These specific, atom-directed alterations, also termed 'zero-size' labels, can act as probes to study the status of proteins in complex biomolecules. In the field of chemical biology, fluorine-containing compounds are typically used as imaging agents, for example in magnetic resonance imaging , or as probes for 19 F-NMR for applications in protein structure determination and protein engineering . However, applications of fluorine labeling in vibrational spectroscopy of proteins have not been reported.