Syntheses and structural studies of platinum(II) complexes of O-methylselenomethionine and related ligands

doi:10.1016/j.ica.2006.03.008

Inorganica Chimica Acta

Volume 359, Issue 10, 1 July 2006, Pages 3252-3256

https://doi.org/10.1016/j.ica.2006.03.008 Get rights and content

Abstract

The complexes dichloro[2-(phenylselanyl)ethanamine]platinum(II), dichloro[2-(benzylselanyl)ethanamine]platinum(II) and dichloro(O-methylselenomethionine)platinum(II) have been prepared and the structure of dichloro(O-methylselenomethionine)platinum(II) has been determined by single crystal X-ray diffraction. The Pt(II) is in a square planar environment and is coordinated by two cis chloride ligands and a chelating O-methylselenomethionine ligand. The cytotoxicities of the compounds have been assessed in the human cell lines HeLa and K562 and they are at least threefold less toxic than cisplatin in both cell lines.

Graphical abstract

Introduction

For some time now there has been considerable interest in the use of sulfur containing ligands as platinum rescue agents and it has been shown, for instance, that l-MetH may be used to reduce cisplatin toxicity [1], [2], [3]. Given the chemical similarities between sulfur and selenium it is not surprising that selenium containing compounds have also been exploited in an effort to reduce the toxicity of platinum drugs and selenomethionine 1 has been shown to reduce the renal toxicity of cisplatin in rats and mice [4]. It is with these considerations in mind that we have begun to investigate the chemistry of platinum(II) with bidentate ligands containing both amine and selenium donor groups.

The preparation of the palladium(II) and platinum(II) dihalide complexes of selenomethionine 1 has been reported by Faraglia and Fregona [5] who showed that complexes of the form M(sem)X₂ (M = Pd(II), X = Cl⁻ or Br⁻; M = Pt(II), X = Cl⁻) (for example 2) were readily formed when MX₂ reacted with selenomethionine. Structurally related complexes derived from methionine, such as 3, have also been described and the cytotoxic properties and in vivo activity of this compound have been examined [6]. In a recent report we have described our structural studies on hydrogen-bonded networks formed by dimerization of platinum(II) dichloro complexes formed from the ligands 2-(phenylselanyl)ethanamine (4) and 2(benzylselanyl)ethanamine (5) [7]. These complexes, like those of composition M(sem)X₂, also contain a bidentate single bond Se-(CH₂)_nNH₂ ligand system. In the present work, we describe the preparation of these ligands and the corresponding platinum (II) dichloro complexes 10 and 11. We also describe the synthesis of O-methylselenomethionine 6, the corresponding platinum(II) complex 12 [dichloro(O-methylselenomethionine)platinum(II)] as well as the crystal structure obtained for this complex.

Section snippets

General

NMR spectra were obtained on a Varian Unityplus 400 spectrometer at 400 MHz for ¹H spectra, 100 MHz for ¹³C spectra, 85 MHz for ¹⁹⁵Pt spectra and 76.2 MHz for ⁷⁷Se spectra. ¹⁹⁵Pt spectra were externally referenced to potassium tetrachloroplatinate at −1630 ppm. ⁷⁷Se spectra were externally referenced to diphenyldiselenide at 464 ppm. ¹⁹⁵Pt spectra were recorded in N-methylpyrrolidinone (NMP). ESI-MS spectra were recorded on a quadrupole ion trap Finnigan-MAT LCQ mass spectrometer equipped with

Results and discussion

The ligand 2-(phenylselanyl)ethanamine (4) was prepared according to a published procedure [12] and the synthetic routes to the other ligands are given in Scheme 1. The ligand 2-(benzylselanyl)ethanamine (5) was prepared from reaction of 2-bromo-(N-boc)ethanamine (7) [8] with sodium benzylselenolate (prepared through reduction of dibenzyldiselenide with sodium borohydride), followed by acidic deprotection. As both the free amine and the hydrochloride salt of 5 proved hygroscopic and difficult

Supplementary material

Crystallographic data has been deposited with the Cambridge Crystallographic Data Centre. CCDC No. 279957. Copies of the data can be obtained, free of charge, on application to The Director, CCDC, Union Road 12, Cambridge CB2 1EZ, UK (fax: +44 1223/336 033 or e-mail: [email protected]).

Acknowledgment

Support of this work by The National Health and Medical Research Council (W.D. Mc F., V.M., W.A.D.) is gratefully acknowledged.

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Syntheses and structural studies of platinum(II) complexes of O-methylselenomethionine and related ligands

Abstract

Graphical abstract

Introduction

Section snippets

General

Results and discussion

Supplementary material

Acknowledgment

Inorg. Chim. Acta

Toxicology

J. Inorg. Biochem.

J. Inorg. Biochem.

Neurotoxicology

J. Pharm. Pharmacol.