135192-19-7Relevant articles and documents
Aqueous chemistry of mixed-amine cis- and transplatin analogues. Intramolecular preference for a kinetic six-membered ring over a thermodynamic five-membered ring ortho-platination product
Bednarski, Patrick J.,Ehrensperger, Edmund,Sch?nenberger, Helmut,Burgemeister, Thomas
, p. 3015 - 3025 (2008/10/08)
A series of mixed-amine cis- and transplatin analogues, containing benzylamine and 2-phenylethylamine functionalities, were synthesized and the aqueous solution chemistry investigated. The cis- and trans-dichloroplatinum(II) isomers having the neutral ligands ammine and 1,2-bis(4-methoxyphenyl)ethylamine (1 and 4), ammine and 2-(4-methoxyphenyl)-1-phenylethylamine (2 and 5), and ammine and bis(4-methoxyphenyl)methylamine (3 and 6) were synthesized in >98% isomeric purity. With the aim of investigating the pharmacoactivation of this class of compounds, a reversed-phase HPLC assay was developed for determining the rates of Pt-Cl hydrolysis of the cis-configured isomers. The precolumn addition of KBr to the reaction solutions trapped the aquachloro- and diaquaplatinum hydrolysis products as their bromo adducts. The separations of dichloro-, bromochloro-, and dibromoplatinum complexes allowed the quantification of their time-dependent concentrations, and the hydrolysis rate constants for 1-3 could be determined. It was found that, following Pt-Cl hydrolysis, an intramolecular ortho-platination occurred with 1-6. Proton NMR studies showed that, for the trans-configured 4 and 5, the kinetically favored, six-membered ring cycloplatinated products were formed specifically over the thermodynamic, five-membered ring ones. For the cis-configurated 1, the kinetic product was formed selectively. The six-membered cycloplatinated ring could be converted into the five-membered, thermodynamically favored one by heating in dilute KCl. The implications of these novel findings are discussed from both mechanistic chemical and pharmacological points of view.
