An open and shut case? Chemistry to control xanthene dyes

Fluorescent dyes are an indispensable part of the scientific enterprise. Xanthene-based fluorophores, like fluorescein and rhodamine, have been in continual use across numerous fields since their invention in the late 19^th century. Modern methods to synthesize and expand the scope of xanthene dye chemistry have enabled new colors, enhanced stability, and improved brightness. Modifications to the 3-position of xanthene dyes have been, until recently, less well-explored. Here, we discuss how small changes to the identity of the substituent at the 3-position of fluoresceins and rhodamines can profoundly alter the properties of xanthene dyes, with the potential to unlock new applications at the interface of chemistry and biology.