Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Chemistry. 2010 Jan 11;16(2):568-72. doi: 10.1002/chem.200901591.
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 (Zn(2+)) is the second most abundant heavy metal ion in the human body after iron, and detection of chelatable Zn(2+) in biological studies has attracted much attention. Herein, we present a novel, highly sensitive off-on fluorescent chemosensor for Zn(2+) 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 Zn(2+), chemosensors would offer a better signal-to-noise ratio. However, it is difficult to quench the fluorescence completely before Zn(2+) binding, and most sensor molecules still show very weak fluorescence in the absence of Zn(2+). But even though the sensor shows a weak fluorescence in the absence of Zn(2+), this fluorescence can be further suppressed by selecting an excitation wavelength that is barely absorbed by the Zn(2+)-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 Zn(2+). The usefulness of 1 for monitoring Zn(2+) 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 Zn(2+)-sensitive off-on fluorescent sensor molecule that employs the ICT mechanism; most off-on sensor molecules for Zn(2+) employ the photoinduced electron transfer (PeT) mechanism.
荧光成像技术是一种用于可视化活细胞、组织切片和整个生物体中生物分子的强大工具，对于阐明生物现象非常重要。此外，锌（Zn(2+)）是人体内仅次于铁的第二丰富的重金属离子，因此在生物研究中检测可螯合的 Zn(2+)引起了广泛关注。在此，我们提出了一种基于内电荷转移（ICT）机制的新型、高灵敏的用于 Zn(2+)的荧光化学传感器。我们设计高灵敏度传感器分子的原理如下。如果在没有 Zn(2+)的情况下可以完全猝灭荧光，那么化学传感器将提供更好的信噪比。然而，在与 Zn(2+)结合之前，很难完全猝灭荧光，并且大多数传感器分子在没有 Zn(2+)的情况下仍然显示非常弱的荧光。但是，即使传感器在没有 Zn(2+)的情况下显示出微弱的荧光，通过选择几乎不被无 Zn(2+)的传感器分子吸收的激发波长，也可以进一步抑制荧光。我们专注于在 4-氨基-1,8-萘二甲酰亚胺染料平台内对 ICT 进行精细控制，设计并合成了一种新的化学传感器（1），当加入 Zn(2+)时，它表现出明显的荧光增强，吸收光谱发生蓝移。1 用于监测 Zn(2+)变化的有效性在活 HeLa 细胞中得到了证实。已经有一些关于基于 4-氨基-1,8-萘二甲酰亚胺的荧光传感器分子的报道。然而，1 是第一个采用 ICT 机制的 Zn(2+)灵敏的荧光开-关传感器分子；大多数用于 Zn(2+)的开-关传感器分子采用光诱导电子转移（PeT）机制。
