In:
Collection of Czechoslovak Chemical Communications, Institute of Organic Chemistry & Biochemistry, Vol. 69, No. 1 ( 2004), p. 63-72
Abstract:
Density functional study has been performed for a new anticancer agent, cis -[PtCl 2 (NH 3 )(2-picoline)] ( 1 ), 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: cis -[PtCl 2 (NH 3 )(3-picoline)] ( 2 ), cis -[PtCl 2 (NH 3 )(pyridine)] ( 3 ) and cisplatin. The interesting structural feature of 1 is almost perpendicular orientation of the 2-picoline ligand with respect to the molecular plane. In the remaining complexes, 2 and 3 , the tilt of the pyridine ring is smaller. The position of the methyl group in 1 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 3 bond, and the Pt-Cl bond trans to 2-picoline is weaker than the cis Pt-Cl bond. Thus, both the trans effect of the 2-picoline ligand and a steric hindrance of Pt in 1 can be of key importance in the different mode of binding of this drug to DNA, in comparison with cisplatin.
Type of Medium:
Online Resource
ISSN:
0010-0765
,
1212-6950
DOI:
10.1135/cccc20040063
Language:
English
Publisher:
Institute of Organic Chemistry & Biochemistry
Publication Date:
2004
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