Gust, Ronald and Schönenberger, Helmut and Kritzenberger, Juergen and Range, Klaus Juergen and Klement, Ulrich and Burgemeister, Thomas (1993) Crystal structure, solution chemistry, and antitumor activity of diastereomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes. Inorganic chemistry 32 (26), pp. 5939-5950.
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Complete 3-dimensional x-ray crystal structure analyses of meso- and S,S-PtCl2L (L = 1,2-bis(2-hydroxyphenyl)ethylenediamine] (I and II, resp.) were carried out. After anisotropic refinement of F-values by least squares, R is 0.098 for I and 0.048 for II. I and II crystallize with Z = 4, monoclinic symmetry and space group P21/n for I and space group P21 for II. I and II build dimeric units. The ethylenediamine ligand of I is puckered and exists in an envelope conformation, while the mols. of the dimeric units of II show both the envelope and the half-chair conformation. Both arom. rings of I are equatorially arranged and fixed by intramol. H bonds from the amino protons to the phenolic O. The hydroxy group of the axially standing ring of I is not involved in intramol. N-H...O bridges since it is oriented opposite to the NH2 groups. In soln., however, this OH group is oriented and builds H-H...O bonds, too. The influence of the 3-dimensional structure on the reactivity of the complexes was studied through the substitution of the Cl- leaving groups by I-. The substitution follows an associative mechanism, whereby the rate consts. are given by the equation kobs = ks + kI-[I-] in accordance with the possible reaction pathways. Ks is the rate const. for the I- coordination after hydrolysis and kI- the rate const. for the direct nucleophilic attack. Due to the shielding of the Pt by the axially oriented arom. ring, the reactivity of I is decreased compared to II. The reactivities correlate very well with the antitumor results in vivo on the P388 leukemia of the mouse and in vitro for the NIH-OVCAR 3 cell line. In accordance with the high reactivity the best antitumor effects were found for I. For the P388 leukemia of the mouse a dose of 6.6 micro mol/kg given on days 1-5 leads to survival of all the animals at the end of the test.
|Additional information (public):||CAN 120:22364 78-7 Inorganic Chemicals and Reactions 20461-54-5 (Iodide) Role: RCT (Reactant), RACT (Reactant or reagent) (kinetics of substitution of chloride in platinum hydroxyphenylethylenediamine complex by); 138258-84-1P; 142760-37-0P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and crystal structure leukemia inhibitor activity and kinetics of substitution of chloride in, by iodide)|
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Retired Professors > Prof. Schönenberger|
|Keywords:||Crystal structure Molecular structure (of platinum hydroxyphenylethylenediamine diastereomeric complexes) Substitution reaction (of platinum hydroxyphenylethylenediamine diastereomeric complexes with iodide) Kinetics of substitution reaction (coordinative, of platinum hydroxyphenylethylenediamine diastereomeric complexes with iodide) Isomerism and Isomers (diastereo-, of platinum hydroxyphenylethylenediamine complexes) Neoplasm inhibitors (leukemia, platinum hydroxyphenylethylenediamine diastereomeric complexes as) crystal structure platinum hydroxyphenylethylenediamine complex leukemia inhibitor platinum hydroxyphenylethylenediamine complex kinetics substitution halo platinum hydroxyphenylethylenediamine complex platinum hydroxyphenylethylenediamine structure substitution kinetics|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||12 Nov 2010 06:45|
|Last Modified:||12 Nov 2010 06:45|