Anti-cancer work
Cancer is a deadly disease which plagues humanity. One of the most successful treatment options involve chemotherapy, which is the administration of drugs to reduce tumor growth. Platinum based drugs occupy a vital part of this treatment, but these drugs are accompanied with severe side-effects. Scientists are hence searching other transition metal complexes as potential answers to this ongoing issue.
In 2016 a research area addressing these challenges was established by B. Blom at the MSP in collaboration with the EPFL in Switzerland (Prof. Paul Dyson), the University of Cape Town Medical School (Prof. Sharon Price) and Chemistry Department (Dr. Siyabonga Ngubane), the Technische Universitaet Graz (Dr. Judith Baumgartner/Prof. Christoph Marschner), and AMIBM at Maastricht University (Dr. Dario Romano).
We are currently pursuing, in a rational way, novel metal-based systems for potential anti-cancer applications, and considering agents which are suitable for further detailed biological mechanistic and pre-clinical studies.
Staff
Research topics
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.
Single crystal X-ray diffraction structures of three pro-drugs studied in our laboratory. Incorporation of the elements Sn and Ge can fine-tune biological activity.
A series of novel Osmium based pro-drugs bearing the elements Sn, Sb and As currently under investigation as new types of anti-cancer agents.
DFT optimized structure of a titanium pre-catalyst, investigated as an ethene polymerisation catalyst precursor.
DFT optimized structures of active group IV (Titanium) catalysts used in the production of UHMWPE (Ultra-High Molecular Weight Polyethylene)
Electronic structures of catalysts (Ti based) used to generate UHMWPE, based on DFT studies. The HOMO and LUMO orbitals are depicted.
Publications
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T. Nabiyeva, C. Marschner, B. Blom
Synthesis, Structure and Anti-Cancer Activity of Osmium Complexes Bearing p-Bound Arene Substituents and Phosphane Co-Ligands: A Review
Eur. J. Med. Chem. 2020, 201, 112483 -
M. Odachowski, C. Marschner, B. Blom
A Review on 1,1-Bis(diphenylphosphino)methane bridged homo- and heterobimetallic complexes for anticancer applications: synthesis, structure, and cytotoxicity
Eur. J. Med. Chem. 2020,204, 112613 -
C. Serbu, C. Marschner, B. Blom
Homo and Heterobimetallic Complexes Bearing m-diphosphane Bridges Involved in Biological Studies: Part 1: Iron, Ruthenium and Osmium, Polyhedron
Submitted, 2020. -
D. BenYosef, D. Romano, P. J. Dyson, B. Blom
Facile Synthesis of Heterobimetallic [FeII(m-diphosphine)RuII] and Homobimetallic [FeII(m-diphosphine)FeII] Complexes and their in vitro Cytotoxic Activity on Cisplatin-resistant Cancer Cells
Inorg. Chim. Acta. 2020, Accepted. -
N. Aldeghi, D. Romano, C. Marschner, S. Biswas, S. Chakraborty, S. Prince, S. Ngubane, B. Blom
Facile entry to germanate and stannate complexes [(η6-arene)RuCl(η2-dppm)]+[ECl3]- (E = Ge, Sn) as potent anti-cancer agents, J. Organomet. Chem. 2020, https://doi.org/10.1016/j.jorganchem.2020.121214 -
B. Herry, L. K. Batchelor, B. Roufosse, D. Romano, J. Baumgartner, M. Borzova, T. Reifenstahl, T. Collins, A. Benamrane, J. Weggelaar, M. C. Correia, P. J. Dyson, B. Blom
Heterobimetallic [Ru(m-dppm)Fe] and Homobimetallic [Ru(m-dppm)Ru] Complexes as Potential Anti-cancer Agents
Submitted, J. Organomet. Chem. 2019. https://doi.org/10.1016/j.jorganchem.2019.120934 -
Berg, Clara; Chari, Suviti; Jurgaityte, Kaste; Laurora, Alice; Naldony, Mateusz; Pope, Frances; Romano, Dario; Medupe, Thato; Prince, Sharon; Ngubane, Siyabonga; Blom, B.
Modulation of the solubility properties of arene ruthenium complexes bearing stannyl ligands as potential anti-​cancer agents
J. Organomet. Chem. 2019, 891, 12. -
C. Deacon-Price, D. Romano, T. Riedel, P. Dyson and B. Blom
Synthesis, Characterisation and Cytotoxicity Studies of Ruthenium Arene Complexes Bearing Trichlorogermyl Ligands
Inorg. Chim. Acta. 2019, 484, 513. -
O. Renier, C. Deacon-Price, J. E. B. Peters, K. Nurekeyeva, C. Russon, S. Dyson, S. Ngubane, J. Baumgartner, P. J. Dyson, T. Riedel, H. Chiririwa, B. Blom
Synthesis and In Vitro (Anticancer) Evaluation of η6-Arene Ruthenium Complexes Bearing Stannyl Ligands, Inorganics 2017, 5(3), 44.
Student participation
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
Projects
- Synthesis of germyl and stannyl ruthenium complexes as anti-cancer agents.
- Synthesis of ruthenium salt complexes with silver anions as potent anti-cancer complexes
- Bimetallic Iron and Ruthenium complexes brdiged by a diphosphine tether as anti-cancer agents
- Synthesis of new Ruthenium salt complexes bearing germanate and stannate anions as highly active and selective anti-cancer complexes
- Preparation of homo and heterobimetallic iron and ruthenium complexes bridged by dppe and dppb
- Ionic and neutral Iron and Rhodium bimetallic complexes
- Neutral and ionic homo and heterobimetallic Ru/Ir complexes
- Osmium Arene anti-cancer complexes
- Phosphane Palladium and platinum bimetallic agents as anti-cancer complexes.