Exploration, development and understanding of novel antibacterial transition metal complexes.

Antimicrobial resistance (AMR) is rising rapidly around the world, causing over 1 million deaths worldwide in 2019. This number is expected to rise to over 10 million deaths by 2050 if our dwindling antibiotic arsenal is not replenished. Recently we have shown that transition metal complexes have promising antimicrobial properties while not being more toxic towards

human cells than purely organic molecules. In this project, we are employing efficient synthetic methodologies together with automation and machine learning to systematically explore the metalloantibiotic chemical space. Promising compounds will be explored further to better understand their biological properties and antibacterial mechanisms of action.

The specific objectives of this project are: - Setting up the high-throughput automated synthesis of new metal complexes (both manually and by utilising automated synthesis systems (Opentrons) - Evaluating the antibacterial profile of the synthesized compounds to identify the ones with the best activity profile

- Rational chemical development of promising compounds utilising medicinal chemistry approaches - Investigation of the mechanism of action of lead compounds utilising microbiology techniques (including microscopy, plate reader assays, mass spectrometry and more) - Utilisation of the obtained data to train machine learning models able to predict

subsequent generations of antibacterial metal compounds. The ultimate goal will be to identify lead compounds that will go into in vivo studies while also advancing our scientific understanding on how metalloantibiotics achieve their biological effects. Taken together this research could lead to the development of novel

antibiotics in the future.