Lanthanide complexes as chiral probes and labels

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.

The project relates to the EPSRC Physical Science capability theme, notably in the direct involvement with synthetic coordination/supramolecular chemistry. Industry in the UK has strategic interests in developing new security tagging/labelling methodology and in promoting new chemical probe applications (e.g. GE-Amersham/ GSK). These companies will be made aware of the scientific advances defined in this work, either via academic channels of conference dissemination and primary publications, or by direct contact, once commercial confidentiality is properly protected. These cases will be handled by the University's Business and Innovations Service: n.b. Durham Chemistry was placed top for Impact in REF 2014, and the PI and Co-I was responsible for one of the 4* case studies.

The PI and co-I will continue to cooperate with research groups around Europe (e.g. PI via participation in the European Society for Molecular Imaging) exchanging information, publicising key advances and organising short-term scientific missions to selected research groups.

Nationally, the background to this project links to the EPSRC Challenge theme, Healthcare Technologies (involving Medical Imaging and Biological Chemistry), creating impact by improved predictive/diagnostic capability through the development of new types of optical probe.

The project also relates to imaging technology that relates to the 'Imaging Technologies in Healthcare', the 'Global Uncertainties' and 'Manufacturing the Future' themes. In the EPSRC 2016 Plan, the UK's connectedness is to be supported by devising "innovative cost effective ways of delivering services ... through transformational technologies that connect people things and data together in safe, smart, secure and ... trustworthy ways".

As a separate advance, the development of portable adapted cameras for use in security tagging could take advantage of differential image contrast associated with the circular polarisation of emission, in tandem with time-resolved detection.
Such a strategy is potentially of general utility and may be applicable to documents, currency, drugs, explosives and labels on high value consumer products. Contact will be made with the North of England based companies, DelaRue and Innovia , once proof-of-concept is established in both tagging and in optimising the instrumentation for rapid assessment.