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

• recognition of C–G, G–C, and A–A base pairs, respectively [139][140]. While still in relatively early stages of development, the Janus-wedge triplex has already shown intriguing potential as a diagnostic or therapeutic approach for Huntington’s or related genetic diseases [139]. Fluorescent nucleobases in PNA

• : Because PNA has become a key component of many assays and diagnostics, development of fluorescent nucleobases as labels for PNA has attracted considerable attention. 2-Aminopurine (Figure 10), a fluorescent structural isomer of adenine [141], was one of the first fluorescent nucleobases used in PNA [142

• -aminopurine in PNA probes. Hudson and co-workers developed several fluorescent PNA nucleobases derived from phenylpyrrolocytosine [143][144][145]. One of the most promising analogues, mmguaPhpC (Figure 10), formed a stronger base pair with G than the native C–G pair which was followed by a 30–70% decrease of

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• –c are shown to undergo a novel cascade imination-heterocylization in the presence of the organic base DIPEA to provide 1-indolyl-3,5,8-substituted γ-carbolines 3aa–ea in good yields. The γ-carbolines are fluorescent and exhibit anticancer activities against cervical, lung, breast, skin, and kidney

• traces of any β-carboline product were observed, which proves that the heterocyclization reaction is highly regiospecific. Optical properties of γ-carbolines Interestingly, the γ-carboline derivatives were found to be highly fluorescent under UV light irradiation. A systematic literature survey revealed

• that the structural core of carbolines had been widely exploited for the development of organic fluorescent entities, and in general, their UV absorbance ranges between 340 to 380 nm. For a deeper insight into the optical properties of the novel substituted γ-carbolines, absorption and emission studies

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

• nucleosides 151c,d and 154a,b when incorporated into oligonucleotides enabled fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs) [24]. Nielsen and co-workers [15] synthesized a series of double-headed nucleosides 5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2′-deoxyuridine (157a), 5-(1

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• applications ranging from organic thin‐film transistors (OTFTs), organic light-emitting diodes (OLEDs), dye‐sensitized solar cells (DSSCs), fluorescent probes, organic photovoltaics (OPVs) to the high hole mobility semiconductors, blue light-emitting materials, nonlinear optical materials and so forth [5][6][7

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

• –fluorescein isothiocyanate and fluorescein isothiocyanate–dextran fluorescent probes were subjected to HGCM and HGCM-vTA samples with a comparatively shorter releasing experiment than the one performed for RhB dye (Supporting Information File 1, Figure S4a). The static experiment principally relies on

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

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

• , 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

• as fluorescent probe in bioanalytical chemistry [15][16]. Because of these attractive properties of this lead structure, numerous berberine derivatives have been synthesized in order to further improve the biological activity [17][18][19][20][21][22][23][24][25][26]. Among those derivatives

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

• synthetic route being optimized over time [151][152]. The stability of these derivatives is similar to those of LNA [150][151][152], with the added advantage of additional coupling reactions to fluorescent groups [151], or small molecules being possible either during solid-phase synthesis (SPS) [153][154

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

• a tight junction barrier has formed within these cells and can be used to determine the ability of the LNPs to pass through the BBB (Supporting Information File 1, Figure S3A). Additionally, we further confirmed our junctions using fluorescent microscopy on the barrier layers to confirm expression

• through direct addition by 1.6–1.8-fold (Figure 2B). Additionally, the mean fluorescent intensity (MFI) was found to be 2–2.3-fold higher in the target TZM-bl cells in both barrier and nonbarrier treatment groups compared to the control HeLa cells, indicating a higher accumulation of LNPs in the target

• (phosphate-buffered saline, PBS) conditions (Figure 4A). Additionally, we confirmed LNP uptake by the monocyte-derived macrophages (MDMs) using fluorescent microscopy (Figure 4B). We found that all LNPs containing the Cy5 oligonucleotide were observable under the microscope (Figure 4B) and that all

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• ][36][37][38][39][40][41][42][43]. Highly reactive and selective bromination reactions have been achieved using a stoichiometric amount of MnO2 [44] or a catalytic amount of Li2MnO3 [45] under fluorescent light irradiation in the presence of Br2 (Scheme 1d). Hill [46] and Groves [47][48][49] have

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• substrates under 23 W CFL (compact fluorescent lamp) irradiation, affording the desired imidazole derivative 10 by utilizing DMSO as the solvent at room temperature (Scheme 4). It is worth noting that, unlike most reported intermolecular electron-transfer via an EDA complex pathway, this approach transfers

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

• synthesised possessing four or five N+ or four Ts modifications and a fluorescent label (6-FAM) at the 3ʼ-end (Table 1) was tested. Asynchronously growing NIH3T3 mouse fibroblasts were incubated with the ONs for 12 hours, fixed in 4% paraformaldehyde before the cells were processed for fluorescent confocal

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• classic organic dyestuffs. In that study, two highly fluorescent dibenzosuberenone-based dihydropyridazine dyes, 3a,b, were synthesized, and it was found that they can be used as a selective and sensitive sensor of fluoride anions (Scheme 1, Table 1) [55]. In another work, we reported the design

• fluorescent dyes 3a,b in detail. In the present study, the effects of functional groups with different conjugations on maximum absorbance (λmax, abs) and emission (λmax, ems), and wavelengths of dihydropyridazines 3c–f and 3k were investigated. Compounds 3c,d, with high conjugation, show the highest

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

• intrinsically disordered proteins remains unclear. 6 Fluoroprolines in crystal structures of proteins Several high-resolution crystal structures have been reported for proteins containing fluoroprolines. In a study of enhanced green fluorescent protein from Aquorea victoria, fluoroprolines were incorporated at

• ten proline positions [117]. The incorporation of R-Flp resulted in an insoluble protein, indicating associated folding issues. In contrast, the protein containing S-Flp produced a well-structured fluorescent protein, exhibiting faster folding kinetics and producing crystals suitable for diffraction

• subdomain [129], T. thermohydrosulfuricus lipase [130][131][132], human ubiquitin [133], single-chain Fv format protein [134], KlenTag DNA polymerase [135], thioredoxin A [120], β2-microglobulin [136], red fluorescent protein [137][138], Pin1 WW domain [139], bacteriophage T4 fibritin C-terminal domain [106

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• 6-O-analogues are less common [61]. Azolylpurine derivatives are important due to their potential as drug candidates. They can be used as agonists and antagonists of adenosine receptors [58][64][65][66] and against Mycobacterium tuberculosis [60]. They also show useful fluorescent properties [11][67

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

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• % for fluorescent compounds [1][2][3][4]. For TADF materials, a small energy gap between the lowest singlet and triplet excited states (ΔEST) is essential to permit the efficient up-conversion of triplet excitons to singlet excitons via reverse intersystem crossing (rISC) [5][6][7]. The rISC process can

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

• Subrata Nath Alexander Kappelt Matthias Spengler Bibhisan Roy Jens Voskuhl Michael Giese Organic Chemistry, University of Duisburg Essen, Universitätsstraße 7, 45141 Essen, Germany 10.3762/bjoc.17.13 Abstract The first example of halogen-bonded fluorescent liquid crystals based on the interaction

• derivatives. Therefore, tetrafluoroiodostilbene (F4St) and a series of fluoroiodoazobenzenes (F4Az, F3Az, F2Az, F2’Az) were employed as halogen bond donors and combined with nitro-cyanostilbene (NO2-Cn) as fluorescent halogen bond acceptor (see Figure 1) to form halogen-bonded liquid crystals. The series of

• -induced emission properties were combined with alkoxystilbazoles to form hydrogen-bonded mesogens. Since NO2-Cn is known to be fluorescent, we were curious how the formation of the halogen-bonded complexes affects the AIE behaviour of NO2-Cn. Therefore, we studied the photophysical properties of 1:1

Circularly polarized luminescent systems fabricated by Tröger's base derivatives through two different strategies

• Cheng Qian,
• Yuan Chen,
• Qian Zhao,
• Ming Cheng,
• Chen Lin,
• Juli Jiang and
• Leyong Wang

Beilstein J. Org. Chem. 2021, 17, 52–57, doi:10.3762/bjoc.17.6

• luminescence with glum values of +0.0021, and −0.0025, respectively. The second way to fabricate the rac-TBPP-based CPL-active material is to co-gel the fluorescent rac-TBPP with a chiral ᴅ-glutamic acid gelator DGG by co-assembly strategy. At the molar ratio of rac-TBPP/DGG = 1:80, the glum value of the co

• and applied in practice [4][5][6]. Among them, the fluorescent materials emitting circularly polarized luminescence (CPL) have attracted intensive interest owing to their wide applications in various researching fields including 3D displays, chiroptical materials, and so on [7][8][9][10]. Circular

• dichroism (CD) absorption spectra reflect the chirality of the fluorescent materials in the ground state, and circularly polarized luminescence (CPL) spectra reflect the chirality of fluorescent materials in the excited electronic state. Therefore, the CD and CPL spectrum are the two most important tools to

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

• electrophoresis [7]. However, the application of these analytical methods in mercury detection is limited due to the complex sample pretreatment procedures, expensive instruments, and other factors [8][9]. Fluorescent-probe instruments have been widely used due to the advantages of the simple operation, low cost

• , and high sensitivity [10][11][12]. In recent years, many fluorescent molecular probes have been reported. Because Hg2+ has a very strong quenching effect on fluorescence, most of the fluorescent molecular Hg2+ probes are of the fluorescence-quenching type and are easily interfered with by other

• probe [23], OST as a probe for the detection of mercury has not been reported. In this paper, OST was used as a fluorescent probe since the fluorescence intensity of OST at 406 nm increased significantly when Hg2+ was added. The probe had a high selectivity and sensitivity for Hg2+ recognition and can

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• phosphates examined were barely fluorescent in methanol, with an emission quantum yield (Φem) in the 0.005–0.06 range (see Table 2 and Supporting Information File 1 for further details). We thus focused on compounds 1e, 1h, 3a and 3c as the model substrates. In the case of compounds 1e and 1h, we observed

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• fluorescence techniques have attracted immense interest. Synthetic peptide-based fluorescent probes are advantageous over protein-based sensors, since they are synthetically accessible, more stable, and can be easily modified in a site-specific manner for selective biological applications. Peptide receptors

• labeled with environmentally sensitive/FRET fluorophores have allowed direct detection/monitoring of biomolecules in aqueous media and in live cells. In this review, key peptide-based approaches for different biological applications are presented. Keywords: fluorescent probe; fluorophores; molecular

• organic fluorophore (reporter) with a specific peptide sequence is the common approach for designing peptide-based fluorescent probes [16]. Fluorophores on peptidic arms perform as reporter during the interaction with biomolecules [17][18]. The interaction with biomolecules will alter the fluorescence

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• present. System B functions in a similar manner (Figure 4B), but instead of the aptamer carrying the fluorescent label, it utilizes two complementary sequences, one carrying fluorescein (2f) and the other carrying DABCYL (2q). First, the change in fluorescence was investigated for all sequences of the

• , Figure S7b). This strongly suggests that the modified aptamers are still specific. The binding assays were repeated using the respective aptamers lacking the fluorescein label (1a, 1b, 1c, and 1d; Figure S8 in Supporting Information File 1). Without the fluorescent marker, a quantification of the eluted

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of

• bound to the G4-DNA, such as fluorescent light-up effects and the formation of ICD bands, which are mostly pronounced with linker length of n = 4 (with a2) and n = 5 (with 22AG). This significant influence of the complex structure on the optical properties of the ligand provides some evidence that each

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• information protection at the molecular level. Keywords: artificial receptors; cell surface modification; fluorescent probes; molecular cryptography; Introduction In living cells, information is processed and transferred via a series of recognition and signaling events, which normally begin by the binding

• selectively bind a hexa-histidine tag (His-tag). ODN-1 can also be modified with a second functional group (X), such as a fluorescent dye, to afford X-ODN-1 (Figure 1A and Figure 1B). In this way, the binding of X-ODN-1 to the bacteria will lead to the presentation of X on the cell surface (Figure 1A). A

• labeled bacteria during cell division (Figure 2B). Another research direction in our group, which also involves the development of unconventional fluorescent probes, is the information protection at the molecular level [4][5][6]. In such studies [4][5][6], the emission patterns generated by the probes are