Synthesis and study of Pt(II)-aromatic amines complexes of the t cis- and trans-Pt(amine) 2 (NO 3 ) 2 and cis-Pt(amine) 2 (R(COO) 2 ) Fernande D. Rochon * , Gassan Massarweh, Catherine Bonnier De ´partement de chimie, Universite ´ du Que ´bec a ` Montre ´al, C.P. 8888, Succ. Centre-ville, Montre ´al, Canada H3C 3P8 Received 10 September 2007; accepted 17 September 2007 Available online 21 September 2007 Abstract Complexes of the types cis- and trans-Pt(amine) 2 (NO 3 ) 2 with amines containing a phenyl group were synthesized and studied m by IR and multinuclear magnetic resonance spectroscopies. The cis complexes could be synthesized pure only with the am Ph–R–NH 2 (R = alkyl), while pure trans compounds were synthesized with all the studied amines. In 195 Pt NMR spectroscopy, the dinit- rato complexes of the amines Ph–R–NH 2 were observed around 1700 ppm for the cis isomers and at about 1580 for the trans c plexes. For the other amines, where a phenyl ring is directly attached to the amino group, the signals were observed at lower fields, 1528 ppm for cis-Pt(PhNH 2 )(NO 3 ) 2 and around 1450 ppm for allthe trans isomers. There is a linear relationship between the d(Pt) of the Pt(amine) 2 (NO 3 ) 2 complexes and the pK a of the protonated amines. The coupling constants 2 J( 195 Pt– 1 HN) are larger in the cis compounds (ave. 76 Hz) than in the trans isomers (ave. 63 Hz). The complexes cis-Pt(amine) 2 (R(COO) 2 ) with bidentate dicarb- oxylato ligands were also synthesized and characterized mainly by IR spectroscopy. The compounds apparently decompos are too insoluble in other solvents for solution studies. Ó 2007 Elsevier B.V. All rights reserved. Keywords: Platinum; Aromatic amine; Nitrato; Carboxylato; NMR; IR 1. Introduction The antitumor drug cisplatin (cis-Pt(NH 3 ) 2 Cl 2 ) is still one of the mostwidely used drugs in chemotherapy. Its mechanism of action has been studied by several authors, but there are stillmany uncertainties, since its reactions are extremely complex [1,2]. The drug remainsmostly unchanged in the plasma in the presence of a high chloride concentration (103 mM) and can cross the cell membrane because of its neutrality. The chloride ion concentration is much lower inside the cells (4 mM) and in these condi- tions, cis-Pt(NH 3 ) 2 Cl 2 producesdifferentionic species, which can bind to DNA [3] leading to the eventual cell death. Its mechanism of action involves aquation or hydro- lysis reactions,which have been studied in a few laboratories. A good review of the influence of the structure on the activity of Pt drugs has been published [4]. When the ligands NH 3 in cisplatin are replaced by primary amines, the antitumor properties can increase, especially with cyc amines [5–7], but the latter compounds have often a mor limited activity spectrum. Furthermore, several of the mo active compounds are quite insoluble [8]. In the amine sy tem, the most active compounds usually have the cis geo etry, although a few trans compounds have been shown possess some antitumor properties. Our research group has recently undertaken a systema study on complexes of the types cis- and trans-Pt(ami- ne) 2 X 2 (X = I or Cl) with differentaliphatic amines [9,10]. These complexes have been known for a long tim but their purity has not been well investigated. We have found that multinuclear magnetic resonance spectroscop is an excellentechnique to determine the purity of the 0020-1693/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2007.09.024 * Corresponding author. Tel.: +1 514 987 3000x4896; fax: +1 514 987 4054. E-mail address: rochon.fernande@uqam.ca (F.D. Rochon). www.elsevier.com/locate/ica Available online at www.sciencedirect.com Inorganica Chimica Acta 361 (2008) 1437–1446