Abstract

Iminoether derivatives of the formula trans-[PtCl2{HN=C(R)OR'}(2)] proved to be endowed with remarkable antitumor activity in vivo. Moreover, these trans compounds were more cytotoxic than their cis congeners, a trend opposite to that generally observed for corresponding platinum complexes with ammines. The imino ligands can have either E or Z configuration about the C=N double bond, and in the case of R = R' = Me, the E configuration is by far thermodynamically preferred. However, substitution of chloride anions with neutral ligands (L) alters the relative stability of the E and Z isomers. Upon investigation of the derivatives with L = PPh3, AsPh3, Me2S=O, and (H2N)(2)C=S, it has been concluded that an electrostatic interaction between the oxygen lone pair of the iminoether and the platinum center, fostered by the net positive charge of the complex and the low dielectric constant around the metal core provided by the hydrophobic L ligands, stabilizes the Z configuration. The same factors can favor iminoether isomerization. These conclusions are fully supported by X-ray crystal data. In the case of a reaction with thiourea, an aminic group of thiourea can substitute the methoxy group of a cis-iminoether, leading to the formation of a cyclic compound in a process reminiscent of the McLafferty rearrangement. Such a rearrangement could play a role in the interaction of the platinum-iminoether compounds with target DNA and proteins.

Autore Pugliese

• Pacifico Concetta , Intini Francesco Paolo

Tutti gli autori

• PACIFICO C.;INTINI F.P.;NATILE G.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2013

ISSN

0020-1669

ISBN

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Numero di citazioni Wos

3

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

2

Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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