Article
Chemistry, Multidisciplinary
Ian Dance
Summary: This study investigates the mechanism of the conversion of N-2 to NH3 catalyzed by nitrogenase. The authors propose a detailed mechanism for the reaction, where D-2 first binds to a Fe atom and then two H atoms transfer synchronously to D-2 to form HD. The HD molecules dissociate sequentially and the flanking H atoms are recovered through proton translocation and electron combination. This mechanism is consistent with experimental observations and provides insights into the catalytic process of nitrogenase.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Raphael Robidas, Claude Y. Legault
Summary: A mechanism is proposed to explain the formation of benzobicyclo[3.2.0]heptane derivatives from 1,7-enyne derivatives bearing a terminal cyclopropane, which has been previously reported.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Alexander G. Sturm, Uhut S. Karaca, Myron Heinz, Thorsten Felder, Kenrick M. Lewis, Norbert Auner, Max C. Holthausen
Summary: In this study, an energetically and environmentally benign synthetic protocol for the highly selective conversion of SiCl4 to HSiCl3 was reported. The protocol utilized organohydridosilanes as recyclable hydrogen transfer reagents and onium chlorides as efficient catalysts. This same protocol was also used for the quantitative conversion of higher oligosilane residues generated from Siemens processes.
Article
Chemistry, Multidisciplinary
C. -C. George Yeh, Christos Pierides, Guy N. L. Jameson, Sam P. de Visser
Summary: Thiol dioxygenases are important enzymes for human health, involved in detoxification and catabolism of toxic thiol-containing natural products. Recent studies show that differences in activity between CDO and MDO are due to variations in ligand coordination, with changes in substrate positioning and enzyme turnover caused by a positively charged Arg residue. The substrate scope of MDO with cysteinate and 2-mercaptosuccinic acid is explored and their reactivity is predicted.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Chieh-Chih George Yeh, Thirakorn Mokkawes, Justin M. Bradley, Nick E. Le Brun, Sam P. de Visser
Summary: Ferritins are widespread diiron enzymes that play a role in iron detoxification and oxidative stress responses, as well as serving as metabolic iron storage. Computational studies have provided insights into the structure and reactivity of ferritins, revealing the importance of the active site tyrosine residue and a potential cation binding site. The findings offer new details on the early mechanistic steps of ferritin enzymes.
Article
Chemistry, Multidisciplinary
Pedro Ferreira, Pedro A. Fernandes, Maria J. Ramos
Summary: Extremophile microorganisms synthesize compatible solutes to protect intracellular proteins, with MG being a common solute that not only protects proteins but also prevents certain diseases. The study investigates the catalytic mechanism of MG synthesis by MGS enzyme from Rhodothermus marinus using computational methods.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Xiaomei Shen, Zhenzhen Wang, Xuejiao J. Gao, Xingfa Gao
Summary: Nanozymes are inorganic nanomaterials with enzyme-like catalytic activities. The research on nanozymes is a hot topic in interdisciplinary science involving materials, chemistry, and biology. DFT calculations have played an increasingly important role in exploring the mechanisms and kinetics of nanozymes by providing atomistic-level insights into the microscopic processes. This review summarizes the research progress and focuses on the computational studies that complement experimental findings and promote the understanding of nanozyme mechanisms and kinetics.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Yi Zhang, Thirakorn Mokkawes, Sam P. de Visser
Summary: DFT calculations reveal a novel mechanism of aromatic defluorination by P450 Compound I, involving either an epoxide intermediate or a 1,2-fluorine shift in an electrophilic intermediate. The presence of a proton donor is crucial, as a strong Fe-F bond can be formed in the absence of one. This study provides insights into the potential application of cytochrome P450 enzymes in biocatalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Amanda L. Kwan, Robert H. Morris
Summary: This article introduces the largest-scale asymmetric catalytic process for the industrial production of (S)-metolachlor, which is achieved through the hydrogenation of N-(2-ethyl-6-methylphenyl)-1-methoxypropan-2-imine. The authors propose a plausible proton-first, outer-sphere mechanism based on density functional theory calculations that explains the reduction of the sterically hindered bond in the imine.
Article
Chemistry, Physical
Die Bai, Man Li, Rong-Zhen Liao
Summary: The merging of transition-metal-catalyzed C-H bond activation with electro-oxidation has become a promising approach for oxidative C-H bond functionalization. However, the specific effects of electro-oxidation on the reaction mechanism of transition-metal catalysis have rarely been studied. In this computational study, the rhodium-catalyzed electrochemical C-H phosphorylation of 2-phenylpyridine by diphenylphosphine oxide was investigated to reveal the mechanistic details. The calculations showed that C-H activation prefers to occur at the Rh(III) state, P-H activation at the Rh(IV) state, and reductive elimination at the Rh(V) state. The mechanistic insights obtained from this study are valuable for understanding transition-metal-catalyzed electro-oxidative C-H bond functionalization.
Article
Chemistry, Multidisciplinary
Yu Cao, Ekaterina Toshcheva, Walid Almaksoud, Rafia Ahmad, Tatsuya Tsumori, Rohit Rai, Ya Tang, Luigi Cavallo, Hiroshi Kageyama, Yoji Kobayashi
Summary: In this study, we demonstrate the robust ammonia synthesis activity of the nitride hydride compound Ca3CrN3H, which activates dinitrogen through active sites where calcium provides the primary coordination environment. DFT calculations indicate that an associative mechanism is favored, unlike the dissociative mechanism found in traditional Ru or Fe catalysts. This work showcases the potential of alkaline earth metal hydride catalysts and other related 1D hydride/electrides for ammonia synthesis.
Article
Chemistry, Multidisciplinary
Yang Wei, Melissa Conklin, Yong Zhang
Summary: Engineered heme protein biocatalysts provide an efficient and sustainable approach for the synthesis of amine-containing compounds through C-H amination. A quantum chemical study reveals that nitrene formation is the rate-determining step in the overall reaction, and the catalyst with a serine ligand exhibits the highest reactivity.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Physical
Ronen Kruchinin, Oswaldo Dieguez
Summary: In this article, density-functional theory calculations are used to study the energetics of CO2 reduction to methane via the Sabatier reaction on sulfur-based transition-metal dichalcogenides (TMDs) with non-, Ni- and Cu-doping. It is found that sulfur-based TMDs with Ni/Cu doping exhibit better indicators for catalytic performance of the CO2 reduction reaction compared to non-doped and doped TMDs without active sites. Furthermore, the role of the chalcogen and dopant atoms in influencing bonding strength and type is found to have a much bigger influence on the reaction than the transition metal.
Article
Chemistry, Physical
Kuiyong Dong, Haifeng Zheng, Yongliang Su, Ahmad Humeidi, Hadi Arman, Xinfang Xu, Michael P. Doyle
Summary: Catalyst-directed access leads to the formation of three different products from the same reactants involving different metals, showcasing the tremendous potential of this approach for diversity-oriented synthesis.
Article
Chemistry, Physical
Margareta R. A. Blomberg, Pia Adelroth
Summary: Based on experimental and computational studies, it is found that the direct coupling mechanism can reduce nitric oxide to nitrous oxide and water without further reduction or protonation. Experiments also show that nitrous oxide can be formed without the presence of flavin cofactors. Density functional theory calculations are used to determine the energy profile of this direct coupling mechanism and it is consistent with experimental data. This study also provides explanations for the entire catalytic cycle of the enzyme.
Article
Biochemical Research Methods
Giulio Tesei, Joao M. Martins, Micha B. A. Kunze, Yong Wang, Ramon Crehuet, Kresten Lindorff-Larsen
Summary: DEER-PREdict is a software program designed to predict distance distributions and relaxation enhancement rates of proteins from ensembles of protein conformations. It efficiently operates on large conformational ensembles, with demonstrated performance and accuracy in experimentally characterized protein systems such as HIV-1 protease and T4 Lysozyme. The open-source program combines molecular modeling and simulations with experiments to provide useful tools for interpreting experimental results and validating molecular models of flexible proteins.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Polymer Science
Agusti Emperador, Ramon Crehuet, Elvira Guardia
Summary: The study found that TIP4P/2005 is the only water model that accurately simulates the fast association/dissociation dynamics of ubiquitin protein and accurately identifies its binding surface, highlighting the critical role of water models in describing protein self-association processes.
Article
Engineering, Chemical
Anera Svarc, Melinda Fekete, Karel Hernandez, Pere Clapes, Zvjezdana Findrik Blazevic, Anna Szekrenyi, Dino Skendrovic, Durda Vasic-Racki, Simon J. Charnock, Ana Vrsalovic Presecki
Summary: A multi-enzyme route for atorvastatin side-chain production was proposed, with detailed studies on the individual reactions and optimization using a mathematical model to improve process metrics. The results showed potential for process improvement through a sequential multienzyme one pot process.
CHEMICAL ENGINEERING SCIENCE
(2021)
Article
Chemistry, Applied
Mathias Pickl, Roser Marin-Valls, Jesus Joglar, Jordi Bujons, Pere Clapes
Summary: This study presents a two-enzyme cascade reaction plus in situ oxidative decarboxylation method for transforming both common and uncommon l-alpha-amino acids into 2-substituted 3-hydroxycarboxylic acid derivatives. The biocatalytic cascade achieved high substrate conversion and enantiomeric excess, with subsequent in situ oxidative decarboxylation leading to the final products.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Physical
Carlos J. Moreno, Karel Hernandez, Simon J. Charnok, Samantha Gittings, Michael Bolte, Jesus Joglar, Jordi Bujons, Teodor Parella, Pere Clapes
Summary: Three enzymatic routes have been reported for the synthesis of gamma-hydroxy-alpha-amino acids through tandem aldol addition-transamination reactions. The resulting chiral molecules can be further transformed into valuable chiral alpha-amino-gamma-butyrolactones, which are important intermediates for pharmaceutical synthesis.
Article
Chemistry, Multidisciplinary
Sandra Bosch, Esther Sanchez-Freire, Maria Luisa del Pozo, Morana Cesnik, Jaime Quesada, Diana M. Mate, Karel Hernandez, Yuyin Qi, Pere Clapes, Durda Vasic-Racki, Zvjezdana Findrik Blazevic, Jose Berenguer, Aurelio Hidalgo
Summary: This study successfully selected thermostable enzyme variants in Thermus thermophilus through an activity-independent method, which can improve enzyme stability and operational stability without changing the kinetic parameters.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Jan-Patrick Steitz, Leonhard Krug, Lydia Walter, Karel Hernandez, Caroline Roehr, Pere Clapes, Michael Mueller
Summary: Thiamine diphosphate (ThDP) dependent enzymes play an important role in asymmetric C-C bond formation through benzoin-type condensation reactions. In this study, a subclass of (myco)bacterial ThDP-dependent enzymes with an extended donor substrate range was identified. The introduction of functionalized alpha-keto acids, accessible by known aldolase-catalyzed transformations, greatly broadens the donor substrate range of ThDP-dependent enzymes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Physical
Virgil Helaine, Cedric Gastaldi, Marielle Lemaire, Pere Clapes, Christine Guerard-Helaine
Summary: Aldolases are powerful enzymes for C-C bond formation in biocatalysis due to their outstanding stereoselectivity, ease of setting up reactions without cofactor recycling, availability of various types and families, and feasibility under mild operating conditions. Recent major discoveries have expanded the scope of both nucleophile and electrophile substrates, leading to significant advancements in the field.
Article
Biology
Nicolai Tidemand Johansen, Marta Bonaccorsi, Tone Bengtsen, Andreas Haahr Larsen, Frederik Gronbaek Tidemand, Martin Cramer Pedersen, Pie Huda, Jens Berndtsson, Tamim Darwish, Nageshewar Rao Yepuri, Anne Martel, Thomas Gunther Pomorski, Andrea Bertarello, Mark Sansom, Mikaela Rapp, Ramon Crehuet, Tobias Schubeis, Kresten Lindorff-Larsen, Guido Pintacuda, Lise Arleth
Summary: This study investigates the conformation and dynamic behavior of the Mg2+ channel CorA using small-angle neutron scattering, molecular dynamics simulations, and solid-state nuclear magnetic resonance spectroscopy. The researchers find that CorA undergoes conformational equilibria between multiple states and that conducting states become more populated in the absence of Mg2+. These findings are crucial for understanding the functional regulation of CorA.
Correction
Multidisciplinary Sciences
Kerry Blair, Muhammad Tehseen, Vlad-Stefan Raducanu, Taha Shahid, Claudia Lancey, Fahad Rashid, Ramon Crehuet, Samir M. Hamdan, Alfredo De Biasio
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kerry Blair, Muhammad Tehseen, Vlad-Stefan Raducanu, Taha Shahid, Claudia Lancey, Fahad Rashid, Ramon Crehuet, Samir M. Hamdan, Alfredo De Biasio
Summary: Using cryo-EM structures and functional assays, we have discovered the mechanism of action of DNA Ligase 1 (Lig1) and the sliding clamp PCNA in lagging strand synthesis. Lig1 recruits PCNA to nicked DNA using specific PCNA-interacting motifs, and facilitates substrate handoff from FEN1 for ligation. Additionally, PCNA forms a defined complex with FEN1 and nicked DNA, and recruits Lig1 for DNA transfer.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Applied
Mathias Pickl, Markus Ebner, Samantha Gittings, Pere Clapes, Wolfgang Kroutil
Summary: Although optical pure amino alcohols are highly demanded, their synthesis remains challenging due to the requirement of elaborate protection strategies. This study presents a multi-enzymatic methodology that allows the synthesis of enantioenriched 1,3-amino alcohols from commodity chemicals. By utilizing a Type I aldolase and enzymatic transamination, both diastereomers of the 1,3-amino alcohol motif were accessible, resulting in the desired amino alcohols with high enantioselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Physical
Carlos J. Moreno, Karel Hernandez, Samantha Gittings, Michael Bolte, Jesu's Joglar, Jordi Bujons, Teodor Parella, Pere Clapes
Summary: This study presents a tandem biocatalytic stereodivergent route for the preparation of chiral 2-hydroxy acids and 2-hydroxy-4-butyrolactone derivatives using simple and achiral starting materials. The strategy involves aldol addition reactions and subsequent reduction reactions, utilizing aldolases and ketoreductases from E. coli, Pseudomonas putida, and Pseudomonas syringae pv. tomato DSM 50315. A total of 29 structurally diverse compounds were synthesized with high enantiomeric excess and isolated yields.
Article
Chemistry, Multidisciplinary
Grayson J. Ford, Christopher R. Swanson, Ruth T. Bradshaw Allen, James R. Marshall, Ashley P. Mattey, Nicholas J. Turner, Pere Clapes, Sabine L. Flitsch
Summary: This study presents a three-component strategy for the stereoselective enzymatic synthesis of amino-diols and amino-polyols. Through biocatalytic aldol reactions and reductive aminations, stereoselective formation of amino-polyols was achieved without the need for intermediates isolation.
Article
Chemistry, Multidisciplinary
Grayson J. Ford, Christopher R. Swanson, Ruth T. Bradshaw Allen, James R. Marshall, Ashley P. Mattey, Nicholas J. Turner, Pere Clapes, Sabine L. Flitsch
Summary: A three-component strategy was developed for the stereoselective enzymatic synthesis of amino-diols and amino-polyols. The strategy utilized a diverse set of prochiral aldehydes, hydroxy ketones, and amines as starting materials, combining biocatalytic aldol reactions and reductive aminations. Stereoselective formation of the desired enantiomers of amino-polyols was observed and confirmed by X-ray crystallography.
