New Roles for Classic Cobalt Chemistry Richard Hartshorn

New Roles for Classic Cobalt Chemistry Richard Hartshorn, Department of Chemistry University of Canterbury

Alfred Werner • Coordination Theory • Nobel Prize 1913 • Inert metal ions

Nitrogen Mustards • Very nasty molecules

Photo-activated Cytotoxins D Ru(II/III) Co(III/II) A

Strategies • Binding site geometries • Numbers of donors • Construct ligand on one of the metal ions

Binding Site Geometry

Binding Site Geometry

Numbers of Donors

Numbers of Donors

Numbers of Donors

Numbers of Donors

Numbers of Donors

Construct Ligand on Metal

Constructed Bridging Ligands (OC-6)-bis(2, 2’-bipyridine-κ 2 N){3 -(pyridin-2 -yl) [1, 2, 4]triazino[6, 5 -f][1, 10]phenanthroline-κ 2 N}ruthenium(II)

Formation of [(bpy)2 Ru(pytp)Co(tren)]5+ [Ru(bpy)2(pytp)]2+ + [Co(tren)(OTf)2]+

Pytp as a Bridging Ligand

Pytp as a Bridging Ligand (OC-6)-(OC-6 -34)-bis(2, 2’-bipyridine-1κ 2 N)[N, N-bis(2 -amino-2κNethyl)ethane-1, 2 -diamine-2κ 2 N]{μ-3 -(pyridin-2 -yl 2κN)[1, 2, 4]triazino-2κN 2 -[6, 5 -f][1, 10]phenanthroline-1κ 2 N} rutheniumcobalt(5+)

Ligand Release (tren)

Emission Spectra

Lifetime 212 ns 72 ns

Electron Transfer Rate kobs = krad + ket kmono ≈ krad Heterodinuclear Case ket = kobs - kmono= 9. 6 x 106 s-1

Oxygen Dependence

Potential Use for O 2 Dependence

Other Amines

Cytotoxic Targets and Models

Cobalt(III) Complex of N-(2 hydroxyethyl)ethane-1, 2 -diamine

Cobalt(III) Complex of N-(2 hydroxyethyl)ethane-1, 2 -diamine

X-Ray Crystal Structure

Classic Examination Question

Hydroxyethyl Groups

Hydroxyethyl Groups

Chloroethyl Group

Chloroethyl Group

Chloroethyl Group

Chloroethyl Group

Dinuclear Mustards

Chloroethyl Group

Non-innocent Hydroxyethyl Group

Non-innocent Hydroxyethyl Group

Non-innocent Hydroxyethyl Group

Non-innocent Hydroxyethyl Group

Non-innocent Hydroxyethyl Group

Chloroethyl Group

Chloroethyl Group

Multiple Hydroxyethyl Groups (2)

Multiple Hydroxyethyl Groups (3) • Two anions per complex

Chloroethyl Groups Directly

Chloroethyl Groups Directly

Multiple Chloroethyl Groups (2)

Future Directions • Getting Co-mustards onto Ru(II) • Charge control • Cell toxicity • Localisation within cells/tumour models

The Past

The Future

Three Weeks Ago

Last Week

Acknowledgements • Ramin Zibaseresht • Alan Downward • Janadari Kariyawasam • Dr Matt Polson • Dr Evan Moore