Lanthanide complexes as chiral probes and labels

自从法拉第第一次宣称“偏振光是分子状态最微妙的研究者”以来，科学家们一直在寻求利用光固有的手性。在平面上偏振的光是左手圆偏振分量和右手圆偏振分量的和。光的圆偏振光的开发是罕见的，但它提供了独特的机会，如生物科学光学袍的发展，在创建新的安全标签/标签功能和在图像对比度的发展，基于偏振光的左和右组分的相对肠。圆偏振发光（CPL）是圆二色性（CD）的发射模拟物，一段时间以来，圆二色性通过左、右手光的微分吸收来检测手性体系。从本质上讲，CPL是一种更灵敏的光学技术，但它还没有真正用于生活或材料科学的应用。在达勒姆，稀土元素铕的非常明亮的化合物最近被创造出来，它不仅是被设计出来的最明亮的红光发射体，而且还以优先手性发射光。使用这些新化合物，可以更快、更容易地检测它们的CPL，同时还开发了新的仪器，可以在光谱学和显微镜下研究它们的CPL行为。该项目将研究如何使用这些明亮的红色发射器来标记或标记文件或印刷标签，从而开辟其在安全应用中用于验证真实身份的可能性。例子可能包括纸币、法律文件、名牌服装的高端品牌标签或官方文件，如护照。此外，新分子将被设计和创造出来，与体内参与磷酸基团转移的各种酶结合。例如，蛋白酪氨酸磷酸酶仅占细胞磷酸化总量的0.05%，但在粘附、细胞周期控制以及细胞生长和分化等关键生物学功能的调控中发挥着关键作用。针对磷酸化酪氨酸位点的抗体通常用于许多实际应用，包括监测酶活性，但它们的使用受到成本高和稳定性差的阻碍。化学探针可以直接可视化这一特定酶活性范围的活性，并且可以用于药物筛选应用，因为这些关键酶的抑制剂对制药部门非常感兴趣。使用铕化合物选择性地与酪氨酸磷酸化的位点相互作用，可以观察到手性CPL特征，识别位点和该位点周围氨基酸的性质。因此，铕化合物可以作为选择性化学探针，通过诱导CPL反应来指示酪氨酸是否被磷酸化以及它在生物分子中的何处被修饰。我们将详细研究这些特性，并评估它们的范围和效用。

Ever since Faraday first declared that 'polarised light was a most delicate investigator of molecular condition', scientists have sought to exploit the intrinsic handedness of light. Light that is polarised in a plane is the sum of left handed and right handed circularly polarised components. The exploitation of the circular polarization of light is rare, yet it offers unique opportunities in areas such as the development of optical robes for the biosciences, in the creation of new security labelling/tagging features and in the development of image contrast, based on the relative intestines of the left and right handed components of polarised light. Circularly polarised luminescence (CPL) is the emission analogue of circular dichroism (CD), that has been used for some time to examine chiral systems by virtue of the differential absorption of left and right handed light. Intrinsically, CPL is a much more sensitive optical technique, but is has not really been used at all in life or material science applications. In Durham very bright compounds of the rare earth element europium have been created recently, that are not only the brightest emitters of red light that have been devised but also emit light with a preferential handedness. Using these new compounds, it is much faster and easier to detect their CPL, and new instrumentation has been developed in tandem, that allows their CPL behaviour to be studied both in spectroscopy and in microscopy. The project will examine how these bright red-emitting emitters of light can be used to tag or label documents or printed labels, thereby opening up the possibility of their use in security applications for validation of true identity. Examples might include bank notes, legal documents, high end branded labels for designer clothing or official documents, such as passports. In addition, new molecules will be designed and created that bind to a wide range of enzymes in the body that are involved in the transfer of a phosphate group. For example, the protein tyrosine phosphatases account for 0.05% of the total phosphorylation in cells, but play a key role in the regulation of critical biological functions, e.g. adhesion, cell cycle control and the ways that cells grow and differentiate. Antibodies specific to phosphorylated tyrosine sites are commonly used for many practical applications, involving monitoring enzyme activity, but their use is hampered by high cost and poor stability. Chemical probes that can directly visualise the activity of this specific range of enzymes activity are required and could be used in drug screening applications, as the inhibitors of these key enzymes are of great interest to the pharmaceutical sector. Using europium compounds that interact selectively with these sites where tyrosine has been phosphorylated, a chiral CPL signature can be observed, that identifies the site and the nature of the amino-acids around that site. Thus the europium compounds can serve as selective chemical probes to signal , by an induce CPL response, whether the tyrosine is phosphorylated and where in the biomolecule it has been modified. These properties will be studied in detail and their scope and utility evaluated.