Final Report Summary - METBIOCAT (Metal catalysis in biological habitats: New strategies for optical bio-sensing and targeted therapy)
The project METBIOCAT aimed at the development of biorthogonal metal-promoted transformations of exogenous substrates in complex biological settings, including living mammalian cells. Key for attaining the proposed objectives is the use of a multidisciplinary approach involving work in organic synthesis, metal catalysis, biomolecular recognition and chemical and cell biology.
After a difficult start, the project is yielding results that confirm the feasibility of many of the proposed hypothesis. Therefore, we have developed a variety of metal-promoted transformations that can take place in the complex environment of a living mammalian cell. These reactions go from simple uncaging processes, to isomerizations, cyclizations, cycloadditions or even carbene additions. Up to now we have made active complexes based on Ru, Pd, Cu and Au transition metals. Playing with ligand design, we can adjust not only reactivity, but also toxicity, cellular uptake and even targeting properties. Therefore, among other developments, we demonstrated that it is possible to perform meta-mediated transformations in the mitochondria of living cells, or achieve simultaneous, mutually orthogonal reactions of different substrates using gold and ruthenium complexes.
We have demonstrated that these complexes can promote a localized transformation of designed exogenous probes into fluorescent products and/or bioactive compounds. More recent work has also demonstrated that it is possible to build designed metal-based nanostructures that can work as efficient heterogeneous reactors inside cells. These systems present a longer time stability than discrete transition metal complexes, something that is especially attractive for potential in vivo applications. We are also obtaining promising results in the preparation of metallo-miniproteins capable of working inside living cells. These are important steps towards the future goal of obtaining artificial metalloenzymes that can work in the same settings than natural metalloenzymes.
After a difficult start, the project is yielding results that confirm the feasibility of many of the proposed hypothesis. Therefore, we have developed a variety of metal-promoted transformations that can take place in the complex environment of a living mammalian cell. These reactions go from simple uncaging processes, to isomerizations, cyclizations, cycloadditions or even carbene additions. Up to now we have made active complexes based on Ru, Pd, Cu and Au transition metals. Playing with ligand design, we can adjust not only reactivity, but also toxicity, cellular uptake and even targeting properties. Therefore, among other developments, we demonstrated that it is possible to perform meta-mediated transformations in the mitochondria of living cells, or achieve simultaneous, mutually orthogonal reactions of different substrates using gold and ruthenium complexes.
We have demonstrated that these complexes can promote a localized transformation of designed exogenous probes into fluorescent products and/or bioactive compounds. More recent work has also demonstrated that it is possible to build designed metal-based nanostructures that can work as efficient heterogeneous reactors inside cells. These systems present a longer time stability than discrete transition metal complexes, something that is especially attractive for potential in vivo applications. We are also obtaining promising results in the preparation of metallo-miniproteins capable of working inside living cells. These are important steps towards the future goal of obtaining artificial metalloenzymes that can work in the same settings than natural metalloenzymes.