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Prof Orde Q Munro

Position:  DST/NRF South African Research Chairs Initiative (SARChI) Professor of Bioinorganic Chemistry and Chair of Inorganic Chemistry
Qualification:  BSc(Hons) PhD (Witwatersrand), MACS, MSPP
Department: Chemistry
Phone: 011 717 6737
Email: Orde.Munro@wits.ac.za

Biography

Professor Munro graduated with a Ph.D. in bioinorganic chemistry (heme-peptide model systems for heme proteins) from WITS University in April 1996. He then spent 18 months as a post-doctoral researcher working on the synthesis, spectroscopy, X-ray structures, and molecular simulations of iron porphyrins with Prof. Robert Scheidt at the University of Notre Dame (Indiana, USA). In July 1997 he joined the Department of Chemistry at the University of Natal (which became the University of KwaZulu-Natal in 2004), where he continued to work on metalloporphyrins and other functional coordination compounds until July 2015. While at UKZN, Prof. Munro served a 3-year term (2012-2015) as Academic Leader – Chemistry on the Pietermaritzburg campus in the School of Chemistry & Physics. He is a member of the American Chemical Society and the recipient of numerous awards, including the National Research Foundation (NRF) President’s Award (2000), the Vice Chancellor’s Research Award (UKZN, 2007), and the Raikes Medal of the South African Chemical Institute (2008). In 2011/2012 Prof. Munro held a Visiting Fulbright Scholarship at the University of Central Florida (College of Medicine) working with Prof. Mark Muller on mechanistic studies of a new class of gold-based anticancer compounds. He is a participant in the Developmental Therapeutics Program (DTP) of the NIH (USA) and a member of the Scientific Advisory Board of TopoGEN Inc. In 2014, he was awarded the SASOL Innovator of the Year Medal for his work on novel anticancer metallodrugs. Prof. Munro rejoined WITS University in August 2015 as the DST/NRF Chair in Bioinorganic Chemistry, is Professor of Bioinorganic Chemistry, and Chair of Inorganic Chemistry.

Research Interests

Overview: The work centers on structure, function, and mechanism elucidation in bioinorganic and inorganic chemistry. Significant effort is devoted to fundamental studies aimed at delineating the physical, chemical, and biochemical behavior of novel complexes of metal ions. The compounds of interest include porphyrins, metalloporphyrins, pyrrole-based macrocycles, and other metal chelates often, but not always, of relevance in biology, medicine, and/or biochemistry (Figure 1). Computational (in silico) design methods are used to create novel metallodrug candidates and semi-synthetic metalloenzymes. Since structure normally underpins function, much of the group’s work is structure-based and employs appropriate methods such as X-ray crystallography and molecular/macromolecular simulations to gain a fundamental understanding of chemical structures and their conformational behavior at atomic resolution. Over the years, many MSc and PhD-level students (as well as academic and technical staff) have been trained in the art and science of small molecule crystallography. Recent efforts have moved into the realm of protein crystallography. Specific studies now focus on macromolecular structures of metal-based anticancer agents (e.g. metallointercalators bound to DNA), semi-synthetic metalloproteins, and molecular recognition/imaging of receptor proteins as the research program shifts closer to the interface between chemistry and biology.

   

Figure 1. Core research areas & approaches.       

 

Figure 2. New gold(III)-based metallodrug candidates and their molecular mechanisms of action. (a) Cytotoxic isoquinoline-amide chelates of gold(III). (b) Cytotoxic bis(pyrrolide-imine) macrocyclic complexes of gold(III).

Click here to view Expertise

Brief Highlights (Anticancer and Antibacterial Metallodrugs): Since 2008, research focused on the design of pyrrole-based chelates and macrocycles of gold(III) as well as isoquinoline-amide chelates of this metal has been pursued. We have discovered and patented novel catalytic inhibitors and poisons of human topoisomerases I and II (Top1 and Top2), pivotal nuclear enzymes that regulate DNA supercoiling and replication. These two enzymes are validated anticancer targets since they are present at higher levels in tumor cells (relative to normal cells) and their inhibition by cytotoxic compounds induces apoptosis (controlled cell death) and thus tumor regression. Our work has shown that gold(III) chelates with appropriate ligands bind either to the DNA nucleobase targets of Top1 and Top2 by intercalation (Top1 and Top2 inhibitors) or irreversibly to the ternary DNA-drug-enzyme catalytic intermediates (e.g. Top2 poisons). In the case of the gold(III) macrocycles, the metal ion is irremissible for activity and we have been able to show that the lead compound fails to bind to DNA unless the gold(III) ion is present to stabilize the intercalation adduct through electrostatic binding of the metal ion to a thymine carbonyl oxygen. Current work involves novel complexes of the metals Au(III), Cu(II), Pd(II), and Ga(III).

 

Collaborators: My current, active collaborations involve work with the following scientists in the RSA and abroad:

  • Prof. Daniela Bezuidenhoudt (WITS University)
  • Prof. Manuel Fernandes (WITS University)
  • Prof. Karl Rumbold (WITS University)
  • Dr. Matthew Akerman and Prof. Stephen Ojwach (Univ. of KZN)
  • Prof. Delia Haynes (Univ. of Stellenbosch)
  • Prof. Len Barbour (Univ. of Stellenbosch)
  • Dr. Kyle Rohde (UCF, Orlando)
  • Prof. Mark Muller (TopoGEN, Colorado)
  • Prof. Yuk-Ching Tse-Dinh (Florida International University)

Selected Publications

Nikolayenko, V.I., van Wyk, L.M., Munro, O.Q. and Barbour, L.J., 2018. Supramolecular solvatochromism: mechanistic insight from crystallography, spectroscopy and theory. Chemical Communications, 54, pp.6975-6978.

Gupta, R., Felix, C.R., Akerman, M.P., Akerman, K.J., Slabber, C.A., Wang, W., Adams, J., Shaw, L.N., Tse-Dinh, Y.C., Munro, O.Q. and Rohde, K.H., 2018. Evidence for Inhibition of Topoisomerase 1A by Gold (III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus. Antimicrobial Agents and Chemotherapy, 62(5), pp.e01696-17.

Haynes, D.A., van Laeren, L.J. and Munro, O.Q., 2017. Cobalt Porphyrin–Thiazyl Radical Coordination Polymers: Toward Metal-Organic Electronics. Journal of the American Chemical Society, 139 (41), pp 14620–14637.

Magubane, M. N., Nyamato, G. S. Ojwach, S. O. and Munro, O. Q., 2016. Structural, Kinetic, and DFT Studies of the Transfer Hydrogenation of Ketones Mediated by (Pyrazole)pyridine Iron(II) and Nickel(II) Complexes. RSC Advances, 6(69), pp.65205-65221.

Akerman, K.J., Fagenson, A.M., Cyril, V., Taylor, M., Muller, M.T., Akerman, M.P. and Munro, O.Q., 2014. Gold (III) Macrocycles: Nucleotide-Specific Unconventional Catalytic Inhibitors of Human Topoisomerase I. Journal of the American Chemical Society, 136(15), pp.5670-5682.

Bezuidenhout, D.I., Van der Westhuizen, B., Swarts, P.J., Chatturgoon, T., Munro, O.Q., Fernández, I. and Swarts, J.C., 2014. Redox Behaviour of Cymantrene Fischer Carbene Complexes in Designing Organometallic Multi‐tags. Chemistry-A European Journal20(17), pp.4974-4985.

Wilson, C.R., Fagenson, A.M., Ruangpradit, W., Muller, M.T. and Munro, O.Q., 2013. Gold (III) complexes of pyridyl-and isoquinolylamido ligands: structural, spectroscopic, and biological studies of a new class of dual topoisomerase I and II inhibitors. Inorganic Chemistry, 52(14), pp.7889-7906.

Munro, Orde Quentin, Kate Julie Akerman, and Matthew Piers Akerman. "GOLD COMPLEXES FOR USE IN THE TREATMENT OF CANCER." U.S. Patent 20,130,090,472, issued April 11, 2013.

Field, J.S., Munro, O.Q. and Waldron, B.P., 2012. Sorption of small molecule vapours by single crystals of [Pt {4′-(Ph) trpy}(NCS)]SbF6 where trpy= 2, 2′: 6′, 2′′-terpyridine: a porous material with a structure stabilised by extended π–π interactions. Dalton Transactions, 41(18), pp.5486-5496.

Chemaly, S.M., Brown, K.L., Fernandes, M.A., Munro, O.Q., Grimmer, C. and Marques, H.M., 2011. Probing the Nature of the CoIII Ion in Corrins: The Structural and Electronic Properties of Dicyano-and Aquacyanocobyrinic Acid Heptamethyl Ester and a Stable Yellow Dicyano-and Aquacyanocobyrinic Acid Heptamethyl Ester. Inorganic Chemistry50(18), pp.8700-8718.

Field, J.S., Wilson, C.R. and Munro, O.Q., 2011. Non-covalent interactions between cations in the crystal structure of [Pt {4′-(p-tolyl)trpy}Cl] SbF6, where trpy is 2, 2′: 6′, 2 ″-terpyridine, underpin the salt’s complex solid-state luminescence spectrum. Inorganica Chimica Acta374(1), pp.197-204.

Field, J.S., Grimmer, C.D., Munro, O.Q. and Waldron, B.P., 2010. Speciation in solution, solid state spectroscopy and vapochromism of [Pt (trpy)(NCS)] SbF6 where trpy= 2, 2′: 6′, 2′′-terpyridine. Dalton Transactions, 39(6), pp.1558-1567.

Munro, O.Q., Camp, G.L. and Carlton, L., 2009. Structural, 103Rh NMR and DFT Studies of a Bis (phosphane) RhIII–Porphyrin Derivative. European Journal of Inorganic Chemistry2009(17), pp.2512-2523.

Field, J.S., Ledwaba, L.P., Munro, O.Q. and McMillin, D.R., 2008. Crystal structures and photoluminescent properties of the orange and yellow forms of [Pt {4′-(o-ClC 6 H 4) trpy}(CN)]SbF6: an example of concomitant polymorphism. CrystEngComm10(6), pp.740-747.

Munro, O.Q., Joubert, S.D. and Grimmer, C.D., 2006. Molecular recognition: preorganization of a bis (pyrrole) Schiff base derivative for tight dimerization by hydrogen bonding. Chemistry-A European Journal, 12(31), pp.7987-7999.

Hofmann, A., Jaganyi, D., Munro, O.Q., Liehr, G. and van Eldik, R., 2003. Electronic tuning of the lability of Pt (II) complexes through π-acceptor effects. Correlations between thermodynamic, kinetic, and theoretical parameters. Inorganic Chemistry42(5), pp.1688-1700.

Munro, O.Q., Shabalala, S.C. and Brown, N.J., 2001. Structural, Computational, and 59Co NMR Studies of Primary and Secondary Amine Complexes of Co (III) Porphyrins. Inorganic Chemistry40(14), pp.3303-3317.

Munro, O.Q., Madlala, P.S., Warby, R.A., Seda, T.B. and Hearne, G., 1999. Structural, conformational, and spectroscopic studies of primary amine complexes of iron (II) porphyrins. Inorganic Chemistry, 38(21), pp.4724-4736.

Munro, O.Q. and Scheidt, W.R., 1998. (Nitro) iron (III) porphyrins. EPR detection of a transient low-spin iron (III) complex and structural characterization of an O atom transfer product. Inorganic Chemistry, 37(9), pp.2308-2316.

Cheng, B., Munro, O.Q., Marques, H.M. and Scheidt, W.R., 1997. An Analysis of Porphyrin Molecular Flexibility Use of Porphyrin Diacids. Journal of the American Chemical Society119(44), pp.10732-10742.

Munro, O.Q., Marques, H.M., Debrunner, P.G., Mohanrao, K. and Scheidt, W.R., 1995. Structural and Molecular Mechanics Studies on Highly Ruffled Low-Spin (Porphinato) iron (III) Complexes. Journal of the American Chemical Society117(3), pp.935-954.

Nikolayenko, V.I., van Wyk, L.M., Munro, O.Q. and Barbour, L.J., 2018. Supramolecular solvatochromism: mechanistic insight from crystallography, spectroscopy and theory. Chemical Communications, 54, pp.6975-6978.

Gupta, R., Felix, C.R., Akerman, M.P., Akerman, K.J., Slabber, C.A., Wang, W., Adams, J., Shaw, L.N., Tse-Dinh, Y.C., Munro, O.Q. and Rohde, K.H., 2018. Evidence for Inhibition of Topoisomerase 1A by Gold (III) Macrocycles and Chelates Targeting Mycobacterium tuberculosis and Mycobacterium abscessus. Antimicrobial Agents and Chemotherapy, 62(5), pp.e01696-17.

 

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