Publications
462 results found
Ritzefeld M, Zhang L, Xiao Z, et al., 2024, Design, synthesis and evaluation of inhibitors of hedgehog acyltransferase, Journal of Medicinal Chemistry, Vol: 67, Pages: 1061-1078, ISSN: 0022-2623
Hedgehog signaling is involved in embryonic development and cancer growth. Functional activity of secreted Hedgehog signaling proteins is dependent on N-terminal palmitoylation, making the palmitoyl transferase Hedgehog acyltransferase (HHAT), a potential drug target and a series of 4,5,6,7-tetrahydrothieno[3,2-c]pyridines have been identified as HHAT inhibitors. Based on structural data, we designed and synthesized 37 new analogues which we profiled alongside 13 previously reported analogues in enzymatic and cellular assays. Our results show that a central amide linkage, a secondary amine, and (R)-configuration at the 4-position of the core are three key factors for inhibitory potency. Several potent analogues with low- or sub-μM IC50 against purified HHAT also inhibit Sonic Hedgehog (SHH) palmitoylation in cells and suppress the SHH signaling pathway. This work identifies IMP-1575 as the most potent cell-active chemical probe for HHAT function, alongside an inactive control enantiomer, providing tool compounds for validation of HHAT as a target in cellular assays.
Rzepa HS, 2023, Teaching FAIR in computational chemistry: managing and publishing data using the twin tools of compute portals and repositories, CANADIAN JOURNAL OF CHEMISTRY, Vol: 101, Pages: 725-733, ISSN: 0008-4042
Mies T, White AJP, Rzepa HS, et al., 2023, Syntheses and Characterization of Main Group, Transition Metal, Lanthanide, and Actinide Complexes of Bidentate Acylpyrazolone Ligands, INORGANIC CHEMISTRY, Vol: 62, Pages: 13253-13276, ISSN: 0020-1669
Braddock D, Rowley B, Lickiss P, et al., 2023, On the use of triarylsilanols as catalysts for direct amidation of carboxylic acids, Journal of Organic Chemistry, Vol: 88, Pages: 9853-9869, ISSN: 0022-3263
Triarylsilanols are reported as the first silicon-centred molecular catalysts for direct amidation of carboxylic acids with amines as identified after a screen of silanols, silanediols, disiloxanediols and incompletely condensed silsesquioxanes as potential homogeneous catalysts. Subsequent synthesis and testing of various electronically differentiated triarylsilanols identify tris(p-haloaryl)silanols as more active than the parent triarylsilanol, where the bromide congener was found to be the most active. Catalyst decomposition can be observed by NMR methods, but RPKA methods reveal that product inhibition is operative, where tertiary amides are more inhibitory than secondary amides. Studies using an authentically synthesised triaryl silylester as a putative intermediate in the catalytic system enable a plausible mechanism to be proposed as supported by computations.
Rzepa HS, 2023, Teaching FAIR in computational chemistry: managing and publishing data using the twin tools of compute portals and repositories, CANADIAN JOURNAL OF CHEMISTRY, ISSN: 0008-4042
Cavalli ES, Mies T, Rzepa HS, et al., 2022, Pyrimidine nucleosides syntheses by late-stage base heterocyclization reactions, Organic Letters, Vol: 24, Pages: 8931-8935, ISSN: 1523-7052
An efficient two-step procedure for the syntheses of pyrimidine nucleosides is presented. A series of glycosyl 5-(aminomethylene)-1,3-dioxane-4,6-dione derivatives were prepared from β-anomeric isonitriles by reaction with Meldrum’s acid or by allowing aminomethylene Meldrum’s acid to react with an 1-aldofuranosyl halide or acetate. The resultant 5-(aminomethylene)-1,3-dioxane-4,6-dione derivatives underwent reaction with benzyl- or 2,4-dimethoxybenzyl isocyanate via transacylation to provide uridine-5-carboxylic acid derivatives and related nucleosides. These nucleoside carboxylic acids were converted into other C-5 derivatives by bromo-decarboxylation with N-bromosuccinimide.
Braddock D, Duran-Corbera A, Nilforoushan M, et al., 2022, (±)-Polysiphenol and other Analogues via Symmetrical Intermolecular Dimerizations: a Synthetic, Spectroscopic, Structural and Computational Study, Journal of Natural Products, Vol: 85, Pages: 2650-2655, ISSN: 0163-3864
We report an improved total synthesis of 4,5-dibromo-9,10-dihydrophenanthrene-2,3,6,7-tetraol, (±)-polysiphenol, via intermolecular McMurray dimerization of 5-bromovanillin and subsequent intramolecular oxidative coupling as the key steps. The synthetic route is applicable to 4,5-dichloro- and 4,5-difluoro-halologues (as well as a 4,5-dialkyl-analogue). Distinctive AA′BB′ multiplets in their 1H NMR spectra for the dimethylene bridges of the dibromo and dichloro compounds reveal them to be room-temperature stable atropisomers, while for the difluoro compound they present as a singlet. X-ray crystal structure determinations of their tetramethylated synthetic precursors show atropisomeric twist angles of 48°, 46°, and 32°, respectively, with the former representing the largest yet observed in any 4,5-disubstituted-9,10-dihydrophenanthrene. DFT computational studies reveal an unprecedented two-stage atropisomeric interconversion process involving time-independent asynchronous rotations of the dimethylene bridge and the biaryl axis for halologues containing chlorine or bromine, but a more synchronous rotation for the difluoro analogue.
Rzepa HS, Arita M, Miyamoto K, et al., 2022, A combined DFT-predictive and experimental exploration of the sensitivity towards nucleofuge variation in zwitterionic intermediates relating to mechanistic models for unimolecular chemical generation and trapping of free C<sub>2</sub> and alternative bimolecular pathways involving no free C<sub>2</sub>, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 24, Pages: 25816-25821, ISSN: 1463-9076
Rzepa HS, Kuhn S, 2022, A data-oriented approach to making new molecules as a student experiment: Artificial intelligence-enabling FAIR publication of NMR data for organic esters (vol 60, 93, 2022), MAGNETIC RESONANCE IN CHEMISTRY, Vol: 60, Pages: 1032-1043, ISSN: 0749-1581
Dumon AS, Rzepa HS, Alamillo-Ferrer C, et al., 2022, A computational tool to accurately and quickly predict <SUP>19</SUP>F NMR chemical shifts of molecules with fluorine-carbon and fluorine-boron bonds, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 24, Pages: 20409-20425, ISSN: 1463-9076
- Author Web Link
- Cite
- Citations: 2
Braddock D, Limpaitoon N, Oliwa K, et al., 2022, A stereoselective hydride transfer reaction with contributions from attractive dispersion force control, Chemical Communications, Vol: 58, Pages: 4981-4984, ISSN: 1359-7345
The experimentally determined stereochemical outcome of an unprecedented hydride transfer from a lithium alkoxide to an aldehyde is reported, as deconvoluted by the combined use of a single enantiomer alkoxide in conjunction with a deuterium label. The stereoselective outcome is consistent with a computationally predicted transition state model stabilised by contributions from attractive dispersion forces.
Hanson RM, Jeannerat D, Archibald M, et al., 2022, IUPAC specification for the FAIR management of spectroscopic data in chemistry (IUPAC FAIRSpec) - guiding principles, Pure and Applied Chemistry, Vol: 94, Pages: 623-636, ISSN: 0033-4545
set of guiding principles for the development of a standard for FAIR management of spectroscopic data are outlined and discussed. The principles form the basis for future recommendations of IUPAC Project 2019-031-1-024 specifying a detailed data model and metadata schema for describing the contents of an “IUPAC FAIRData Collection” and the organization of digital objects within that collection. Foremost among the recommendations will be a specification for an “IUPAC FAIRData Finding Aid” that describes the collection in such a way as to optimize the findability, accessibility, interoperability, and reusability of its contents. Results of an analysis of data provided by an American Chemical Society Publications pilot study are discussed in relation to potential workflows that might be used in implementing the “IUPAC FAIRSpec” standard based on these principles.
Rzepa H, Davies AN, 2022, Open publishing FAIR spectra for and by students, Spectroscopy Europe, Vol: 34, Pages: 30-36, ISSN: 0966-0941
Cave-Ayland C, Bearpark M, Romain C, et al., 2022, CHAMP is a HPC Access and Metadata Portal, Journal of Open Source Software, Vol: 7, Pages: 3824-3824
Rzepa HS, 2022, The Long and Winding Road towards FAIR Data as an Integral Component of the Computational Modelling and Dissemination of Chemistry, ISRAEL JOURNAL OF CHEMISTRY, Vol: 62, ISSN: 0021-2148
Rzepa HS, Kuhn S, 2022, A data-oriented approach to making new molecules as a student experiment: artificial intelligence-enabling FAIR publication of NMR data for organic esters, MAGNETIC RESONANCE IN CHEMISTRY, Vol: 60, Pages: 93-103, ISSN: 0749-1581
- Author Web Link
- Cite
- Citations: 6
Rzepa HS, 2021, Routes involving no free C<sub>2</sub> in a DFT-computed mechanistic model for the reported room-temperature chemical synthesis of C<sub>2</sub>, PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol: 23, Pages: 12630-12636, ISSN: 1463-9076
- Author Web Link
- Cite
- Citations: 4
Alamillo-Ferrer C, Nielsen CD-T, Salzano A, et al., 2021, Understanding the Diastereopreference of Intermediates in Aminocatalysis: Application to the Chiral Resolution of Lactols, JOURNAL OF ORGANIC CHEMISTRY, Vol: 86, Pages: 4326-4335, ISSN: 0022-3263
Rzepa HS, 2021, A thermodynamic assessment of the reported room-temperature chemical synthesis of C<sub>2</sub>, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723
- Author Web Link
- Cite
- Citations: 3
Bachrach SM, Rzepa HS, 2020, Cycloparaphenylene Mobius trefoils, CHEMICAL COMMUNICATIONS, Vol: 56, Pages: 13567-13570, ISSN: 1359-7345
- Author Web Link
- Cite
- Citations: 1
Yildiz CB, Leszczynska KI, Gonzalez-Gallardo S, et al., 2020, Equilibrium Formation of Stable All-Silicon Versions of 1,3-Cyclobutanediyl, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 59, Pages: 15087-15092, ISSN: 1433-7851
- Author Web Link
- Cite
- Citations: 23
Yildiz CB, Leszczyńska KI, González-Gallardo S, et al., 2020, Bildung Stabiler All-Silicium Varianten von 1,3-Cyclobutandiyl im Gleichgewicht, Angewandte Chemie, Vol: 132, Pages: 15199-15204, ISSN: 0044-8249
Sebest F, Lachhani K, Pimpasri C, et al., 2020, Cycloaddition reactions of azides and electron-deficient alkenes in deep eutectic solvents: pyrazolines, aziridines and other surprises, Advanced Synthesis & Catalysis, Vol: 362, Pages: 1877-1886, ISSN: 1615-4150
The reaction of organic azides and electron‐deficient alkenes was investigated in a deep eutectic solvent. A series of highly substituted 2‐pyrazolines was successfully isolated and their formation rationalised by DFT calculations. The critical effect of substitution was also explored; even relatively small changes in the cycloaddition partners led to completely different reaction outcomes and triazolines, triazoles or enaminones can be formed as major products depending on the alkene employed.
Klein JEMN, Knizia G, Rzepa HS, 2019, Epoxidation of Alkenes by Peracids: From Textbook Mechanisms to a Quantum Mechanically Derived Curly-Arrow Depiction, CHEMISTRYOPEN, Vol: 8, Pages: 1244-1250, ISSN: 2191-1363
- Author Web Link
- Cite
- Citations: 6
Shernyukov AV, Genaev AM, Salnikov GE, et al., 2019, Elevated reaction order of 1,3,5-tri-<i>tert</i>-butylbenzene bromination as evidence of a clustered polybromide transition state: a combined kinetic and computational study, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 17, Pages: 3781-3789, ISSN: 1477-0520
- Author Web Link
- Cite
- Citations: 8
Du Y, Barber T, Lim SE, et al., 2019, A solid-supported arylboronic acid catalyst for direct amidation, CHEMICAL COMMUNICATIONS, Vol: 55, Pages: 2916-2919, ISSN: 1359-7345
- Author Web Link
- Cite
- Citations: 31
Barba A, Dominguez S, Gomez C, et al., 2019, Workflows allowing creation of journal article Supporting Information and FAIR-enabled publication of Spectroscopic data, ACS Omega, Vol: 4, Pages: 3280-3286, ISSN: 2470-1343
There is an increasing focus on the part of academic institutions, funding agencies, and publishers, if not researchers themselves, on preservation and sharing of research data. Motivations for sharing include research integrity, replicability, and reuse. One of the barriers to publishing data is the extra work involved in preparing data for publication once a journal article and its supporting information have been completed. In this work, a method is described to generate both human and machine-readable supporting information directly from the primary instrumental data files and to generate the metadata to ensure it is published in accordance with findable, accessible, interoperable, and reusable (FAIR) guidelines. Using this approach, both the human readable supporting information and the primary (raw) data can be submitted simultaneously with little extra effort. Although traditionally the data package would be sent to a journal publisher for publication alongside the article, the data package could also be published independently in an institutional FAIR data repository. Workflows are described that store the data packages and generate metadata appropriate for such a repository. The methods both to generate and to publish the data packages have been implemented for NMR data, but the concept is extensible to other types of spectroscopic data as well.
Wittenburg P, Sustkova HP, Montesanti A, et al., 2019, The FAIR Funder pilot programme to make it easy for funders to require and for grantees to produce FAIR Data
There is a growing acknowledgement in the scientific community of theimportance of making experimental data machine findable, accessible,interoperable, and reusable (FAIR). Recognizing that high quality metadata areessential to make datasets FAIR, members of the GO FAIR Initiative and theResearch Data Alliance (RDA) have initiated a series of workshops to encouragethe creation of Metadata for Machines (M4M), enabling any self-identifiedstakeholder to define and promote the reuse of standardized, comprehensivemachine-actionable metadata. The funders of scientific research recognize thatthey have an important role to play in ensuring that experimental results areFAIR, and that high quality metadata and careful planning for FAIR datastewardship are central to these goals. We describe the outcome of a recent M4Mworkshop that has led to a pilot programme involving two national sciencefunders, the Health Research Board of Ireland (HRB) and the NetherlandsOrganisation for Health Research and Development (ZonMW). These fundingorganizations will explore new technologies to define at the time that arequest for proposals is issued the minimal set of machine-actionable metadatathat they would like investigators to use to annotate their datasets, to enableinvestigators to create such metadata to help make their data FAIR, and todevelop data-stewardship plans that ensure that experimental data will bemanaged appropriately abiding by the FAIR principles. The FAIR Funders designenvisions a data-management workflow having seven essential stages, wheresolution providers are openly invited to participate. The initial pilotprogramme will launch using existing computer-based tools of those who attendedthe M4M Workshop.
Sebest F, Casarrubios L, Rzepa HS, et al., 2018, Thermal Azide-Alkene Cycloaddition Reactions: Straightforward Multi-gram Access to Δ²-1,2,3-Triazolines in Deep Eutectic Solvents, Green Chemistry, Vol: 20, Pages: 4023-4035, ISSN: 1463-9262
The multi-gram synthesis of a wide range of 1,2,3-triazolines via azide–alkene cycloaddition reactions in a Deep Eutectic Solvent (DES) is reported. The role of DES in this transformation as well as the origin of the full product distribution was studied with an experimental/computational-DFT approach.
Rzepa HS, Arkhipenko S, Wan E, et al., 2018, An accessible method for DFT calculation of B-11 NMR shifts of organoboron compounds, Journal of Organic Chemistry, Vol: 83, Pages: 8020-8025, ISSN: 0022-3263
The study of boron-mediated reactions in organic synthesis and reactions of organoboron compounds is greatly facilitated by the use of 11B NMR. However, the identification and characterization of reaction intermediates in often complex systems is far from trivial, as 11B NMR does not provide any detailed structural information. Greater insight into the structures present in such systems can be obtained by using DFT chemical shift calculations to support or exclude proposed reaction intermediates. In this article, we report a rapid and accessible approach to the calculation of 11B NMR shifts that is applicable to a wide range of organoboron compounds.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.