Multicore Artificial Metalloenzymes Derived from Acylated Proteins as Catalysts for the Enantioselective Dihydroxylation and Epoxidation of Styrene Derivatives

Abstract

Artificial metalloenzymes (AME's) are an interesting class of selective catalysts, where the chiral environment of proteins is used as chiral ligand for a catalytic metal. Commonly, the active site of an enzyme is modified with a catalytically active metal. Here we present an approach, where the commercial proteins lysozyme (LYS) and bovine serum albumin (BSA) can be converted into highly active and enantioselective AME's. This is achieved by acylation of the proteins primary amino groups, which affords the metal salts in the core of the protein. A series of differently acylated LYS and BSA were reacted with K OsO (OH) , RuCl , and Ti(OMe) , respectively, and the conjugates were tested for their catalytic activity in dihydroxylation and epoxidation of styrene and its derivatives. The best suited system for dihydroxylation is fully acetylated LYS conjugated with K OsO (OH) , which converts styrene to 1,2-phenylethanediol with an enantioselectivity of 95 % ee (S). BSA fully acylated with hexanoic acid and conjugated with three moles RuCl per mole protein shows the highest ee values for the conversion of styrene to the respective epoxide with enenatioselectivities of over 80 % ee (R), a TON of more than 2500 and a yield of up to 78 % within 24 h at 40 °C. LYS has two favored selective binding sites for the metal catalyst and BSA has even three. The AME's with titanate in the active center invert the enantioselectivity of styrene epoxidation.

Proteins as diverse, efficient, and evolvable scaffolds for artificial metalloenzymes

“…2A) for ring-opening metathesis polymerisation 19 or metal salts such as K 2 OsO 2 (OH) 4 , RuCl 3 , and Ti(OMe) 4 for dihydroxylation and epoxidation activity. 20 Similarly, lipase has been frequently used for the generation of artificial metalloenzymes. 21,22 It is natively stable 23,24 and commercially available so that covalent anchoring of a palladium pincer catalyst (Fig.…”

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

“…It was reasoned that the observed enantioselectivity was attributable to blocking of the primary amino groups in the protein to prevent non-specific osmium binding. Inspired by this, instead of polymers, N -acetylated (AA), N -propionylated (PA), and N -hexanoylated (HA) lysozyme and BSA were recently prepared as protein scaffolds of the ArM for enantioselective oxidation [ 47 ]. Although these modified proteins are not soluble in organic solvents, they form stable suspensions.…”

“…Selected results of oxidation reactions catalyzed by acylated protein-bearing metal ions in organic solvents[47].…”