Swapping selenium for sulfur in an analog of d-luciferin makes the compound glow red, rather than the usual yellow-green gleam of d-luciferin, when it meets up with the firefly luciferase enzyme (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201105653). Stanford University’s Nicholas R. Conley, W. E. Moerner, and coworkers developed the selenium-substituted compound, aminoseleno-d-luciferin, by replacing sulfur with selenium in amino-d-luciferin, an orange-glowing analog of the firefly’s key light-up chemical. They hoped that red-shifting the compound would allow its emission to be observed from deeper within tissue, thereby making it superior to d-luciferin in bioluminescence imaging studies. The selenium substitution had little effect on the compound’s ability to bind to luciferase, but it had less light output than amino-d-luciferin in in vitro studies, in part because of its lower quantum yield. In vivo, the selenium-substituted compound was about as good as amino-d-luciferin, presumably because of a trade-off between its greater tissue penetration and its lower quantum yield. Because 77Se is a stable nucleus for magnetic resonance imaging (MRI), the researchers believe the compound could find use in bimodal bioluminescence-MRI studies.