Design and Synthesis of a Highly Sensitive Off-On Fluorescent Chemosensor for Zinc Ions Utilizing Internal Charge Transfer

Fluorescence imaging is a powerful tool for the visualization of biological molecules in living cells, tissue slices, and whole bodies, and is important for elucidating biological phenomena. Furthermore, zinc (Zn2+) is the second most abundant heavy metal ion in the human body after iron, and detection of chelatable Zn2+ in biological studies has attracted much attention. Herein, we present a novel, highly sensitive off–on fluorescent chemosensor for Zn2+ by using the internal charge transfer (ICT) mechanism. The rationale of our approach to highly sensitive sensor molecules is as follows. If fluorescence can be completely quenched in the absence of Zn2+, chemosensors would offer a better signal‐to‐noise ratio. However, it is difficult to quench the fluorescence completely before Zn2+ binding, and most sensor molecules still show very weak fluorescence in the absence of Zn2+. But even though the sensor shows a weak fluorescence in the absence of Zn2+, this fluorescence can be further suppressed by selecting an excitation wavelength that is barely absorbed by the Zn2+‐free sensor molecule. Focusing on careful control of ICT within the 4‐amino‐1,8‐naphthalimide dye platform, we designed and synthesized a new chemosensor (1) that shows a pronounced fluorescence enhancement with a blueshift in the absorption spectrum upon addition of Zn2+. The usefulness of 1 for monitoring Zn2+ changes was confirmed in living HeLa cells. There have been several reports on 4‐amino‐1,8‐naphthalimide‐based fluorescent sensor molecules. However, 1 is the first Zn2+‐sensitive off–on fluorescent sensor molecule that employs the ICT mechanism; most off–on sensor molecules for Zn2+ employ the photoinduced electron transfer (PeT) mechanism. Keen sensors! We present a highly sensitive fluorescent chemosensor based on 4‐amino‐1,8‐naphthalimide, which shows an off–on fluorescence change concomitantly with the appearance of a new absorption band at λ=380 nm in response to zinc ions.