Article
Chemistry, Multidisciplinary
Zhi-Chen Wu, K. N. Houk, Dale L. Boger, Dennis Svatunek
Summary: This study investigates the reaction mechanism of 1,2,3-triazines and 1,2,3,5-tetrazine with amidines, revealing that the reaction proceeds through an addition/N-2 elimination/cyclization pathway. Contrary to previous expectations, the rate-limiting step in this transformation is the initial nucleophilic attack of amidines on azine C4.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Tobias Koengeter, Can Qin, Binh Khanh Mai, Qinghe Liu, Yucheng Mu, Peng Liu, Amir H. Hoveyda
Summary: This paper presents a stereoretentive strategy for catalytic cross-metathesis reaction between tri-, Z- or E-di, or monosubstituted olefins and Z- or E-2-bromo-2-butene, leading to the formation of various trisubstituted alkenyl bromides. The method is applicable for the generation of products containing polar moieties or sterically hindered alkenes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Lukas Hoff, Simon D. Schnell, Andrea Tomio, Anthony Linden, Karl Gademann
Summary: A silver-mediated Pd-catalyzed cross-coupling method for 3-bromo-1,2,4,5-tetrazine with boronic acids was presented in this study. It was found that electronic modification of the dppf ligand played a crucial role in achieving good turnover. Using this fast method, a variety of alkyl-, heteroatom-, and halide-substituted aryl- and heteroaryl-tetrazines were successfully prepared, with yields up to 87%.
Article
Chemistry, Multidisciplinary
Thomas Cheviet, Ilyana Gonzales, Suzanne Peyrottes
Summary: N-carbamoyl aziridines were transformed into alpha-methylene phosphonate aziridines through a unique mechanism in the presence of n-BuLi and the nucleophilic butyl. The nature of the final compound depends on the base used.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Domenic P. Pace, Raphael Robidas, Uyen P. N. Tran, Claude Y. Legault, Thanh Vinh Nguyen
Summary: A practical and mild catalytic method for the synthesis of substituted pyrans and furans using molecular iodine has been reported, offering a facile alternative under solvent-free conditions at ambient temperature and atmosphere. Mechanistic insights into this seemingly simple reaction were revealed through a combination of experimental studies and density functional theory calculations.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Zheng-Wang Qu, Hui Zhu, Stefan Grimme
Summary: The study on catalytic aromatic chlorination using N-chlorosuccinimides under mild conditions has revealed a novel catalytic mechanism and highlighted the potential role of O=SMe(2) as efficient Cl(+) and H(+) shuttles in the reaction. These mechanistic insights can aid in the rational design of novel dual functional halonium transfer catalysts.
Article
Chemistry, Organic
Nhan N. H. Ton, Binh Khanh Mai, Thanh Vinh Nguyen
Summary: Hydroboration reaction of alkynes is an efficient tool for accessing organoboron compounds, and a novel method using tropylium salts as catalysts has been reported for metal-free hydroboration. This method allows easy access to a wide range of vinylboranes. Experimental studies and DFT calculations revealed an uncommon mechanistic pathway triggered by the hydride abstraction of pinacolborane with tropylium ion.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ira Novianti, Toshiyuki Kowada, Shin Mizukami
Summary: A universal strategy, named Clip to Click, was developed to control the reactivity of tetrazine in the inverse electron-demand Diels-Alder (IEDDA) reaction. Incorporating a chemical bridge into macrocyclic tetrazine rendered it unreactive towards trans-cyclooctene. Computational study revealed that the unreactive property of macrocyclic tetrazines is mainly due to the high distortion energy of tetrazine. We demonstrated that cleaving the macrocyclic linker can activate the tetrazine moiety for the IEDDA reaction.
Article
Chemistry, Organic
Yi-Lun Shih, Yen-Ku Wu, Mamoru Hyodo, Ilhyong Ryu
Summary: A catalytic amount of decatungstate photocatalyst under black light irradiation was able to promote the oxidative cleavage of C=C bonds with molecular oxygen, resulting in the formation of both aromatic and aliphatic ketones. The use of a high-power ultraviolet light-emitting diode at 365 nm for the continuous flow reaction of alpha-methylstyrene significantly reduced the reaction time.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Melin Tataroglu, Fethiye Aylin Sungur
Summary: In this study, alternative pathways for the Beckmann rearrangement reaction at elevated temperatures were elucidated using the DFT computational method. The results explained the details of the reaction through the formation of Meisenheimer complexes, which are highly stable species due to the presence of aromatic ring systems. Understanding the Beckmann rearrangement mechanism is important for the synthesis of selective amides and lactams.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Physical
Jiayu Huang, Brian K. Kendrick, Dong H. Zhang
Summary: Ultracold chemical reactions involve collisions at temperatures near absolute zero, which can lead to significant reactivity in molecular systems with barrierless and exoergic reaction pathways. The study reveals that the geometric phase can significantly alter the outcome of ultracold reactions, and quantum control techniques may be effective in controlling reactivity.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Organic
Julien Braire, Aurelie Mace, Rania Zaier, Marie Cordier, Joelle Vidal, Claudia Lalli, Arnaud Martel, Francois Carreaux
Summary: An improvement in the catalytic enantioselective allylboration of isatins with 2-allyl-1,3,2-dioxaborolane in the presence of chiral BINOL derivatives is reported, offering an efficient one-step access to enantioenriched N-unprotected 3-allyl-3-hydroxy-2-oxindoles. The origins of the high enantioselectivity and the key role of the alcohol additive have been investigated.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Julien Braire, Aurelie Mace, Rania Zaier, Marie Cordier, Joelle Vidal, Claudia Lalli, Arnaud Martel, Francois Carreaux
Summary: An improvement in the catalytic enantioselective allylboration of isatins with 2-allyl-1,3,2-dioxaborolane in the presence of chiral BINOL derivatives is reported. The high enantioselectivity of this reaction is due to the internal hydrogen bonding and the addition of alcohol additive, as shown by DFT calculations and kinetics study.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Eric C. R. Mckenzie, Seyyedamirhossein Hosseini, Mayank Tanwar, Matthew Neurock, Shelley D. Minteer, Stephen C. Jacobson
Summary: Carbon-halogen bond cleavage has been extensively studied for the formation of complex natural products, while the reduction of halogenated phenols has received less attention. In this study, a homogeneous electrocatalytic method was reported for the electro-reduction of brominated phenols. Nickel(II) salen catalyst was found to have the lowest overpotential for C-Br reduction and was used for all substrates. The reduction mechanism was further elucidated through chronoamperometric studies and density functional theory calculations.
JOURNAL OF PHYSICAL CHEMISTRY C
(2023)
Article
Chemistry, Organic
Dace Cirule, Irina Novosjolova, Erika Bizdena, Maris Turks
Summary: A new approach was developed for the synthesis of C6-substituted 2-triazolylpurine derivatives, resulting in a series of products with up to 87% yields obtained through SNAr reactions. The study demonstrates the ability of the 1,2,3-triazolyl ring at the C6 position of purine to act as an effective leaving group.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Titas Deb, Julian Tu, Raphael M. Franzini
Summary: This article reviews the mechanisms and substituent effects of some of the principal metal-free bioorthogonal reactions, based on inverse-electron demand Diels-Alder reactions, 1,3-dipolar cycloadditions, and the Staudinger reaction. Modified versions that link these reactions to a dissociative step are further discussed, with the aim to aid the advancement of bioorthogonal chemistry.
Article
Chemistry, Multidisciplinary
Julian L. Kessler, Grace Kang, Zhao Qin, Helen Kang, Frank G. Whitby, Thomas E. Cheatham, Christopher P. Hill, Yang Li, S. Michael Yu
Summary: This study reveals that N-substituted glycines have the potential to stabilize the triple-helix structure, making them valuable for synthesizing collagen-mimetic peptides with unprecedented side chain diversity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Correction
Chemistry, Multidisciplinary
Lik Hang Yuen, Srikanta Dana, Yu Liu, Samuel I. Bloom, Ann-Gerd Thorsell, Dario Neri, Anthony J. Donato, Dmitri Kireev, Herwig Schuler, Raphael M. Franzini
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Rodrigo Galindo-Murillo, Lauren Winkler, Jingwei Ma, Fatjon Hanelli, Aaron M. Fleming, Cynthia J. Burrows, Thomas E. Cheatham
Summary: This study investigates the specific ligand recognition of abasic sites in G-quadruplex using riboflavin and guanine as examples. The results show that riboflavin can only stabilize abasic site-containing G-quadruplex in the presence of an adjacent OG-modified base.
Article
Chemistry, Multidisciplinary
Tamilselvan Rajasekaran, Graeme C. Freestone, Rodrigo Galindo-Murillo, Barbara Lugato, Lorena Rico, Juan C. Salinas, Hans Gaus, Michael T. Migawa, Eric E. Swayze, Thomas E. Cheatham, Stephen Hanessian, Punit P. Seth
Summary: The study investigates the impact of restricting rotation around the sugar-phosphate backbone on the hybridization kinetics of modified oligonucleotides. Experimental and molecular dynamics simulation results suggest that backbone-constrained compounds and conformationally preorganized LNA analogues contribute to improving the hybridization properties of modified oligonucleotides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Olivia Love, Maria Carolina Pacheco Lima, Casey Clark, Sean Cornillie, Shelly Roalstad, Thomas E. Cheatham
Summary: Flexible loop regions of proteins play critical roles in biological processes and accurate sampling of their 3D structures is vital for drug design and molecular system knowledge. Experimental techniques may not provide high-resolution information for flexible loop domains due to their complex and dynamic nature. In silico methods using molecular dynamics can overcome this limitation. This study evaluates the ability of the AMBER protein force field to model the conformations of dihydrofolate reductase (DHFR), a protein complex with flexible loops whose conformations depend on the presence of ligands and cofactors. Results suggest that the AMBER force field may not accurately sample the expected loop conformations, indicating a potential imbalance in the available force field parameters.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Rodrigo Galindo-Murillo, Thomas E. Cheatham
Summary: This study shows that unbiased molecular dynamics simulations with extended sampling times and multiple independent DNA sequences can accurately reproduce the low-frequency Hoogsteen base pairing in duplex DNA. The experimental results demonstrate that the frequency of Hoogsteen base pairing is within the range of approximately 0.1-1.0%. The study also presents the reliability of current nucleic acid force fields and tools in simulating naturally occurring base-pairing and opening events.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Alba L. Montoya, Marta Glavatskikh, Brayden J. Halverson, Lik Hang Yuen, Herwig Schuler, Dmitri Kireev, Raphael M. Franzini
Summary: DNA-encoded chemical libraries (DECLs) provide valuable information about the chemical ligand space for therapeutic targets. By exploiting DECL screening data, it is possible to predict novel ligands and identify potential drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Lauren Winkler, Thomas E. Cheatham III
Summary: Polarizable force fields, particularly the Drude polarizable force field, have the potential to accurately model biomolecules in molecular dynamics simulations by accounting for atomic polarizability. However, benchmarking the Drude force field with flexible single-stranded structures has not been achieved in this study. Simulations of the r(GACC) tetranucleotide revealed that the force field produced stable but inconsistent structures, suggesting a misbalance of forces and an inability to accurately model other RNA structures.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Lauren Winkler, Rodrigo Galindo-Murillo, Thomas E. Cheatham III
Summary: Flexible nucleic acid structures are challenging to resolve experimentally, but molecular dynamics simulations can provide insight into their dynamics and populations. This study evaluates nucleic acid force fields using the DNA mini-dumbbell as a model system, and finds that recent force fields generate structures that agree well with experiments, albeit with different distributions of potentially anomalous structures.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Organic
Tamilselvan Rajasekaran, Graeme C. Freestone, Rodrigo Galindo-Murillo, Barbara Lugato, Hans Gaus, Michael T. Migawa, Eric. E. Swayze, Thomas E. Cheatham III, Punit P. Seth, Stephen Hanessian
Summary: This manuscript describes a chemical strategy to preorganize a trinucleotide subunit in a conformation suitable for base pairing, using bis-phosphonate esters bridging hydrocarbon tethers to create macrocyclic analogues. The synthesis and incorporation of eight P-stereoisomers of these analogues into oligonucleotides (ONs) is described, and their effect on hybridization kinetics with RNA is characterized. The size of the macrocyclic tether and configuration at phosphorus significantly influenced the on-rates and off-rates of the modified ONs. The results highlight the potential of backbone-constrained macrocyclic nucleic acid analogues in modulating hybridization kinetics.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
William K. K. Weigel, Alba L. L. Montoya, Raphael M. M. Franzini
Summary: DNA-encoded libraries (DELs) are widely used for drug discovery, and understanding their design principles is crucial for improving library quality. This study examined different aspects of library topology and its impact on DEL properties and chemical diversity. A descriptor called DELTA was introduced to analyze and compare different DEL topologies, revealing that topology's effect on chemical space coverage is secondary to building block selection. It was also found that topology plays a significant role in determining the potential interactions with target proteins. The study highlighted the challenges of predicting DEL productivity based solely on chemical space analysis.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Organic
Dennis Svatunek, Konrad Chojnacki, Titas Deb, Hannah Eckvahl, K. N. Houk, Raphael M. Franzini
Summary: By exploiting differences in frontier molecular orbital interaction energies in transition states, we achieved orthogonal click reactions. We found that five-membered cyclic dienes are inert to isonitriles but readily react with strained alkynes, while tetrazines with bulky substituents readily react with isonitriles. Strained alkynes show an opposite reactivity pattern. We successfully demonstrated this approach by orthogonally labeling two proteins with different fluorophores.
Article
Computer Science, Interdisciplinary Applications
Patrick Schmitz, Scott Yockel, Claire Mizumoto, Thomas Cheatham, Dana Brunson
Summary: Research computing and data infrastructure are increasingly important, requiring skilled professionals to assist researchers in utilizing technical resources. However, the roles and recruitment of these professionals are challenging and poorly understood. Organizations like the Campus Research Computing Consortium are working to address these issues.
COMPUTING IN SCIENCE & ENGINEERING
(2021)
Article
Multidisciplinary Sciences
Samuel L. Scinto, Didier A. Bilodeau, Robert Hincapie, Wankyu Lee, Sean S. Nguyen, Minghao Xu, Christopher W. Am Ende, M. G. Finn, Kathrin Lang, Qing Lin, John Paul Pezacki, Jennifer A. Prescher, Marc S. Robillard, Joseph M. Fox
Summary: Bioorthogonal chemistry involves high-yielding chemical reactions in biological environments that are rapid and selective, playing essential roles in various fields such as biomedical imaging and drug delivery. Its applications are diverse and include genetic code expansion, drug target identification, and antibody-drug conjugation.
NATURE REVIEWS METHODS PRIMERS
(2021)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
