Molecular Structure and Bonding in Platinum-Picoline Anticancer Complex: Density Functional Study

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Title:Molecular Structure and Bonding in Platinum-Picoline Anticancer Complex: Density Functional Study
Creators:
Michalska, Danuta
Wysokiński, Rafał
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 69, 1, pp. 63-72
Uncontrolled Keywords:Trans effect, <i>Ab initio</i> calculations, Cisplatin, DFT calculations, <i>cis</i>-[PtCl<sub>2</sub>(NH<sub>3</sub>)(2-picoline)], Structure-reactivity relationship, Platinum anticancer agents, AMD473

Abstract

Density functional study has been performed for a new anticancer agent, <i>cis</i>-[PtCl<sub>2</sub>(NH<sub>3</sub>)(2-picoline)] (<strong>1</strong>), AMD473, now clinically tested. The molecular structure, natural charges, orbital occupancies, vibrational frequencies and metal-ligand stretching force constants were calculated using the modified Perdew-Wang functional (mPW1PW) with the combined D95V(d,p) and LANL2DZ basis set. For comparison, analogous calculations were performed for: <i>cis</i>-[PtCl<sub>2</sub>(NH<sub>3</sub>)(3-picoline)] (<strong>2</strong>), <i>cis</i>-[PtCl<sub>2</sub>(NH<sub>3</sub>)(pyridine)] (<strong>3</strong>) and cisplatin. The interesting structural feature of <strong>1</strong> is almost perpendicular orientation of the 2-picoline ligand with respect to the molecular plane. In the remaining complexes, <strong>2</strong> and <strong>3</strong>, the tilt of the pyridine ring is smaller. The position of the methyl group in <strong>1</strong> introduces steric hindrance to an axial approach of the Pt metal. The natural bond analysis (NBO) has provided detailed insight into the electronic donor-acceptor interactions within the platinum coordination sphere. The results clearly indicate that the Pt-N(py) bond is stronger than Pt-NH<sub>3</sub> bond, and the Pt-Cl bond <i>trans</i> to 2-picoline is weaker than the <i>cis</i> Pt-Cl bond. Thus, both the trans effect of the 2-picoline ligand and a steric hindrance of Pt in <strong>1</strong> can be of key importance in the different mode of binding of this drug to DNA, in comparison with cisplatin. <p>

Title:Molecular Structure and Bonding in Platinum-Picoline Anticancer Complex: Density Functional Study
Creators:
Michalska, Danuta
Wysokiński, Rafał
Uncontrolled Keywords:Trans effect, <i>Ab initio</i> calculations, Cisplatin, DFT calculations, <i>cis</i>-[PtCl<sub>2</sub>(NH<sub>3</sub>)(2-picoline)], Structure-reactivity relationship, Platinum anticancer agents, AMD473
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:69
Number:1
Page Range:pp. 63-72
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20040063UNSPECIFIED
ID Code:2196
Item Type:Article
Deposited On:06 Feb 2009 17:16
Last Modified:06 Feb 2009 16:16

Citation

Michalska, Danuta; Wysokiński, Rafał (2004) Molecular Structure and Bonding in Platinum-Picoline Anticancer Complex: Density Functional Study. Collection of Czechoslovak Chemical Communications, 69 (1). pp. 63-72. ISSN 0010-0765

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