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Systematic Exploration of Novel Chemical Spaces for New Antimicrobial Agents

Systematic Exploration of Novel Chemical Spaces for New Antimicrobial Agents

Our group is interested in the synthesis, characterisation and biological evaluation of transition metal complexes as antimicrobials (www.thefreilab.com). We prepare large libraries of hundreds of compounds and evaluate their antibacterial properties. While these assays can be read-out by eye, this is an error-prone and low-throughput procedure. With the TECAN Infinite M Nano (Figure 1) acquire with support from the UniBern Forschungsstiftungs grant we can read out up to 96 compounds (Figure 2), with high precision in a fraction of the time. However, our use of the plate-reader is not limited to antimicrobial assays. We also utilise it for haemolysis assays where we determine if a given compound has the (unwanted) capacity to destroy red blood cells (Figure 3).

Figure 1. The Infinite M Nano Plate Reader acquired with financial support by the UniBern Forschungsstiftung.
Figure 2. A 96 well plate containing 84 different metal complexes to be tested for antimicrobial properties.
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Figure 3. A 96 well plate with 64 different compounds in combination with human blood. Turbid wells indicate that the present compound causes (undesirable) damage to the red blood cells.
Figure 4. Time-resolved UV/Vis Spectra of 96 different catalytic reactions

Furthermore. we have also utilise the plate-reader for mode of action studies, utilising fluorescent dyes to e.g. quantify if bacterial membranes are destroyed. We also monitored 96 catalytic reactions performed by our compound library in real time over 12 h to compare the catalytic performance of 96 metal compounds at once (Figure 4).

Overall, the acquisition of this instrument has had rippling benefits throughout all areas of our research, and we keep finding novel ways to utilise it.

Dr. Angelo Frei
Departement für Chemie, Biochemie und Pharmazie

www.thefreilab.com

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