Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• hopeless to expect catching energy differences as small as that between P5.1/P5.2 by molecular modelling. Instead, we discuss qualitatively the conformational properties of the macrocycle in the two diastereomers of P5 to determine if conformers may exist with high interconversion barriers, and suggest an

• frame and is coloured according to its corresponding re-weighted relative free energy. Data is calculated on the cumulative last 500 ns of 15 accelerated molecular dynamics runs for each SMC peptide. Molecular modelling of the conformational preferences of the SMC stapled peptides P5 (with cis or trans

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

• long-term release of therapeutic agents in environments modelling the human body [51]. A further example of multi-stimuli responsive cryogels includes the work by Dragan et al., who prepared semi-interpenetrating polymer networks (semi-IPN) hydrogels comprising DMAEMA and either potato starch or

• 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

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• are also observed without enzyme. Swiss homology modelling of SmTS1. A) Superimposition of the SdS crystal structure (green) with the SmTS1 model (cyan). B) Active site residues of SdS. C) Active site residues of SmTS1. Active site residues that are smaller than in SdS are labelled in red. Green

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• , which results in a various number of tailored models [75][76][77], like the Flory–Huggins–van Santen (FHS) model. The FHS model shows that the combinatorial entropy of mixing is much smaller for macromolecules than for compounds with a low molar mass. For modelling of phase diagrams with LCST and/or

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• present are a current limitation. To combat this, we decided to expand these series with ab-initio computational molecular modelling. We focused on the structural modelling of three series. The ground-state geometries of several members of these series were optimized at the wB97-XD/cc-pVDZ level of theory

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• (pKaH = 13.6) [2]. Moreover, due to the stability of the monocation they display significantly lower second dissociation constants (pKa2H ≈ 3.0). X-ray crystallographic studies and modelling studies have shown that the first protonation occurs mainly on the N4 nitrogen atom, weakening substantially the

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

• gangliosides, such as GD1α, promote tumor-cell adhesion during metastasis [13]. The cholinergic neuron-specific gangliosides GQ1bα and GT1aα may contribute to the pathogenesis of Alzheimer’s disease [14]. Previously, we described a deductive apparatus of a formal system for modelling the enzymes of mucin-type

• substrate. The formal language on which the method is based is a modelling language for glycosyltransferases, and can be used to classify the types of reaction catalyzed according to simple rules. We identify extension of a linear oligosaccharide as the default mode of action (Equation 1), where x and y are

• ], Tellurium [39], or other modelling software supporting this format. Glycan structures can be imported or exported as GlycoCT [40], and exported as Linear Code [41] or IUPAC condensed linear formats. Sets of structures can be downloaded as CSV or GlycoCT. A key function of Glycologue is the ability to

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• and triplet states were ascertained by an analysis of the natural transition orbitals (NTO) obtained from the TDA-DFT calculations [34]. We first investigated the strength of the acceptor groups by modelling phenyl-substituted acceptors and compared their LUMO energies as well as the energies of the

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• compound 2, the conformational analysis of this molecule by NMR and molecular modelling studies, a comparison of the photostabilities of parent compound 1 vs derivative 2, and a comparison of the inhibitory activities of 1 vs 2 towards both AChE and BACE-1. Results and Discussion Synthesis Jacobsen and co

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• the lack of carbohydrate-specific modelling tools have often been named as the principal causes for these issues [18]. Heterogeneity of glycoproteins Unlike protein synthesis, which is encoded in the genome and follows a clear template, glycan biosynthesis is not template-directed. A single

• atomic model will be expected as the final result of the study. Modelling of carbohydrates into 3D maps can be more complex than modelling proteins [33], although recent advances in software are closing the gap [34][35][36]. However, to date it remains true that most model building software is protein

• -centric [15]. As a consequence, the glycan chains in glycoprotein models that have been elucidated before recent developments in carbohydrate validation and modelling software tend to contain a significant amount of errors: wrong carbohydrate nomenclature [13], biologically implausible glycosidic linkage

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

• carried out in structural glycobiology, typically using various software. In this perspective article, we outline developments in the computational tools for the sketching, visualisation and modelling of glycans. The article also provides details on the standard representation of glycans, and

• areas of chemical and biochemical fragmentations followed by analysis using mass spectroscopy, nuclear magnetic resonance, crystallography and computational modelling. There have been some initiatives by independent research groups worldwide, that pushed the development of visual tools to improve some

• of molecules; thus, it provides challenges in the development of force fields for accurate modelling of such variations in charge distributions. The monosaccharides can further form a large number of oligosaccharides which can enormously increase the conformational space, due to a high number of

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• for a separation of the two distinct peaks thus giving a finer level of glycan detail. Problems aligning and comparing the large cohort data with Gaussian modelling of electrophoretic data HappyTools calibration and quantitation worked well with the single bioreactor condition shown in Figure 1A–C

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• fact that glycoforms follow recurrent sequence patterns, clearly suggests that the glycans 3D structure is also non-random and very likely sequence-determined. We use computer modelling to gain insight into these relationships and to define a framework to understand how subtle modifications to the

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• macrocycle was present, as judged by proton resonances in the 1H NMR spectrum, which along with the reaction mixture turning dark brown and the presence of a black precipitate suggested degradation. In order to evaluate the templating effect of the N,N’-dihexyl-1,4-butanediamide (3), molecular modelling

• = 0.0450, Rsigma = 0.0402) which were used in all calculations. The final R1 was 0.0454 (I > 2σ(I)) and wR2 was 0.1180 (all data). CCDC Deposition Number 1968472. Molecular modelling Monte Carlo conformational searches with the MMFF force field were carried out with the Spartan ‘18 software [30]. For each

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• within a solid. By treating them as pseudo-particles that have the same charge but increased mass, this better reflects experimental observations and permits better system modelling [82]. In materials with high dielectric constants, the charges are shielded from each other, and the exciton readily

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• automated reaction planning, as well as a starting point for microkinetic modelling. Keywords: C–H activation; density functional theory; reaction prediction; Introduction Periodically, our knowledge of chemistry is enriched with new transformations that provide significant breakthroughs by enabling new

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• stirred at 70 °C until disappearance of the starting material as monitored by TLC. Then, the mixture was filtered on Celite and concentrated under reduced pressure. The crude product was purified by flash chromatography using the indicated solvent mixture as eluent. Molecular modelling. Calculations were

• inertia analysis was carried out by calculation of the lowest energy conformation of compounds 3–39 and block buster drugs. The conformation calculation was performed using the built-in AMMP molecular mechanics algorithm with default parameters of the VEGA ZZ molecular modelling software package v.3.0.1

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• Afef Mabrouki Malek Fouzai Armand Soldera Abdelkader Kriaa Ahmed Hedhli Laboratory of Molecular Organic Chemistry, National Higher Engineering School of Tunis, 5 avenue Taha Hussein, Montfleury, 1089, Tunis, Tunisia LR99ES16 Physics Laboratory of Soft Matter and Electromagnetic Modelling

Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea

• Aleksandr I. Kobelev,
• Nikita A. Tretyakov,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Michael Rubin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280

• success [19]. Thus, recent development of 3D modelling methods facilitated investigations on the importance of 3D properties of small-molecular drug candidates [20][21][22] and inspired chemists to develop diversity-oriented methods for complex 3D molecules [23][24]. Considering that to the best of our

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• nonlinear curve fitting program PRISM 5.0 (Graph Pad, San Diego, California, USA). Molecular docking studies Homology modelling of human ENPP1 and ENPP3 Homology models of ENPP1 and ENPP3 were developed by our research group [34][35][36][42] because the X-ray crystallographic structures were not available

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• affinity. Herein we describe the synthesis of 1, its photoswitching, and affinity changes between both forms in pseudo-physiological conditions, further rationalized by energy-minimized molecular modelling structures. Results and Discussion The synthetic pathway for the preparation of molecule 1 is shown

• modelling. Reversible Ca2+ liberation and subsequent uptake was evidenced using a fluoroionophore. While the simultaneous observation of fluorescence and absorption was conveniently followed at low concentration, any future biological practical use would undoubtedly require use at much higher concentrations

• the absorption at a certain wavelength. The x-intercept gives the log Kd. Molecular modelling: The molecular structure of 1E·Ca2+ and 1Z·Ca2+ were built with AMPAC 10.1. A geometry optimization was performed by energy minimization using the PM6 method; solvation was not considered. Synthetic

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• (≈1000 days at 25 °C); one of the most stable azo photoswitches reported to date. We further extended the family of arylazopyrazoles with the help of theoretical modelling and discovered 3pzH to be near quantitatively (>98%) switched back and forth between isomers, with a long thermal isomerization half

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• generating a complex odour impression, an exact determination which proteins are linked to which smells or molecules is a very ambitious task. Hence, studies towards understanding interactions led to a Nobel Award in 2002 [29][30][31]. Even today correct modelling and protein crystallisation are immense

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• , thanks to through-space interactions. Modelling suggested that changing the relative orientation/distance of the chromophores would allow cooperative TPA enhancement to be achieved [51]. Thus, multistilbazole molecular structures of different topologies and number of dipolar chromophores, including small

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• affinity by receptor 9 was towards sulfate dianion (Ka = >104 M−1) out of all the tested anions found the trend was I− > Br− > Cl− > F− > OAc− with the dissociation constants of 4.6 × 102, 3.9 × 102, 2.3 × 102, 2.3 × 102 and 1.5 × 102 M−1, respectively. By carrying out extensive molecular modelling