New activation mechanism for half-sandwich organometallic anticancer complexes

被引：42

作者：

Banerjee, Samya ^{[1
]}

Soldevila-Barreda, Joan J. ^{[1
]}

Wolny, Juliusz A. ^{[2
]}

Wootton, Christopher A. ^{[1
]}

Habtemariam, Abraha ^{[1
]}

Romero-Canelon, Isolda ^{[1
]}

Chen, Feng ^{[1
]}

Clarkson, Guy J. ^{[1
]}

Prokes, Ivan ^{[1
]}

Song, Lijiang ^{[1
]}

O'Connor, Peter B. ^{[1
]}

Schuenemann, Volker ^{[2
]}

Sadler, Peter J. ^{[1
]}

机构：

[1] Univ Warwick, Dept Chem, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England

[2] Univ Kaiserslautern, Dept Phys, Erwin Schrodinger Str 46, D-67663 Kaiserslautern, Germany

来源：

CHEMICAL SCIENCE | 2018年 / 9卷 / 12期

基金：

英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

C-H ACTIVATION; LIGAND PROTONATION; RHODIUM COMPLEXES; CATALYSTS; HYDROGEN; CYCLOPENTADIENYL; CHEMISTRY; EVOLUTION; ISOPRENE; NITROGEN;

D O I：

10.1039/c7sc05058e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The Cp-x C-H protons in certain organometallic Rh-III half-sandwich anticancer complexes [((5)-Cp-x)Rh(N,N)Cl](+), where Cp-x = Cp*, phenyl or biphenyl-Me4Cp, and N,N = bipyridine, dimethylbipyridine, or phenanthroline, can undergo rapid sequential deuteration of all 15 Cp* methyl protons in aqueous media at ambient temperature. DFT calculations suggest a mechanism involving abstraction of a Cp* proton by the Rh-hydroxido complex, followed by sequential H/D exchange, with the Cp* rings behaving like dynamic molecular twisters'. The calculations reveal the crucial role of p orbitals of N,N-chelated ligands in stabilizing deprotonated Cp-x ligands, and also the accessibility of Rh-I-fulvene intermediates. They also provide insight into why biologically-inactive complexes such as [(Cp*)Rh-III(en)Cl](+) and [(Cp*)Ir-III(bpy)Cl](+) do not have activated Cp* rings. The thiol tripeptide glutathione (-l-Glu-l-Cys-Gly, GSH) and the activated dienophile N-methylmaleimide, (NMM) did not undergo addition reactions with the proposed Rh-I-fulvene, although they were able to control the extent of Cp* deuteration. We readily trapped and characterized Rh-I-fulvene intermediates by Diels-Alder [4+2] cyclo-addition reactions with the natural biological dienes isoprene and conjugated (9Z,11E)-linoleic acid in aqueous media, including cell culture medium, the first report of a Diels-Alder reaction of a metal-bound fulvene in aqueous solution. These findings will introduce new concepts into the design of organometallic Cp* anticancer complexes with novel mechanisms of action.

引用

页码：3177 / 3185

页数：9

共 39 条

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