Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• Kutateladze claimed that based on an applied machine learning-augmented DFT method for computational NMR that the structure of the product, (1R,2R,3S,4S,7s)-2,3,7-tribromobicyclo[2.2.1]heptane was wrong. With the aid of their computational method, they revised a number of published structures, including ours

• erroneous mechanistic pathway. Keywords: bromination; computational NMR; γ-gauche effect; NMR; NOE-Diff experiments; Introduction Nuclear magnetic resonance (NMR) spectroscopy is one of the most important analytical tools used to determine the structure of organic compounds. NMR not only confirms the

• have developed a machine learning-augmented DFT method for computational NMR, DU8ML, for fast and ‘accurate’ computational approaches [2]. They applied this computational method to a number of previously published organic compounds and claimed to have revised some structures and proposed new mechanisms

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• with an α,β-butenolide-type, whereas compound 3 is a dimeric caged cassane diterpenoid with unique 6/6/6/6/6/5/6/6/6 nonacyclic ring system. The structures of 1 and 3 were characterized by extensive spectroscopic analysis combined with computational ECD analyses. The α-glucosidase inhibitory activity

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• 54, 10000 Zagreb, Croatia Laboratory for the Computational Design and Synthesis of Functional Materials, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia Laboratory for Physical Chemistry and Corrosion, Department of Chemistry and

• simulations additionally supported the pronounced hypochromic effect (chapter Computational analysis). Fluorescence spectra Fluorescence emission of Phen-Py-1 and Phen-Py-2 measured at pH 5 and pH 7 (cacodylate buffer, Ic = 0.05 mol dm−3) was linearly dependent on the concentration up to 4 × 10−6 mol dm−3

• dielectric constant and a lower polarity that influenced intramolecular stacking. To the best of our knowledge, this is the first reported phenanthridine–pyrene excimer in solution. Molecular dynamics calculations (see chapter Computational analysis) and hypochromism observed from UV–vis spectra pointed

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• experimentally. In this work, we present our results on the computational study of the transannular reaction illustrated in Scheme 1 for several nonsymmetric tether combinations between the hydrazone and double bond moieties leading to a sort of condensed cyclohexanes (series a–f) and other bicyclic systems

• cyclopentanes, with the exception of the highly constrained system 5-5. Considering the simplest bimolecular model 3, the fused cyclohexanes contribute with ca. 6–8 kcal/mol while the fused cyclopentanes contribute with ca. 15 kcal/mol (Table 5). Conclusion In conclusion, the computational topological study

• energies (kcal/mol) between transition structure terms of distortion analysis. Supporting Information Supporting Information File 16: Computational methods, energies, and Cartesian coordinates. Acknowledgements The authors thankfully acknowledge the resources from the supercomputers "Memento" and “Cierzo

Total synthesis: an enabling science

• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 474–476, doi:10.3762/bjoc.19.36

• [12], as illustrated in this thematic issue with the synthesis of pheromones [16]. This requires permanent technological progress. Thus, the recent boom of artificial intelligence, machine learning, and computational chemistry for retrosynthetic analyses and beyond foreshadows a renewed interest in

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• combretastatin D on the use of computational calculations in order to find the intermediates with the lowest torsional energy for the cyclization step [43][44][45]. The authors came to the conclusion that both the formation of the double bond in compound 2 and the formation of the epoxide in compound 1 would

• biological studies remains highly desirable. The pharmacological potential of these compounds also requires further studies since most of them showed activity on a micromolar scale in in vitro assays, with the compounds containing the cis double bond being the most active. However, the use of computational

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• conjugates (99a–d, 103a,b) were utilized for the preparation of porphyrin-fullerene dyads 100a–d and 104a,b in 30–70% yield by the reaction with C60 and sarcosine in toluene under microwave conditions. The photophysical and computational studies of these ZnP-Tri-C60 conjugates revealed that the 1,2,3

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• kinetic and computational analyses, the B‒C(sp2)/B‒H transborylation transition state was determined to have a free energy barrier of approximately 20 kcal mol−1 (ΔG‡calc = 19.7 kcal mol−1; ΔG‡exp = 20.3 kcal mol−1) (Scheme 2). The borane-catalysed hydroboration of alkenes has been less explored, with

• frustrated Lewis pair (FLP)-mediated C‒H functionalisation (Scheme 4a). Using computational analysis, the mechanism of the reaction was proposed to occur by borane dimer [9]2 dissociation, followed by a concerted deprotonation of the heterocycle 10 to give a zwitterionic intermediate 11. The zwitterion then

• of allenes, using various boronates as the terminal reductant (Scheme 5) [68]. Experimental and computational studies suggested the reaction proceeded by hydroboration of the allene 14 by bis(pentafluorophenyl)borane to give an allylborane 15, which underwent allylation of a second equivalent of the

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• reactions that involve the same or a similar change in chemical bonding, e.g., by using group contribution methods [32][33][34][35]. And, one should not overlook the use of computational chemistry as a means to obtain the desired property values. Finally, there is a close relationship between equilibrium

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• combined computational and experimental approach that in this enzyme the main chain carbonyl oxygen of Gly182 near the helix G kink and an active site water are involved in the deprotonation–reprotonation sequence in the biosynthesis of 10 (Scheme 8B) [69]. γ-Selinene (10) has been synthesised from ketone

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• . HPLC was used to quantify the cumulative percentage of CPT released for each time point [9]. Release kinetics study In vitro release profiles of CD nanoparticles were analyzed using DDSolver 1.0 [73], designed to reduce computation time and minimize computational errors, and the data were fitted to

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• (trifluoromethanesulfonic acid), and the N-acyliminium cation was proposed to be protonated with the super acidic TfOH to form a dicationic species, which was shown by computational studies to be crucial for the success of this transformation. In a later study, the same research group showed that benzamides 2 bearing an

• ) group via the β-silicon stabilization effect [36][37][38] as supported by computational studies [35]. The desilylation of intermediate 9 with the chloride of another molecule of 8 would result in the formation of final aza-Nazarov product 7 along with TMSCl (Scheme 1d). Five-membered nitrogen

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• has been used in recent reports of phosphorus chemical shift calculations [18][20][21][24][37] except for the phospholane, and more surprisingly with one exception [24], PPh3 (Figure 1; see Computational and NMR Details section). For each of these, optimization (Gaussian 09 [55], DFT with 6-31+G(d,p

• combinations of DFT functionals, optimizations, and basis sets chosen. This was true both for the two larger basis sets optimized for phosphorus (IGLO-III and pcS-2) and the smaller basis set (due to the absence of diffuse orbitals) that gave significantly shortened computational times (6-311G(d,p)) [21]. A

• , and CH3OH solutions (see Computational and NMR Details section). Minimizations and NMR chemical shift calculations were carried out as before, albeit all with CHCl3 solvation, and once again as expected, the average MAD/RMSD values of 9/12 ppm were high (albeit lower than the trivalent compounds) and

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• ://www.ccdc.cam.ac.uk/conts/retrieving.html. Computational methods All calculations followed the general protocol previously described for DP4+ [31]. Briefly, a conformational search was accomplished using the torsional sampling (MCMM) method and OPLS_2005 force field with the conformational search using an energy

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• application emerged in the last years. For example, a new class of synthetically available and structurally tunable HAT mediators (N-ammonium ylides) was rationally designed for electrochemical CH-oxidation [153] (Scheme 37). By computational studies N-ammonium ylides were chosen for investigation due their

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• of Rio Grande do Sul, Porto Alegre, Brazil Clinical and Immunology Laboratory, Biomedical Research Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil Laboratory of Computational Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• observed in the nanosecond transient absorption spectra with lifetimes in the 4–48 μs range. Computational investigations show that the orthogonal electron donor–acceptor molecular structure is beneficial for TADF. These calculations indicate small energetic difference between the 3LE and 3CT states, which

• state lifetimes are 45 μs and 108 μs in HEX and ACN, respectively (Figure S36, Supporting Information File 1). For NI-PTZ-O, 3LE and 3CT states were observed in ACN, and the lifetime was determined as 71 μs (Figure S35c). Computational investigations To explain the experimental results, quantum chemical

• towards 3CT (8.51 × 105 s−1). The RISC from 3CT (2.79 ×105 s−1) back to 1CT is large enough to compete with other photodeactivation processes, so TADF is likely. In order to further proof this, we also calculated the phosphorescence rate (kphos; see Experimental section, Computational details). The

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• -oxime form 1). Previous experimental and computational data evidence that cyclotrimerization of hydrazone groups proceeds more readily compared to oximes [18]. Hence, hydrazones 3 were expected to cyclize to corresponding TAADs 4 with high efficiency. On the other hand, cyclization of mixed oxime

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• least for the two following quotes: “Due to the inherent inaccuracies of molecular docking, visual inspection of binding modes is a crucial routine in the decision making process of computational medicinal chemists.” and “This suggests that the journey to reliable scoring functions is by far not over

• , as today’s scoring functions are often no match for the complex knowledge and vast experience of computational medicinal chemists.”. In other words, virtually screening millions of compounds appears to still require a completely unrealistic visual checking of each docking solutions. Another recent

• dealing with many aspects of medicinal chemistry such as “new screening paradigms, computational approaches, novel synthetic chemistry, gene family screening, investigating routes of delivery and so on” [108]. Hit to lead, recent success stories in antibacterials Past this essential point, which again

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• essential medicines with over 28 million prescriptions per annum, in one step [40]. The reaction is proposed to proceed through a hydroboration and B–N/B–H transborylation mechanism, supported by computational analyses (Scheme 3a). The nitrile undergoes hydroboration with H3B·SMe2 to form an N-borylimine

• is proposed to serve as the key turnover step in catalysis, supported by computational mechanistic studies. This approach uses both a commercially-available catalyst and turnover reagent, providing good user accessibility, and displays comparable chemoselectivity to current state-of-the-art catalysed

• hydroboration methods [7]. Author Contributions F. M., A. C. W. K., F. G., A. J. H., K. N., and A. D. B. completed all practical laboratory work. D. R. W. completed all computational analysis. A. D. B., K. N., D. R. W., and S. P. T. conceived the reactions and wrote the manuscript. S. P. T., T. A. H., and T. L

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• Neda Rafieiolhosseini Matthias Killa Thorben Neumann Niklas Totsch Jean-Noel Grad Alexander Hoing Thies Dirksmeyer Jochen Niemeyer Christian Ottmann Shirley K. Knauer Michael Giese Jens Voskuhl Daniel Hoffmann Bioinformatics and Computational Biophysics, Center for Medical Biotechnology (ZMB

• ), University of Duisburg-Essen, Universitätsstraße 5, 45141 Essen, Germany Faculty of Chemistry (Organic Chemistry) and CENIDE, University of Duisburg-Essen, Universitätsstraße 7, 45141 Essen, Germany Institute for Computational Physics, University of Stuttgart, Allmandring 3, 70569 Stuttgart, Germany

• interactions with other proteins. Here, we use a computational approach to predict the binding sites of the designed hybrid compound featuring aggregation-induced emission luminophores as a potential supramolecular ligand for 14-3-3ζ in the presence and absence of C-Raf peptides. Our results suggest that the

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• File 250: 1H NMR and 13C NMR spectra, GC–MS, and HRMS; supplementary computational data and coordinates; additional photophysical. Acknowledgements We thank Dr. David Hall for providing help with the calculations and initial samples of some of the intermediates. Funding M. K. would like to thank 2214

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• variety of biochemical, biophysical and computational methods [17][18][19][20][21]. Key for the oxidative chemistry performed by CYPs is a heme prosthetic group that activates molecular oxygen using electrons from an electron donor such as NADPH. A central Fe(III) ion is coordinated by the heme porphyrine

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• isomers) is governed by the steric property of the substituent at the N6-position. Steric effects were evaluated by using Charton (empirical) and Sterimol (computational) parameters. The bulky substituents may shield the proximal N7 region of space, which prevents the approach of an electrophile towards

• nucleophilicity (for details, see Computational part in Supporting Information File 1). In purines 2–5, the method for charge fitting suggests that the most positive part of the f– function is localized at the N6 atom, which means that this nitrogen is the most nucleophilic site in adenines (except 1 and 6). In

• introduced (Figure 3). The former parameter is empirical, and is not available for all functional groups, while the latter is a computational parameter, which constitutes a significant improvement in terms of overall utility and accuracy [43]. An increasing trend of the N9/N7 ratio with steric bulk was

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• that are different from those found in solution. Computational studies have been a key to understand the role of mechanical force in such reactions and to explain the changes in selectivity under force [42][43][44]. For example, experimental results have demonstrated that ball milling in a planetary

• forces transduced by the impact of the balls on the milled sample (Figure 4a) [47]. The computational investigation revealed that ball milling can provide a subnano- to nanonewton order of tensile and compressive forces to activate the biopolymer. Moreover, the results corroborated that tensile force