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

Abstract

Olefin metathesis catalysts like AquaMet are vulnerable to different decomposition pathways under biologically relevant conditions. Currently, stabilizing strategies are focused on approaches with limited relevance for application under biologically relevant conditions. Initial attempts to stabilise AquaMet by encapsulation within a supramolecular metallocage showed that the nitrate counterions of the cage improve the activity of the catalyst. We show that the chloride ligands of AquaMet can be replaced with nitrates by simple anion‐exchange. Catalytic studies into metathesis of a diallyl substrate showed that the presence of nitrate generates higher yields of the ring‐closed product compared to AquaMet alone, under aqueous and biological conditions. Kinetic studies support that the nitrate‐containing catalyst both initiates faster and performs catalysis at a much faster rate than AquaMet, while the rate of catalyst deactivation was similar. This new strategy of kinetic protection of a transition metal catalyst may have future applications for other catalytic reactions applied in vivo.

Gas Evolution as a Tool to Study Reaction Kinetics Under Biomimetic Conditions

“…The best results were achieved with 2.5 mol % catalyst and 100 mM substrate in the presence of 140 mM NaCl, a salt being naturally present in the cellular environment. With the optimized conditions at hand, the reaction was then performed in a home‐built automated ‘bubble counter’ device [34,35] (See SI for more details; Figure S1) to monitor the volumetric evolution of ethene gas over the course of the reaction (Figure S4) [36] . After reaction completion, the yield of the 2‐butene‐1,4‐diol product was also determined from the same reaction mixture by 1 H NMR spectroscopy using an external standard (See SI for more details; Figure S5, Table S2).…”

“…With the optimized conditions at hand, the reaction was then performed in a home-built automated 'bubble counter' device [34,35] (See SI for more details; Figure S1) to monitor the volumetric evolution of ethene gas over the course of the reaction (Figure S4). [36] After reaction completion, the yield of the 2-butene-1,4-diol product was also determined from the same reaction mixture by 1 H NMR spectroscopy using an external standard (See SI for more details; Figure S5, Table S2). These measurements were done to 1) confirm that one equivalent of ethene is formed alongside one equivalent of product and 2) establish that ethene evolution is a reliable measure for the yield and can therefore be used to obtain kinetic profiles of the model reaction under biomimetic conditions.…”

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

“…Reek et al have recently demonstrated this kinetic protection for a ring-closing metathesis reaction under biological conditions in the lab, where a catalyst with faster reaction rates is able to generate higher amounts of the desired product in the presence of poisonous biomolecules compared to a similar catalyst with much slower reaction rates. [66] Although this strategy works well for this metathesis reaction, in-depth mechanistic insights may be required in order to apply this concept to other reactions.…”

Gas Evolution as a Tool to study Reaction Kinetics under Biomimetic Conditions

“…With the optimized conditions at hand, the reaction was then performed in a home-built automated "bubble counter" device [27], [28] (See SI for more details; Figure S1) to monitor the volumetric evolution of ethene gas over the course of the reaction (Figure S4). [29] After reaction completion, the yield was also determined by 1 H NMR spectroscopy to 1) confirm that one equivalent of ethene is formed alongside one equivalent of product, and 2) establish that ethene evolution is a reliable measure for the yield and can therefore be used to obtain kinetic profiles of the model reaction under biomimetic conditions (Figure S5, Table S2). The reproducibility of this protocol was confirmed by a duplicate experiment that afforded an identical kinetic profile and yield compared to the first reaction.…”