B3LYP, Lanl2DZ basis sets at density functional theory (DFT) method has been used on a ground state geometry optimized for all proposed structures that have been involved in this study. Structural parameters such as bond lengths, bond angles and dihedral angles have been calculated in the same way to achieve a global reactivity description of Pt(IV) complex. We suggested a minimal energy structure of diaminobis((4-hydroxy-4-butanol)oxy)platinum(IV) chloride complex (DOP) as a new chemotherapy formula of cis-platinum complex. The reactive site of nucleophilic attachment at DOP occurs on carbon atoms due to their positive charge, while other atoms (nitrogen, oxygen, chlorine) are carried negative charges due to the delocalization of electron pair by a resonance effect. Bonds of Pt-Cl with 2.290 ? are more reactive bounds toward the replacement reactions than other chemical bonds in the DOP complex. Investigation revealed that the thermodynamic functions values are increased due to increasing vibrational intensities of cisplatin complex. The fourth transition state (TS4) is the most probable transition state than other suggested transition states for both guanine and adenine bases. The TS4 of platinum complex binding with guanine is the most probable by a factor of -18.134 a.u. of optimization energy value than other suggested states. TS4-guanine is the most probable than other suggested states by factor 7.354 kcal/mol of zero point energy (ZPE).
Hence, platinum complex (DOP) is binded with guanine base of DNA through N7.
INTRODUCTION
Anticancer chemical compounds in the recent years hold potential for their activity as chemotherapies. Platinum (IV) complexes are more inert than platinum (II) complexes due the resistant to unwanted side-reactions at human body [1]. All cis-platinum complexes are reactive as prodrugs when starting activation by bioreduction to release the cytotoxic Pt(II) compo-nent. These complexes contained two axial ligands, which they could be used to influence the reduction kinetics [2] lipophilic, cellular accumulation [3] and activity [4] of platinum species.
Platinum based drugs are very effective anticancer agents which are widely used at clinic treatments and half of all chemotherapeutic regimens administered to patients include a platinum complex drug [5] as cisplatin, carboplatin and oxali-platin drugs are triggered cancer cell death by binding to nuclear DNA and they are distorted the structure of DNA [6]. The reactivity and selectivity of the most cisplatin complexes are
A Comparative Reactivity Study of Adenine versus Guanine Base through Transition State Formation with cis-Platinum(IV) Complex using DFT L.H. KHDIUM and A.A. ALI DREA* Department of Chemistry, College of Science, University of Babylon, Hilla 51002, Iraq *Corresponding author: E-mail: aadreab22@yahoo.com; liqaa.aljailawi@uokufa.edu.iq Received: 9 July 2018; Accepted: 30 August 2018; Published online: 30 November 2018; AJC-19168 B3LYP, Lanl2DZ basis sets at density functional theory (DFT) method has been used on a ground state geometry optimized for all proposed structures that have been involved in this study. Structural parameters such as bond lengths, bond angles and dihedral angles have been calculated in the same way to achieve a global reactivity description of Pt(IV) complex. We suggested a minimal energy structure of diaminobis((4-hydroxy-4-butanol)oxy)platinum(IV) chloride complex (DOP) as a new chemotherapy formula of cis-platinum complex. The reactive site of nucleophilic attachment at DOP occurs on carbon atoms due to their positive charge, while other atoms (nitrogen, oxygen, chlorine) are carried negative charges due to the delocalization of electron pair by a resonance effect. Bonds of Pt-Cl with 2.290 ? are more reactive bounds toward the replacement reactions than other chemical bonds in the DOP complex. Investigation revealed that the thermodynamic functions values are increased due to increasing vibrational intensities of cisplatin complex. The fourth transition state (TS4) is the most probable transition state than other suggested transition states for both guanine and adenine bases. The TS4 of platinum complex binding with guanine is the most probable by a factor of -18.134 a.u. of optimization energy value than other suggested states. TS4-guanine is the most probable than other suggested states by factor 7.354 kcal/mol of zero point energy (ZPE).
Hence, platinum complex (DOP) is binded with guanine base of DNA through N7.
Keywords: DFT studies, Adenine, Guanine base, cis-Platinum(IV) complex.
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which allows others to copy and redistribute the material in any medium or format, remix, transform, and build upon the material, as long as appropriate credit is given and the new creations are licensed under the identical terms.
reacted in the blood as a nucleophile and never reaching the tumour. The limitation of bioavailability of the drug is due to undesirable interactions and preclude oral administration [7].
Attentions have been increased about this chemotherapy agents by academic researchers and investigations are occurs through experimental and computational calculations. Density func-tional theory (DFT) method is employed to investigate the thermal stability and mechanical properties of Pt(VI) complex [8]. It is believed that the platinum(IV) complexes act as pro-drugs that are activated extra- or intracellular in vivo by reduc-tion that transforms them to square planar platinum(II) comp-lexes by an elimination of the axial ligands [9]. The preparation of some platinum(IV) complex is given up the anti-proliferative potency of the complexes that are correlated with their lipophilic as well as with their cellular accumulation, but not with their reduction potentials [10,11].
We have suggested a new optimized geometry of diamino-bis((4-hydroxy-4-butanol)oxy)platinum(IV) chloride (DOP)
AASSIIAANNJJOOUURRNNAALLOOF FCC HHEEMMIISSTTRRYY
https://doi.org/10.14233/ajchem.2019.21566
Asian Journal of Chemistry; Vol. 31, No. 1 (2019), 114-120complex and simulated its reactivity toward DNA bases through different suggested transition states. The energetic and structural parameters of Pt(IV) complex and all other suggested struc-tures are calculated to prove our opinion about this new structure of cis-platinum complex.
EXPERIMENTAL
Computations were performed using Gaussian 09 [12] and molecular structures were plotted with Gauss View program [13]. Our calculations were carried out with the B3LYP density functional [14,15]. All optimizations were calculated without any symmetry constraints using Lanl2DZ basis set [16]. Charges obtained from natural bond orbitals (NBO) [17] procedure were determined to verify the trends of Mulliken population analysis. MO analyses were performed to ab initio calculations used to study model systems mimicking interactions in a polar solvent or crystal. The reason is that the polar solvent and counter ions very efficiently compensate for the electrostatic effects associated with ions.
To understand better the coordination properties, the total energy, electronic and nuclear energies were calculated for DOP complex, like HOMO, LUMO orbitals and their energies. The electronic transition energy of DOP complex and the single point were obtained by using time-dependent density functional theory TD/DFT with B3LYP calculations [18]. The electronic spectra of diaminobis((4-hydroxy-4-butanol)oxy)platinum(IV) chloride (DOP) complex were calculated.