A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• kinetic model describing the components and the non-negativity constraint on the absorbance, can help to guide the decomposition of the data into chemically meaningful concentration traces and species-associated spectra (SAS) [38]. Global and target analysis is one of the methods employed in recent

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• that the most substituted C–H site next to a ketone will form the more stable carbanion (thermodynamic anion), whereas the least substituted carbanion will be the least stable carbanion (kinetic anion). This can generally be controlled by the type of base used. For the reaction in Scheme 1a, n-BuLi is

• commly used, which is known to lead to the kinetic anion. Because our ML model relies on the principle of lowest energy, it predicts the site with the lowest pKa value as the site of reaction (thermodynamic carbanion) and does not account for the type of base used. Going to Scheme 1b, we look at a

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• less coordinating counterion is more reactive to activate the olefin. We also conducted kinetic studies on how the olefin and amide structures impacted the overall reaction rate. The more electron-rich olefins generally proceeded faster than the electron-poor ones, suggesting that a significant

• positive charge was likely built up on the olefin prior to the nucleophilic addition. On the other hand, the electronic nature of the para-substituted benzamides had little impact on the overall reaction rate as both electron-rich and electron-deficient benzamides proceeded with similar kinetic profiles

• . All the kinetic plots are shown in Figure 1. With the optimized conditions and kinetic information in hand, we turned our attention to the amide substrate scope. In this case, both electron-rich and -deficient benzamides proceeded to the desired products in reasonable yields and high

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• under otherwise identical conditions gave a completely different spectrum (Figure 1B, red) and we assume that the triplet state of Aza-H is almost fully quenched by oxygen at the selected delay, which is supported by additional kinetic measurements (see below). The second transient species is identified

• transient species in Ar-saturated/air-saturated solution is also reflected in the kinetic traces at 440 nm and 640 nm (Figure 1B, inset). Following the decay of the transient triplet species (³Aza-H), essentially the same signal is reached irrespective of the presence of oxygen or argon in the solution. The

• competes with ionization already during the laser pulse. Kinetic measurements of the radical cation species show multiexponential decay, probably due to recombination of the radical cation and radical anion (Figure 2A, inset). Despite the reported absorption maximum for 4CP•− at 398 nm [72], we were unable

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• phenyl substituents, have been synthesized and shown to adopt non-planar conformations with the ortho-alkyl groups located above and below the most reactive 1,3-carbons of the furan ring. These bulky substituents provide a strong measure of kinetic stabilization. Thus, 1,3-dimesitylisobenzofuran and 1,3

• photooxidative resistance, especially along the acene-like segment, plus a strong measure of kinetic stabilization at the 1,3-carbons of the furan ring. As described here, there are compelling reasons to contemplate the synthesis of large, persistent isoacenofurans with unusually small HOMO–LUMO gaps. In this

• isoacenofurans. Thus, unless there is a need for improved kinetic stabilization of the most reactive 1,3-carbons on the furan ring, there appears little benefit of utilizing highly hindered 2’,4’,6’-triisopropyl (compound 24) or 2’,4’,6’-tri-tert-butyl (compound 25) substituents, especially as these compounds

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• . Evaluation of 1,4-azaphosphinine derivatives as inhibitors of hCDA, engineered A3B and wild-type A3A Evaluation of hCDA inhibition We monitored the hCDA-catalysed deamination of dC at 286 nm [70] and analysed the kinetic profiles at various inhibitor concentrations using a global regression analysis of the

• kinetic data using Lambert’s W function [71]. This method provides better estimates for the Michaelis–Menten constant (KM) and maximum velocity (Vmax) than nonlinear regression analysis of the initial rate (V0). It is also superior to any of the known linearised transformations of the Michaelis–Menten

• provides the initial velocity of deamination of ssDNA substrates, including the modified ones [56], in the presence of A3 enzymes. Consequently, the Michaelis–Menten kinetic model can be used to characterise substrates and inhibitors of A3. Both anomers of the nucleoside Va were individually incorporated

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• ) and 3-oxa-1,4-BCHs (123) (Figure 19) [58]. The experimental distribution coefficient (logD) of 2- and 3-oxa-1,4-BCHs 122 and 123 is reduced compared to equivalent para-benzene 121 while the kinetic aqueous solubility (KS) is increased. The intrinsic clearance rate in mouse liver microsomes (CLint) is

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• and kinetic experiments or crystallization of the active homodimer will be required to resolve the catalytic mechanism. If NnlA is specific for NNG as suggested by these results, it is worth speculating about potential functions of NNG and other nitramine natural products. Bacterial natural products

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• a side note, it should be mentioned that Hutchings and colleagues reported the hydrochlorination of ethylene with Lewis acids on solid supports [52]. However, this work solely focuses on kinetic studies and is therefore not discussed in this report. Reactions with in situ-generated HCl HCl gas can

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• for inositol dehydrogenases. (b) Comparison of the hygromycin A (red) and hygromycin A-like (orange) biosynthetic gene clusters. A more detailed comparison can be found in Supporting Information File 1, Table S2. Kinetic parameters for Hyg17. Supporting Information Supporting Information File 36

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• effect remains if the local structure of the linker consisting of an alkyl group and a pyrene group is maintained. Therefore, it is likely that the kinetic behavior of a protein immobilized with a single PASE linker exhibits an activation barrier-type energy surface between the bi-stable conformations on

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• Ruichen Lan Brock Yager Yoonsun Jee Cynthia S. Day Amanda C. Jones Chemistry, Wake Forest University, 1834 Gulley Rd., Winston-Salem, NC, 27109, USA 10.3762/bjoc.20.43 Abstract Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried

• undertaking a 1H NMR spectroscopic kinetic survey of solvent, ligand, and substituent effects on the general reaction 1 → 3 (with a variety of N-protecting groups), to supplement known qualitative observations. We found that, (1) electron-withdrawing phosphines accelerate hydroamination, (2) reactions are

• faster with more Lewis basic urea substrates, (3) mixed solvents are uniquely able to enhance rates, with protic methanol and DCM identified as the best combination, and (4) kinetic isotope effects are variable depending on the concentration of protons in solution with small deuterium KIE’s at low

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• corresponding 2,2-difluoroketones [15]. In related kinetic studies concerning the electrophilic 2-fluorination of 1,3-diketones with Selectfluor [16][17], we demonstrated that the rate-determining step for difluorination was enolization of the intermediate 2-fluoro-1,3-diketone. Monofluorination of 1,3

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• ). This is also the basic compound used in the transformations that are studied in this work due to the high kinetic stability and good solubility ensured by the tert-butyl groups. The largest positive charge of the C(1)–C(2)–C(3) segment is concentrated at the C(2) atom. The charge at the other

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• . An immobilization level of 900 response units (RU) was obtained. A reference surface was always present in flow cell 1, allowing for the subtraction of bulk effects and non-specific interactions with streptavidin. The mammalian-produced CMA1 was injected in single cycle kinetic over the flow cell

• experiments, nine concentrations of LacNAc (Elicityl, #GLY008) from 10 to 0 mM with a dilution coefficient of two supplemented with a fixed concentration of 0.8 µM was injected into the cell surface in multiple cycle kinetic with an association time of 500 s and a dissociation time of 12 s at a flow rate of

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• photochromic N,N'-diacyl derivatives of indigo, first examples of photochromic indigos containing aromatic N,N'-substituents 1984: first report on intra- and intermolecularly bridged photochromic N,N'-substituted indigos (follow-up studies in 1989, 2021) 1985: detailed kinetic studies of the thermal backward Z

• the lack of steric restriction [57]. The thermal Z–E isomerization of N,N'-diacylindigos was further investigated by Sueishi and co-workers in 1985 [58]. In this study, the kinetic experiments for a range of derivatives 9a, 9c, 9d, 9g, 9i–m bearing various N,N'-diacyl substituents in different

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• great attention in organic synthesis. Various methods [9], including reductive hydrogenation [10][11], kinetic resolution [12][13][14], functionalization of indole [15], and de novo construction of chiral 2-substituted indolines, have been developed [16][17][18][19][20]. In recent years, the metal

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• File 6: Experimental procedures and spectral data (NMR, mass spectra) and key kinetic studies. Funding This work received financial support from the Fundação para a Ciência e Tecnologia (FCT Portugal) through the project UIDB/50006/2020 | UIDP/50006/2020.

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• positioning of the [2 + 2] CA or RE step as the rate-determining step may depend upon the structural attributes of the electrophiles and nucleophiles. In 2023, Nielsen et al. conducted an exhaustive kinetic analysis of the [2 + 2] CA–RE reaction involving 4-trimethylsilylethynylaniline and TCNE by leveraging

• between AB and P, from which C1 is generated. Notably, this additional route significantly accelerates the overall reaction. The researchers reported that the conversion of the ABP complex into C1 transpired at a markedly accelerated rate compared with the conversion of AB alone, with a kinetic constant

• 100 °C to generate 30c. Conversely, the transformation of 28b proceeded at 45 °C, and the smallest macrocycle 28a reacted with TCNE at 0 °C. Kinetic investigations revealed that the rate-determining step in the reaction involving 28a–c with TCNE was the second-order [2 + 2] CA step, succeeded by the

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• nanotubular-shaped fullerene inside the peapod. Kinetic analysis with the variable-temperature (VT) SMART-TEM method for the aforementioned C60 dimerization has also been reported by these authors [9]. They concluded that the SWCNT, which accumulates energy by the interaction with the electron beam, activates

• of dimer 1-Cs•+ (see Supporting Information File 1, Figure S9). However, TS-2 is significantly lower in energy. Therefore, in gas phase, dimer 1-D2h•+ is predicted to be the thermodynamic and the kinetic product. Once our methodology was validated, the energy profile for the formation of dimer 1-Cs

• pseudopotentials [16] while valence electron density was expanded in plane waves with a maximum kinetic energy of 400 eV. The model of SWCNT was 29.61 Å long and with a diameter of 13.65 Å, embedded in a box of 30 × 30 Å of vacuum in the plane perpendicular to the nanotube axis. The gas-phase structures were in a

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• (regime 1), the hydrogen generation rate is typically limited by the available photon flux and can be approximated first order with respect to light intensity. For higher photon fluxes, kinetic limitations appear (second regime) since the larger amount of charge carriers present in the photocatalysts

• and reaction rate [42], which was used in this work to fit the experiment results (see Equation 4). where is the average (observed) reaction rate, k* is the kinetic rate constant, θ is the surface coverage of the photocatalyst, α is the optical density, ϕ is the quantum yield, qp is the volumetric

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• with several Michael acceptors [34]. In this work we present the formation of stable zwitterions from the reaction of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol (1) and a variety of different Michael acceptors and disclose kinetic investigations on the zwitterion formation with carbonyl and non

• donors attached to the alkyl substituent of the phosphonium center (Figure 3). This hypothesis is further supported by the observation of two very different chemical shifts for the two amide protons in the 1H NMR spectrum of 2b in CDCl3 giving resonance at 5.21 and 8.58 ppm. Kinetic studies In the next

• . The strong Michael acceptors were methyl acrylate (E = −18.84) bearing a carbonyl-based electron-withdrawing group and acrylonitrile (E = −19.05) featuring a geometrically different electron-withdrawing group. Acrylamide was selected as a weak (E = −21.8), carbonyl-based Michael acceptor. The kinetic

NMRium: Teaching nuclear magnetic resonance spectra interpretation in an online platform

• Luc Patiny,
• Hamed Musallam,
• Alejandro Bolaños,
• Michaël Zasso,
• Julien Wist,
• Metin Karayilan,
• Eva Ziegler,
• Johannes C. Liermann and
• Nils E. Schlörer

Beilstein J. Org. Chem. 2024, 20, 25–31, doi:10.3762/bjoc.20.4

• a reaction substrate and product or analysis of kinetic studies that include several data points) or overlaying of 2D spectra, for example, to show the different outcomes of related experiments such as COSY/TOCSY or HSQC/HMBC. Students will be enabled to learn these online comparison aspects by

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• reaction enabled us to perform a kinetic analysis of AvaA7, which confirmed that AvaA7 catalyzes the denitrification of 3-diazoavenalumic acid in avenalumic acid biosynthesis. This study deepened our understanding of the highly reducing type II polyketide synthase system as well as the diazotization

• of 3-aminocoumaric acid (3-ACA, 3) and 3-AAA (7) with considerably higher efficiency than AvaA6 in avenalumic acid biosynthesis. We also performed kinetic analysis of AvaA7, which catalyzes the denitrification of 3-DAA (8) in avenalumic acid biosynthesis, using the highly efficient diazotase CmaA6

• diazotization catalyzed by CmaA6 was much higher than that of AvaA6; almost 100% of 3-ACA and 3-AAA were converted to corresponding aromatic diazo compounds 4 and 8, respectively (Figure 3C). Kinetic analysis of AvaA7 catalyzing denitrification of 3-DAA The high conversion efficiency of 3-AAA (7) to 3-DAA (8