Michael Peter Coogan

Uptake and localisation of rhenium fac-tricarbonyl polypyridyls in fluorescent cell imaging experiments.

The synthesis of a series of rhenium fac tricarbonyl bisimine complexes and their application as lumophores in fluorescence imaging of yeast and human adenocarcinoma cells is reported. A wide range of complexes are synthesised with varying charges and lipophilicities, all of which have photophysical properties which make them suitable as cell imaging agents. After attempts to apply these as imaging agents in various strains of yeast which showed limited uptake, an investigation was undertaken of their applications as imaging agents in mammalian cells. In general the uptake was high and short-term toxicity and photobleaching appear to be low. The patterns of uptake and localisation are correlated with structural and electronic features of the complexes in an attempt to establish ground-rules for the design and application of rhenium complexes in imaging of eukaryotes.

Complexes in context:attempting to control the cellular uptake and localisation of rhenium fac-tricarbonyl polypyridyl complexes

Transition metal lumophores are now well established as agents for cell imaging, but we are still not able to predict generally and with confidence their cellular localisation, or, for that matter, their uptake efficiencies. While many such complexes have been shown to illuminate cells, genuine applications in biomedical research will only be developed when their uptake and localisation are better understood. This perspective is not a comprehensive review of luminescence, but is an overview of attempts to control uptake and localisation, focussing on a personal account of this groups development of imaging agents based on the Re(CO)(3) bipyridine core, and our attempts to understand and control their cellular behaviour.

A Rhenium Tricarbonyl 4′-Oxo-terpy Trimer as a Luminescent Molecular Vessel with a Removable Silver Stopper†

Shining metal cups: A luminescent tube of triangular cross-section and stoppered by a silver ion (see picture: Re yellow, N blue, O red) is formed in two steps from commercial materials. The silver ion can be removed to give a tube, and both species are potential hosts for small ions and molecules; a change in luminescence is triggered by the encapsulation of silver.

Multimodal radio- (PET/SPECT) and fluorescence imaging agents based on metallo-radioisotopes: current applications and prospects for development of new agents

This perspective focuses on complexes of radioactive metal ions applied in multimodal radio- and optical imaging. The application of metal ions in radioimaging techniques such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) has advantages over lighter nuclei in terms of half-life, but there are particular issues related to their speciation (particularly leaching from complexes) and with the combination of certain ions with fluorescent systems. The basic coordination chemistry of the ions involved and issues relating to biological conditions and their compatibility with optical imaging techniques are reviewed, the current literature presented in context, and the prospect of exploiting the intrinsic luminescence of certain metal-ligand complexes is discussed.

Biologically Compatible, Phosphorescent Dimetallic Rhenium Complexes Linked through Functionalized Alkyl Chains: Syntheses, Spectroscopic Properties, and Applications in Imaging Microscopy

A range of luminescent, dimetallic complexes based upon the rhenium fac-tricarbonyl diimine core, linked by aliphatic chains of varying lengths and functionality, have been synthesized and their photophysical properties examined. Each complex displays characteristic (3)M(Re)L(diimine)CT emission in aerated acetonitrile solution, with long lifetimes in the range of 129-248 ns and corresponding quantum yields in the range 3.2-8.0%. In aqueous solution, as opposed to acetonitrile, the complexes generally show a small hypsochromic shift in λ(em) and an extension of the (3)MLCT lifetime, attributed to a hydrophobically driven association of the alkyl chains with the rhenium-bound diimine units. In live cell imaging experiments using MCF7 cells the complexes all show good uptake by non-energy dependent mechanisms without endosomal entrainment, and with varying propensity to localize in organelles. The degrees of uptake and localization properties are discussed in terms of the length and chemical nature of the linkers, and in terms of the likely interactions between these and the various cellular components encountered.

The importance of cellular localisation of probes: synthesis, photophysical properties, DNA interactions and cellular imaging properties of rhenium dppz complexes with known cellular localisation vectors

The synthesis, photophysical properties, DNA binding, DNA cleavage and cellular imaging behaviour of a range of complexes of the type [Re(CO)3(dppz)(PyR)]+ are reported, where PyR represents a range of substituted pyridines which have previously been studied for cellular localisation of related complexes. Confocal imaging experiments confirm that the complexes retain the variety of cellular localisation behaviour associated with the PyR units in other complexes, and suggest applications as probes for oligonucleotides in specific cellular compartments (e.g. mitochondrial DNA). This study illustrates the importance of considering cellular localisation as a prime consideration in the design of probes for in vivo application.

A ‘Sleeping Trojan Horse’ which transports metal ions into cells, localises in nucleoli, and has potential for bimodal fluorescence/PET imaging

A rhenium polypyridine-based molecular vessel is membrane impermeant when empty, but, upon loading with metal ions, the cationic form is taken up by MCF-7 cells, localising in nucleoli. The luminescence of the vessel and its copper binding ability suggest potential as a bimodal fluorescence/PET imaging agent.

Factors influencing the reverse-Cope approach to 1,2,5-oxadiazinanes from allylamines and nitrones: Optimization of a new vicinal diamine synthesis

Abstract Nitrones generated from formaldehyde and N-alkyl-hydroxylamines are particularly suitable reactants in tandem reverse-Cope∼Meisenheimer reactions leading to oxadiazinanes and thence N-hydroxydiamines and vicinal diamines, from allylamines.

Functionalisation of terpyridine complexes containing the Re(CO)3+ moiety

The investigation into the substitution and addition chemistry of Re(sigma(2)-terpy)(CO)(3)Cl shows that the chloride in Re(sigma(2)-terpy)(CO)(3)Cl (1) may be substituted for acetonitrile to give [Re(sigma(2)-terpy)(CO)(3)(CH(3)CN)][PF(6)] (2), but in the cationic complex [Re(sigma(2)-terpyMe)(CO)(3)Cl][PF(6)] (4), where the pendant pyridine has been methylated, substitution of the chloride could not be achieved using standard conditions. However, use of [Re(sigma(2)-terpyMe)(CO)(3)I][PF(6)] (3) results in the formation of [Re(sigma(2)-terpyMe)(CO)(3)(CH(3)CN)][PF(6)](2) (5). The acetonitrile ligand in complex 2 was found to be labile and could be substituted by pyridine donors.

Single amino acid chelate complexes of the M(CO)3+ core for correlating fluorescence and radioimaging studies (M = 99mTc or Re)†

Single amino acid chelates (SAACs) and SAAC-like bifunctional ligands can be exploited in the design of a variety of bioconjugates for facile metallation with the M(CO)3 (+) unit with M = (99m) Tc or Re. When the donor groups of the ligand are quinolone, thiazole or other similarly conjugated heterocycles, the rhenium complexes are fluorescent, affording complementary and isostructural fluorescent probes to the radioactive (99m) Tc analogues. The versatility of the approach has been demonstrated by the preparation of bioconjugates incorporating peptides, biotin, folic acid, thymidine and vitamin B12 . In addition, the unusual photophysical properties observed for rhenium of the [bisthiazole-diamino butane-Re(CO)3 (+) ] derivative [BTBA-Re(CO)3 ](+) are discussed.