Cavity Size Engineering of a β-Barrel Protein Generates Efficient Biohybrid Catalysts for Olefin Metathesis

Abstract

Incorporation of a synthetic metal catalyst into a protein scaffold yields a biohybrid catalyst, with a remarkable performance in aqueous media and the broad reaction scope of organometallic catalysts. A major challenge for efficient catalysis is the design of the interface between the protein scaffold and the metal catalyst. Until now, protein scaffolds have primarily been engineered by exchanging individual amino acids to anchor metal catalysts and alter their immediate environment. Here, cavity size engineering of the β-barrel protein nitrobindin was performed by duplicating multiple β-strands to generate an expanded variant. The approach of cavity size engineering enabled covalent incorporation of bulky catalysts at excellent coupling efficiencies and yielded excellent conversions in olefin metathesis, including ring-closing metathesis, ring-opening metathesis polymerization, and cross metathesis (conversions up to 99% and turnover numbers up to 10000).

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

“…Methods have been developed to enlarge the cavity or to introduce additional structural motifs to improve the protein–metal interaction. In case of NB4, two additional β-sheets were introduced to give a variant comprising 12 β-sheets, denoted expanded NB ( NB4exp ) [ 62 ]. These two additional β-sheets increased the cavity volume from 855 Å 3 to 1399 Å 3 ( Fig.…”

“…These two additional β-sheets increased the cavity volume from 855 Å 3 to 1399 Å 3 ( Fig. 2 ) [ 62 ].…”

“…NB4exp was subjected to conjugation of catalysts Ru-4/5/6 . Indeed, all catalysts underwent covalent anchoring with high conjugational yield (confirmed via ICP–OES and ESIMS) [ 62 ]. Upon catalysis, Ru-5@NB4exp as well as Ru-6@NB4exp showed high activity in the ROMP of norbornene 7 with TONs up to 10,000.…”

“…Upon catalysis, Ru-5@NB4exp as well as Ru-6@NB4exp showed high activity in the ROMP of norbornene 7 with TONs up to 10,000. For the catalyst Ru-4 with the short linker, the activity of Ru-4@NB4exp dropped to TON = 3,000, even though the conjugation was almost quantitative [ 62 ]. However, this “influence” on the activity could not be transferred to the regio- and stereoselectivity of the polymer microstructure.…”

“…Apart from ROMP, the artificial metatheases based on NB4exp were capable of catalyzing both CM and RCM. This makes NB4exp based biohybrid catalysts the first artificial metatheases to catalyze all basic metathesis reactions [ 62 ].…”