Prof Gregory Smith

Professor

http://www.gregsmith-research.uct.ac.za/ (research)

Biography

BSc (1992), University of Natal, Pietermaritzburg, RSA
BSc Honours (1995), MSc (1997), PhD (2004), University of the Western Cape, RSA
Junior Lecturer (1997—1998), University of South Africa, RSA
Visiting/Postdoctoral Fellow (2005—2006), University of Bristol, UK
Lecturer (2004—2009)
Senior Lecturer (2010—2013), University of Cape Town, RSA
Associate Professor, (2014 – 2022) University of Cape Town, RSA
Professor, (2023 – present) University of Cape Town, RSA
Recipient of the Distinguished Teacher Award (2011)
South African Chemical Institute Raikes Medal (2011)

Research Interests

The use of transition metals in the fields of catalysis and medicine is a fast-growing area of interest, particularly linked to the improvement of the economy, especially for a developing country such as South Africa. South Africa has access to a range of transition metals, especially the Platinum group metals, essential in both fields of catalysis and medicine.

Catalysis is one of the most important technologies in modern times and is continuing to make great impact on industrial economies. In the South African context, there are large quantities of organic feedstocks, such as alkanes and alkenes that can be selectively transformed into value-added chemicals. To effect these transformations, new catalysts are required.

Catalysis

Our research interests are aimed at the development and synthesis of new transition metal complexes and an investigation into their applications in catalysis and as new materials. In these projects, various transition metal complexes are based on imine and phosphorus-containing ligands that will be investigated initially as mononuclear catalysts. We have previously prepared multinuclear imine-based catalysts for olefin oligomerisation/polymerization reactions and for Heck cross-coupling reactions, and will use our current understanding of these systems to develop more efficient systems. Catalytic reactions that we primarily focus on include polymerization, oligomerisation and hydroformylation of alkenes and carbon-carbon cross-coupling reactions.

Another question we seek to address is the synthesis of environmentally friendly catalysts. This stems from studies on linear polynuclear and dendritic catalysts that maintain high activity and selectivity and can be easily separated from reaction mixtures. The immobilization of transition metal catalysts on polymeric or dendritic supports offers a number of advantages. The supported complexes can be readily separated from reaction mixtures, facilitating recycling of the catalysts to avoid environmental toxicity and makes purification of products easier. This area bridges the gap between homogeneous and heterogeneous catalysis. The rationale for this study is to synthesize alternative, cheaper, more efficient catalysts that will be of interest to the South African industry.

Bioorganometallic Chemistry

Transition metal complexes are an important resource for the generation of chemical diversity in the search for novel therapeutic and diagnostic agents. Cisplatin represents one of the most active and clinically useful metal complexes in the treatment of cancer. However, cisplatin induces normal tissue toxicity, particularly to the kidney, and the development of acquired drug resistance can occur in initially responsive disease types. The field of bioorganometallic chemistry stemmed from the discovery if titanocene dichloride, the first organo-transition metal compound to be studied as an alternative to cisplatin, which underwent numerous clinical evaluations. Despite the successes of cisplatin and related platinum antitumour agents, research into non-platinum anticancer agents has evolved due to problems associated with platinum-based chemotherapies.

The use of metallomacromolecules as biological and therapeutic agents is a prolific area of research, due to their multivalency, which lead to increased interaction between a dendrimer-drug conjugate and target bearing multiple receptors, further improving the selectivity to cancer cells. Tumours can be specifically targeted by exploiting the ‘enhanced permeability and retention’ (EPR) effect, a phenomenon in which macromolecules can accumulate at the tumour site due to an increase in blood vessel permeability within diseased tissues compared to normal tissues.

In order to exploit size selective uptake of drugs into tumour cells effectively, macromolecular large compounds are required. Our current interest focuses on the investigation of metallomacromolecules as molecular tools in biological applications, especially as chemotherapeutics and as diagnostic agents. These projects therefore intend to combine the cytotoxicity of certain PGM complexes with dendrimers, as either potential therapeutic and/or imaging agents, in view to obtain a synergistic effect of the multibranched system.

Representative Publications

Selective Targeting of Regulated Rhabdomyosarcoma Cells by Trinuclear Ruthenium(II)−Arene Complexes

Athi Welsh, Karabo Serala, Sharon Prince, Gregory S. Smith*
JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67, 6673
Exploring the modulatory influence on the antimalarial activity of amodiaquine using scaffold hybridisation with ferrocene integration

Mziyanda Mbaba, Taryn M. Golding, Reinner O. Omondi, Roxanne Mohunlal, Timothy J. Egan, Janette Reader, Lyn-Marie Birkholtz, Gregory S. Smith*
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 271, 116429
Trinuclear ruthenium(II) polypyridyl complexes: Evaluation as photosensitizers for enhanced cervical cancer treatment
Athi Welsh, Refilwe Matshitse, Saif F. Khan, Tebello Nyokong, Sharon Prince, Gregory S. Smith*
JOURNAL OF INORGANIC BIOCHEMISTRY, 2024, 256, 112545
Aminoquinoline-based Re(I) tricarbonyl complexes: Insights into their antiproliferative activity and mechanisms of action
Paige S. Zinman, Athi Welsh, Reinner O. Omondi, Saif Khan, Sharon Prince, Ebbe Nordlander, Gregory S. Smith*
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2024, 266, 116094
Aminoquinoline-based ruthenium(II) and iridium(III) polypyridyl complexes: Investigating potential photosensitisers for cancer treatment via photodynamic therapy
Paige S. Zinman, Athi Welsh, Sharon Prince, Gregory S. Smith*
JOURNAL OF ORGANOMETALLIC CHEMISTRY, 2024, 1013, 123183
Evaluation of a trinuclear heteroleptic bis-cyclometalated iridium(III) complex as a photoredox catalyst for visible light-mediated hydrothiolation reactions

Tara K. Davids, Wade F. Petersen and Gregory S. Smith∗
INORGANIC CHEMISTRY COMMUNICATIONS, 2023, 149, 110384.
Modular synthesis of antimalarial quinoline-based PGM metallarectangles

Taryn M. Golding, Mziyanda Mbaba and Gregory S. Smith*
DALTON TRANSACTIONS, 2021, 50, 15274.
Evaluation of the subcellular localisation of a quinoline-containing fluorescent cyclometallated Ir(III) complex in Plasmodium falciparum

Diana R. Melis, Chiao-Yu Hsiao, Jill M. Combrinck, Lubbe Wiesner and Gregory S. Smith*
CHEMBIOCHEM, 2021, 22, 1-6.
Diversiﬁcation of quinoline-triazole scaffolds with CORMs: Synthesis, in vitro and in silico biological evaluation against Plasmodium falciparum

Fatima-Zahra Ishmail, Diana R. Melis, Mziyanda Mbaba and Gregory S. Smith*
JOURNAL OF INORGANIC BIOCHEMISTRY, 2021, 215, 111328.
Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

Mziyanda Mbaba, Taryn M. Golding and Gregory S. Smith*
MOLECULES, 2020, 25, 5276.
Antimicrobial evaluation of neutral and cationic iridium(III) and rhodium(III) aminoquinoline-benzimidazole hybrid complexes

Nadia Baartzes, Audrey Jordaan, Digby F. Warner, Jill Combrinck, Dale Taylor, Kelly Chibale and Gregory S. Smith*
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 206, 112694.
Quinoline-triazole half-sandwich iridium(III) complexes: synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies

Diana R. Melis, Christopher B. Barnett, Lubbe Wiesner, Ebbe Nordlander and Gregory S. Smith*
DALTON TRANSACTIONS, 2020, 49, 11543-11555.