O4px 1 pt7d0
3.9171
316.52 nm
0.0051
100
102
102
103
105
112
112
113
112
112
0.11546
0.45846
0.15296
0.19809
0.20967
n-?*
43O4py 1 pt7d0
20O4py 1 pt7d0
20O4py 1 pt7d+2
21O4pz 1 pt7d0
42O4px 1 pt7D0
4.0511
306.05
0.0144
102
105
113
113
0.49511
0.17929
n-?*
20O4py 1 pt7d+2
42O4px 1 pt7d+2
4.2190
293.87
0.0585
99
100
103
112
112
113
0.33411
0.13319
0.11235
n-?*
10O4px 1 pt7d0
43O4py 1 pt7d0
21O4pz 1 pt7d+2
International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 7 ISSN: 2319-1058
Chemical shifts of 13C and 1 H -NMR in complex A were investigated by DFT /B3LYP/LanL2DZ (5D,7F) using
NMR with GIAO. Calculated chemical shifts of 13C and 1 H -NMR in complex A are shown in Figure 8 (a,b) .The
chemical shifts of 13C and 1 H-NMR in complex A as referred by TMS were separated around 28 ppm -192 ppm,
and 1.75 ppm – 12.5 ppm, respectively. This behavior was influenced by magnetic shielding effect on the Pt(IV)
complex .The separated chemical shifts of 13C and 1H-NMR were caused by nuclear spin interaction in carbon, and
proton atoms on Pt(IV) complex .The chemical shift was mainly caused by hybridization of d spin in metal. The
chemical shifts of 13C and 1 H NMR Pt (IV) complex depended on the electron density distribution with a slight
deviation of charge density on Pt (IV) complex [31]
Figure 8. NMR spectra calculated for Pt(IV) complex at DFT/B3LYP/LanL2DZ at levels of theory.
IV.CONCLUSION
? The geometry optimized structure of Pt (IV) complex have been calculated using DFT based on B3Lyp /LanL2DZ
at level of theory in vacuum.
A-C NMR
I.
B-H NMR
International Journal of Innovations in Engineering and Technology (IJIET)
http://dx.doi.org/10.21172/ijiet.84.001
Volume 8 Issue 4 August 2017 8 ISSN: 2319-1058
? The symmetry of complex A form is C1 refer to asymmetrical distribution in the complex A .The output of
this complex A gave C1 symmetry which is wrong symmetry
? Thermodynamic calculation of complex A by using DFT/B3Lyp/LanL2DZ which is endothermic and
nonspontaneous (268.8867, 202.4278 and energy gap is 0.01141 at k Cal/mole units.
? The stabilized structure of Pt(IV) complex comes out by total energy which equal to -1482.398 a.u units .
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