Homogeneous and enzymatic catalysis offer complementary means to generate enantiomerically pure compounds. Incorporation of achiral biotinylated rhodium-diphosphine complexes into (strept)avidin yields artificial metalloenzymes for the hydrogenation of N-protected dehydroamino acids. A chemogenetic optimization procedure allows one to produce (R)-acetamidoalanine with 96% enantioselectivity. These hybrid catalysts display features reminiscent both of enzymatic and of homogeneous systems.

We report on the generation of artificial metalloenzymes based on the noncovalent incorporation of biotinylated rhodium-diphosphine complexes in (strept)avidin as host proteins. A chemogenetic optimization procedure allows one to optimize the enantioselectivity for the reduction of acetamidoacrylic acid (up to 96% ee (R) in streptavidin S112G and up to 80% ee (S) in WT avidin). The association constant between a prototypical cationic biotinylated rhodium-diphosphine catalyst precursor and the host proteins was determined at neutral pH: log K(a) = 7.7 for avidin (pI = 10.4) and log K(a) = 7.1 for streptavidin (pI = 6.4). It is shown that the optimal operating conditions for the enantioselective reduction are 5 bar at 30 degrees C with a 1% catalyst loading.

Bundle up: The introduction of streptavidin (as a linker) between two FeII(terpyridine–bis‐biotin) connectors affords a one‐dimensional metal–organic protein framework (MOPF). In the presence of calcium ions and CO2 vapors, these MOPF aggregates form protein bundles that template the biomineralization of calcite.

Dedicated to Professor George M. WhitesidesCatalysis offers efficient means to produce enantiopure products. Traditionally, enzymatic and homogeneous catalysis have evolved independently to afford mild, robust, active, and highly selective catalysts. [1, 2] Both systems are often considered complementary in terms of substrate and reaction scope, operating conditions, enantioselectivity mechanism, reaction medium, etc. For the optimization of activity and selectivity, directed-evolution methodologies (combined with an efficient selection or screening tool) outperform combinatorial ligand libraries. [3][4][5][6][7][8][9][10][11][12][13] With the hope of alleviating some of the inherent limitations of both enzymatic and organometallic catalysis, two approaches have recently witnessed a revival: 1) organocatalysis [14][15][16][17][18][19] and 2) artificial metalloenzymes based on either covalent [20,21] or supramolecular anchoring [22] of a catalytic moiety in a macromolecular host. [23][24][25][26][27][28][29][30] Inspired by the early works of Whitesides and Wilson, [22] we recently reported artificial metalloenzymes based on the biotin-avidin technology. [31][32][33][34][35] Herein, we report our efforts to produce substrate-specific and S-selective artificial metalloenzymes based on the biotin-avidin technology for the hydrogenation of a-acetamidodehydroamino acids.The starting point for the chemogenetic-optimization procedure presented herein is the identification of [Rh(cod)-(biot-1)] + &S112G Sav (cod = 1,5-cyclooctadiene, biot =[*] Dr.

Dedicated to Professor Dieter Seebach on the occasion of his 70th birthdayPalladium-catalyzed CÀC bond-forming reactions play a prominent role in the construction of complex organic molecules. [1][2][3][4] As this versatile precious metal is absent in natural enzymes, nature has devised very different strategies to create C À C bonds for the construction of complex natural products. [5][6][7] The palladium-catalyzed asymmetric allylic alkylation (AAA) is a CÀC bond-forming reaction that has attracted much attention. [4,[8][9][10][11][12][13] In this transformation, the enantiodiscrimination event occurs through the external attack of a soft nucleophile on a palladium-bound h 3 -allyl moiety (Scheme 1 a). [4,12] The AAA thus bears resemblance to enzymatic reactions, in which the substrate(s) need not necessarily bind to the active site of the enzyme for the reaction to proceed with high stereoselectivity. [7] In recent years, there has been increasing interest in the creation of artificial metalloenzymes for enantioselective catalysis. For this purpose, an active-catalyst precursor is anchored in a biomolecule, which provides the chiral environment. [14][15][16][17][18][19][20][21][22][23] The enantioselective reactions implemented thus far include ester hydrolysis, [24] dihydroxylation, [25] epoxidation, [26,27] sulfoxidation, [28][29][30][31][32] hydrogenation, [33][34][35][36][37][38][39][40][41][42][43] transfer hydrogenation, [44,45] and Diels-Alder reactions. [46][47][48][49][50] Inspired by the early studies of Wilson and Whitesides, [33] several research groups [34,35,41] have exploited the biotinavidin technology to ensure the localization of a biotinylated catalytic moiety within (strept)avidin (either avidin or streptavidin). This methodology has allowed the creation of artificial metalloenzymes for enantioselective hydrogenation and transfer-hydrogenation reactions. [33][34][35][36][37][38][39][40][41][42][43][44][45] Herein we describe our efforts to create artificial metalloenzymes for the AAA. We show that a combination of chemical and genetic optimization allows the identification of [Pd(h 3 -allyl)(biotin-spacer-ligand)] + &(strept)avidin catalysts that afford both R and S alkylation products (in up to 90 and 82 % ee, respectively; Scheme 1).With the aim of identifying the most promising chelating ligand, we evaluated five different biotinylated scaffolds in the presence of (strept)avidin (Scheme 2). Little, if any, conversion was detected (Table 1, entry 1): Most of the starting 1,3-diphenylallylacetate was hydrolyzed to the corresponding 1,3-diphenylallyl alcohol. We therefore screened various surfactants that are commonly used in aqueous Scheme 1. The postulated enantiodiscrimination event in the AAA in a) a homogeneous catalytic system and b) an artificial metalloenzyme. The host protein (streptavidin, brown) displays high affinity for the anchor (biotin, green triangle). The introduction of an amino acid spacer (red star) combined with a chelating ligand (purple) allows the chemical optimizat...