Orthogonal metal catalysis in biological systems

  1. Alejandro Gutiérrez González
Dirigida por:
  1. José Luis Mascareñas Cid Director
  2. Fernando José López García Director

Universidad de defensa: Universidade de Santiago de Compostela

Fecha de defensa: 30 de marzo de 2023

Tribunal:
  1. Carlos Saa Rodríguez Presidente
  2. David Díaz Díaz Secretario/a
  3. Angela Casini Vocal
Departamento:
  1. Departamento de Química Orgánica

Tipo: Tesis

Resumen

Over the past two decades, the development of bioorthogonal chemistry has revolutionized the chemical tools available for cell research. In this thesis, we have developed novel ruthenium complexes that enable ruthenium-catalyzed azide-thioalkyne cycloadditions to occur under highly efficient micromolar conditions, even in the presence of cells. Moreover, we have successfully translated rutheniumcatalyzed alkene-alkyne coupling into aqueous and bioorthogonal conditions, enabling the modification of peptides to occur efficiently under micromolar conditions. Furthermore, we have engineered a new ruthenium isomerization reaction that can take place inside living mammalian cells, which can be used to effectively deplete the natural cell levels of GSH. Finally, we have demonstrated that discrete organometallic catalysts can be used in combination with natural enzymes to create a primitive artificial metabolic network, even inside living cells.