Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals

• Sally Bloodworth,
• Cerys Willoughby and
• Simon J. Coles

Beilstein J. Org. Chem. 2025, 21, 864–876, doi:10.3762/bjoc.21.70

• data, but only 47 shared any primary data at all (Figure 3a). Of these, most (39) shared ‘MODEL’ data derived from in silico modelling – i.e., Cartesian coordinates associated with modelled structures in thermochemical calculations or binding studies (Figure 3b). 72% of these coordinates were given in

• reusability. Conclusion An examination of the data sharing practices of authors across 240 organic chemistry papers indicates that less than 20% of articles have any associated primary data, and these are predominantly Cartesian coordinates associated with in silico modelled structures, generally shared in

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• prediction of drug-like properties, in silico evaluations of ADMET (absorption, distribution, metabolism, excretion, and toxicity) characteristics of all potential drug candidates were conducted using the pkCSM online tool [28]. The resulting data are presented in Table 3. The absorption capability of the

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• , using a scientific programming language called Julia, the collected data can be fitted to the kinetic model parameters, and in silico optimization of the reaction parameters can be performed. Machine-learning-driven optimization of chemical reactions Historically, optimization of chemical reactions has

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• product. Specifically, it is now possible to predict the order and identity of the BBs in NRPs based solely on the nucleic acid sequences of its BGC [40][41][42][43][44][45][46][47][48][49]. These algorithms not only obviated the need for culture and gene expression, dereplication can now be done in

• silico to avoid rediscovery. They are the cornerstone of chemical structure metagenomics; a few examples in this area of research are described below. NRP biosynthesis and structure prediction NRPs are biosynthesized by either type I or II nonribosomal peptide synthetase (NRPS) [50][51]. Type I NRPS is a

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• an in silico approach to design asymmetric frustrated Lewis pairs (FLPs) aimed at controlling reaction stereochemistry. Four FLP scaffolds, incorporating diverse Lewis acids (LA), Lewis bases (LB), and substituents, were assessed via volcano plot analysis to identify the most promising catalysts. By

• strategically modifying LB substituents to induce asymmetry, a stereoselective catalytic scaffold was developed, favouring one enantiomer from both epoxide enantiomers. This work advances the in silico design of FLPs, highlighting their potential as asymmetric CCU catalysts with implications for optimising

• an asymmetric FLP and consequently an asymmetric catalyst. The subsequent study explores the asymmetric insertion of CO2 into chiral PO catalysed by the proposed in silico designed catalyst. Computational Details During the benchmark to choose the best catalyst, the reported geometries were optimised

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• , an observation that is in good agreement with previously obtained data on bisurea catalysts [36]. To further distinguish between the SN1 and SN2 mechanisms, the authors performed an in silico simulation of the non-catalysed reaction to determine the possible potential energy surface and found that

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• energies of relevant species either via force field or quantum chemical methods to assess the properties of a reaction such as activation energies or selectivity. Irrespective of the degree of automation, in silico calculations are often less time-sensitive than wet-lab experiments and can be used to

• data is paramount for predictive modelling. Depending on the problem at hand, different sources of data are available (Figure 1). Apart from experimental data, the creation of large amounts of in silico data is possible with sufficient computational resources [31][32]. While this approach is useful in

• Field (AEIF), which are calculated for each CPA substituent (R) by observing the electrostatic potential of a quarternary ammonium ion with the substituent of interest (NMe3R+). The authors performed unsupervised clustering on an in silico library to select a ‘Universal Training Set’ (UTS) consisting of

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• of condensed thiazoles and tetrazoles. In silico assessment of ADMET parameters shows that most compounds meet the lead-likeness requirements. The biological profiles of new compounds demonstrate high probability levels of activity against the following pathogens/diseases: Candida albicans, Alphis

• gossypii, Tripomastigote Chagas, Tcruzi amastigota, Tcruzi epimastigota, Leishmania amazonensis, and Dengue larvicida. Keywords: dihydropyrimidinone/thione/selenone; green chemistry; in silico biological profile; multicomponent reaction (MCR); thiopyrandioxide; Introduction Multicomponent reactions (MCRs

• ]. We hope that compound 2r and its analogues obtained in this work can be further deeply studied by in silico and in vitro methods to discover the compound most suitable for clinical trials. The structures of the synthesized compounds 2a–r were confirmed by spectral data. The 1H NMR spectra of the

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• ) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs

• several precursors, forming superclusters. The RiPPMiner platform [5] was used to predict in silico post-translational modifications of the mature lanthipeptides. Based on these predictions, several clusters did not contain precursor peptides with a predicted lanthipeptide heterocycle formation and were

• liquenicidin VK21, and as the experimental results confirm, despite the in silico predictions, clostrisin does not form heterocycles. These differences in primary and secondary structure could be responsible for the divergent biological activities we encountered. In silico characterization of the post

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• dimethylated [81][123]. Polytheonamides are originally derived from the marine sponge Theonella swinhoei, which is colonised by various symbiotic bacteria. The polytheonamide encoding BGC poy includes two B12-dependent rSAM C-MTs, namely PoyB and PoyC. In silico modelling and alignment of the structures of

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• selection of hypervalent iodine compounds have also been assessed in silico to determine the strengths of their σ-holes (Figure 3). Togni’s CF3-benziodoxole reagent (I-5, 0.029 e) possessed the weakest σ-hole from among those analyzed, consistent with monovalent iodobenzene (I-2) [72]. Difluoroiodobenzene

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• sequencing technology has resulted in the introduction of an alternative approach towards novel natural product scaffolds: Genome mining. Genome mining is an in-silico natural product discovery strategy in which sequenced genomes are analyzed for the potential of the associated organism to produce natural

• already known metabolites [14]. In-silico dereplication can be performed on two levels: First, BGCs identified by genome mining can be compared to characterized BGCs [17]. Second, in many cases NP core structures can be predicted from genome sequence information and the predicted structures can then be

• associated NP [56][57][58]. In silico dereplication to eliminate BGCs associated with known NPs is one of the major functions of genome mining to avoid the time-consuming and costly re-isolation of known NPs. For instance, the antiSMASH platform compares putative BGCs with reference databases to detect BGCs

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• metabolic functions. Here, we describe a new UbiA-like prenyltransferase (Ptase) Ubi-297 encoded in a conserved operon of several bacterial taxa, including marine Flavobacteria and the genus Sacchromonospora. In silico analysis of Ubi-297 homologs indicated that members of this Ptase group are composed of

• their substrate scope by heterologous production and enzymatic bioassays. Results of our study showcase that marine bacteria harbor still a broad unexplored enzymatic repertoire. Results and Discussion In silico analysis of Ptases in marine Flavobacteria and the genus Saccharomonospora In a first step

• obtained after washing and ultracentrifugation. Substrate specificity of UbiA-297 Based on our in silico analysis and previous mass-spectrometry-guided metabolomic analysis of marine Flavobacteria and members of the genus Saccharomonospora [29][30], we anticipated hydroxylated aromatic or even quinoline

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• underexplored. However, in silico genome mining identified multiple secondary metabolite biosynthetic gene clusters in selected strains from minor actinomycetes genera, implying their comparable biosynthetic capacities to those of the already proven genera [19]. Encouraged by these reports, we examined the

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• interactions between anionic sulphate groups and the primary amine group present in doxorubicin which confers a positive charge under physiological conditions. This interaction was confirmed by in silico modelling. While the carriers did not show any cytotoxicity, cell viability was reduced in the presence of

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• experimentally discovering the TFs regulating glycosylation. The findings would likely vary between cell types, and thus additional efforts are necessary before a wet-lab-validated framework emerges. Orthogonal datasets containing other ChIP-Seq and omics data may also enhance in silico validation. Some examples

• , degree of experimental evidence, and the statistical approaches taken by other investigators can influence the set of TF–gene relationships found. In addition to in silico validation, perturbational experiments, such as performing CRISRP-Cas9 knockouts with single-cell RNA-Seq, followed by glycomics

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• those of the central nervous system, where they function in intercellular recognition and communication. We describe an in silico method for determining the metabolic pathways leading to the most common gangliosides, based on the known enzymes of their biosynthesis. A network of 41 glycolipids is

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• high anticonvulsant activity after tests in silico and in vivо [7]. Moreover, compounds C and D reveal high activity as casein kinase 2 (CK2) inhibitor and high antitumor activity which makes compounds to be promising anticancer drugs [8]. There are quite a few methods for the synthesis of the

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• of CPD with the model nitrostyrene 1h was simulated in silico to predict the reaction pathway, the reaction rate constants, and the activation enthalpies. Density functional theory calculations were conducted for the reactants, products, and transition states using the B3LYP [64][65][66] and M062X

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• characterisation of the binding reaction. Computational methods are used to predict PPIs and interfaces. The advantage of performing in silico experiments includes narrowing down the number of the binding partners to be tested in vitro or in vivo. Computational methods include supervised machine learning, where

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• rotamers in hand, an Eyring plot was generated, and the enthalpy and entropy of activation were derived (Table 2). The structural identification of the major and minor rotamers was not attempted by NMR, but in silico investigations of 3a supported the intuitive notion that the rotamer of lower energy was

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• approach by investigating the in-silico binding of a peptide and glycopeptide epitope of the glycoprotein Mucin 1 (MUC1) binding with the antibody AR20.5. To study the binding, we performed molecular dynamics simulations using OpenMM and then used the Galaxy platform for data analysis. The same analysis

• under observation, could be readily applied to other binding problems as part of a general strategy in drug design or mechanistic analysis. Keywords: binding; conformation; Galaxy; glycoprotein; in silico; Introduction A typical sequence of events in research and discovery is noticing a critical

• . and others [14][16] provides a foundation for further investigation into the binding of glycopeptide antigens to antibodies using computational modeling. Molecular dynamics (MD) simulations and analysis thereof are a well-known ingredient of the in-silico process for mechanistic screening of

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• hand, the Glycan Modeler allows in silico N-/O-glycosylation for glycan-protein complexes and generates a “most relevant” glycan structure through Glycan Fragment Database (GFDB) [68] search which gives proper orientations relative to the target protein. In the absence of target glycan sequence in GFDB

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• . Conclusion To construct a functional chemical sensor, extensive interdisciplinary effort is required. A variety of problems must be addressed in several development stages, all of which were attended to in this work. The conceptual design of macrocyclic anion receptors led to in silico complexation studies

• , Laboratory of Molecular Science and Engineering, Åbo Akademi University, Biskopsgatan 8, FI-20500 Turku/Åbo, Finland 10.3762/bjoc.16.157 Abstract Carboxylate sensing solid-contact ion-selective electrodes (ISEs) were created to provide a proof-of-concept ISE development process covering all aspects from in

• silico ionophore design to functional sensor characterization. The biscarbazolylurea moiety was used to synthesize methylene-bridged macrocycles of different ring size aiming to fine tune selectivity towards different carboxylates. Cyclization was achieved with two separate strategies, using either amide