Transition metal-catalyzed reactions are widely used for carbon–carbon bond formation in chemical synthesis, owing to their efficiency and reliability. However, the catalysts are often sensitive to moisture or oxygen so adapting transition metal-catalyzed reactions to work in living organisms has proven difficult, which limits their use for in situ synthesis. Synthesis of non-endogenous chemicals at the site of use (such as synthesis of a drug inside a tumor) offers opportunities to control targeting and limit systemic toxicity. However, although transition metal-catalyzed reactions have been demonstrated in animals, and ruthenium-based catalysts have been used for reactions in blood serum, whole blood is a complex medium and such reactions are typically very inefficient and require high catalyst loadings.
Now, Nasibullin et al. have reported an albumin-based artificial metalloenzyme (ArM) containing ruthenium that can catalyze olefin metathesis (a reaction that forms carbon–carbon bonds from alkenes) in whole blood. The catalyst, known as AlbRu–I, is anchored into a hydrophobic binding pocket of human serum albumin. AlbRu–I works with a low loading (1–5 mol%) and retained its activity after soaking in blood for 24 h. To showcase the substrate scope and versatility the team synthesized a range of molecular scaffolds via ring-closing metathesis; sequential ring-closing metathesis and aromatization; and olefin cross metathesis. Collectively, these results showed the potential of AlbRu–I for the synthesis of carbocyclic molecules in blood.
This is a preview of subscription content, access via your institution