Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• , trihydroxy nucleoside 14b was protected with TBDPS to carry out the synthesis of the target nucleoside monomer 9b through a chemical pathway. However, the poor yield of this reaction compelled us to abandon the route as high solubility of the TBDPS-protected dihydroxy nucleoside in aqueous phase withstood

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• phenethyl group was chosen for the development of the one-pot PEG elongation approach for PEG synthesis although other groups that meet the two criteria can be used as well. Using the phenethyl group for protection, the monomer 2 was chosen for the stepwise PEG synthesis. The simplest method for its

• synthesis would be to react (PEG)4, which is commercially available and inexpensive, with styrene to give 6 [32], and tosylation of 6 to give the monomer (Scheme 3). However, the reported conditions for the synthesis of 6 without using an expensive catalyst gave low yields. We did not test the conditions

• under basic conditions to give 7. Removal of the DMTr group of 7 under acidic conditions gave 6, which was tosylated to give 2. This route is longer than the other two, but the products of all the steps are easy to purify, and it is our preferred route. With the monomer 2 in hand, the stepwise synthesis

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• properties Cryogels are macroporous hydrogels with interconnected porosity, with high swelling capacities and large surface areas. Ultimately, many of the final cryogel properties are dependent on the choice of polymer/monomer composition used. However, other factors such as crosslinking, pore size, wall

• crosslinking (ratio of monomer to crosslinking agent), while the degree of crosslinking is tuned in physically crosslinked cryogels by varying the number of freeze–thaw cycles. Pore size, wall thickness, and wall density are of significant importance for cryogels properties [16]. Thicker walls and higher wall

• densities typically result in improved mechanical properties and are influenced by the concentration of monomer or precursors used as well as the type of crosslinking in the cryogel. Moreover, the processing conditions used when synthesising cryogels have a vast effect on the internal structure. An

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• ) Diazido monomer, bisphenol A di(3-azido-2-hydroxypropan-1-ol) (Az-3) was synthesized according to a described method [46]. Az-3 was obtained as light yellowish viscous oil and was directly used without further purification, yield 98%. 1H NMR (500 MHz, CDCl3) δ 7.15 (m, 4H), 6.82 (m, 4H), 4.16 (m, 2H), 4.0

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• enabled not only comparison of nanoparticles with and without TPP, but also the effect of the shell material, pPEGMA and pMPC. The synthesis of p(MPC-co-PENAO)-b-p(MMA) and p(PEGMA-co-PENAO)-b-p(MMA) nanoparticles has been described in our earlier publication [28]. Initially, the monomer 4-(N-(S

• -((phenylcarbonothioyl)thio)pentanoic acid, but it was modified with ethylene glycol. During the polymerization of the water-soluble polymers, fluorescein O-methacrylate was added at a ratio of CTA to fluorescent monomer of 1:0.3. This means more that three out of ten polymer chains will be labelled, which is sufficient

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• of polymerization of ≈7) leaving speculation about a higher degree of polymerization for the THF-insoluble component of PAZ-Br2. The UV–vis spectrum of the chloroform-soluble fraction of PAZ-Br2 displayed absorption bands in the 190–330 nm region like the azulene monomer, and a long tail with a broad

• band spanning 400–800 nm in NMP solution with a maximum at 591 nm. Accordingly, the optical energy gap for the polymer 31 was the lowest (1.65 eV) in comparison to dimer 29 (2.15 eV) and monomer, 2-aminoazulene (24, 3.15 eV) emphasizing the advantage associated with inducing a 2,6-connectivity along

• forms of monomer 24, dimer 29, and polyazulene 31 were further red-shifted and their respective energy gaps were also reduced compared to their neutral forms. The oxidation potential for the neutral (−0.23 V) and protonated forms of polyaminoazulene 31 (0.70 V) was significantly different unlike the

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• . Interestingly, the individual monomers usually do not exhibit responsive properties. However, the combination within a copolymer leads to a pronounced thermoresponse. A prominent representative of such behavior is poly(acrylamide-co-acrylonitrile), which is assembled from a fully soluble, hydrophilic monomer

• continuous development and improvement of polymerization techniques, more and more diverse copolymers can be synthesized. Very recently, Kertsomboon et al. succeeded in preparing a copolymer (poly(AAm-co-MDO)) of acrylamide and a degradable, hydrophobic monomer based on a ring opening polymerisation of

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• improved by a variety of methods like plasma treatment, NaOH hydrolysis treatment or a micro deposition system. This study outlines a potential approach to coat medical-grade PCL with a thin hydrogel that requires no initiator or catalyst – just a deoxygenated aqueous monomer solution and UV light. We

• coating and monomer concentration (Supporting Information File 1, Figure S2). As the next step, scaffolds were investigated with respect to their wettability. In order to simulate aqueous conditions in cell culture medium or after implantation, samples were immersed in water for 0, 10, 20 and 30 min

• . Results for three negative controls (cleaned scaffold, scaffold irradiated without monomer solution, and scaffold immersed in monomer solution without irradiation) can be found in Supporting Information File 1, Figure S3, and have no staining. The irradiation time was varied between 10 min, 20 min, and 30

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• polymerization of acrylate/epoxy monomer blends) can also be carried out upon NIR light with the proposed systems. Keywords: cyanine; NIR light; photochemistry; Introduction Photopolymerization processes are well established due to the specific features and advantages. Indeed, the reaction is carried out at

• and the tertiary aromatic amines 3-(dimethylamino)benzyl alcohol (DABA) and N-phenylglycine (NPG), respectively, for the polymerization of a benchmark monomer (PETIA, Scheme 2). The polymerization profiles were recorded by real-time Fourier transform infrared spectroscopy (FTIR, the procedure is

• combination with an amine and an iodonium salt, iod, for the free radical polymerization of a benchmark acrylate monomer and compared to a reference initiating system based on IR 813 (Scheme 2) [7]. As the different dyes presented above exhibit good absorption properties at 785 nm, the photoinitiating

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

•  6C) [182]. To avoid the chemical formation of this challenging bond, natural compounds containing 1,2-cis linkages could be exploited. α-, β- and γ-cyclodextrins offered a good starting material to prepare stereoselectively a 6-O-methylated α(1–4)-glucopolysaccharides consisting of 6–20 monomer units

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• monomer has been used [27]. The reactivity of the above-mentioned chemical groups has enabled the attachment of various amine-functionalized groups onto the 5-position of pyrimidines via both the modified monomeric building blocks and post-synthetic ON chemistry [27][28][31][32][33][34][35][36][37][38][39

• as building blocks for incorporation into PS-ONs (Table 3B, 26, 27). In this study, two modifications of the N4-spermine-modified 2’-O-MOE-cytidine monomer 26 was incorporated into a 12-mer PS-ON centrally and at the 5’-end, resulting in significant increases in Tm (by more than 16 °C) towards

• at the C-5 position of a 2’-OMe-uridine monomer, positioning the group in the major groove of the formed duplex, had a significant stabilizing effect on RNA binding (Table 2A, 18) [62]. Another method for introducing spermine at the N4 position involved the reaction of spermine and 4-N-p

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• , appears to be the most promising conformationally constrained PNA analogue. Vilaivan and co-workers developed pyrrolidinyl PNA based on an α/β-dipeptide backbone that is one atom longer than the canonical PNA and contains two amide bonds and two cyclic moieties in one monomer (Figure 4) [61]. Cyclobutane

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• popular and most studied direction in the creation of OSCs is the use of polymer structures containing an isoindigo fragment in a monomer unit associated with a different number of thiophene substituents (Scheme 12). By the example of one of the simplest representatives of this type of polymers, a

• was only 0.99%, while the Stille method gave a polymer 24a characterized by an efficiency of 1.66% (Scheme 14). Strengthening the donor effect of the monomer unit can be achieved by lengthening the thiophene chain up to three fragments [37][38][39][40][41]. In this case, additional possibilities arise

• the above described study, Liu et al. demonstrated that this type of compounds is promising by means of introducing fluorine atoms into the thiophene ring [43]. The use of compound 29c (ratio of monomer units n/m = 2:1) as an acceptor component of the OSC made it possible to achieve one of the highest

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• terminal carbons only. Double-headed nucleosides are synthetically derived nucleoside scaffolds that are known to impact significantly secondary structures in nucleic acids [29]. Some oligonucleotides containing a particular double-headed nucleotide monomer have been found to form a three-way junction

• phosphitylation at the secondary hydroxy group afforded the double-headed nucleoside monomer 19 (Scheme 5) [45]. The synthesized double-headed nucleoside 19 was introduced in oligonucleotides and its impact on the secondary nucleic acid structure was studied. It was revealed that the double-headed nucleoside 19

• was well accommodated in a hybrid DNA:RNA duplex and stabilized bulged duplex and three way junctions [45]. The potential of the double-headed nucleoside 19 in secondary nucleic acid structures was compared with the earlier reported monomer 11 and found to be inferior to double-headed nucleoside 11

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

• similarity to natural tissues, meaning that they are stable networks with high water content [1][2][3]. The simplest synthesis of hydrogels can be conducted in an aqueous solution of a water-soluble monomer and crosslinker (bi- or more functional) in the presence of an initiator (generally radical initiation

• represents a family of materials where variety of synthetic routes can be applied to form photoactive matter with altered properties, i.e., monomer supramolecular assembly to attain a monomer complex prior to carbonization results in enhanced porosity and photoactivity since ordered structures are formed

• yellow powder was ultrasonicated in water to obtain a g-CN aqueous colloidal dispersion. The freshly prepared CM/water colloidal dispersion was mixed with water-soluble monomer (N,N-dimethylacrylamide, DMA) and crosslinker (N,N’-methylenebisacrylamide, MBA) followed by the addition of the redox couple

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

•  7D) monomer which has been shown to stabilize oligonucleotides similarly to unmodified LNA with a nuclease resistance greater than PS-modified oligonucleotides [157]. Incorporation of selenium at C2' in a thymine-bearing LNA nucleoside (Figure 7E) has been demonstrated to have a hybridization ability

• modifications [207]. 2',4'-diF-ANA (Figure 9D) also adopted the northern (C3'-endo) sugar pucker despite the 2'-βF, which generally leads to the adoption of a southern or eastern pucker [208]. This monomer was found to have minimal effects on the thermal stability of nucleic acid duplexes. However, when

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

• bearing BCNS groups comprising nine and ten synthetic steps, respectively. In comparison, the synthesis of an N+ monomer requires only four synthetic steps starting from commercially available 1,4-butane sultone that does not have any silica gel purification [38]. The incorporation of the N+ modification

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

• multiple GuNA[Me] modification to A-form duplexes is also believed not to affect the structures. Conclusion We successfully synthesized GuNA[Me] phosphoramidites bearing either an A, G, or mC nucleobase. Each monomer was derived from the corresponding 2'-amino-LNA in two steps and introduced into

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• °C provided a hydrocarbon oil in 92% yield, 71.4% of which were attributable to styrene monomer [156]. A decrease of 56 kJ mol−1 for the activation energy of PS depolymerisation was calculated in the presence of the catalysts. More recently, high-porosity montmorillonite (Mt) was used to prepare Mg

• ). Hydrolysis. Methods for the metal-catalysed hydrolysis of PET were developed, allowing for the recovery of costly TPA monomer (Scheme 4, top). TPA was obtained in 97.1% yield at full PET conversion, using 70 wt % aqueous ZnCl2 as catalyst at 180 °C and no organic solvent [194]. However, a high ZnCl2/PET

• resulting polymers with excellent mechanical properties (e.g., stiffness, toughness, hardness), isosorbide is used as monomer in the production of a variety of plastics [249][250]. By contrast, the rigidity results in a poor reactivity as depolymerising agent [251]. 3.2.2 Polylactic acid (PLA): PLA is a

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

• upon interaction. These results demonstrated that the site-specific 19F signal of 5-FTrp187 could be directly employed as a reliable reporter to monitor the monomer/dimer exchange dynamics. Moreover, it could also be employed to characterize the ED helix–helix dimer interface in more detail by means of

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

• binding constants Kx, which are related to the free energy change ΔG and thus due to ΔG = ΔH − TΔS, also the entropy change ΔS is revealed. Table 5 summarizes the results from the full titration curve fitting. The values correlate to the binding of one monomer of the polymer to Flavy and/or photoacid. For

• small counterion release may contribute (likely, it is ionic repulsion due to the excess of positive charges (l < 1.0) in combination with changes in hydration shells that make this region endotherm). The last binding step starts at l = 0.16 (molar ratio 0.075), equal to 17 monomer units per poly

• correspond to the binding of one monomer of the polymer with Flavy and/or photoacid. Percentages of the absorption of the Flavy molecule at the C states at λ = 500 nm after a complete cycle depending on the loading ratio. Concentration ratio dependence: hydrodynamic radii for the different states of both

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

• ) photopolymerization under visible-light irradiation in an aqueous solution [48]. Briefly, the supramolecular PDI–CB[7] complex in Figure 15 acts as a photocatalyst at a low concentration (1 ppm relative to the monomer), which could be utilized for the preparation of a series of homo- or block copolymers with an

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

• be achieved by a ring–chain-based polymerization [11]. In this context, Sijbesma and Meijer reported an early example of a low-molecular weight VII using a ditopic monomer which undergoes supramolecular polymerization at elevated temperatures (Figure 1) [12][13]. The system consists of two self

• precoordinating effect to favor the cyclic form at lower temperatures. Thus, the alkylene-bridged monomer A shows no effect in terms of viscosity improvement. In contrast, the gem-dimethyl unit in monomer B leads to sufficient stabilization of the cyclic form at lower temperatures. This allows a ring–chain

• and VI of Nynas NS8. In Nexbase 3020, compound 4 showed an even higher RVT effect. Therefore, the development of a low molecular-weight monomer that undergoes supramolecular polymerization at elevated temperatures and can thus act as a viscosity index improver was successfully realized. Experimental

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

• trimesic acid scaffold by PyBOP coupling in DMF and NMM as weak base. After subsequent size exclusion chromatography, the ready to use azide-functional monomer 7 was isolated in high purity. The peptide amphiphile was finally conjugated to the propargylated sulfated [G2] oligoglycerol dendron 8 via a

• mixture was subsequently purified by size exclusion chromatography to yield 85% of the oligosulfated monomer II. Characterization of the supramolecular polymers of I and II The self-assembly behavior of the peptide-based materials can be readily investigated using CD spectroscopy. The supramolecular

• conditions, supramolecular polymer formation with a length of several hundred nanometers is observed at monomer concentrations as low as 25 µM. Evaluation of the L-selectin binding efficacy The L-selectin binding behavior of the sulfated supramolecular polymer resulting from II was assessed using a

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

• because the methods normally neglect self-interactions. The advantages of homooligomeric complexes over monomer proteins include an increase in the diversity of the functions [61], allosteric regulation [62], protection against denaturation [63], and the oligomers being able to form without increasing the

• complex formation include domain swapping and the formation of leucine zippers. In domain swapping, a region from the monomer interacts with the adjacent protein partner, forming the protein–protein interface. Most of the times, the interacting region is present on either the N- or C-terminus, although

• tryptophan, the equilibrium between the monomer and the oligomer formation is shifted towards the latter [75][76]. Examples of PPIs within higher-order protein complexes PPIs are responsible for the assembly of large protein complexes, such as capsid proteins in viruses and protein containers. This section