Gnaim Samer, Green Ori, Shabat Doron
Department of Organic Chemistry, School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Chem Commun (Camb). 2018 Feb 22;54(17):2073-2085. doi: 10.1039/c8cc00428e.
The majority of known chemiluminescent compounds produce light through oxidation-dependent mechanisms. The unique notion of triggering chemiluminescence by a chemical reaction other than oxidation was first introduced by Schaap in 1987 with the development of chemically and enzymatically activated phenoxy-dioxetanes. Such dioxetanes are distinctive among chemiluminescent molecules since the oxidized high-energy species, the dioxetane, is stable for years at room temperature. Light emission is selectively activated by deprotection of the phenol-protecting group. The chemiluminescence quantum yields of such dioxetanes are relatively high in organic solvents like DMSO. In aqueous solution, however, light emission efficiency drops by approximately 10 000-fold due to energy loss to water molecules. As we sought to understand the low light emission efficiency in water, we realized that the dioxetane chemiexcitation leads to the release of an excited state benzoate molecule, which is a very weak emitter under aqueous conditions. Thus, we reasoned that emission in aqueous solution could be enhanced, if the emissive nature of the excited benzoate formed in water is improved. Introduction of an electron-withdrawing acrylic group at the ortho position of the phenol donor resulted in an excited benzoate species that emits light with high efficiency in aqueous solutions. A striking 3000-fold increase in chemiluminescence emission was observed by simply using an acrylonitrile substituent on the dioxetane probe. For the first time, scientists now have an effective single-entity chemiluminescent probe that can be used to evaluate biological processes. This discovery promoted us to develop numerous highly efficient chemiluminescent probes for detection of different enzymes and analytes in aqueous solution. We anticipate that further studies in this direction will lead to even better chemiluminescence probes with quantum yield emissions that are even higher than that of the luciferin/luciferase system. In this Feature Article, we describe the insights that led us to develop these unprecedented luminophores and the historical perspective that led to the current generation of chemiluminescent phenoxy-dioxetane probes.
大多数已知的化学发光化合物通过氧化依赖机制产生光。1987年，沙普随着化学和酶促活化苯氧基二氧杂环丁烷的发展，首次提出了通过氧化以外的化学反应引发化学发光的独特概念。这种二氧杂环丁烷在化学发光分子中很独特，因为氧化后的高能物种二氧杂环丁烷在室温下能稳定存在数年。通过酚保护基团的脱保护选择性地激活发光。在二甲基亚砜等有机溶剂中，这种二氧杂环丁烷的化学发光量子产率相对较高。然而，在水溶液中，由于向水分子的能量损失，发光效率下降了约10000倍。当我们试图理解水中低发光效率的原因时，我们意识到二氧杂环丁烷化学激发会导致激发态苯甲酸酯分子的释放，而该分子在水性条件下是非常弱的发光体。因此，我们推断，如果水中形成的激发苯甲酸酯的发光性质得到改善，水溶液中的发光就可以增强。在酚供体的邻位引入吸电子丙烯酸基团，产生了一种激发态苯甲酸酯物种，该物种在水溶液中高效发光。通过在二氧杂环丁烷探针上简单地使用丙烯腈取代基，观察到化学发光发射显著增加了3000倍。科学家们首次拥有了一种有效的单实体化学发光探针，可用于评估生物过程。这一发现促使我们开发了许多高效的化学发光探针，用于检测水溶液中的不同酶和分析物。我们预计，在这个方向上的进一步研究将导致产生甚至更好的化学发光探针，其量子产率发射甚至高于荧光素/荧光素酶系统。在这篇专题文章中，我们描述了促使我们开发这些前所未有的发光体的见解以及导致当前一代化学发光苯氧基二氧杂环丁烷探针的历史背景。
