A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• )) and includes a chiral auxiliary, an amino acid, and a bifunctional linker capable to arrange the components in the Schiff base complex. Such templates provide a significant C–H acidity at the α-amino acid carbon and a possibility for recycling of the chiral auxiliaries (for reviews see [5][14][15][16

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• Biotechnology, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia 10.3762/bjoc.19.40 Abstract Two novel conjugate molecules were designed: pyrene and phenanthridine-amino acid units with a different linker length between the aromatic fragments. Molecular

• a pH-dependent excimer formation that is significantly red-shifted relative to the pyrene and phenanthridine fluorescence. While the conjugate with a short linker showed negligible spectrophotometric changes due to the polynucleotide addition, the conjugate with a longer and more flexible linker

• exhibited a micromolar and submicromolar binding affinity for ds-polynucleotides and inactivated a mutant of dipeptidyl peptidase enzyme E451A. Confocal microscopy revealed that the conjugate with the longer linker entered the HeLa cell membranes and blue fluorescence was visualized as the dye accumulated

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

• a similar synthetic protocol to link porphyrin 71 to a fluorescein 72 through a 1,2,3-triazole linker to form the porphyrin-fluorescein conjugate 73 in 91% yield (Scheme 14). Furthermore, the fluorescence study of conjugate 73 revealed an intramolecular energy transfer between fluorescein and

• -triazole linker significantly influences the charge separation, charge recombination, and photoinduced electron transfer processes. Since, the through-bond distance is approximately the same for all the synthesized ZnP-Tri-C60 conjugates, therefore, the variation in charge separation and charge

• -triazole-ruthenium(II) conjugates 112a,b and 116a,b in 18–20% yield. Their photophysical and electrochemical studies revealed that the orbital energies depend on the ligands/linker, connecting pattern of linkers, and the presence of Zn metal ions in the porphyrin core. Ligand exchange studies also

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• of an ether linker on the pyrazine ring, with a two methylene unit chain length between the heterocyclic core and benzylic substituent, improved the potency of these compounds [16]. Hence, scaffolds 1–3 were then converted into a series of ether-linked triazolopyrazines with phenethyl alcohol or

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• spectra of the dimers possess several features, making them quite different from the spectra of their starting materials. The spectra of the dimers with the urea linker in water contain much fewer distortions in the hydrogen and carbon signals than the spectra of a corresponding azido-compound, so they

• look more like the symmetrical partially methylated compounds without azido group. This phenomenon could be attributed to the increased molecular symmetry after the dimerization with this type of spacer. A methyltriazole ether linker connects the CD moieties in dimers 4, 9, and 10. The aromatic part of

• desymmetrization of the molecule caused by a partial and reversible self-inclusion of the triazole moiety into the CD cavity, as was previously studied in detail for the CD dimers prepared by CuAAC reaction [15]. Although such self-inclusion was not prominent for dimers based on the short propargyl ether linker

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• interactions [5][6][7]. For example, a binding curve generated for the interaction between an RGD-peptide (C-PEG6-GGRGDGP) and its integrin (α5,β1) target is shown in Figure 4 below. A PEG-linker was added to the RGD-peptide so that the peptide would not be buried in the polymer coating the surface of the

• array, a scenario that would make it unavailable for binding to the integrin receptor in the subsequent analytical experiment. The PEG-6-linker was selected because it was effective and readily available from commercial sources. This linker was functionalized with a cysteine on the end opposite the

• peptides were placed on the array along with a fluorescent dye (LRSC, lissamine rhodamine) that was used to make sure the placement chemistry was working. The array used was coated with the borate ester diblock copolymer (Figure 2), and the peptides were attached to this polymer through a PEG-6 linker in

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

• . The tuning of the energy order of the CT and LE states is achieved by oxidation of the PTZ unit into the corresponding sulfoxide, whereas conformation restriction is imposed by introducing ortho-methyl substituents on the phenyl linker, so that the coupling magnitude between the CT and the 3LE states

• minimal impacts on the geometry and the 3LE state energy in the dyad, was rarely explored [8]. We also modified the energy of the CT states by increasing the distance between the electron donor and acceptor by using an intervening phenyl linker between the NI and the PTZ moieties (NI-Ph-PTZ and NI-PhMe2

• -PTZ) [36]. The electronic coupling between the NI and PTZ units differ these two dyads. Finally, in NI-PhMe2-PTZ with methyl substituents, the phenyl linker adopts an orthogonal geometry with respect to the NI moiety, inducing a weaker coupling than that in NI-Ph-PTZ. The photophysical properties of

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

• ], or structural motifs in xeno nucleic acids [18]. In continuation of our work on ferrocenoyl-substituted pyrimidine nucleobases [19], we report herewith a combined theoretical and experimental work on purine series. The novelty of these compounds is the carbonyl linker which connects the

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• lifetimes showed a marked increase upon replacement of the nitrogen linker for phosphorus. Nitrogen-linked g-CN showed exciton lifetimes of 4.2 µs, while the introduction of a phosphorus linker in g-h-PCN increases the lifetime to 67 µs, with g-h-PCN300 showing lifetimes of 42 µs. We have also observed a

Synthesis, optical and electrochemical properties of (D–π)₂-type and (D–π)₂Ph-type fluorescent dyes

• Kosuke Takemura,
• Kazuki Ohira,
• Taiki Higashino,
• Keiichi Imato and
• Yousuke Ooyama

Beilstein J. Org. Chem. 2022, 18, 1047–1054, doi:10.3762/bjoc.18.106

• the two dyes: OTK-2 has a cross-conjugated system due to the involvement of the 1,3-phenylene unit as an additional linker, but OTT-2 has a conjugated system. Therefore, it is interesting to reveal the optical and electrochemical properties of (D–π)2-type fluorescent dyes, making a comparison with (D

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• their catalytic site, while the remaining 7 isoforms of class III, known as sirtuins, are dependent on the NAD+ coenzyme [3][4]. According to current knowledge, HDAC inhibitors usually have several structural subunits: a zinc chelating group, a hydrophobic linker, and a hydrophobic (usually aromatic

• )-ones we have developed an efficient synthesis of hitherto unknown pyrimidine-based hydroxamic acids, wherein the hydroxamic acid residue is attached to the pyrimidine ring by a methylene linker of varying length. The 1H NMR spectra show that the synthesized hydroxamic acids in solution exist as an

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• 7 in Figure 5), which consisted of the twisted A–π–D–π–A structure with N-(4-aminophenyl)carbazole (CzPA) as electron donor unit, pyridine as electron acceptor unit, and 9,9-dioctylfluorene (F) as π-conjugated linker [32]. Compound 7 showed remarkable dual-fluorescence properties when mixed with a

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• illustrates the opportunities in running enantioselective catalysis in mixed-ligand frameworks. Instead of constructing supramolecular catalysts by functionalization of the linker units, a different approach can be adopted where a catalytically active molecule is encapsulated inside a confined space, as

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -alkylene-linkers, the diastereoselectivity decreases with increasing linker length (79/33/12% de for C3/C6/C12-linkers, respectively). This is in line with an expected localization of the macrocycle around the ester functionality due to weak [C–H···O] interactions from the COOCH2 group to the macrocycle

• , which leads to a greater distance between the amine and the chiral macrocycle with increasing chain length. For rotaxanes (R,R/S)-30d–f, which commonly feature a p-xylylene-linker, but different N-substituents, it was found the N-benzyl group gives rise to the best diastereoselectivity (79/55/95% de for

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• HDACs [14]. Trichostatin contains a hydroxamic acid as zinc-binding motif, inspiring the design of a wide range of synthetic HDAC inhibitors. The essential Zn2+-binding group is attached to a non-polar linker, delivering it inside the cavity through a narrow channel. The cap region is responsible for

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• –Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to

• Supporting Information File 1, Figure S4). As a conclusion from those experiments, it was hypothesised that the linker might be too rigid resulting in a distorted structure, which has also been previously reported for thioether cross-linked cysteines bearing a biphenyl template within the staple [20]. Hence

• , a linker with a higher degree of flexibility was designed. This goal was achieved by a modification of amine-containing amino acids in the i + 4 position through coupling to 4-carboxyphenylboronic acid, followed by intramolecular SMC. Different linker lengths were achieved by introducing ʟ-2,4

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

• protecting group or cleaving the linker under more basic conditions is not common. In contrast, the use of acid-labile protecting groups or linkers involving carrying out reactions under less acidic conditions and removing the protecting group or cleaving the linker under more acidic conditions is more

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

• both cryogels and ceramics into a mould, and a physical cross-linker was used to realise the drug theophylline after stimuli had been achieved. Due to the layer system, drug release could occur without diffusion of the subsequent layers, controlling the speed of the release in the ceramic cryogel. In

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

• backbone, resulting in the blue shift of absorption bands (λmax around 350 nm). Interestingly, the ethynyl linker in 17 was assisting the effective delocalization despite the presence of the n-alkyl group at position 6, as evidenced by its large red-shifted absorption at 456 nm compared to 19. The

• -polyazulenes 45 containing a thienyl linker. Synthesis of azulene-bithiophene 48 and azulene-benzothiadiazole 52 copolymers. Conditions: (a): (i) Na2CO3, Aliquat 336, Pd(PPh3)4, 100 °C, toluene, 90% (ii) NBS, CHCl3/HOAc, −10 °C, 83%, (b): Na2CO3, Aliquat 336, Pd(PPh3)4, toluene, 110 °C, 9%, (c): Na2CO3

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

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

• (e.g., Fmoc and Lev) [269][280][281]. These compounds could be prepared entirely on a solid support, or following a solution-phase fragment (or block) coupling. In this case, the branch produced by AGA, employing a traceless linker [118], was converted into a glycosyl donor and coupled to the mannan

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

• ], and the triazole-linker variant carrying three cationic charges (57) [95] stabilized the formed triplex by 28.0 °C and 30.5 °C, respectively [94][95]. These cationic 2’-amine-functionalized LNA modifications (51–57) all gave high binding affinity towards RNA with excellent nuclease resistance, making

• shielding mediated by the salt ions [106]. Additionally, this class of ONs showed high resistance towards nuclease-catalyzed degradation [106]. Subsequently, two variants of this phosphoramidate linker strategy were synthesized, one being the N,N-(dimethylaminopropyl)phosphoramidate linkage (monomers 73 and

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• [104]. The manganese(I)-catalyzed intermolecular alkenylation of tryptophan-containing peptides 32 was performed under basic conditions, yielding hybrid peptides 34 without racemization, containing a trans-alkene linker bearing biologically active motifs in chemo- and site-selective manners assisted by

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

• (Figure 2B). An innovative design links the two ends together with an ethylene glycol linker (Figure 2C), which reduced the unfavorable loss of entropy by converting the binding event from a trimolecular to a bimolecular process [34][35][36]. The new bis-PNAs (Figure 2C) showed about two orders of

• connected E to the PNA backbone with a linker two atoms longer than in standard PNA, which was suggested to circumvent the 5-methyl group of thymine and enable hydrogen bonding to the 4-oxo group [110]. More recent work [111] has questioned the originally proposed hydrogen bonding scheme shown in Figure 7

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

• acceptor anchor units. Nonfullerene OSC based on perylene diimide-derived isoindigo. Isoindigo as an additive in all-polymer OSCs. Bisisoindigos with different linker structures. Nonthiophene oligomeric monoisoindigos for OSCs. The simplest examples of polymers with a monothienylisoindigo monomeric unit