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Functional Coordination Chemistry

Final Report Summary - FCC (Functional Coordination Chemistry)

FCC The Functional Coordination Chemistry of well-defined series of lanthanide complexes has been examined. A series of very bright europium coordination complexes was discovered; their brightness exceeds that of red fluorescent protein, as a consequence of their high molar absorptivity in the range 337 to 380 nm and their high quantum yields. The complexes have been structurally modified to allow their use in live cell microscopy and spectral imaging. Certain complexes stain mitochondrial or lysosomal organelles selectively, offering a real alternative to commercial stains, as they resist photobleaching, are addressed using low-power pulsed excitation methods and are non-toxic. Other versions exhibit a pH or pX dependence (X = bicarbonate, lactate or citrate) allowing, for example, the lysosomal or cytoplasmic pH to be monitored in real time in the living cell. The range of probes, dyes and stains has been granted the UK Trademark, 'EuroTracker'.
Proof-of-concept fluorine magnetic resonance imaging in vivo was demonstrated using conjugates of glycol chitosan labelled with paramagnetic lanthanide complexes bearing trifluoromethyl groups. In the course of this work, t-butyl labelled analogous complexes were developed allowing simultaneous proton MR dual imaging of the probe and the water signal. The t-butyl signal was observed selectively, as it could be shifted more than ± 80 ppm from the diamagnetic region where the water and fat signals occur. Using thulium and dysprosium or terbium complexes, temperature measurement in vivo was also undertaken, as the t-butyl shift behaved as a sensitive thermometer. The enhanced sensitivity of the approach, made possible by the 200-fold increase in the relaxation rate of the observed signal, allowed enhanced signal intensity to be acquired per unit time (ca. 25 fold over diamagnetic controls). In this way, the amount of complex that needed to be administered (mouse model studies in collaboration with Newcastle University) was about 0.05 mol/kg, which is less than the does given for Gd-based contrast agents used in clinical practice for contrast enhanced MR imaging. Such work paves the way for triple proton MR imaging : where the water signal and the t-butyl signal of two complexes of a common ligand are simultaneously observed: a proof-of-concept phantom study was carried out in May 2016, validating the approach.
In a third strand of the work, bright chiral europium complexes were resolved using chiral HPLC. Their circularly polarised emission is the brightest ever observed, allowing consideration of their use as reporter probes in complex media or as luminescent chiral tags for security labelling and imprinting. These complexes can be spectrally observed over the 580 to 725 nm range using 5 micromolar solutions within 8 minutes, with with a good signal/noise ratio (>20:1). Furthermore, probes that respond to their local chiral environment have been developed, e.g. responding to the enantiomeric composition of lactate or mandelate solutions, or , generating a unique 'chiral' fingerprint when they bind reversibly and selectively to the phosphate group in certain phosphorylated peptides.