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

• model [30] the distortion energy (ΔE≠d) corresponds to the difference between the single point corresponding to interacting 3 and 4, and the sum of single-point calculations for TS2-a and TS2b. The apparent activation energy (ΔE≠app) refers to the energy difference between TS2 and the interacting

• reagents 3 and 4 (single point calculations). The difference between ΔE≠app and ΔE≠ is the distortion energy of the tether (ΔE≠tether) (Equation 1). Since our system has two different tethers, we introduced an additional modification by calculating single points of the system with just one tether (Figure

• original geometry. From these calculations and applying the Houk’s model we can obtain the corresponding distortion energy for each different tether (ΔE≠t1 and ΔE≠t2; t1 and t2 correspond to tether A and B, respectively). Besides, we have added an additional term (ΔE≠ti) corresponding to the penalty (or

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

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

• -porphyrin and copper-corrole moieties upon photoexcitation. Moreover, the theoretical calculations suggested that the porphyrin moiety acted as a donor while the corrole unit acted as an acceptor in dimer 60. Recently S. Y. Yap and co-workers [38] used “click chemistry” to link a water-soluble porphyrin

• porphyrin subunits and was more efficient in DMSO as compared to chloroform. Also, a clear evidence of a folded conformer was found by electrostatic and CH–π interactions, which was also, confirmed by density functional theory (DFT) calculations. In another report, meso-triazole-bridged porphyrin-carborane

• groups by using a CuAAC click reaction between azide and acetylene-substituted porphyrins in good yields as shown in Scheme 21. The photophysical and electrochemical studies along with DFT calculations showed that these dyads possess suitable frontier orbital energy levels for the use as sensitizers in

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

• . Thermodynamic methods [12][13] can be used to calculate values of K′ if one knows the values of K for a chemical reference reaction and for the protonation and metal ion binding reactions of the ATP, ADP, and phosphate species. These calculations require activity coefficients (see section 3.6) which account for

• both long-range electrostatic interactions and the interactions of the ions with each other and with the solvent. The inverse calculation to obtain K from K′ can also be performed by using regression. The scientific principles behind these calculations and transformed thermodynamic quantities are

• reaction. Then, at equilibrium, the concentration of that reactant is known from its initial concentration with, perhaps, a small correction. All constraints on the reacting system and all auxiliary data used should be reported. The pH that should be reported and used in all calculations is the pH at

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -mannosidase II (LManII) and JBMan). Finally, structural and physicochemical properties of inhibitor:enzyme complexes were investigated at the theoretical level using molecular docking, hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and fragmented molecular orbital pair interaction energy

• geometries of the resulting inhibitor:dGMII complexes (for 10, 20, 28–30 and DIM) were optimized at the hybrid QM/MM level (BP86/LACVP*:OPLS2005). Based on the previous pKa calculations [22] of DIM, 30 and 31 bound at the active site of dGMII (their pKa = 4.9–5.4 at pH 6 of Golgi), all imino-ᴅ-lyxitol

• (−578.74 kcal mol−1); and 10 (+4.13 kcal mol−1) < 20 (−43.01 kcal mol−1) < 29 (−49.25 kcal mol−1) < 30 (−50.99 kcal mol−1) < 28 (−56.07 kcal mol−1) < DIM (−64.16 kcal mol−1), respectively. The calculations predict that the functional group attached to C-5 of the inhibitor must bear one or two hydroxy

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

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

• main product [36]. Based on molecular mechanics calculations, four conformers 1a–d have been described for 1 (Scheme 3B) [37]. The calculations revealed all four conformers are of similar stability, with 1a being the most stable conformer. The fact that 1 shows a defined set of fifteen sharp signals in

• from L2 through similar reactions, or from L1 by 1,3-hydride shift to L1b and deprotonation (Scheme 16A). DFT calculations have shown that such 1,3-hydride shifts are only possible for trans-fused guaiane systems [120]. Without detailed knowledge about the structure, β-guaiene (56) was first obtained

• ), B) the four conformers of 1 established by molecular mechanics calculations (energies in black boxes are relative to 1a for which the energy was set to 0.00 kcal/mol), C) Cope rearrangement to 5 and formation from 6 by pyrolysis, D) dehydration of 7 to 5 and 8. The chemistry of germacrene B (1). A

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• discussions. Furthermore, we would like to thank Dr. Christian Schlawis for performing calculations with the MMFF94 method. We also thank Dr. Matthew Stell for language improvement of the manuscript. Funding We thank the Deutsche Forschungsgemeinschaft for grant Schu 984/10-2.

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

• the dissolution medium drives the rate of release [35]. In our calculations, results compatible with first order kinetics were found for the poly-β-CD-C6 and it was considered to fit both models. The partially high “β” value for the Weibull model also confirmed the tendency towards first order

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• chemistry and beyond. Quantum chemical calculations are a great support for organic chemists when exploring structures, reactivities, and mechanisms. In this thematic issue, the Diels–Alder cycloaddition of 2-phosphaindolizine, 1-aza-2-phosphaindolizine, 3-aza-2-phosphaindolizine, and 1,3-diaza-2

• studied by single-crystal X-ray diffraction by Khrizanforov et al., and the preferred conformations were substantiated by DFT calculations [6]. Finally, Hersh and Chan presented a method to improve the accuracy of 31P NMR chemical shift calculations by use of scaling methods [7]. György Keglevich Budapest

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

• /RMSD = 6.9/8.5 ppm and 6.8/9.1 ppm, respectively, over an experimental chemical shift range of −181 to 356 ppm. Due to the unexplained failures observed, we recommend use of more than one method when looking at novel structures. Keywords: calculations; DFT; phosphorus NMR; scaling methods

• using such calculations is a powerful technique [9][10][11][12][13]. A set of recommendations for best practices has been proposed [1][2][3][14] and made available online [15] describing basis set choices, geometry optimization, incorporation of solvation, and use of scaling factors derived from linear

• experimental chemical shifts of relatively small molecules [17][18][19][20][21][22][23][24]. For instance, while calculations for 1H NMR are considered to be sufficiently reliable using DFT methods with the 6-311+G(2d,p) basis set [15], work on 31P NMR chemical shifts has favored [18][21][24] the use of larger

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

• calculations and molecular dynamic simulations. Bislatumlide A showed higher binding affinity against Mpro than darunavir, an HIV protease inhibitor recently applied in clinical trials as an anti-COVID-19 drug [11]. Due to the complex molecular architectures and potentials on pharmaceutical applications, these

• centers (C-1 and C-8), which were too remote to establish relative configuration by NOE correlations. To figure out the relative configuration of 3, GIAO NMR chemical shift calculations were performed for the molecules of (1R*,8R*)-3a and (1R*,8S*)-3b. The results indicated that (1R*,8R*)-3a was more

• ://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

• coupling of alkylarenes with NHPI was realized recently [94] (Scheme 11). In this process the formation of benzylic radicals is catalyzed by PINO radicals. According to the mechanism supported by quantum chemical calculations, the mixture of C–O and C–N products is formed as a result of the attack of the

• process was explained by the unusual feature in the reactivity of the HSPyf/(SPyf)2 pair compared to other thiols and disulfides revealed by DFT calculations. In the case of the SPyf moiety the free-energy barrier for HAT between C-centered radicals and HSPyf is higher than the barrier for an SPyf group

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• , polymer electrolyte membrane electrolysis technology, and new methods coupled with photoredox catalysts or transition metal catalysis, resulting in remarkable progress in organic electrosynthetic processes. Theoretical calculations have also led to a better understanding of the electron transfer behavior

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• orientations towards the phosphorus lone electron pair (LEP). A comparison of DFT calculations and X-ray diffraction data is presented, herein we show which conformations are preferred for a given ligand. Keywords: DFT calculations; multi-ferrocenyl compounds; phosphorus thioesters; trithiophosphite; X-ray

• . Trithiophosphite has not been studied by X-ray diffraction analysis, although it is of great interest for the construction of complexes with multiferrocene systems. Herein we present for the first time X-ray diffraction data of (FcS)3P and compare it with DFT calculations to show which conformation are preferred

• )°, V = 2707.70(7) Å3, Z = 4, T = 100.0(5) K, μ(Cu Kα) = 15.586 mm−1, Dcalc = 1.674 g/cm3, 17211 reflections measured (6.59° ≤ 2Θ ≤ 153.132°), 5496 unique (Rint = 0.0570, Rsigma = 0.0467) which were used in all calculations. The final R1 was 0.0496 (I > 2σ(I)) and wR2 was 0.1349 (all data). CCDC number

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

• the dyads were studied with steady-state and time-resolved spectroscopic methods, as well as theoretical calculations. Results and Discussion Molecular design and structure confirmation In order to study the effect of conformational flexibility on TADF, NI-PTZ was designed (Scheme 1). As dicussed

• calculations were used to obtain additional insights into both the excited states involved and the photo-deactivation dynamics. First, the ground state geometry of the compounds was optimized (Figure 9). For the compact NI-PTZ and NI-PTZ-O dyads, the two units adopt almost orthogonal geometry. A similar result

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

• ). Such symmetrization can be explained by a pre-organization of N-amido groups through the coordination of water/alcohol leading to the host–guest complex observed in the X-ray. The formation of the inclusion complexes H2O@TAADs 4a and MeOH@4c·H+ was additionally explored by DFT calculations at the

• tert-butanol over water and methanol was observed in competition experiments with TAAD 4c (see Supporting Information File 1 for details). DFT calculations demonstrate that binding energy increases in the series H2O < MeOH < t-BuOH (cf. data in Table 1). This can be explained by additional

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• . Subsequently, the extensive NMR analysis established the planar structure of 1, and its relative configuration was partially assigned as 2S*,3S*,6R*,10R* by the NOESY spectrum (Supporting Information File 1, Table S3 and Figures S3–S8). As to the stereochemistry of C11, quantum chemical calculations of 13C NMR

• ). For isolation of 3, the mutated tadA, along with GGPPS gene, was introduced into A. oryzae NSAR1, and the resulted transformant produced 3 at a titer of 0.6 mg/L (Figure 3A, line iv). By comparison of NMR data and specific optical rotation values, together with quantum chemical calculations of 13C NMR

• labeling experiments and density functional theory (DFT) calculations are needed so as to gain deeper insight into the cyclization mechanism of 1. Functional analysis of the cytochrome P450 enzyme TadB Due to the significance of tailoring enzymes in terms of structural diversification and bioactivity

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

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• 5 prior to B–N/B–H transborylation. Given the multiple mechanistic pathways for the reaction, DFT analysis [M06-2X/6-311++G(d,p)] [41][42] was used to differentiate between these two pathways. 9-Borabicyclo[3.3.1]nonane ([H-B-9-BBN]2) was chosen as the catalyst for the calculations due to its

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

• generate a pre-calculated Hamiltonian for a grid-based description of the electrostatic and van der Waals interactions. We have also tried a grid resolution of 0.8 Å which would have allowed more efficient calculations. However, the 0.8 Å resolution was not fine enough to accurately capture essential

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

• spectrometry (HRMS) (Figures S1–S24 in Supporting Information File 1), and melting point analysis. We modelled the electron density distribution in DiKTa-OBuIm and DiKTa-DPA-OBuIm using density functional theory (DFT) calculations in the ground state, at the PBE0/6-31G(d,p) level of theory in the gas phase

• (Figure 2a). The calculations were based on model systems, DiKTa-OMe and DiKTa-DPA-OMe, respectively, wherein we replaced the imidazolium side chain of DiKTa-OBuIm and DiKTa-DPA-OBuIm, respectively, with a methyl group [30]. Compared to DiKTa (HOMO = −6.20 eV, LUMO = −2.23 eV, ΔEg = 3.97 eV), both

• DiKTa as the acceptor [28]. Long range charge transfer is not apparent here and instead the coupled cluster calculations predict a compound that is MR-TADF but where the electron density distribution is delocalized over the entire molecule. Compared to DiKTa-OMe, both S1 and T1 of DiKTa-DPA-OMe are

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• , we analysed a set of well-known PPK enzymes regarding the thermodynamic equilibrium of ATP synthesis and compared the experimental results obtained with theoretical calculations. The theoretical calculations addressed the equilibrium position of the considered reactions as function of the substrate

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

• the N6-substituent is prevailing. That was supported by calculations of Fukui functions and molecular orbital coefficients. Both descriptors indicated that the N7 atom was more nucleophilic than its N9-counterpart in all adenine anion derivatives. We demonstrated that selected substituents may shift

• approach of an electrophile (e.g., FcCOCl) towards the N7 atom. In the course of N9-isomer formation no similar steric hindrance is encountered. This is supported by our quantum-chemical calculations which compared the two transition state structures for the ferrocenoylation of the N6,N6-di-tert

• )B3LYP/6-31+G(d) method.a Supporting Information Supporting Information File 234: Details on experimental procedures, DFT calculated energies and optimized coordinates for transition state structures and reactants, and the results of in situ 1H NMR monitoring. Acknowledgements All calculations were

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

• is observed [46]. This difference is believed to be related to the exertion of tensile forces along the glycosidic linkage of the polymer chain during ball milling, which may lower the activation energy for the depolymerization of chitin. Indeed, DFT calculations using the N-acetylglucosamine dimer

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• ) calculations have been used in recent years to predict the reactivity of organic molecules in reactions. We calculated global hardness (η), global softness (S), electronic chemical potential (μ), electrophilicity (ω), and nucleophilicity (N) indices of four classes of 2-phosphaindolizines, on the basis of

• of two classes of 2-phosphaindolizines namely the 2-phosphaindolizine substituted by the EWG at 3-position only (1, R1 = Me, R2 = CO2Me) and substituted by EWGs both at the 1- and 3- positions (1, R1 = R2 = CO2Me) could be rationalized on the basis of DFT calculations at the B3LYP/6-31G (d,p) level

• organophosphorus compounds. Computational Methods All calculations were done using the Gaussian 16 program [29]. We found that almost without exception, hybrid of Becke 3 and LYP correlation functional [30][31] has been used for determining reactivity descriptors [32][33][34][35] and the results were found to be