Precious Metal Anticancer Complexes with New Mechanisms of Action
- Prof. Peter Sadler (University of Warwick)
- Thursday 19 October 2017
2333 CC Leiden
There is enormous scope for investigation of the therapeutic properties of the elements of the periodic table. Inorganic compounds can be designed to have specific biological activity, which for metals depends on the metal itself and its oxidation state, the types and numbers of coordinated ligands, and the coordination geometry. Both kinetic (rates of ligand exchange) and thermodynamic (bond strengths, redox potentials) properties of metal complexes can determine biological activity. Multi-targeting mechanisms of action of metal complexes offer new approaches to combatting drug resistance.
These concepts will be illustrated by our recent work on the design of low-spin d6 Ru(II), Os(II), Ir(III) and Pt(IV) complexes as anticancer (and antimicrobial) agents. These include inert complexes which can be activated by light allowing delivery of active ligands, as well as generation of reactive metal centres and radicals. Organometallic arene and cyclopentadienyl complexes can target DNA and the redox balance in cells. Transfer hydrogenation catalysts can achieve the interconversion of coenzyme NAD+ and NADH. We are exploring the use of gels and polymer micelles for drug delivery, the latter, unexpectedly, revealing dynamic metal atom coordination chemistry and sources of precious metal nanocrystals. Studies of in-cell activation of complexes, and their mapping in cells by nano-focussed synchrotron x-ray fluorescence, will also be discussed.
- N.P.E. Barry, P.J. Sadler Chem. Commun. 2013, 49, 5106.
- P. Chellan, P.J. Sadler Phil. Trans. Roy. Soc. A 2015, 373: 20140182.
- N.A. Smith, P. Zhang, S.E. Greenough, M.D. Horbury, G.J. Clarkson, D. McFeely, A. Habtemariam, L. Salassa, V.G. Stavros, C.G. Dowson, P.J. Sadler Chem. Sci., 2017, 8, 395.
- V. Venkatesh, N. Kumar Mishra, I. Romero-Canelón, R.R. Vernooij, H. Shi, J.P.C. Coverdale, A. Habtemariam, S. Verma, P.J. Sadler J. Amer. Chem. Soc. 2017, 139, 5656.
- P. Zhang, C.K.C. Chiu, H. Huang, Y.P.Y. Lam, A. Habtemariam, T. Malcomson, M.J. Paterson, G.J. Clarkson, P.B.O’Connor, H. Chao, P.J. Sadler Angew. Chem. Int. Ed. 2017, in press (DOI: 10.1002/anie.201709082).
- J.M. Hearn, I. Romero-Canelón, A.F. Munro, Y. Fu, A.M. Pizarro, M.J. Garnett, Ultan McDermott, N.O. Carragher, P.J. Sadler Proc. Natl. Acad. Sci. USA 2015, 112, E3800;
- J.J. Soldevila-Barreda, I. Romero-Canelón, A. Habtemariam, P.J. Sadler Nature Commun. 2015, 6, 6582.
- Z. Liu, I. Romero-Canelón, B. Qamar, J.M. Hearn, A. Habtemariam, N.P.E. Barry, A.M. Pizarro, G.J. Clarkson, P.J. Sadler Angew. Chem. Int. Ed. 2014, 53, 3941.
- J.M Hearn, G.M. Hughes, I. Romero-Canelón, A.F. Munro, B. Rubio-Ruiz, Z. Liu, N.O. Carragher, P.J. Sadler Metallomics 2017, in press (DOI: 10.1039/c7mt00242d).
- N.P.E. Barry, A. Pitto-Barry, A.M. Sanchez, A.P. Dove, R.J. Procter, J.J. Soldevila-Barreda, N. Kirby, I. Hands-Portman, C.J. Smith, R.K. O’Reilly, R. Beanland, P.J. Sadler Nature Commun. 2014, 5, 3851.
- C. Sanchez-Cano, I. Romero-Canelón, Y. Yang, I.J. Hands-Portman, S. Bohic, P. Cloetens, P.J. Sadler Chem. Eur. J. 2017, 23, 2512.
- R.J. Needham, C. Sanchez-Cano, X. Zhang, I. Romero-Canelón, A. Habtemariam, M.S. Cooper, L. Meszaros, G.J. Clarkson, P.J. Blower, P.J. Sadler Angew. Chem. Int. Ed. 2017, 56, 1017.