Launching Werner Complexes into the Modern Era of Catalytic Enantioselective Organic Synthesis DOI
Aaron R Wegener, Connor Q. Kabes, John A. Gladysz

et al.

Accounts of Chemical Research, Journal Year: 2020, Volume and Issue: 53(10), P. 2299 - 2313

Published: Sept. 4, 2020

ConspectusReactions catalyzed by transition metal complexes almost always entail binding of one or more reactants to the center, and nearly every corner "chiral pool" has been picked over in efforts develop enantioselective catalysts. As reported Alfred Werner 1911–1912, salts formally D3-symmetric [Co(en)3]3+ trication (en = ethylenediamine) were among first chiral inorganic compounds be resolved into enantiomers. These air- water-stable are substitution-inert, so for 100 years they languished without application organic synthesis. We then showed that when rendered soluble media lipophilic anions such as fluorinated tetraarylborates BArf–, become potent catalysts a variety carbon–carbon carbon–heteroatom bond forming reactions.These involve substrate activation hydrogen bonding coordinated NH2 units (pKa ca. 15), "second coordination sphere" mechanism. Only modest enantioselectivities obtained with 3BArf– related chromium, rhodium, iridium, platinum salts. However, high achieved three en ligands replaced 1,2-diphenyl analogues (S,S)- (R,R)-H2NCHPhCHPhNH2. Here only BArf– anion is required solubilize trication, number mixed-salt (2X–BArf–) have evaluated. Alternatively, dimethylamino group can tethered backbone ligand, providing bifunctional obviate any need an external base. Interestingly, counteranions modulate somewhat. do not significantly outperform benchmark achiral anions. Cagelike hexaaminecobalt(III) known sepulchrates sarcophagines, which feature secondary NH donor atoms, also serve catalysts, but very low.In spinoff application, certain found superb solvating agents", leading distinct sets NMR signals enantiomers analytes Lewis basic functional groups. Loadings 10–25 mol % generally suffice, best way assaying enantiomeric purities host compounds. Also, mixtures several simultaneously analyzed. It surprising perform well recognition phenomena excel catalysts.In this Account, stereochemical properties preceding treated, arcana specialists field. include use charcoal equilibrating configurations cobalt stereocenter Sephadex separating diastereomers. Other types metal-containing hydrogen-bond-donor briefly surveyed (noncoordinating effective), including developed other mechanisms enantioselection all these transformations remain obscure. The optimum diastereomer set varies from reaction reaction, suggesting "phenotypic plasticity" allows adaption processes.

Language: Английский

The importance of catalytic promiscuity for enzyme design and evolution DOI
Reuben B. Leveson‐Gower, Clemens Mayer, Gérard Roelfes

et al.

Nature Reviews Chemistry, Journal Year: 2019, Volume and Issue: 3(12), P. 687 - 705

Published: Nov. 15, 2019

Language: Английский

Citations

267
Artificial Metalloenzymes: Challenges and Opportunities DOI Creative Commons
Holly J. Davis, Thomas R. Ward

ACS Central Science, Journal Year: 2019, Volume and Issue: 5(7), P. 1120 - 1136

Published: July 16, 2019

Artificial metalloenzymes (ArMs) result from the incorporation of an abiotic metal cofactor within a protein scaffold. From earliest techniques transition metals adsorbed on silk fibers, field ArMs has expanded dramatically over past 60 years to encompass range reaction classes and inspired approaches: Assembly taken multiple forms with both covalent supramolecular anchoring strategies, while scaffolds have been intuitively selected evolved, repurposed, or designed in silico. Herein, we discuss some most prominent recent examples highlight challenges opportunities presented by field.

Language: Английский

Citations

235
Advances in ultrahigh-throughput screening for directed enzyme evolution DOI
Ulrich Markel, Khalil Essani,

Volkan Besirlioglu

et al.

Chemical Society Reviews, Journal Year: 2019, Volume and Issue: 49(1), P. 233 - 262

Published: Dec. 9, 2019

This review summarizes how ultrahigh-throughput screening methods employ cells and biomimetic compartments to access the vast, unexplored diversity of biocatalysts with novel functions derived from directed evolution metagenomics libraries.

Language: Английский

Citations

222
A guide to secondary coordination sphere editing DOI
Marcus W. Drover

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(6), P. 1861 - 1880

Published: Jan. 1, 2022

This tutorial review showcases recent (2015-2021) work describing ligand construction as it relates to the design of secondary coordination spheres (SCSs). Metalloenzymes, for example, utilize SCSs stabilize reactive substrates, shuttle small molecules, and alter redox properties, promoting functional activity. In realm biomimetic chemistry, specific incorporation SCS residues (e.g., Brønsted or Lewis acid/bases, crown ethers, groups etc.) has been shown be equally critical function. contribution illustrates how fundamental advances in organic inorganic chemistry have used such SCSs. These imaginative contributions driven exciting findings many transformations relevant clean fuel generation, including molecule H+, N2, CO2, NOx, O2) reduction. most cases, these reactions occur cooperatively, where both metal are requisite substrate activation.

Language: Английский

Citations

90
Can Machine Learning Revolutionize Directed Evolution of Selective Enzymes? DOI Open Access
Guangyue Li, Yijie Dong, Manfred T. Reetz

et al.

Advanced Synthesis & Catalysis, Journal Year: 2019, Volume and Issue: 361(11), P. 2377 - 2386

Published: March 20, 2019

Abstract Machine learning as a form of artificial intelligence consists algorithms and statistical models for improving computer performance different tasks. Training data are utilized making decisions predictions. Since directed evolution enzymes produces huge amounts potential training data, machine seems to be ideally suited support this protein engineering technique. has been used in science long time with purposes. This mini‐review focuses on the utility an aid selective enzymes. Recent studies have shown that ASRA Innov'SAR well guides when performing saturation mutagenesis at sites lining binding pocket enhancing stereoselectivity activity. magnified image

Language: Английский

Citations

113
Recent Advances in Biocatalysis with Chemical Modification and Expanded Amino Acid Alphabet DOI
Amol D. Pagar, Mahesh D. Patil, Dillon T. Flood

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(10), P. 6173 - 6245

Published: April 22, 2021

The two main strategies for enzyme engineering, directed evolution and rational design, have found widespread applications in improving the intrinsic activities of proteins. Although numerous advances been achieved using these ground-breaking methods, limited chemical diversity biopolymers, restricted to 20 canonical amino acids, hampers creation novel enzymes that Nature has never made thus far. To address this, much research devoted expanding protein sequence space via modifications and/or incorporation noncanonical acids (ncAAs). This review provides a balanced discussion critical evaluation applications, recent advances, technical breakthroughs biocatalysis three approaches: (i) modification cAAs, (ii) ncAAs, (iii) incorporated ncAAs. Furthermore, approaches result on functional properties mechanistic study are extensively reviewed. We also discuss design artificial with ncAAs incorporated. Finally, we current challenges future perspectives expanded acid alphabet.

Language: Английский

Citations

94
Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies DOI
Guangfan Zheng, Zhi Zhou, Guoxun Zhu

et al.

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(7), P. 2890 - 2896

Published: Dec. 9, 2019

Cyclopropane rings are a prominent structural motif in biologically active molecules. Enantio- and diastereoselective construction of cyclopropanes through C-H activation arenes coupling with readily available cyclopropenes is highly appealing but remains challenge. A dual directing-group-assisted strategy was used to realize mild redox-neutral RhIII -catalyzed cyclopropylation N-phenoxylsulfonamides enantioselective, diastereoselective, regioselective fashion cyclopropenyl secondary alcohols as cyclopropylating reagent. Synthetic applications demonstrated highlight the potential developed method. Integrated experimental computational mechanistic studies revealed that reaction proceeds via RhV nitrenoid intermediate, Noyori-type outer sphere concerted proton-hydride transfer from alcohol Rh=N bond produces observed trans selectivity.

Language: Английский

Citations

88
De novo metalloprotein design DOI
Matthew J. Chalkley, Samuel I. Mann, William F. DeGrado

et al.

Nature Reviews Chemistry, Journal Year: 2021, Volume and Issue: 6(1), P. 31 - 50

Published: Dec. 6, 2021

Language: Английский

Citations

84
Engineering and emerging applications of artificial metalloenzymes with whole cells DOI

Malte Wittwer,

Ulrich Markel, Johannes Schiffels

et al.

Nature Catalysis, Journal Year: 2021, Volume and Issue: 4(10), P. 814 - 827

Published: Oct. 20, 2021

Language: Английский

Citations

58
Revealing the Nature of the Second Branch Point in the Catalytic Mechanism of the Fe(II)/2OG-Dependent Ethylene Forming Enzyme DOI Creative Commons
Simahudeen Bathir Jaber Sathik Rifayee, Midhun George Thomas, Christo Christov

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The study explores the second branchpoint of EFE catalytic mechanism, which determines product distribution ethylene and 3-hydroxypropionate formation using QM/MM simulations on WT A198L variants EFE.

Language: Английский

Citations

1