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

Synthesis and characterisation of multimeric salicylaldimine thiosemicarbazones and their  Pd(II) and Pt(II) complexes
Tameryn Stringer, Denver T. Hendricks, Hajira Guzgay and Gregory S. Smith*
Polyhedron, 2012, 31, 486-493.

Synthesis and in vitro Evaluation of Palladium(II) Salicylaldiminato Thiosemicarbazone Complexes against Trichomonas Vaginalis
Prinessa Chellan, Tameryn Stringer, Ajit Shokar, Padraick J. Dornbush, Guillermo Vazquez-Anaya, Kirkwood M. Land, Kelly Chibale and Gregory S. Smith
Journal of Inorganic Biochemistry, 2011, 105, 1562-1568.

Neutral Palladium(II) Complexes with P,N Schiff-base ligands: Synthesis, Characterisation and Catalytic Oligomerisation of Ethylene
Mokgolela M. Mogorosi, Tebello Mahamo, John R. Moss, Selwyn F. Mapolie, J. Chris Slootweg, Koop Lammertsma and Gregory S. Smith
Journal of Organometallic Chemistry, 2011, 696, 3585-3592.

Ferrocenylthiosemicarbazones Conjugated to a Poly(propyleneimine)Dendrimer Scaffold: Synthesis and In Vitro Antimalarial Activity 
Setshaba D. Khanye, Jiri Gut, Philip J. Rosenthal, Kelly Chibale and Gregory S. Smith*
Journal of Organometallic Chemistry, 2011, 696, 3296-3300.

Targeted and multifunctional arene ruthenium chemotherapeutics
Gregory S. Smith and Bruno Therrien
Dalton Transactions, 2011, 40, 10793-10800.

Hydroformylation activity of multinuclear rhodium complexes coordinated to dendritic iminopyridyl and iminophosphine scaffolds
Nathan C. Antonels, John R. Moss and Gregory S. Smith
Journal of Organometallic Chemistry, 2011, 696, 2003-2007.

Pd Nanosized Particles Supported on Chitosan and 6-Deoxy-6-Amino Chitosan as Recyclable Catalysts for Suzuki-Miyaura and Heck Cross-coupling Reactions
Banothile C.E. Makhubela,  Anwar Jardine and  Gregory S. Smith
Applied Catalysis A: General, 2011, 393, 231-241.

Antiproliferative activity of chelating N,O- and N,N-ruthenium(II) arene functionalised poly(propyleneimine) dendrimers scaffolds
Preshendren Govender, Anna K. Renfrew, Catherine M. Clavel, Paul J. Dyson, Bruno Therrien, and Gregory S. Smith
Dalton Transactions, 2011, 40, 1158-1167.

Synthesis, Structure and in Vitro Biological Screening of Palladium(II) Complexes of Functionalsed Salicylaldimine Thiosemicarbazones as Antimalarial and Anticancer Agents
Prinessa Chellan, Nelusha Shunmoogam-Gounden, Denver T. Hendricks, Jiri Gut, Philip J. Rosenthal, Carmen Lategan, Peter J. Smith, Kelly Chibale and Gregory S. Smith
European Journal of Inorganic Chemistry, 2010, 3520-3528.

Gold(I) derived thiosemicarbazone complexes with rare halogen-halogen interaction-reduction of [Au(damp-C¹,N)Cl₂]
Setshaba D. Khanye, Nikoletta B. Bathori, Gregory S. Smith and Kelly Chibale
Dalton Transactions, 2010, 39, 2697-2700.

Photocontrolled Living Anionic Polymerisation of Silicon-Bridged [1]Ferrocenophanes with Fluorinated Substitutents: Synthesis and Characterisation of Fluorinated Polyferrocenylsilane (PFS) Homopolymers and Block Copolymers
Gregory S. Smith, Sanjib K. Patra, Lawrence Vanderark, Saowanit Saithong, Jonathan Charmant and Ian Manners
Macromolecular Chemistry and Physics, 2010, 211, 303-312.

Rhodium(I) iminophosphine poly(propyleneimine) dendrimers: Synthesis, characterisation and molecular structure of a mononuclear analogue
Nathan C. Antonels, Bruno Therrien, John R. Moss and Gregory S. Smith
Inorganic Chemistry Communications, 2009, 12, 716-719.

Synthesis and structural characterisation of binuclear palladium(II) complexes of salicylaldimine dithiosemicarbazones
Tameryn Stringer, Prinessa Chellan, Bruno Therrien, Nelusha Shunmoogam-Gounden, Denver T. Hendricks and Gregory S. Smith
Polyhedron, 2009, 28, 2839-2846.

Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds
Preshendren Govender, Nathan C. Antonels, Johan Mattsson, Anna K. Renfrew, Paul J. Dyson, Bruno Therrien, John R. Moss and Gregory S. Smith
Journal of Organometallic Chemistry, 2009, 694, 3470-3476.

Synthesis, characterization, reactivity and molecular structure of arene-osmium complexes: A new synthetic entry into (h⁶-arene)osmium(II) chemistry
Hadley S. Clayton, Banothile C.E. Makhubela, Hong Su, Gregory S. Smith and John R. Moss
Polyhedron, 2009, 28, 1511.

The application of novel dendritic nickel catalysts in the oligomerization of ethylene Rehana Malgas, Selwyn F. Mapolie, Steve O. Ojwach, Gregory S. Smith, James Darkwa
Catalysis Communications, 2008, 9, 1612-1617.

Norbornene Polymerisation using Multinuclear Nickel Catalysts Based on a Polypropyleneimine Dendrimer Scaffold
Rehana Malgas-Enus, Selwyn F. Mapolie and Gregory S. Smith
Journal of Organometallic Chemistry, 2008, 693, 2279-2286.