Protection of a Gold Catalyst by a Supramolecular Cage Improves Bioorthogonality

Abstract

Gold catalysts exhibit poor compatibility with cellular components. We show that encapsulation of a gold catalyst within the cavity of a supramolecular cage improves the reactivity of the gold complex under biological conditions. The gold complex catalyzes an intramolecular hydroarylation to produce a fluorescent dye. The encapsulated gold is able to produce this dye in higher yields compared to the free gold under aqueous aerobic conditions and in the presence of biological additives.The substrate was found to be highly cytotoxic, meaning that a very low substrate concentration of 1 μM is required to carry its transformation inside living cells; however, catalysis in cell culture media carried out at micromolar range is found to be inhibited. Although this specific reaction cannot be applied inside living cells, we present a viable strategy to improve the reactivity of gold catalysts in vivo.

Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular Solutions

“…While the reaction catalysed by the free gold complex was completely inhibited by the presence of biological additives, the reaction proceeded when the gold complex was encapsulated within the protective cavity of the cage, leading to formation of a fluorescent amino coumarin product, albeit in lower yields than the reaction in the absence of biological additives. The cage was shown to be impermeable to the cell membrane, so evaluation of the reaction inside cells was not possible [76] . Therefore it is still unknown if this strategy will also aid other catalysts for other reactions in cells.…”

“…The cage was shown to be impermeable to the cell membrane, so evaluation of the reaction inside cells was not possible. [76] Therefore it is still unknown if this strategy will also aid other catalysts for other reactions in cells. (a) Ga 4 L 6 tetrahedral cage encapsulates small cationic catalysts for: size-selective rhodium catalysed isomerisation of allyl alcohols and ethers; [72b] tandem enzyme catalysis-gold catalysed allene hydroalkoxylation; [73a,c] and tandem ruthenium catalysed allyl alcohol isomerisationenzyme catalysis.…”

Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular Solutions

“…The cage was shown to be impermeable to the cell membrane, so evaluation of the reaction inside cells was not possible. [76] Therefore it is still unknown if this strategy will also aid other catalysts for other reactions in cells.…”

Kinetic Protection of a Water‐Soluble Olefin Metathesis Catalyst for Potential Use under Biological Conditions

“…To the best of our knowledge, an olefin metathesis catalyst has never been protected from an aqueous environment by encapsulation within a water‐soluble supramolecular host. In addition, water‐soluble supramolecular cages are also known to provide protection from biomolecules under biological conditions, by providing a protective barrier between the catalyst and the biomolecules and reducing their interaction with the metal centre [24] . We therefore looked to design an alternative strategy to protect an olefin metathesis catalyst from both water‐induced decomposition and from biomolecule poisoning using a water‐soluble supramolecular cage, in order to improve its reactivity under biological conditions.…”