Swapping isotopes improves fluorescent dyes

Abstract

Fluorescence microscopy is a powerful tool for biological research. Researchers would like brighter, more stable fluorophores that enable longer imaging experiments. Rhodamine dyes are particularly bright and stable, and they can be tuned by incorporating various substituents into their structure. But even rhodamines have room for improvement. A team led by Luke D. Lavis of the Howard Hughes Medical Institute’s Janelia Research Campus has upped rhodamines’ game by making a simple switch—replacing hydrogen atoms with their more massive chemical twin, deuterium ( JACS Au 2021, DOI: 10.1021/jacsau.1c00006 ). Instead of deuterating the xanthene core, the researchers deuterated the alkylamino substituents. The deuteration improved the brightness and stability of the dyes without causing unwanted shifts in their fluorescence spectra. The improvements result from isotope effects that slow processes that destabilize and dim the dyes. For cellular imaging, the dyes enabled experiments with longer duration and higher signal. In addition, the researchers