Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• synthesis [32][33][34][35]. Integration of g-CN into hydrogels has been popularized in the last four years, where g-CN nanosheets can be implemented into hydrogels through embedding [36] or covalent binding [37][38] for the target application such as reinforced hydrogels [39] and hydrogels for photoredox

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• some cases can be undesirable. Recent studies from our group have been carried out on the use of halogens as a binding motif in cubanes [15], bicyclo[1.1.1]pentane [16], and nonplanar porphyrins [17]. Another reason to investigate the effect of meso-halogenation of porphyrins is due to the potential of

• [18], the conformation of the porphyrin core can play a key role in the binding of small molecules or on its efficiency as an organocatalyst as demonstrated by Roucan et al. [19]. With the continuing interest in nonplanar porphyrins [20] and their relevance for the in vivo functioning of porphyrin

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• alkaloids that were isolated in the mid-1990s from the Caribbean sponge bataella sp. From a biological point of view, the batzelladines have received attention due to their reported activity as inhibitors of HIV gp120-human CD4 binding. Chiral N-tert-butanesulfinyl aldimine (SS)-58 was used as a precursor

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• . Keywords: amino sugars; deoxyfluorination; fluorinated carbohydrates; hexosamine hemiacetals; thioglycosides; Introduction Fluorinated carbohydrates are versatile carbohydrate mimetics used to probe or manipulate the recognition of carbohydrates by carbohydrate-binding proteins or carbohydrate-processing

• enzymes [1][2][3][4][5][6][7]. The introduction of additional fluorine atoms into a monofluorinated carbohydrate is an attractive way of modulating the binding affinity and pharmacokinetic properties of fluorinated glycomimetics. Hydrophobic segments incorporating multiple C–F bonds could (1) reduce the

• desolvation penalty associated with binding of hydrophilic natural carbohydrates [8], and (2) create additional contacts with the binding cavity via electrostatic and dipolar interactions with C–F bonds [9][10], new intermolecular hydrogen bonds [11], or rearrangement of hydrogen bond-mediating water

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

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• functionality. Thus, this synthetic route represents the first successful Cu-mediated coupling reaction of berberine substrates. The DNA-binding properties of the 10-O-arylberberine derivatives with duplex and quadruplex DNA were studied by thermal DNA denaturation experiments, spectrometric titrations as well

• , it has been found that berberine (1a) exhibits a selective cytotoxicity against cancer cells [12][13], which is mainly based on its DNA-binding properties [14]. Since the complexation with DNA leads to significant changes of the fluorescent quantum yields of the bound berberine, it can also be used

• berberrubine. And herein, we report the application of this Cu-mediated coupling reaction for the synthesis of 10-O-arylated berberine derivatives as unexpected reaction product, along with first experiments that demonstrate the G4-DNA-binding properties of this class of berberine derivatives. Results and

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• techniques, such as crystallography, have provided insights to rationalize numerous properties including binding affinity, nuclease stability, and trends observed in the gene silencing. In this review, we discuss the chemistry, biophysical, and structural properties of a number of chemically modified

• improving metabolic stability, pairing properties (RNA affinity), protein binding and transport/cellular uptake are concerned, chemical modifications are a prerequisite for the discovery and development of oligonucleotide therapeutics [11][12][13][14][15]. Thus, the natural PS and 2'-OMe backbone

• modifications provide improved resistance to degradation by exo- and endonucleases and they both affect protein binding [16][17]. Eight of the now approved 13 oligonucleotide drugs feature the PS modification in the backbone and all four approved siRNA therapeutics: ONPATTRO® (patisiran, 2018), GIVLAARI

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• acids (H-HAIYPRH-NH2) was identified via phage display [24] and has a high affinity (≈10 nM) for the transferrin receptor [24][25]. This peptide does not compete with endogenous transferrin binding and has been used to successfully enhance drug delivery to brain tissue [15][22][24][25][26]. Both

• of the nature of the target proteins. CCR5, a cell surface receptor, is internalized upon ligand binding before recycling back to the cell surface or processed for degradation in the lysosome [34]. On the other hand, gp120 is a viral surface protein that is involved in viral entry through

• [22]. In 1997 and 2002, Kircheis et al. developed a polyethyleneimine (PEI)-conjugated transferrin molecule at a ratio of PEI/transferrin 21.4 nmol:270 nmol and observed that transferrin shielded the PEI, decreasing toxicity and increasing target cell uptake through binding to the transferrin receptor

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