Review
Biochemistry & Molecular Biology
Brigitta Elsaesser, Peter Goettig
Summary: Experimental evidence for enzymatic mechanisms is often limited and biased by the methods used. Despite apparent contradictions, opposing views often turn out to be special cases of a more comprehensive and superior concept.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Organic
Jesus de Maria Perez, Mateo Alajarin, Alberto Martinez-Cuezva, Jose Berna
Summary: The catalytic activity of degenerate succinamide-based [2]rotaxanes can be modulated by changes at their macrocyclic component. The variation in catalytic efficiency is correlated with the electronics and dynamics of the entwined macrocycle.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Meixia He, Jean-Marie Lehn
Summary: Optimizing C=N bond formation and C/N component exchange is crucial in Dynamic Covalent Chemistry (DCC). The synergistic effect achieved by combining metallo- and organo-catalysis leads to a powerful co-catalysis strategy for bond formation in DCC through interconnected chemical transformations, showing true catalytic effects. The presence of metal salts and auxiliary amines accelerates reaction rates and turnover, indicating marked rate accelerations and turnover through true catalysis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Ge-Yun You, Xiao-Feng Liu, Pei-Wen Fang, Lu-Fang Liang, Cheng-Hao Dai, Bin Feng
Summary: A study on the activity of chiral sulfinyl imine-thioether ligands in Pd-catalyzed asymmetric allylic alkylation reaction reveals the significant effect of the structure of sulfinamide motifs on the reaction yield and enantiomeric excess.
Review
Chemistry, Inorganic & Nuclear
Zeyneb Kaya, Embarek Bentouhami, Katrin Pelzer, Dominique Armspach
Summary: Cavity-shaped ligands can act as containers for metal centers, influencing the coordination sphere of metals, particularly in asymmetric metal catalysis. The spatial control around the coordinated substrate is crucial for achieving high ee values in asymmetric metal-catalyzed reactions. Various approaches, both covalent and supramolecular, have been used to achieve enantiodiscrimination in these reactions by metal complexation within or near chiral capsular environments.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Biochemical Research Methods
Ningning Zhang, Changzhu Wu
Summary: This study proposes an advanced artificial enzyme by polymeric modularity as an efficient aldolase mimic for aqueous asymmetric aldol reactions. The tailored conjugates exhibited remarkable catalytic performance and excellent selectivity. Additionally, the artificial enzyme showed high tolerance and reusability.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Rajiv K. Kar
Summary: Hybrid quantum mechanics/molecular mechanics (QM/MM) is one of the most reliable approaches for accurately modeling and studying the complex pharmaceutical discovery system. Classical mechanics has significantly accelerated the drug discovery process in the past decade. However, the current challenge is the large pool of false positives, which require extensive validation. Hybrid QM/MM is an effective solution for accurately studying ligand binding, structural mechanisms, free energy evaluation, and spectroscopic characterization. This article highlights the methodological details relevant to cost-effective hybrid QM/MM methods. This approach, combined with traditional pharmacoinformatics methods, could be a reliable strategy to balance the cost and accuracy of the calculations.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Physical
Kemiao Hong, Jirong Shu, Shanliang Dong, Zhijing Zhang, Yicheng He, Mengting Liu, Jingjing Huang, Wenhao Hu, Xinfang Xu
Summary: An achiral dirhodium complex and chiral phosphoric acid cooperatively catalyze the asymmetric three-component reaction of enynal with alcohol and imine, resulting in the formation of chiral alpha-furyl-beta-amino carboxylates with good to high yields and excellent stereoselectivity. This method efficiently prepares complex furan derivatives with adjacent quaternary and tertiary stereocenters.
Article
Chemistry, Multidisciplinary
Tino P. Golub, Malte Fessner, Elric Engelage, Christian Merten
Summary: In this study, the dynamic stereochemistry of a biphenyl-2,2'-bis(proline amide) catalyst in weakly and strongly hydrogen bonding solvents was characterized. The preferred axial stereochemistry of the catalyst was found to be determined by solute-solvent interactions, with explicit consideration of solvation with DMSO molecules being essential for accurate prediction. The study also investigated the stereochemistry of the enamines and imidazolidinones formed in the reaction, demonstrating that the VCD spectra analysis can directly deduce the stereochemistry without the need for further detailed analysis of NMR spectra. This study highlights the use of VCD spectroscopy for in situ characterization of intermediates in asymmetric catalysts.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Yunliang Yu, Nazarii Sabat, Meriem Daghmoum, Zhenhao Zhang, Pascal Retailleau, Gilles Frison, Angela Marinetti, Xavier Guinchard
Summary: Enantioselective tandem cycloisomerization/addition reactions of 2-alkynyl enones with 1- and 2-naphthols were investigated using gold(I) catalysts featuring hybrid phosphine-phosphoric acid chiral ligands, based on the tethered counterion-directed catalysis strategy. The reactions proceeded at low catalyst loading (0.2-1 mol%) without the need for silver additives, and the naphthols acted as both O- and C-nucleophiles, resulting in the formation of addition products with high enantioselectivity. The mechanism of these reactions was elucidated by DFT calculations.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Dan-Ni Yan, Li-Xuan Cai, Pei-Ming Cheng, Shao-Jun Hu, Li-Peng Zhou, Qing-Fu Sun
Summary: The adaptive molecular capsule with structural changes upon substrate binding allows for efficient photocatalysis, paving the way for artificial systems mimicking enzyme catalysis. The capsule undergoes quantitative transformation when substrates bind to its hydrophobic cavity, facilitating aerobic photooxidation for the sulfide guests under mild conditions. Through the transformable nature of the catalyst and the hydrophilicity of the sulfoxide product, desired turnover numbers and product selectivity have been achieved.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Mengyao Tang, Huanchao Gu, Shunlong He, Subramani Rajkumar, Xiaoyu Yang
Summary: An efficient protocol for kinetic resolution of tertiary alcohols has been developed via unprecedented asymmetric enamide-imine tautomerism process enabled by chiral phosphoric acid catalysis. This method is particularly effective for a series of 1,1-dialkyl substituted allyl alcohols, producing chiral tertiary alcohols that are difficult to access through other asymmetric methods. Facile and versatile transformations of the chiral products demonstrate the value of this kinetic resolution method.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Medicinal
Fan Zhang, Tao Zeng, Ruibo Wu
Summary: Natural products and their derivatives are widely used in various industries, especially pharmaceuticals. Modern engineered biosynthesis offers an alternative approach for producing diverse natural products. However, natural enzymes often exhibit unsatisfactory catalytic characteristics and require further enzyme engineering modifications. QM/MM, a computational tool extensively used in enzyme catalysis, has been increasingly applied in rational enzyme engineering for natural product biosynthesis. This review summarizes recent advances in QM/MM computational investigation on enzyme catalysis and enzyme engineering and discusses the challenges and perspectives for future QM/MM-assisted enzyme engineering in natural product biosynthesis.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Chemistry, Physical
Kai Wu, Junhai Huang, Lei Shao
Summary: The synthesis of chiral amines is important in the pharmaceutical industry. IRED, a promising biocatalyst, has been found to catalyze direct asymmetric reductive amination and conjugate reduction, producing valuable amine diastereomers. This review provides insights into the catalytic mechanisms of IREDs and highlights their potential for industrial applications.
Article
Chemistry, Multidisciplinary
Tai-Ping Zhou, Wen-Hao Deng, Yuzhou Wu, Rong-Zhen Liao
Summary: This study investigated the reaction mechanism of the nonheme diiron toluene/o-xylene monooxygenase (ToMO) through calculations. The findings suggest that the peroxodiferric species plays a crucial role as the reactive intermediate, and the formation of the phenol product is facile. The first step of the ortho-hydroxylation reaction was determined to be rate-limiting.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Guillermo Marcos-Ayuso, Agusti Lledos, Juan A. Casares
Summary: Experimental studies and calculations show that the oxidative addition of aryl halides to copper complexes follows different paths depending on the nature of the halogen. For bromine, a concerted addition leads to the formation of a C-C coupled product, while for iodine, a different complex is formed and an elimination reaction occurs.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Jose-Emilio Sanchez-Aparicio, Giuseppe Sciortino, Eric Mates-Torres, Agusti Lledos, Jean-Didier Marechal
Summary: This study explores the challenges and solutions in molecular modelling applications in metalloenzyme design. By incorporating new tools in multiscale strategies, particularly substrate diffusion exploration, a deeper understanding of metal-mediated binding and catalytic geometry can be achieved. Using various variants of an artificial Rh-2-based cyclopropanase as examples, DFT calculations and molecular dockings reveal the catalytic mechanisms controlled by the protein.
FARADAY DISCUSSIONS
(2022)
Article
Chemistry, Applied
Gantulga Norjmaa, Gregori Ujaque, Agusti Lledos
Summary: The use of solvent effects in computational modeling of homogeneous catalysis is essential for capturing accurate mechanistic details. While continuum solvent models are commonly used, explicit solvent models are often necessary to provide a more detailed and accurate representation, leading to improved mechanistic understanding of reactions. Through selected examples, this article highlights the limitations of continuum solvent models and the benefits of incorporating explicit solvent molecules in quantum mechanical descriptions.
TOPICS IN CATALYSIS
(2022)
Review
Chemistry, Multidisciplinary
Mirjam R. Schreier, Xingwei Guo, Bjorn Pfund, Yasunori Okamoto, Thomas R. Ward, Christoph Kerzig, Oliver S. Wenger
Summary: Cyclometalated iridium(III) complexes are widely used in organic light emitting diodes and photocatalysis for solar energy conversion and synthetic organic chemistry. This article introduces the development of water-soluble variants of these complexes and explores their applications in aqueous photochemistry. The water-soluble complexes have been used in enzyme-catalyzed photoredox reactions, photoionization to yield hydrated electrons, and photochemical upconversion. However, the development of water-soluble photocatalysts still lags behind organic solvents.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Inorganic & Nuclear
Alina Stein, Alexandria Deliz Liang, Reyhan Sahin, Thomas R. Ward
Summary: The potential of artificial metalloenzymes has increased interest in the design of novel metal-binding sites in proteins. Metal-chelating unnatural amino acids provide a promising solution for engineering active metal sites in a defined way. In this study, four metal-chelating unnatural amino acids were introduced into HaloTag, an attractive scaffold for assembling functional artificial metalloenzymes. By complementation with [(eta(5)-C5H5)Ru(MeCN)(3)](+), HaloTag engineered with 2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid (HQ-Ala-1) was used to assemble an artificial metalloenzyme for improved allylic deamination.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2022)
Correction
Chemistry, Physical
Fadri Christoffel, Nico V. Igareta, Michela M. Pellizzoni, Laura Tiessler-Sala, Boris Lozhkin, Daniel C. Spiess, Agusti Lledos, Jean-Didier Marechal, Ryan L. Peterson, Thomas R. Ward
Article
Biochemistry & Molecular Biology
Agnieszka Krzeminska, Jose-Emilio Sanchez-Aparicio, Jean-Didier Marechal, Agata Paneth, Piotr Paneth
Summary: Disaccharide complexes have shown promise as drug encapsulation and delivery candidates, with strong non-covalent stabilization through electrostatic interactions and hydrogen bonds. They are also biocompatible and biodegradable, making them excellent candidates for self-assembly smart materials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Corentin Rumo, Alina Stein, Juliane Klehr, Ryo Tachibana, Alessandro Prescimone, Daniel Haussinger, Thomas R. Ward
Summary: The selective functionalization of organic compounds is a versatile tool, and artificial metalloenzymes offer an ideal means to modify inert motifs. In this study, quantum mechanics/molecular mechanics simulations were used to identify target residues for genetic optimization of the artificial metalloenzyme. Double-saturation mutagenesis provided detailed insight on the activity and selectivity, leading to the development of artificial metalloenzymes that efficiently catalyze the formation of β- and γ-lactams.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Jaicy Vallapurackal, Ariane Stucki, Alexandria Deliz Liang, Juliane Klehr, Petra S. Dittrich, Thomas R. Ward
Summary: Droplet microfluidics has great potential for ultrahigh-throughput compartmentalization, making it an attractive tool for directed enzyme evolution. In this study, we developed an approach for ultrahigh-throughput screening of an artificial metalloenzyme using commercially available fluorescence-activated cell sorters. The protocol was validated by screening a large library and the results showed good agreement with a traditional screening method. This finding opens up new possibilities for the directed evolution of enzymes using FACS.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Laura Tiessler-Sala, Giuseppe Sciortino, Lur Alonso-Cotchico, Laura Masgrau, Agusti Lledos, Jean-Didier Marechal
Summary: In this study, computational techniques were used to investigate and compare the mechanisms of two heme-binding systems. The results revealed different heme-binding mechanisms between the two systems, with one system having similar conformational spaces in the absence and presence of heme, while the other system only exhibited similar conformations to the holo form when heme was bound. This study highlights the diversity of molecular mechanisms of heme-binding.
INORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Sukanya Luang, Xavier Fernandez-Luengo, Alba Nin-Hill, Victor A. Streltsov, Julian G. Schwerdt, Santiago Alonso-Gil, James R. Ketudat Cairns, Stephanie Pradeau, Sebastien Fort, Jean-Didier Marechal, Laura Masgrau, Carme Rovira, Maria Hrmova
Summary: In this study, the researchers investigate the binding and conformational behavior of beta-D-glucosides in the barley beta-D-glucan glucohydrolase. They find that the Trp286/Trp434 clamp plays a crucial role in substrate hydrolysis. Mutations in the clamp affect processive catalysis, and phylogenomic analysis reveals the evolutionary advantage of the tryptophan clamp.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Merce Alemany-Chavarria, Jaime Rodriguez-Guerra, Jean-Didier Marechal
Summary: TALAIA is a tool for visualizing protein structures that uses a simplified visual grammar to represent the structure and physicochemical aspects of amino acids. It allows users to quickly identify key molecular information and structural features.
Article
Chemistry, Physical
Nico V. Igareta, Ryo Tachibana, Daniel C. Spiess, Ryan L. Peterson, Thomas R. Ward
Summary: By anchoring a metal cofactor within a host protein, artificial metalloenzymes can be created that combine the versatility of transition metals with the power of genetic engineering. In this study, a hydrophobic dimerization domain from superoxide dismutase C was engineered onto a streptavidin host-protein to improve second coordination-sphere interactions. The introduction of the dimerization domain resulted in an inversion of configuration and a fivefold increase in catalytic efficiency of the asymmetric transfer hydrogenase.
FARADAY DISCUSSIONS
(2023)