Researchers at the University of York have developed a robotic system capable of synthesizing hundreds of metal complexes, which has led to the identification of a potential new antibiotic candidate. The findings were published in Nature Communications.
The team, led by Dr Angelo Frei from the Department of Chemistry, used robotics and "click" chemistry to accelerate the process of drug discovery. This approach allowed them to create over 700 complex metal compounds in under a week, a task that would have otherwise taken months.
Postdoctoral researcher Dr David Husbands explained that nearly 200 different ligands were combined with five metals using this automated platform. After synthesis, the researchers screened these compounds for antibacterial activity and toxicity to human cells. Six potential lead compounds were identified.
A standout among these was an iridium-based compound that showed effectiveness against bacteria, including strains similar to MRSA (Methicillin-resistant Staphylococcus aureus), while exhibiting low toxicity to human cells. This indicates a high therapeutic index and positions it as a strong candidate for further development.
Dr Frei said: "This work shows how automation and new chemistry can open up unexplored areas in our search for urgently needed antibiotics."
There is a widespread belief that metal-based drugs are inherently toxic. However, data from the Community for Open Antimicrobial Drug Discovery (CO-ADD) indicate that metal complexes have a higher success rate in being both antibacterial and non-toxic compared to standard organic molecules.
The University of York researchers hope their methodology will prompt more scientists and pharmaceutical companies to investigate metal complexes as antibiotic candidates. They are also working on understanding how their iridium compound attacks bacteria and plan to expand their robotic system to test other metals.
The study also suggests that rapid-synthesis methods like this could be applied beyond medicine, such as in developing new industrial catalysts.
Over one million people die each year from preventable drug-resistant infections globally. As bacterial resistance increases, procedures like hip replacements or chemotherapy could become much riskier without new treatments available.
