Os2–Os4Switch Controls DNA Knotting and Anticancer Activity

Ying Fu; María J. Romero; Luca Salassa; Xi Cheng; Abraha Habtemariam; Guy J. Clarkson; Ivan Prokes; Alison Rodger; Giovanni Costantini; Peter J. Sadler

doi:10.1002/anie.201602995

Os₂–Os₄Switch Controls DNA Knotting and Anticancer Activity

Ying Fu, María J. Romero, Luca Salassa, Xi Cheng, Abraha Habtemariam, Guy J. Clarkson, Ivan Prokes, Alison Rodger, Giovanni Costantini, Peter J. Sadler^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Dinuclear trihydroxido-bridged osmium–arene complexes are inert and biologically inactive, but we show here that linking dihydroxido-bridged Os^II–arene fragments by a bridging di-imine to form a metallacycle framework results in strong antiproliferative activity towards cancer cells and distinctive knotting of DNA. The shortened spacer length reduces biological activity and stability in solution towards decomposition to biologically inactive dimers. Significant differences in behavior toward plasmid DNA condensation are correlated with biological activity.

Original language	English
Pages (from-to)	8909-8912
Number of pages	4
Journal	Angewandte Chemie - International Edition
Volume	55
Issue number	31
DOIs	https://doi.org/10.1002/anie.201602995
Publication status	Published - 25 Jul 2016

Bibliographical note

Funding Information:
We thank the ERC (grant no. 247450 BIOINCMED), EPSRC (grant no. EP/F034210/1), BBSRC (grant no. BB/F011199/1), and Science City/EU ERDF/AWM for funding. G. C. acknowledges financial support through the ERC Grant “VISUAL-MS”. M.J.R. thanks Fundación Barrié fellowship. L.S. thanks the MC CIG fellowship UCnanomat4iPACT (grant no. 321791) and the MINECO grants (CTQ2012-39315 and RYC-2011-07787). We thank colleagues in the EC COST Action CM1105 for stimulating discussions, and Ben Moreton for his help with AFM.

Publisher Copyright:
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Keywords

cancer
DNA
organometallic
osmium
supramolecular

ASJC Scopus subject areas

Catalysis
General Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/anie.201602995

Cite this

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abstract = "Dinuclear trihydroxido-bridged osmium–arene complexes are inert and biologically inactive, but we show here that linking dihydroxido-bridged OsII–arene fragments by a bridging di-imine to form a metallacycle framework results in strong antiproliferative activity towards cancer cells and distinctive knotting of DNA. The shortened spacer length reduces biological activity and stability in solution towards decomposition to biologically inactive dimers. Significant differences in behavior toward plasmid DNA condensation are correlated with biological activity.",

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author = "Ying Fu and Romero, {Mar{\'i}a J.} and Luca Salassa and Xi Cheng and Abraha Habtemariam and Clarkson, {Guy J.} and Ivan Prokes and Alison Rodger and Giovanni Costantini and Sadler, {Peter J.}",

note = "Funding Information: We thank the ERC (grant no. 247450 BIOINCMED), EPSRC (grant no. EP/F034210/1), BBSRC (grant no. BB/F011199/1), and Science City/EU ERDF/AWM for funding. G. C. acknowledges financial support through the ERC Grant “VISUAL-MS”. M.J.R. thanks Fundaci{\'o}n Barri{\'e} fellowship. L.S. thanks the MC CIG fellowship UCnanomat4iPACT (grant no. 321791) and the MINECO grants (CTQ2012-39315 and RYC-2011-07787). We thank colleagues in the EC COST Action CM1105 for stimulating discussions, and Ben Moreton for his help with AFM. Publisher Copyright: {\textcopyright} 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.",

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AU - Clarkson, Guy J.

AU - Prokes, Ivan

AU - Rodger, Alison

AU - Costantini, Giovanni

AU - Sadler, Peter J.

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