US EPA

4336479 

Journal Article 

Light-induced antibiotic release from a coumarin-caged compound on the ultrafast timescale 

Herzig, LM; Elamri, I; Schwalbe, H; Wachtveitl, J 

2017 

1 

Physical Chemistry Chemical Physics
ISSN: 1463-9076
EISSN: 1463-9084 

Royal Society of Chemistry 

19 

22 

14835-14844 

English 

28548167 

10.1039/c7cp02030a 

WOS:000403327200065 

A synthesis route for puromycin caged with the photo-responsive 7-diethylaminocoumarinyl protecting group carbamate was developed. The inactivation and recovery of the cytotoxic effect of puromycin was tested with a XTT cell viability assay. The uncaging mechanism was studied by ultrafast transient absorption spectroscopy and by time-correlated single photon counting. The combination of these results with quantum-chemical calculations provided detailed insights in dynamics upon excitation. Interestingly, a change of the dipole moment due to structural rearrangements of the amino moiety led to an intermolecular charge transfer on the picosecond time-scale. IR measurements marked the successful uncaging via the release of CO2, resulting from the carbamate linker. This decarboxylation constituted the rate-limiting step of the uncaging reaction and occurred on the subsecond timescale. DEACM-puromycin, thus, represents an efficient photo-activatable antibiotic for in-cell applications. 

antiinfective agent; carbamic acid derivative; coumarin derivative; heterocyclic compound; animal; cell line; cell survival; chemistry; insect; light; photolysis; photon; spectroscopy; Animals; Anti-Bacterial Agents; Carbamates; Cell Line; Cell Survival; Coumarins; Heterocyclic Compounds; Insecta; Light; Photolysis; Photons; Spectrum Analysis