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CiQUS researchers have developed a biocompatible ruthenium catalyst that enables highly selective reactions to be performed in biological media.
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The new ruthenium catalysts are effective under high diluted conditions and are light-activatable.
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The results of the study have been published in the prestigious journal Angewandte Chemie.
Image: The new ruthenium catalysts are effective under high diluted conditions and are light-activatable | CiQUS
Reference
A. Gutiérrez-González, P. Destito, J.R. Couceiro, C. Pérez-González, F. López, J.L. Mascareñas. Bioorthogonal Azide‐Thioalkyne Cycloadditions Catalyzed by Photoactivatable Ru(II) Complexes. Angew. Chem. Int. Ed., 2021, 60, 16509-16066
The inner life of a cell hides a large number of different molecules reacting specifically and selectively with each other via enzymes. Thousands of selective transformations take place at the same time, precisely regulating each other. In bioorthogonal chemistry, chemical reactions occur inside of living systems without interfering with native biochemical processes. Given the potential of these reactions to intervene in metabolism and develop biomedical applications, the discovery of new bioorthogonal processes is a major challenge in modern chemistry.
In this context, few years ago MetBioCat Group reported a new bioorthogonal reaction promoted by ruthenium catalysts. The reaction worked efficiently with a variety of azides and thiolkynes in presence of biomolecules such as proteins and aminoacids, offering a multitude of potential applications in biological and medicinal chemistry. However, the method developed at that time had to overcome an important limitation: the reaction was no longer effective at high dilutions, an inherent feature of biological environments.
Now, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS) researchers have shown that a mere shift in the structure of the ruthenium catalyst allows these reactions to be performed under high diluted conditions, while improving the previously achieved selectivity and specificity. In addition, this new generation of ruthenium catalysts only work when activated by light. Led by Prof. José Luis Mascareñas and Prof. Fernando López, the team found that new photoactivatable ruthenium compounds are efficient in biologically complex media as cell lysates, and the selective modification of small peptides and DNA strands in vitro.
“With this new generation of catalysts we have also confirmed that the reaction works in the presence of cells” says Alejandro Gutiérrez, first author of the study. “Being able to control the activation of a catalyst by light is of a great interest for future biological applications in order to determine where and when the reaction can occur. One of the long-term goals is to achieve selective photo-activation of the catalyst in specific cells, in certain regions of cells or even in specific areas of a living being (e.g. in a tumour), to generate therapeutic products and/or diagnostic devices” MetBioCat researchers argue. The results of the study have just been published in the prestigious journal Angewandte Chemie.