Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• ]. The major challenge in designing chemically modified ONs as antigene/antisense agents is to ensure an efficient cellular uptake and nuclease resistance while still maintaining, or ideally increasing, binding affinity and specificity of the ONs towards their DNA or RNA target. Many synthetic analogues

• . For example, both PNA and modified PNAs have excellent chemical stability, are resistant to enzymatic degradation, and have high binding affinity towards complementary DNA and RNA, but have a tendency to aggregate, require high salt conditions, and have low solubility in water [1][25][26]. LNA (BNA

• ) have an enhanced thermal stability in DNA triplexes and duplexes, a high binding affinity to RNA, and are nuclease resistant [22][26][27][28]. These properties have led to LNA (BNA) being used in various therapeutic ONs that have reached clinical trials [29]. However, the multistep synthesis of LNA and

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

• will also influence the kinetics [48][51]. Future extensions to this work will consider the effects of acetylation of sialic acid residues, since this modification reduces the negative charge of the carbohydrate, thus altering binding affinity, while an increased incidence of 9-O-acetylated GD3 is

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• biologically active molecules that already find practical use. It has been found that complexation improves the transportation of a drug and prolongs its effect, and a synergistic effect is observed in some cases [36]. The situation with covalent binding in fullerene–drug conjugates is different. C60 is an

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense

• [Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These

• ]. The modification of oligonucleotides with GuNA[H]-T improved the nuclease resistance, cell membrane permeability, and binding affinity toward complementary single-stranded DNAs (ssDNAs) and RNAs (ssRNAs). We also synthesized and evaluated a GuNA[H]-T analog bearing a methyl group in the guanidine

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• determined by ICP-AES. The analysis of the XPS spectra in the Co 2p region was consistent with the presence of Co2+ and Co3+, with main binding energy peaks at 779.6 and 780.0 eV, along with satellite signal at approximately 786 eV, which in principle could be ascribed to Co3O4 species in the catalyst

• (Figure S4, Supporting Information File 1). Nevertheless, it must be pointed out that the oxidation state of cobalt is difficult to assign from the XPS results, due to the binding energy overlap of the different cobalt oxides [54]. Based on our results and previous reports by other groups on the same area

• 548 spectrometer, using Mg Kα radiation at 250 W and 20 mA. The resolution spectra were taken at 50 eV of pass energy, giving an absolute resolution of ±0.5 eV. The operation base pressure was kept in 10−10 Torr range. The adventitious C 1s binding energy was taken as a charge reference and fixed at

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• safety [15][16][17]. Various effective receptor-binding peptides have been identified by the phage display technology [18]. The peptides can be readily prepared through solid-phase peptide synthesis (SPPS), a highly reproducible method with minimal side reactions. Many peptide–lipid conjugates

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -aminophosphonodichloride 92 with phenol and methyl (S)-2-hydroxypentanoate (18). All synthetic phosphonodepsipeptides 99, 102, and 104 were considered as glutathione-analogue phosphonopeptides as mechanism-based inhibitors of γ-glutamyl transpeptidase for probing the cysteinyl-glycine binding site (Scheme 16) [31

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• example, the volume difference between Pro and Dfp is smaller than the difference between Val and Ile. It is therefore not surprising that Flp and Dfp can in principle be recognized as proline by natural enzyme binding pockets. The successful experimental incorporation of fluoroprolines into proteins

• proline as an external nutrient [65]. Another important transport system is the ATP-binding proline/betaine transporter. In E. coli, this permease activates in the course of osmotic shock response, represented by the transporter gene proP and the proU operon. The genes proV (encoding an ATP-binding

• biosynthesis occurs in an enzyme called aminoacyl-tRNA synthetase (AARS). An AARS usually performs several sequential steps (Figure 10A). First, an amino acid that fits into the binding pocket reacts with a molecule of ATP creating an aminoacyl adenylate. This step is called activation. An aminoacyl adenylate

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• , Otting and co-workers have recently developed a synthetic strategy, based on a continuous exchange cell-free system (CECF), in which a key chitin-binding mutant of release factor RF1 can be removed under conditions that maintain the full activity of the S30 extract, thereby minimizing the incidence of

• that can be used as 19F NMR reporters. Aromatic amino acids have been preferentially used as 19F NMR probes both in binding and in conformational studies owing to their ready availability. However, more recently fluoro-aliphatic, and in particular perfluoro-aliphatic amino acids, have become

• , all peptides where 8 was introduced could be detected even at concentrations as low as 5 μM, demonstrating that pFtBSer is a highly sensitive tool to study binding events by way of 19F NMR chemical shift and nuclear relaxation changes. In addition to homoserine, perfluorinated analogues of both

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• The key purpose of this work is the synthesis of species bearing both an o-dioxolene coordination site and an additional peripheral function capable of binding to a metal ion. The study of coordination abilities of peripheral groups will be the subject of further investigations. In this work we have

• -Quinones 6a, 6b, 6d and 7 have a rigid and almost planar structure, moreover, they bear an additional coordination site at the periphery of the molecule potentially capable of binding of metal ions. Such a topology of the ligands is promising from the viewpoint of its use in the design of coordination

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• binding properties [25] and reactions with bovine serum albumin [27]. Cyclam is known as a tetraamino-macrocyclic ligand, which binds strongly to give complexes with many transition metal cations. While catalytic applications of square planar cyclam complexes are reported for metals, such as Ni [30][31

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• applied in aqueous solution, with the Schmuck binding motif – the guanidiniocarbonyl‐pyrrole zwitterion binding motif – representing a most versatile binding motif with potential from nanostructure design to biomedicine [22][23][24][25]. In addition, it is desirable to establish general concepts that do

• not rely on specific binding motifs. Here, electrostatic self-assembly was shown to yield a variety of supramolecular nanostructures [4][26][27][28][29][30][31][32][33]. We have built the nanoscale assemblies from polyelectrolytes and multiply oppositely charged molecules based on electrostatic

• composition when studying these effects, two ratios were introduced. The loading ratio l describes the small molecule to polyelectrolyte stoichiometry: It is defined as the molar concentration of the negative charges of the photoacid plus the molar concentration of formal Flavy binding sites – formally set to

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• coupling, sparging to dryness followed by C-4–I displacement) with the key pyridine-2-(1H)-one hinge-binding motif revealed from the beginning of the process. Our exploration started from commercially available 2-fluoro-4-iodonicotinic acid (25). Amide coupling using HATU led solely to 26 with no traces of

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• , hydrophobic cavities, and specific guest recognition), they can provide a suitable environment to realize photocatalysis via noncovalent interactions with different substrates. In this minireview, we emphasized the photochemical transformation and catalytic reactivity of different guests based on the binding

• , during the catalytic process, the reactive guest should have a greater binding affinity or the photoproducts should have the lowest binding affinity with the supramolecular host to avoid product inhibition, so as to produce a better catalytic turnover efficiency [14][15]. However, it is quite complicated

• quantum yield of 3.8 × 10−2 and 0.4, respectively. In contrast, for flavins without the zinc(II)–cyclen unit, only small amounts of product were observed, and the quantum yield was 30 times lower compared to that of the assembly with the flavin chromophore possessing a binding site. The mechanism may be

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• entities [14][15][16][17]. However, no examples for supramolecular materials employing this complementary interaction have been reported so far. In the present study we report the first halogen-bonded liquid crystal based on the complementary binding of nitro-cyanostilbene and tetrafluoroiodobenzene

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• , 64293 Darmstadt, Germany 10.3762/bjoc.17.11 Abstract We report novel supramolecular polymers, which possess a reversed viscosity/temperature profile. To this end, we developed a series of ditopic monomers featuring two self-complementary binding sites, either the guanidiniocarbonyl pyrrole carboxylic

• -complementary [14] binding units (BU, blue) and a connecting linker unit (LU, green) to connect the BUs. In this case, the BUs are ureidopyrimidone units, which dimerize due to a fourfold hydrogen bond, thus allowing for strong supramolecular interactions [15]. Due to the flexibility of the LUs, the BUs can

• Meijer, we now developed a series of novel ditopic monomers as potential VIIs. We conducted a systematic variation of both the linker unit and the binding unit in order to investigate structure–property relationships with regard to VII performance and solubility in nonpolar solvents (such as motor oils

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• of rigid supramolecular polymers. Since multivalent sulfated supramolecular structures mimic naturally occurring L-selectin ligands, the corresponding affinity was evaluated using a competitive SPR binding assay and benchmarked to an ethylene glycol-decorated supramolecular polymer. Keywords: L

• , these interactions occur in a multivalent fashion, allowing to overcome drawbacks of the limited strength of noncovalent bonds and to tune the selectivity at the same time [1][2]. The binding of viruses to the membrane of their host cells [3][4][5] as well as the recognition of carbohydrates by lectins

• of multivalent interactions is the extracellular adhesion protein L-selectin. L-Selectin plays a critical role in inflammation processes by supporting the migration of leukocytes to inflammatory sites via adhesion to endothelial cells [19][20][21]. On a molecular level, a cationic binding site [22

The fluorescence of a mercury probe based on osthol

• Guangyan Luo,
• Zhishu Zeng,
• Lin Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 22–27, doi:10.3762/bjoc.17.3

• fluorescence, UV–vis spectrophotometry, mass spectrometry, and 1H NMR spectroscopy, and the recognition mechanism is discussed. The results showed that OST and Hg2+ can form a complex with a stoichiometric ratio of 1:1. The binding constant was 1.552 × 105 L∙mol−1, having a highly efficient and specific

• detection. Study on the mechanism of the OST as a fluorescent Hg2+ probe The binding ratio of the OST–Hg2+ complex The stoichiometric ratio between OST and Hg2+ was determined using the Job method (constant mole variation), and the results are shown in Figure S3, Supporting Information File 1. The maximum

• UV absorption intensity was achieved at n(Hg2+)/n((OST) + (Hg2+)) = 0.5 at 325 nm, indicating that the binding ratio of the OST probe to Hg2+ was 1:1. Combined with mass spectrometry data (Figure 5), the fragment peak of ESIMS at m/z 892.5422 corresponded to [OST2–Hg2]+ (calculated as 892.5429

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

• can only be fully exploited via interactions, either in the form of PPIs or with other metabolites and biomolecules, such as nucleic acids. Thus, the identification of the molecular binding partners that proteins interact with is an interesting avenue to facilitate the discovery of the protein

• (or any other organic molecule [19]) structure. A resolution of up to 0.6 Å (RNA-binding protein FUS, residues 37–42, EMD-0699, PDB: 6KJ4 [20]) were obtained when using this method. Nannenga and Gonen gave a detailed account on MicroED [21]. As another category, mass spectrometry methods are used to

• methods are used to characterise the protein complex and to confirm the presence of certain interactions. Biophysical approaches are important to determine binding affinities, enthalpy changes, entropy changes, and the on- and off-rates of binding, amongst others. Examples include surface plasmon

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• recognition ability can be further strengthened by the introduction of another chiral moiety directly onto the urea N atoms. The systems with double chiral units being located around the binding ureido cavity showed better stereodiscrimination, with the highest selectivity factor being 3.33 (KL/KD) achieved

• for chiral anion recognition, contrary to the cone receptor, a design based on the 1,3-alternate conformer enables the introduction of chiral units into the phenolic functions of the inverted aromatic moieties nearby the ureido cavity responsible for the binding, as in C. This design can be

• enhancing the interactions within the binding cavity. In this context, we realised that further strengthening of the chiral induction can be reached via the synchronous application of chiral units on the ureido moieties as well, as in D. In this paper, we report the preparation and complexation study of the

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• peptidic arms equipped with lysine and an artificial strong anion binding site, the guanidinocarbonylpyrrole (GCP) moiety (Figure 2A). These arms also contain tryptophan for dissimilar aromatic interactions with different nucleobases. The fluorescence intensity of probe 1 increases by more than 4-fold at

• 540 nm in presence of 10 µM ATP (Figure 2B). The ATP binding constant is calculated to be 2.2 × 105 M−1. A fluorescence job plot between 1 and ATP confirms an 1:1 binding stoichiometry between ATP and probe 1. The fluorescence response follows the following order ATP > GTP > UTP > CTP > TTP > PPi

• interacts effectively with double-stranded DNA (dsDNA) as positively charged lysine residues are expected to interact with the phosphate backbone electrostatically. Upon binding to dsDNA, it undergoes a conformational change from the folded to an extended form that switches the fluorescence signal from

Construction of pillar[4]arene[1]quinone–1,10-dibromodecane pseudorotaxanes in solution and in the solid state

• Xinru Sheng,
• Errui Li and
• Feihe Huang

Beilstein J. Org. Chem. 2020, 16, 2954–2959, doi:10.3762/bjoc.16.245

• the hydrogen atoms on the ethoxy groups. It is worth mentioning that we did not find any interaction of the benzoquinone subunit of the host with the guest molecule. Host–guest complexation in solution In order to further study the host–guest binding properties of H and G, we explored the complexation

• , Supporting Information File 1). A Job plot based on the proton NMR data was made to determine the complexation stoichiometry between H and G. The formation signified a 1:1 binding stoichiometry in chloroform-d at room temperature (Figures S5 and S6, Supporting Information File 1). Combined with the mass

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• (GCPs). The use of UV laser excitation enables Raman binding studies of this class of supramolecular ligands at submillimolar concentrations in aqueous solution and provides a selective signal enhancement of the carboxylate binding site (CBS). A current limitation for the extension of this promising

• UVRR approach from peptides to proteins as binding partners for GCPs is the UV-excited autofluorescence from aromatic amino acids observed for laser excitation wavelengths >260 nm. These excitation wavelengths are in the electronic resonance with the GCP for achieving both a signal enhancement and the

• selectivity for monitoring the CBS, but the resulting UVRR spectrum overlaps with the UV-excited autofluorescence from the aromatic binding partners. This necessitates the use of a laser excitation <260 nm for spectrally separating the UVRR spectrum of the supramolecular ligand from the UV-excited