Article
Chemistry, Multidisciplinary
Enzo Olivieri, Na Shao, Roselyne Rosas, Jean-Valere Naubron, Adrien Quintard
Summary: In this study, we have developed a rotating molecular switch based on metal-catalyzed reversible (de)hydrogenation. This switch can switch between alcohol and ketone through reversible (de)hydrogenation reactions. The absence of waste accumulation in this chemical-stimuli-driven switch is of great significance and has potential applications in the design of efficient complex molecular machines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Nanoscience & Nanotechnology
Hongwei Wu, Glib Baryshnikov, Artem Kuklin, Boris F. Minaev, Bin Wu, Long Gu, Liangliang Zhu, Hans Agren, Yanli Zhao
Summary: Enhancing phosphorescence efficiency can be achieved by modifying molecular conformation and crystal growth conditions, with symmetric 3,3 conformers showing higher efficiency compared to unsymmetrical 2,4 conformers. The crystal protection effect and conformation impact play crucial roles in the phosphorescence performance of the molecules.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Multidisciplinary
Maria Drosou, Georgia Zahariou, Dimitrios A. Pantazis
Summary: The study reveals that the tetramanganese-calcium cluster of the oxygen-evolving complex in photosystem II adopts orientational Jahn-Teller isomeric forms in the resting state, which explains previous spectroscopic observations and establishes the functional role of this isomerism in the catalytic process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Ahmed M. Rozza, Marcell Papp, Neil R. McFarlane, Jeremy N. Harvey, Julianna Olah
Summary: This study used a combination of theoretical tools to investigate various aspects of NO binding and reaction intermediates. The results suggest that NO binding leads to conformational changes in the protein.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Soohyung Kim, Ha Young Jeong, Seonghan Kim, Hongsik Kim, Sojeong Lee, Jaeheung Cho, Cheal Kim, Dongwhan Lee
Summary: High-valent metal-oxo species play a crucial role in oxygen atom transfer in the catalytic cycles of metalloenzymes. A newly synthesized nickel(II) complex with an amido multidentate ligand demonstrates the feasibility of using peptide backbones as strong electron-donating ligands to stabilize high oxidation states. Protonation in the secondary coordination sphere serves as the entry point to the catalytic cycle, leading to the formation of high-valent nickel species for oxo-transfer reactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Inorganic & Nuclear
Adam N. Barrett, Callum R. Woof, Christopher A. Goult, Danila Gasperini, Mary F. Mahon, Ruth L. Webster
Summary: The hydrogen/halogen exchange of phosphines has been utilized to establish a method for the synthesis of cyclopolyphosphines. The use of catalytic quantities of iron(III) acetylacetonate significantly improves conversion and selectivity for specific ring sizes. Investigation into the reactivity of Fe(acac)(3) suggests that the iron species acts as a sink for the hydrochloric acid byproduct of the reaction.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Spartak S. Yarovoy, Yakov M. Gayfulin, Anton Smolentsev, Vadim V. Yanshole, Yuri Mironov
Summary: The study revealed the formation mechanism of novel rhenium clusters in aqueous solution, forming stable metallocluster complexes through the substitution of halide ligands in parent compounds. These compounds exhibit good stability in both solid state and aqueous solution.
INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ge Mu, Ryan B. Gaynor, Baylee N. Mcintyre, Bruno Donnadieu, Sidney E. Creutz
Summary: Metalloenzymes extensively use manganese centers for oxidative catalysis, such as water oxidation. The development of bioinspired manganese complexes as improved synthetic catalysts for these processes has been a long-standing motivation. In this study, we report a series of bpy-(imidazole)(n) (n = 1 or 2) (bpy = 2,2 '-bipyridyl) ligands and their Mn2+ complexes. The structures of four Mn2+ complexes are characterized using single-crystal X-ray diffraction, revealing different coordination modes of tridentate and tetradentate ligands. Cyclic voltammetry results indicate ligand-centered reductions and metal-centered oxidations, while UV-vis spectroscopy and TD-DFT calculations show primarily ligand-centered transitions in the complexes. ESI-MS studies in solution provide evidence of ligand reorganization, suggesting complex speciation behavior. However, the low stability of the complexes in aqueous solution prevents their ultimate application as aqueous electrocatalysts. Possible reasons for the low stability and suggestions for improvement are discussed.
Article
Chemistry, Multidisciplinary
Joshua D. Queen, Sini Irvankoski, James C. Fettinger, Heikki M. Tuononen, Philip P. Power
Summary: This study identified the synthesis of aluminum imide and its crystal structure characteristics, revealing unique geometric and mechanical properties of the Al-N bond in aluminum imide. Through DFT calculations, energy decomposition analysis, and spectroscopic studies, a deeper understanding of the properties and interaction mechanisms of aluminum imide was achieved.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Chemistry, Multidisciplinary
Xin Li, Jingkang Wang, Ting Wang, Na Wang, Shuyi Zong, Xin Huang, Hongxun Hao
Summary: This review discusses the theories of nucleation from solution, summarizes the molecular process of nucleation, and explores the relationship between molecular conformation in solution and crystal as well as the impact of solute molecular flexibility on nucleation.
SCIENCE CHINA-CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zhonghua Li, Jianmin Zhou, Xin Zhang, Songgu Wu, Junbo Gong
Summary: The co-crystallization of quercetin with a flexible molecule DPDS in different solvents and conditions resulted in five crystalline phases, which were characterized using X-ray diffraction and thermal analysis. The formation of cocrystal solvates improved the packing efficiency of crystals. Hydrogen bonds and conformations of the parent molecules played a major role in molecular assembly and crystal packing patterns, leading to different physicochemical properties. Fluorescence spectra and quantum-chemical calculations were conducted to explore the difference in the optical-physical properties.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Yancong Tian, Martin Jakoobi, Roman Boulatov, Alexey G. Sergeev
Summary: This study reveals a unique mechanism of transition metal insertion into aromatic rings, requiring cooperativity of two iridium centers. The research provides insight into the role of metal-metal cooperativity in the cleavage of C-C bonds.
Article
Chemistry, Inorganic & Nuclear
Shuo Bai, Daqing Yang, Bingbing Zhang, Ling Li, Ying Wang
Summary: Two lead borate-nitrates with peculiar crystal structures and significant birefringence were successfully synthesized using the high-temperature flux method.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Physical
Awal Noor, Sadaf Qayyum, Zafar Ali, Niaz Muhammad
Summary: Reacting sterically hindered 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with various metal salts in acetonitrile yielded bulky thiourea ligand stabilized monomeric complexes. Structural characterization revealed tetrahedral or square planar geometries for different metal complexes. Intermolecular hydrogen bonding and significant intermolecular interactions in the crystal network were observed. Molecular docking analysis showed higher SARS-CoV-2 enzyme interacting abilities of the synthesized complexes compared to the free ligand. The compounds were characterized by elemental analyses, NMR spectroscopy, and single-crystal X-ray diffraction. (c) 2022 Elsevier B.V. All rights reserved.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Multidisciplinary
Andrea Capucciati, Enrico Monzani, Michela Sturini, Stefania Nicolis, Fabio A. Zucca, Luigi Bubacco, Marco Bortolus, Luigi Zecca, Luigi Casella
Summary: The study uses water-soluble melanin-protein-Fe/Cu conjugates derived from norepinephrine and fibrillar beta-lactoglobulin as reliable models for human brain locus coeruleus neuromelanin (NM). Iron and copper promote catecholamine oxidation and tend to remain coupled in oligonuclear aggregates. The Fe-Cu clusters are EPR silent and affect the H-1 NMR spectra of the conjugates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biotechnology & Applied Microbiology
Karolina Haernvall, Patrik Fladischer, Heidemarie Schoeffmann, Sabine Zitzenbacher, Tea Pavkov-Keller, Karl Gruber, Michael Schick, Motonori Yamamoto, Andreas Kuenkel, Doris Ribitsch, Georg M. Guebitz, Birgit Wiltschi
Summary: Environmentally friendly functionalization and recycling processes for synthetic polymers have gained momentum recently, with enzymes playing a crucial role. This study demonstrates that by engineering the amino acid composition of enzymes, their activity towards synthetic polyesters can be enhanced. The findings highlight the potential of non-canonical amino acids for enzyme engineering and provide new insights for the recycling of synthetic polymers using enzymes.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Gernot F. Grabner, Nikolaus Guttenberger, Nicole Mayer, Anna K. Migglautsch-Sulzer, Christian Lembacher-Fadum, Nermeen Fawzy, Dominik Bulfon, Peter Hofer, Thomas Zuellig, Lennart Hartig, Natalia Kulminskaya, Gabriel Chalhoub, Margarita Schratter, Franz P. W. Radner, Karina Preiss-Landl, Sarah Masser, Achim Lass, Rudolf Zechner, Karl Gruber, Monika Oberer, Rolf Breinbauer, Robert Zimmermann
Summary: This study reports the development and biological characterization of the first small-molecule inhibitor of human ATGL. This inhibitor selectively inactivates ATGL in humans and nonhuman primates, providing a potential therapeutic option for lipotoxicity-driven disorders.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Karl Gruber, Vanessa Csitkovits, Christoph Kratky, Bernhard Kraeutler, Andrzej Lyskowski
Summary: This study reveals the activation mechanism of radical enzymes dependent on coenzyme B-12, by establishing a tight caged radical reaction space in the protein to control the entire reaction pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Guleck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime moiety to amine group has recently been discovered, but the reaction pathway remained unclear. Through studying crystal structures, molecular dynamics simulations, and investigating biocatalytic cascades and intermediates, evidence suggests that the reaction proceeds via an imine intermediate rather than a hydroxylamine intermediate. The imine is further reduced by the ene-reductase to produce the amine product. A non-canonical tyrosine residue contributes to the catalytic activity by protonating the hydroxyl group of the oxime in the first reduction step.
Article
Multidisciplinary Sciences
Katharina Koechl, Tobias Schopper, Vedat Durmaz, Lena Parigger, Amit Singh, Andreas Krassnigg, Marco Cespugli, Wei Wu, Xiaoli Yang, Yanchong Zhang, Welson Wen-Shang Wang, Crystal Selluski, Tiehan Zhao, Xin Zhang, Caihong Bai, Leon Lin, Yuxiang Hu, Zhiwei Xie, Zaihui Zhang, Jun Yan, Kurt Zatloukal, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: Treatment of COVID-19 using soluble ACE2 shows promise, but it requires optimization for emerging viral variants. This study utilized molecular dynamics simulations and a convolutional neural network to assess the binding affinity of multiple spike RBD/hACE2 variants. The high-affinity candidates hACE2-Fc K31W and multi-mutation variants were validated in vitro and their binding affinities with Omicron BA.3, Omicron BA.4/BA.5, and Omicron BA.2.75 RBDs were evaluated in silico. The candidates produced in Nicotiana benthamiana showed significantly reduced IC50 compared to those produced in CHO cells and wild-type hACE2-Fc.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Applied
Sergio Gonzalez-Granda, Georg Steinkellner, Karl Gruber, Ivan Lavandera, Vicente Gotor-Fernandez
Summary: The combination of gold(I) and enzyme catalysis allows for the selective synthesis of a series of nor(pseudo)ephedrine derivatives. This approach involves the hydration of 1-phenylprop-2-yn-1-yl acetate or N-(1-phenylprop-2-yn-1-yl)acetamide using IPrAuNTf2 catalyst, followed by (dynamic) asymmetric biotransamination or bioreduction of the resulting keto ester or keto amide intermediates. Enzyme actions exhibit high stereoselectivity towards methyl ketones, enabling the synthesis of enantio- and diastereomerically enriched products. The use of propargyl esters or amides as starting materials allows for the production of amino alcohol, diol, and diamine derivatives with good yields and high (stereo)selectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Engineering, Chemical
Birgit Grill, Tea Pavkov-Keller, Christoph Grininger, Barbara Darnhofer, Karl Gruber, Melanie Hall, Helmut Schwab, Kerstin Steiner
Summary: Oxidative alkene cleavage is a promising method for synthesizing aldehydes and ketones. The Mn-dependent protein TM1459 from Thermotoga maritima can undergo alkene cleavage of styrene derivatives in the presence of tert-butyl hydroperoxide. However, the enzyme is prone to inactivation due to auto-oxidation in the oxidative environment required for the cleavage reaction. By replacing oxidizable residues, the stability of TM1459 was improved, leading to increased enzyme activity. However, the residue exchanges also affected metal binding.
CHEMIE INGENIEUR TECHNIK
(2023)
Article
Chemistry, Physical
Andrea M. Chanique, Nakia Polidori, Lucija Sovic, Daniel Kracher, Leen Assil-Companioni, Philipp Galuska, Loreto P. Parra, Karl Gruber, Robert Kourist
Summary: Cold-active enzymes have optimal activity at low temperatures, making them useful for preserving heat-sensitive compounds. A cold-active flavin-dependent monooxygenase (FMO) was discovered in an Antarctic organism, showing high activity between 5 and 25 degrees C and promiscuity towards NADH and NADPH. The enzyme exhibits high enantioselectivity and has a unique active site structure.
News Item
Biotechnology & Applied Microbiology
Karl Gruber, Lisa Melton
Summary: A new generation of companies is exploring the use of insect larvae as a protein source for various purposes, including animal feed, fertilizer, biofuels, and food ingredients. Insects offer a cheaper and more sustainable alternative to traditional soy and fishmeal, and can be raised on organic waste.
NATURE BIOTECHNOLOGY
(2023)
Article
Microbiology
Lena Parigger, Andreas Krassnigg, Stefan Grabuschnig, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: The monkeypox virus, similar to smallpox, has caused a recent outbreak affecting 110 countries. Understanding the virus at a molecular level is crucial for studying infection processes, predicting changes, and guiding drug and vaccine development. A study of the virus's structural proteome identified 10,580 candidate open reading frames, which were narrowed down to 1,079 suspected proteins, including 210 representative proteins. These findings provide valuable information for drug discovery, mutational analysis, and vaccine development. Atomistic 3D models of the proteins, including drug-binding sites, were also generated.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Physical
Andrea M. Chanique, Nakia Polidori, Lucija Sovic, Daniel Kracher, Leen Assil-Companioni, Philipp Galuska, Loreto P. Parra, Karl Gruber, Robert Kourist
Summary: Cold-active enzymes maintain high activity at low temperatures, making them useful for avoiding side reactions and preserving heat sensitive compounds. Through genome mining, a cold-active enzyme was discovered in an Antarctic organism, showing high activity at temperatures between 5 and 25 degrees C and displaying promiscuity towards NADH and NADPH, as well as a wide range of ketones and thioesters.
Meeting Abstract
Biochemistry & Molecular Biology
Amit Amit, Nakia Polidori, Karl Gruber
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Glueck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime to amine has been observed in ene-reductases transforming alpha-oximo beta-keto esters. Through structural analysis, molecular dynamics simulations, biocatalytic cascades, and investigation of possible intermediates, it has been determined that the reaction proceeds via an imine intermediate and not through a hydroxylamine intermediate. A non-canonical tyrosine residue in ene-reductase OPR3 was found to play a role in protonating the hydroxyl group of the oxime in the first reduction step.
Article
Medicine, General & Internal
Lena Parigger, Andreas Krassnigg, Tobias Schopper, Amit Singh, Katharina Tappler, Katharina Koechl, Michael Hetmann, Karl Gruber, Georg Steinkellner, Christian C. Gruber
Summary: This study analyzed genomic data of SARS-CoV-2 main protease (M-pro), revealing an accelerated mutational dynamics since December 2021, particularly in a region near the active site. The increased mutational variability in this area may suggest the onset of antiviral resistance development, highlighting the importance of further monitoring and consideration in ongoing drug development.
FRONTIERS IN MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Julia Pitzer, Kerstin Steiner, Christian Schmid, Viktor K. Schein, Christoph Prause, Claudia Kniely, Michaela Reif, Martina Geier, Elena Pietrich, Tamara Reiter, Philipp Selig, Clemens Stuckler, Peter Pochlauer, Georg Steinkellner, Karl Gruber, Helmut Schwab, Anton Glieder, Wolfgang Kroutil
Summary: This study describes an enzyme-catalyzed, racemization-free amidation reaction in an organic solvent for the synthesis of l-prolinamide. Through comprehensive reaction, solvent, and enzyme engineering, high concentrations of the desired product were obtained with excellent optical purity (>99%). This innovative industrial process provides a key intermediate for drug synthesis while avoiding racemization, halogenated solvents, and waste, significantly improving atom efficiency.