Lanthanide complexes as chiral probes and labels

自从法拉第第一次宣布“偏振光是研究分子状态的最精细的研究者”以来，科学家们就一直试图利用光的内在利手性。在平面上偏振的光是左旋和右旋圆偏振分量的总和。对光的圆偏振的利用是罕见的，但它在以下领域提供了独特的机会：为生物科学开发光学长袍，创建新的安全标签/标记特征，以及根据偏振光的左手和右手分量的相对肠部开发图像对比度。圆偏振发光(CPL)是圆二向色性(CD)的发射模拟，利用左右手光差分吸收来研究手性体系已经有一段时间了。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命或材料科学的应用中。在达勒姆，最近已经产生了稀土元素Eu的非常明亮的化合物，它们不仅是已经设计出来的最明亮的红光发射器，而且还优先使用左手发光。使用这些新化合物，可以更快、更容易地检测它们的CPL，并且已经相继开发了新的仪器，使得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光体来标记或标记文件或打印的标签，从而为它们在安全应用中用于验证真实身份开辟了可能性。例子可能包括钞票、法律文件、设计师服装的高端品牌标签或护照等官方文件。此外，还将设计和创造新的分子，这些分子与体内参与磷酸转移的各种酶结合。例如，蛋白质酪氨酸磷酸酶占细胞总磷酸化的0.05%，但在调节关键生物功能，如黏附、细胞周期控制和细胞生长分化方式中发挥关键作用。针对磷酸化酪氨酸位点的抗体通常用于许多实际应用，涉及监测酶活性，但其使用受到成本高和稳定性差的阻碍。需要能够直接显示这一特定酶活性范围的化学探针，并可用于药物筛选应用，因为这些关键酶的抑制剂对制药部门非常感兴趣。使用选择性地与这些酪氨酸被磷酸化的位置相互作用的铕化合物，可以观察到手性CPL特征，它识别该位置和该位置周围的氨基酸的性质。因此，铕化合物可以作为选择性的化学探针，通过诱导CPL反应来通知酪氨酸是否被磷酸化，以及它在生物分子中的哪里被修饰。将对这些特性进行详细研究，并对其范围和用途进行评估。

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.