By replacing a functional group in the firefly molecule luciferin, researchers have pumped up the intensity of light emitted by the luminescent molecule (J. Am. Chem. Soc., DOI: 10.1021/ja104525m). Fireflies light up the night, thanks to the luciferase-catalyzed reaction of oxygen and adenosine-5ʹ-triphosphate with D-luciferin to form an excited-state oxyluciferin molecule. When this molecule relaxes to its ground state, it gives off the yellow-green light characteristic of a firefly’s flicker. Although this chemistry has been known for some time, not much has been done to chemically modify luciferin substrates since the 1960s. Stephen C. Miller, Gadarla Randheer Reddy, and Walter C. Thompson of the University of Massachusetts Medical School report that replacing an aromatic hydroxyl group with an alkylamine that cyclizes onto the luciferin skeleton enabled them to generate molecules that produce a “robust, red-shifted light emission.” The researchers designed the modified luciferins according to the hypothesis that an electron-donating amino group would shift the compound’s emission and that constricting the conformational flexibility of this amine via cyclization would maintain a high quantum yield of bioluminescence. The two new luciferin analogs shown above work particularly well with the commercial modified luciferase Ultra-Glo and could find use in bioluminescence assays, they note.