Dr Orde Munro
- Position: Lecturer of Computational Chemistry
- Areas of expertise: Molecular simulations - small and macromolecular; application of DFT simulations to chemical problems; metallodrug design, development, and mechanism elucidation; X-ray crystallography; spectroscopy.
- Email: O.Munro@leeds.ac.uk
- Location: 2.92b Chemistry West
- Website: Googlescholar | Researchgate | ORCID
I graduated with my Ph.D. in bioinorganic chemistry (heme-peptide model systems for heme proteins) at the University of the Witwatersrand (WITS) in Johannesburg (1996) before spending 18 months as a post-doc fellow at the University of Notre Dame (Indiana, USA). I started my independent academic career in 1997 at the University of Natal (South Africa) working on metalloporphyrins and other functional coordination compounds before moving back to WITS University in August 2015 to take up a 7-year term as the DST/NRF Chair in Bioinorganic Chemistry. In 2023, I joined the University of Leeds to further my interests in teaching and using computational chemistry for research. I was the recipient of a Fulbright Scholarship which I held at the University of Central Florida (USA) in 2011/2012.
- Teaching and Research
Figure 1. Core research areas & approaches.
Key Thrust. 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). Historically, computational (in silico) design methods have been used in our work to create novel metallodrug candidates and to probe metalloproteins and enzymes. 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. We are also interested in conformational analysis and the electronic structures of flexible organic compounds, including ligands and macrocycles and compounds with photo-switchable functional groups. These systems are theoretically and experimentally challenging, which makes them particularly interesting.
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).
Chemotherapeutic Agents. Historically, we’ve designed, synthesized, and tested novel pre-clinical chemotherapeutic agents for cancer, drug-resistant bacterial infections, and pathogenic viruses. The chemotherapeutic agents make use of metal ions such as Au(III) to exert a cytotoxic effect and they fall into the broad category of metallodrugs such as auranofin, bleomycin, and cisplatin. The most important feature of our work is that we spend significant time delineating the mechanism of action of novel compounds. The work therefore hinges on multiple techniques, often involving DFT simulations, and requires collaborative partners (e.g., in cell biology). In contrast to drugs such as cisplatin, which were discovered through serendipity rather than design, our group uses modern computational tools (Gaussian 16 and Schrodinger) to develop and test compounds, through simulations, that target a specific biomolecule such as DNA and the nuclear enzymes that regulate DNA (e.g., human topoisomerase I or II, Figure 2). We are also interested in targeting bacterial DNA gyrase and topoisomerase 1A.
Metallodrug Transport. We have recently studied how human serum albumin (HSA) interacts with metal chelates, specifically metallodrug candidates for cancer chemotherapy and structurally related derivatives, to better understand the stability of the compounds under physiologically relevant conditions. The work shows that metal chelates with tetradentate ligands are surprisingly stable and readily taken up by HSA, binding as fully intact complexes in classical drug-binding pockets within the heart-shaped protein. A recent publication in a prominent new journal describes the work and a professional video abstract is available for viewing: https://bcove.video/3Xkmtdm
Coordination compounds. We have significant expertise in understanding structure and bonding (intra- and inter-molecular) in novel coordination compounds using electronic structure theory calculations (mostly DFT nowadays, as shown in Figure 3). Simulations are used to develop the required theoretical insights to understand experimental data such as NMR chemical shifts and electronic spectra, magnetic properties, reaction mechanisms and catalytic cycles. Fundamental studies underpinned by reliable simulations are critical to making breakthroughs in virtually all branches of chemistry currently; combining theory with experiment often provides the required insights to make these breakthroughs.
Figure 3. DFT simulations enabling elucidation of a radical coupling mechanism.<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://eps.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>
- PhD, Physical Bioinorganic Chemistry, WITS University, 1996
- BSc Honours, WITS University, 1990
- American Chemical Society
- Royal Society of Chemistry
- South African Chemical Society
I will be involved in the design, optimization, and teaching of modules such as computational chemistry and will contribute, on occasion, in areas such as bioinorganic chemistry, physical chemistry, and inorganic chemistry.<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://phd.leeds.ac.uk">research opportunities</a> allow you to search for projects and scholarships.</p>