Article
Chemistry, Organic
Scott T. Shreiber, Albert Granados, Bianca Matsuo, Jadab Majhi, Mark W. Campbell, Shivani Patel, Gary A. Molander
Summary: This study describes an aryl disulfide mediated C-F bond activation method to generate valuable gem-difluoroalky-lindoles. It is the first transition-metal-free redox-neutral C-F bond activation strategy and utilizes readily available commodity reagents under mild reaction conditions. The reaction allows for the use of various substituted indoles and alpha-fluoro-substituted esters. Additionally, this C-F activation method also enables the activation of trifluoromethylated arenes for the preparation of bis-benzylic gem-difluoromethylenes between indole and arene substructures, providing access to a unique chemical space.
Article
Chemistry, Multidisciplinary
Kostiantyn P. Melnykov, Olha Tavlui, Artem Skreminskiy, Yuliya O. Kuchkovska, Oleksandr O. Grygorenko
Summary: The physicochemical properties of fluoroalkyl-substituted heterocyclic amines were analyzed to aid their rational application in medicinal chemistry research. The effects of introducing fluoroalkyl groups on the lipophilicity and aqueous solubility of compounds were complex and dependent on the fluorination pattern, ring size, and substituent conformation. The summarized data provide a useful guideline for fine-tuning compound properties in drug discovery.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Kostiantyn P. Melnykov, Kostiantyn Nazar, Oleh Smyrnov, Artem Skreminskyi, Serhii Pavlenko, Oleksii Klymenko-Ulianov, Svitlana Shishkina, Dmitriy M. Volochnyuk, Oleksandr O. Grygorenko
Summary: A comprehensive study was conducted on the physicochemical properties of mono- and difluorinated azetidine, pyrrolidine, and piperidine derivatives. The basicity of the compounds was mainly determined by the number of fluorine atoms and their distance to the protonation center, while the conformational preferences significantly influenced the pK(a) and LogP values. High metabolic stability was observed for most compounds, except for the 3,3-difluoroazetidine derivative. The title compounds provide valuable building blocks for rational optimization studies in early drug discovery due to their unique properties.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Genesis Infante, Sara Eisler
Summary: Sequential anionic intramolecular cyclizations and modelling were used to access unusual fused heterocyclic frameworks in excellent yields for the first time. Regioselectivity in the cyclizations was controlled by exploiting stereoelectronic effects via n(C-)->pi*((Ph)) interactions, and modelling studies provided insights into the reaction scope.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Lorenz M. Urner, Ga Young Lee, Joseph W. Treacy, Aneta Turlik, Saeed Khan, K. N. Houk, Michael E. Jung
Summary: The 4-anilino-6,7-ethylenedioxy-5-fluoroquinazoline scaffold is proposed as a novel model system for studying weak NH...F hydrogen bonding interactions, with experimental and theoretical methods used to characterize this interaction. The results demonstrate that fluorine can act as a weak hydrogen bond acceptor, and the strength of the hydrogen bond can be modulated through changes in electron distribution and resonance.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Cristina Cabrero, Nerea Martin-Pintado, Stefania Mazzini, Raimundo Gargallo, Ramon Eritja, Anna Avino, Carlos Gonzalez
Summary: Insertion of 2'-deoxy-2',2'-difluorocytidine (dFdC) into a DNA strand or a DNA : RNA hybrid duplex slightly destabilizes the duplex and causes minor local distortions, which are more pronounced in the case of the DNA : RNA hybrid. Analysis of solution structures by NMR shows that dFdC adopts a North sugar conformation in pure DNA, while in DNA : RNA hybrids it adopts a South sugar conformation that facilitates attractive interactions compensating for base pair distortions. These interactions resemble pseudohydrogen bonds found in other nucleic acid structures with fluorine modified sugars.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Physical
Tae-min Yeo, Jin-Myoung Jeon, Sung-Hee Hyun, Hong-Min Ha, Jung-Wook Cho
Summary: This study characterizes the structure and kinetics of the CaO-SiO2-CaF2-Na2O glass system with increasing Li2O contents. It is found that Li2O delays the crystallization of cuspidine by disrupting the interaction of fluorine and lowering its activity.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biochemistry & Molecular Biology
Svetlana A. Kondrashova, Shamil K. Latypov
Summary: The study examines the scopes and limitations of theoretical methods for estimating various NMR metrics of NHCs using computational approximations on a range of model NHCs and their derivatives. It concludes that the most reliable methods are the 31P/13C NMR shifts of NHC-phosphinidene adducts and 13C CSs of carbenes, while the method based on the analysis of 77Se CS NHC-selenoureas has some limitations due to exchange effects. The accuracy of estimating the HEP metric may also be limited due to the nonlinear effect of electron distribution. 13C CSs of NHC-azolium salts are deemed unreliable due to the influence of counterion exchange.
Article
Chemistry, Organic
Salem El Kharrat, Philippe Laurent, Laurent Boiteau
Summary: Novel 2-perfluoroalkylmethyl,4-arylamino substituted tetrahydroquinolines were efficiently synthesized using perfluoroalkyl iodides and monosubstituted anilines. The reaction proceeded through radical bis-addition, Michael addition, and electrophilic aromatic substitution, leading to the target compounds with different substitution patterns.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Carla Rizzo, Sara Amata, Ivana Pibiri, Andrea Pace, Silvestre Buscemi, Antonio Palumbo Piccionello
Summary: The incorporation of fluorine atoms or heterocyclic moieties into drug structures is a common pattern in medicinal chemistry. The combination of these two features is consistently observed in newly synthesized molecular entities with diverse biological activities, as evidenced by the increasing number of Fluorinated heterocyclic compounds approved by the FDA as drugs. This review highlights the biological activity and synthetic aspects of 33 recently FDA-approved fluorinated heterocyclic drugs from 2016 to 2022.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Organic
Marco Thomas Passia, Jan-Hendrik Schoebel, Niklas Julian Lentelink, Khai-Nghi Truong, Kari Rissanen, Carsten Bolm
Summary: In this study, TBS-protected or NH-sulfonimidamides were reacted with beta-alkoxyvinyl trifluoromethylketones under solvent-free mechanochemical conditions to produce 3-trifluoromethyl-substituted three-dimensional 1,2,6-thiadiazine 1-oxides. C4-functionalized products were obtained by starting from cyclic enones and brominations of the initially formed heterocycles. The stability of the products was investigated by varying the pH value and storage under aerobic conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Alexey Sudakov, Bozana Knezic, Martin Hengesbach, Boris Fuertig, Elke Stirnal, Harald Schwalbe
Summary: More than 170 post-transcriptional modifications of RNAs have been identified. However, the detailed investigation of these modifications is limited due to the difficulty in producing large RNAs containing these modifications. This study reports the chemo-enzymatic synthesis of RNA modifications and fluorine-modified analogs, allowing the synthesis of large RNAs. The incorporation of labeled nucleotides in the riboswitch demonstrated the applicability of the modified large RNAs in characterizing RNA fold and dynamics.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Maxime Artault, Thomas Cantin, Melissa Longuet, Kassandra Vitse, Christ Daniel Matatu Mbengo, Frederic Guegan, Bastien Michelet, Agnes Martin-Mingot, Sebastien Thibaudeau
Summary: This study reports a method to reorganize the core structure of aliphatic unsaturated nitrogen-containing substrates by exploiting polyprotonation in superacid solutions. The superelectrophilic activation of N-isopropyl systems allows for the selective functionalization of nitrogen-containing substrates. It is demonstrated that this skeletal reorganization can be controlled through protonation interplay.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Will R. Henderson, Guancen Liu, Khalil A. Abboud, Ronald K. Castellano
Summary: The supramolecular polymerization of 2,11-dithia[3.3]paracyclophanes is achieved through self-complementary intermolecular and transannular amide hydrogen bonding, resulting in an enhanced n -> pi* interaction. Experimental data and computational investigations support the strengthening of this interaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Physical
Christian Bruns, Rainer Ringleb, Isabell Prediger, Frederike Euchner, Johannes Bernarding, Markus Plaumann
Summary: The interest in fluorinated substances has grown due to their diverse properties. NMR spectroscopy, an important analytical method, provides information on the structure and environment changes. Temperature plays a crucial role in most studies, however, measuring it is challenging in certain cases. Despite the difficulties, the potential applications in chemical reactors and medical fields are significant. Polyfluorinated molecules with separate 19F MR signals prove to be ideal for temperature determination without the need for a reference substance. The sensitivity of temperature is influenced by fluorine position and chemical environment.
Article
Biochemistry & Molecular Biology
Amjad Khan, Christopher J. Schofield, Timothy D. W. Claridge
Article
Chemistry, Physical
Lucy van Dijk, Ruchuta Ardkhean, Mireia Sidera, Sedef Karabiyikoglu, Ozlem Sari, Timothy D. W. Claridge, Guy C. Lloyd-Jones, Robert S. Paton, Stephen P. Fletcher
Summary: The study proposes a catalytic cycle for the highly enantioselective Suzuki-Miyaura coupling of boronic acids and racemic allyl halides catalyzed by Rh(i), and reveals the reaction mechanism through kinetic isotope effects and experiments with stable substrates. The findings suggest that the high enantioselectivity is attributed to a common Rh complex formed from both allyl halide enantiomers.
Article
Multidisciplinary Sciences
Marion Schuller, Rachel E. Butler, Antonio Ariza, Callum Tromans-Coia, Gytis Jankevicius, Tim D. W. Claridge, Sharon L. Kendall, Shan Goh, Graham R. Stewart, Ivan Ahel
Summary: ADP-ribosyltransferases use NAD(+) to catalyze substrate ADP-ribosylation and regulate cellular pathways or contribute to bacterial pathogenicity. Recent studies have suggested nucleic acids as targets of reversible ADP-ribosylation. This research provides evidence of specific ADP-ribosylation of DNA in cells through the DarT-DarG system in bacteria, including global pathogens. The study reveals the structure and mechanism of the DarT enzyme, showing its evolution into specific DNA-modifying enzymes and its role in regulating growth through DNA ADP-ribosylation.
Article
Chemistry, Analytical
Jonathan R. J. Yong, Eriks Kupce, Tim D. W. Claridge
Summary: NMR supersequences allow for faster experiments by tailoring the detection of NMR responses. The online tool GENESIS generates pulse programs for NOAH supersequences compatible with Bruker spectrometers. It provides customized supersequences, related scripts, and detailed instructions, while also facilitating the dissemination of new developments in NOAH sequences.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Connor W. Patrick, Joseph F. Woods, Przemyslaw Gawel, Claire E. Otteson, Amber L. Thompson, Tim D. W. Claridge, Ramesh Jasti, Harry L. Anderson
Summary: This study reports a new method for synthesizing stable carbyne insulated molecular wires through the synthesis of polyyne polyrotaxanes. Using an active metal template route with dicobalt carbonyl masked alkyne equivalents, two [3]rotaxanes were successfully synthesized and compared with naked polyyne dumbbell. The results showed that the nanohoop rotaxane exhibited 4.5 times greater thermal stability.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Oncology
James R. Larkin, Susan Anthony, Vanessa A. Johanssen, Tianrong Yeo, Megan Sealey, Abi G. Yates, Claire Friedemann Smith, Timothy D. W. Claridge, Brian D. Nicholson, Julie-Ann Moreland, Fergus Gleeson, Nicola R. Sibson, Daniel C. Anthony, Fay Probert
Summary: This study demonstrates that biomarkers within the blood metabolome analyzed by NMR metabolomics can aid in the early diagnosis of cancer and distinguish between patients with and without metastatic disease in a mixed population of patients referred from primary care.
CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Jimmy Wang, Matthew A. Horwitz, Alexander B. Durr, Francesco Ibba, Gabriele Pupo, Yuan Gao, Paolo Ricci, Kirsten E. Christensen, Tejas P. Pathak, Timothy D. W. Claridge, Guy C. Lloyd-Jones, Robert S. Paton, Veronique Gouverneur
Summary: Asymmetric catalytic azidation using inexpensive sodium azide has been studied using hydrogen bonding phase-transfer catalysis (HB-PTC). The structure of novel hydrogen bonded azide complexes were analyzed computationally, in the solid state by X-ray diffraction, and in solution phase by NMR spectroscopy. This study demonstrates that HB-PTC can be used as an activation mode for inorganic salts other than metal alkali fluorides, showing potential for applications in asymmetric synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Roman Belle, Jos J. A. G. Kamps, Jordi Poater, Kiran Kumar, Bas J. G. E. Pieters, Eidarus Salah, Timothy D. W. Claridge, Robert S. Paton, F. Matthias Bickelhaupt, Akane Kawamura, Christopher J. Schofield, Jasmin Mecinovic
Summary: The substitution of nitrogen with phosphorus substantially affects the interactions between N-epsilon-methyllysine binding proteins and demethylases.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ji-Yuan Du, Tudor Balan, Tim D. W. Claridge, Martin D. Smith
Summary: This study presents a highly enantioselective and ring-closing synthesis of medium ring lactams, utilizing an intramolecular counterion-directed C-alkylation reaction. The resulting product contains complex chiral elements and is formed through an enolate-driven configurational relaxation process to achieve alkylative ring closure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Henrik Gotfredsen, Jie-Ren Deng, Jeff M. Van Raden, Marcello Righetto, Janko Hergenhahn, Michael Clarke, Abigail Bellamy-Carter, Jack Hart, James O'Shea, Timothy D. W. Claridge, Fernanda Duarte, Alex Saywell, Laura M. Herz, Harry L. Anderson
Summary: Researchers have successfully bent linear photonic wires into ring structures using oligo-pyridyl templates, creating nanorings with 24 porphyrin units and a single butadiyne link. This system exhibits two distinct excited state energy transfer processes.
Article
Chemistry, Multidisciplinary
Jonathan R. J. Yong, Eriks Kupce, Tim D. W. Claridge
Summary: NOAH supersequences is a method that combines multiple 2D NMR experiments into one measurement. However, it has been limited to experiments with comparable sensitivity. This study proposes a scheme that overcomes this limitation by combining experiments with very different sensitivities, such as 1,1-ADEQUATE, N-15 HMBC, and C-13 HSQC.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Eriks Kupce, Jonathan R. J. Yong, Goran Widmalm, Tim D. W. Claridge
Summary: The principles of parallel NMR and MRI are utilized in NMR supersequences to generate multiple 2D NMR spectra in one measurement. By simultaneously recording two NOAH supersequences, the information content obtained in a single NMR experiment is significantly increased.
Review
Multidisciplinary Sciences
Eriks Kupce, Lucio Frydman, Andrew G. Webb, Jonathan R. J. Yong, Tim D. W. Claridge
Summary: This article discusses different approaches to accelerate data acquisition and increase sensitivity of NMR measurements through parallelization, enabled by hardware design and/or pulse sequence development. By coupling multiple detectors to samples and using magnetic field gradients and frequency-selective manipulations, parallelization can compress multidimensional acquisition and yield new pulse schemes. The promising future developments are expected through combining these discussed techniques for maximum gains.
NATURE REVIEWS METHODS PRIMERS
(2021)
Article
Chemistry, Multidisciplinary
Francesco Ibba, Gabriele Pupo, Amber L. Thompson, John M. Brown, Timothy D. W. Claridge, Veronique Gouverneur
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Chemistry, Multidisciplinary
Sebastian M. Kopp, Henrik Gotfredsen, Jie-Ren Deng, Tim D. W. Claridge, Harry L. Anderson
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
