基于分子组装的过氧化氢化学发光探针的构筑与性能研究

The overproduction of hydrogen peroxide is implicated in the development of numerous diseases, and there is currently great interest in sensitive visualization of the low level of hydrogen peroxide. In this project, we will develop a novel chemiluminescent nanoprobe based on supramolecular assembly, which can image hydrogen peroxide with high specificity and sensitivity. The nanoparticles were prepared from supramolecular polymers contains peroxalate esters and fluorescent dyes units, which were assembled through intermolecular hydrogen bonds. The chemical reaction between hydrogen peroxide and peroxalate esters can excited the fluorescent dyes, and then achieve the detection of hydrogen peroxide. The use of small organic molecules as assembly units instead of polymers make this method controllable and repeatable. More importantly, chemiluminescence is the emission of light as the result of a chemical reaction without photoexcitation, it offers ultrahigh sensitivity with no noise of photoexcited autofluorescence from the background. The nanoprobe has potentially been adopted for the sensitive and selective imaging of hydrogen peroxide.

过氧化氢在生命活动中起着至关重要的作用, 而过量过氧化氢的存在会引发多种疾病, 因此对体内过氧化氢的检测具有重要意义。本项目拟发展基于分子组装的化学发光纳米探针，为过氧化氢的生物检测提供新技术和新方法。以含草酸酯和含荧光染料的有机小分子为组装基元，通过分子间的氢键作用进行组装形成超分子聚合物纳米颗粒。利用过氧化氢和草酸酯基团的化学反应激发荧光染料发光，实现对过氧化氢的选择性检测。该类探针以结构明确的有机小分子作为组装基元，具有较好的重现性，并且化学发光不需要激发光源，能够避免背景荧光干扰，有望实现在生物条件下对过氧化氢高灵敏度高选择性检测。

在生理条件下有机染料通常处于聚集状态，芳香环在分子之间距离较近时容易发生π-π堆积，如何在含有高密度染料分子的纳米颗粒中防止分子的自猝灭，是制备高荧光量子效率的荧光纳米探针的一大挑战。我们分别基于四重氢键超分子组装体系和β-二酮氟硼络合物固体发光体系构建了具有优异性能的荧光纳米颗粒。一方面，我们通过在纳米颗粒中共聚不同的组装基元，基于四重氢键的超分子组装体纳米颗粒拉近了分子之间的距离，能够实现高效的能量传递。通过共聚大体积的构筑基元抑制荧光团之间的π-π堆积，能够大大提高荧光纳米颗粒的量子产率。另一方面，我们合成了含有咔唑基团的β-二酮氟硼络合物，其具有较强的固体发光和丰富的组装性能，可以在水中自组装形成高量子产率的荧光纳米颗粒。我们以这两类荧光纳米颗粒为基础构筑了含有过氧草酸酯的过氧化氢化学发光纳米探针。此外，我们通过对BODIPY染料结构的巧妙设计对其反应活性和功能进行调控，发展了几类检测生物硫醇的荧光探针。