Anti-cancer work

Combining group 8 transition metals (Fe, Ru, Os) with group 14 elements such as germanium (Ge) and tin (Sn)

While in our studies, sigma bound germyl or stannyl groups (ER3) attached to netural ruthenium complexes seem to retard cytotoxic action, we have found that the formation of ionic complexes bearing Ge and Sn as counter ions (EX3-) combined with the elements Ru in the cation results in extremely potent anti-cancer agents.

Synthesis of neutral and ionic bimetallic complexes bearing two transition metals (Fe and Ru) tethered by a bridging ligand.

Two metal centres seem enhance in vitro cytotoxicity on numerous cell-lines compared to positive controls like cisplatin, showing possible synergic effects.

Synthesis of germyl and stannyl ruthenium complexes as anti-cancer agents.

We have prepared a series of complexes bearing these group 14 elements (Ge and Sn) which were shown to modulate anti-cancer activity significantly. In particular, incorporation of Germanium enhances aquation kinetics, leading to a decrease in activity and in some cases the addition of Sn increases cytotoxicity. We are still exploring this closely in our lab.

Students: C. Deacon-Price and Stefan Latis

Synthesis of ruthenium salt complexes with silver anions as potent anti-cancer complexes

The incorporation of Silver (Ag) into the complexes were shown, on breast cancer to significantly enhance activity as well as selectivity in ruthenium salt complexes. A series of these were prepared and also with iron fully characterized spectroscopically.  Detailed biological studies revealed also long term stability of the drugs, and prevention of cancer cell migration.

Students: Amal Benamrane and Brian Herry

Bimetallic Iron and Ruthenium complexes brdiged by a diphosphine tether as anti-cancer agents

We have shown that incorporation of iron into neutral bimetallic complexes, bearing iron and ruthenium: [Fe,Ru] tethered by neutral diphosphane ligands enhances activity of the anti cancer agents in vitro. We are currently exploring Structure activity relationships on these agents, exploring the effects of increased chain length, and extending the scope of cell-lines for testing via collaborations.

Students: B. Herry, Tilly Odachowski and Robin Neven

Synthesis of new Ruthenium salt complexes bearing germanate and stannate anions as highly active and selective anti-cancer complexes

Ruthenium salt complexes bearing germanate and stannate anions were prepared and fully characterized, also by X-ray diffraction analysis. these were shown to significantly enhance cytotoxic action on several breast cancer cell-lines (MDA-MB-231 and MCF-7). They were also shown to, in a dose-dependent manner, prevent cell migration and were shown to be stable long-term in vitro.

Student: N. Aldeghi

Preparation of homo and heterobimetallic iron and ruthenium complexes bridged by dppe and dppb

Homo [Fe,Fe] and Heterodinuclear [Fe,Ru] chiral bimetallic molecules bearing dppe and dppb tethers were prepared, characterized, and studied on a cisplatin resistant cell-line and shown to be very active in the case of the Fe,Ru systems, but rather inactive in the case of Fe,Fe systems.

Student: D. BenYosef

Ionic and neutral Iron and Rhodium bimetallic complexes

A series of ruthenium and iron neutral and ionic bimetallic complexes with rhodium were prepared and chracterised fully. It was shown that the systems display interesting solution behavior and at low temperatures in NMR show the existence of two conformers. The exact nature of this chemistry is still under investigation by DFT methods.

Students: M. Odachowski and Alix Fowden-Nevin

Neutral and ionic homo and heterobimetallic Ru/Ir complexes

Similar to the theme above, we prepared several bimetallic iridium complexes bearing a ruthenium phosphane tether and characterized these fully. It was also shown at low temperatures to exist as two distinct conformers, possibly eclipsed and gauche. These complexes will be tested for anti-cancer activity shortly.

Student: C. Serbu

Osmium Arene anti-cancer complexes

A wide array of new osmium half-sandwich complexes have been prepared, also bearing the elements As and Sb (arsenic and antimony), along with tin and germanium; and fully characterized spectroscopically. These will be tested as anti-cancer agents and Structure-Activity relationships pursued.

Students: Tomiris Nabiyeva and Stefan Latis

Phosphane Palladium and platinum bimetallic agents as anti-cancer complexes.

As part of an ongoing theme, systems tethered to Palladium and Platinum are also under exploration in our lab. In particular, attempting to enhance the existing cytotoxic activity of Pt and Pd systems by anchoring via tether to other cytotoxically active metals is under exploration.

Student: Talita. Kuipers