Modulation of luminescence intensity of lanthanide complexes by photoinduced electron transfer and its application to a long-lived protease probe
Modulation of luminescence intensity of lanthanide complexes by photoinduced electron transfer and its application to a long-lived protease probe
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DOI：
10.1021/ja060729t
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发表时间：
2006-05-31
影响因子：
15
通讯作者：
Nagano, Tetsuo
中科院分区：
文献类型：
--
作者：
Terai, Takuya;Kikuchi, Kazuya;Nagano, Tetsuo
发光镧系配合物（Tb3+， Eu3+等）在生物应用方面具有优异的性能，包括超长的寿命和大的斯托克斯位移。然而，由于难以设计合适的具有发光开关的配合物，基于镧系元素的功能探针的报道很少。在这里，我们合成了一系列由三部分组成的配合物：镧系螯合物、天线和发光开关。天线是吸收光并将其能量传递给金属的芳香环，开关是具有不同HOMO能级的苯衍生物。如果HOMO能级高于某一阈值，则配合物根本不发光，这表明镧系元素的发光可以通过从开关到敏化剂的光诱导电子转移（PeT）来调节。这种控制镧系元素发光的方法使得合理设计功能镧系元素配合物成为可能，其中发光特性通过生物反应改变。为了证明我们的方法在设计镧系化合物开关方面的实用性，我们开发了一种新的蛋白酶探针，在酶切底物肽时，其发光强度会发生显著变化。该探针与时间分辨测量相结合，在模型实验中被证实可用于抑制剂的筛选以及临床诊断。
Luminescent lanthanide complexes (Tb3+, Eu3+, etc.) have excellent properties for biological applications, including extraordinarily long lifetimes and large Stokes shifts. However, there have been few reports of lanthanide-based functional probes, because of the difficulty in designing suitable complexes with a luminescent on/off switch. Here, we have synthesized a series of complexes which consist of three moieties: a lanthanide chelate, an antenna, and a luminescence off/on switch. The antenna is an aromatic ring which absorbs light and transmits its energy to the metal, and the switch is a benzene derivative with a different HOMO level. If the HOMO level is higher than a certain threshold, the complex emits no luminescence at all, which indicates that the lanthanide luminescence can be modulated by photoinduced electron transfer (PeT) from the switch to the sensitizer. This approach to control lanthanide luminescence makes possible the rational design of functional lanthanide complexes, in which the luminescence property is altered by a biological reaction. To exemplify the utility of our approach to the design of lanthanide complexes with a switch, we have developed a novel protease probe, which undergoes a significant change in luminescence intensity upon enzymatic cleavage of the substrate peptide. This probe, combined with time-resolved measurements, was confirmed in model experiments to be useful for the screening of inhibitors, as well as for clinical diagnosis.