Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• al. [41] and Armitage et al. [42]. These first-generation PNA beacons employed a similar design principle to that of classical DNA beacons, having a hairpin structure carrying a fluorophore and a quencher attached to the stem part. In the normal state, the adopted hairpin structure forced the

• with a quencher and a fluorophore (Figure 5). Seitz proposed that the stem-loop structure was not required because the hydrophobic backbone of PNA tends to adopt a compact structure to minimize hydrophobic surfaces, allowing the fluorophore and quencher labeled at opposite ends of the PNA molecule to

• make a close contact. However, based on their detailed comparative studies between stemless PNA and DNA beacons, the Boston Probes group argued that the quenching was more likely due to hydrophobic and electrostatic interactions between the fluorophore and the quencher. Nevertheless, different

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• qA is an excellent adenine analogue [53]. Unfortunately, the photophysical properties of qA were not satisfactory for an internal FRET fluorophore and, thus, we moved on by modifying the quadracyclic aromatic core but leaving the advantageous base-pairing properties. To this end, we needed to develop

• ., pointing towards the nitro group) [14]. As was mentioned in the synthesis part above, recently we also have developed tCO as an internal fluorophore for RNA systems [50]. The incorporation into RNA oligonucleotides and hybridization with a complementary strand results in normal A-form RNA duplexes

• yields of 20–25% inside duplex RNA, tCO is the brightest internal RNA fluorophore reported to date and, thus, a promising fluorescence reporter and/or FRET donor also in RNA systems [50]. Photophysical properties of quadracyclic adenine analogues in nucleic acids Extending the repertoire of base–base

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• dyes which could be applied as FRET pair. In this case, labeling was achieved in two bioorthogonal reactions, an iEDDA and a SPAAC reaction. Furthermore, dual modification with an azido and an alkyne function enabled fluorophore/biotin labeling using a combination of SPAAC and CuAAC reaction. Efficient

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• the reaction medium. The results suggest that 1 could be used as fluorophore in OFF–ON-type fluorogenic probes. Keywords: dipeptidyl peptidase-4; fluorogenic substrate; fluorometry; small fluorescent molecule; Introduction Fluorescent organic probes have become indispensable for bio-imaging or

• probes can act as good sensors for enzymes but the fluorophore unit is usually large because fused aromatic rings and an elongated π-conjugated system are necessary to impart appropriate fluorescent properties to the probe [14]. The molecular size of the fluorescent probe is therefore large, which is

• sometimes inconvenient in terms of membrane permeability, water solubility, and inhibition of inherent interactions between the probe molecule and the target enzyme. We have developed a new OFF–ON probe with a small fluorescent core unit. The same approach was recently used to produce a fluorophore for a

Energy down converting organic fluorophore functionalized mesoporous silica hybrids for monolith-coated light emitting diodes

• Markus Börgardts and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 768–778, doi:10.3762/bjoc.13.76

• quantum yield of 4.6% upon irradiation at 410 nm. Furthermore, as a proof of concept two different device setups of commercially available UV light emitting diodes, are coated with silica monoliths containing the three triethoxysilylpropyl-substituted fluorophore derivatives. These coatings are able to

• fluorophore derivatives 4 and 5 were accessible by Williamson ether synthesis [24]. The alkyne-functionalized green benzofurazane derivate 6 was obtained by nucleophilic aromatic substitution of 4-chloro-7-nitrobenzo[c][1,2,5]oxadiazole (3) with propargylamine. The alkyne-functionalized derivatives 4, 5 and 6

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• mechanism of their action and their fate inside living cells. The fluorescent labeling of CDs enables their tracking and visualization in biological media and provides useful information about their cell-membrane-penetration ability [2][3]. Besides, fluorophore-appended CDs have been extensively studied and

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• ARTD2 catalysed PAR production [24]. After the times indicated, copper-catalysed click conjugations to a fluorophore-containing azide were performed and the reactions were analysed by SDS PAGE. Then, fluorescent signals were detected and compared to the Coomassie Blue stained gels (Figure 2). Each

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• combines to a blue–yellow fluorophore pair (D1/D5) and to blue–red emitting pairs (D1/D6–D1/D9). The green emitting dyes D2–D4 result all in green–red emitting pairs (D2/D7–D4/D9). The combination of dyes D2–D4 with D5 and D6 is not meaningful for this concept since the fluorescence of the donors and

• combination DNA2aD1–DNA3rD5 revealed a yellow-to-blue contrast of 198 and a quantum yield of 61%. For the blue–red emitting dye combinations the highest red-to-blue contrast of 215 and the highest quantum yield of 71% is achieved in DNA2rD1–DNA3aD8. Finally, among the broadest array of green–red fluorophore

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• followed by click chemistry with the fluorophore. A decreasing labelling intensity at increasing NEM concentrations indicates that NEM also blocks the active site cysteine Cys112 at concentrations above 5 µM and thereby prevents covalent attachment of the probe to PqsD (Figure 3D). We were thus interested

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• -dipyrromethene) [11][12], BOIMPY- (bis(borondifluoride)-8-imidazodipyrromethene) [13] and pyrene-labeled fatty acids [14]. Of course, all these alterations might also affect the membrane structure and its dynamics. While the NBD-fluorophore suffers from unsuitable polarity, a pyrene motif disrupts the unpolar

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• methods [32]. In order to achieve a perfect fit between MGB-conjugates and dsDNA target sequences, the length and the flexibility of the linker that connects two components (polyamide and TFO or fluorophore) in the conjugates should be optimized. It becomes vital for TFO-MGB conjugates because individual

• for the synthesis of MGB-fluorophore and MGB-TFO conjugates via CuAAC (Figure 2). Properties of the conjugates obtained are discussed. Results and Discussion Synthesis of bifunctional linkers Two components in MGB-TFO conjugates must be connected by a linker, which is at least 12 chemical bonds long

• alkyne can be used for labelling of MGB with a fluorophore using "click chemistry" and the amino group can be used to conjugate the probe to TFO or to another polyamide [15] and vice versa. Synthesis of modified polyamides, containing an azide or alkyne group The following polyamides (11–14, Figure 6

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• ] were measured at significantly higher concentrations (0.5 mM) and are broad and structureless. Therefore, they should rather be assigned to fluorophore aggregates (excimers). The spectra of 3Aj were run in solvents of varied polarity (Figure 2) and display the well-known Ham effect (dependence of the

• corresponding aminophosphonate was earlier reported [29]. The aforementioned data suggest possible application of compound 3Aj (and other exhibiting similar emission quantum yield) as molecular probes monitoring micropolarity of the fluorophore environment. On the other hand, water-soluble 4a might be used for

Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

• Phil M. Pithan,
• David Decker,
• Manlio Sutero Sardo,
• Giampietro Viola and
• Heiko Ihmels

Beilstein J. Org. Chem. 2016, 12, 854–862, doi:10.3762/bjoc.12.84

• emission lifetime. Notably, a considerable number of solvatochromic molecules is based on charge-transfer (CT) processes in the excited state resulting from a pronounced donor–acceptor interplay within the fluorophore [8]. Thus, upon excitation of such compounds, a CT – or in charged species a charge shift

• probes, we developed novel 3-arylnaphtho[1,2-b]quinolizinium derivatives. Firstly, we chose the naphthoquinolizinium fluorophore because it should have essentially the same ability to act as an acceptor in the photoinduced CS process as the benzo[b]quinolizinium [18]. But due to its more extended π

• even the intermolecular electron transfer reactions between electron rich aromatic compounds, such as naphthalene and phenanthrene, and the excited benzo[b]quinolizinium fluorophore were shown to be efficient processes [37]. The biaryl derivatives 6b–e exhibit fluorosolvatochromism that is

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• University, Hlavova 8, 12843 Prague 2, Czech Republic 10.3762/bjoc.12.53 Abstract Xanthene dyes can be appended to cyclodextrins via an ester or amide bridge in order to switch the fluorescence on or off. This is made possible through the formation of nonfluorescent lactones or lactams as the fluorophore

• glucopyranose units (α-, β- and γ-CD, respectively). Native CDs do not adsorb light in the UV–vis region (200–800 nm), but they can be converted into spectroscopically active compounds by modification with a chromophore/fluorophore unit. Fluorophore-appended CDs can be appropriate systems to detect

• a convenient tool for the synthesis of amides and esters [10]. The first example of xanthene-dye-appended cyclodextrin based on the modification of the carboxylic moiety of the fluorophore was reported by Ueno’s group [11]. In the study, they modified 6-monotosyl-β-CD with the sodium salt of

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• enantiomers of tartaric acid and also bound bind strongly with other sugar acids [61] (Figure 9). While, we were very happy with these results, we realised that the system could be improved by changing the fluorophore from binol, to a much better fluorophore such as anthracene. Therefore, we combined the

• collaborate and in particular we worked together to improve the chiral discriminating systems. In order to improve the chiral systems we designed sensors using a d-PET rather than the normal a-PET fluorescence sensing mechanism. With d-PET systems the fluorophore is the electron donor and the protonated amine

• for acidic guests such as tartaric acid and sugar acids [62][63][64][65] (Figure 11). The best chiral discriminating d-PET system was constructed using a phenothiazine fluorophore 17 and 18 [66]. The phenothiazine fluorophore was chosen because it is a very strong electron donor. These sensors

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• peptides that respond to only one kinase [108][109]. This can be viewed as a lock and key approach, while as described herein, many groups have shown that the differential sensing approach may be more applicable for certain applications. Thus, we took a suite of peptides containing the SOX fluorophore, and

Bright molecules for sensing, computing and imaging: a tale of two once-troubled cities

• A. Prasanna de Silva

Beilstein J. Org. Chem. 2015, 11, 2774–2784, doi:10.3762/bjoc.11.298

• needed to have a binding strength (βNa) of 10 M−1 in neutral water. An N-(2-methoxy)phenylaza-15-crown-5 ether [37] fitted the bill, besides having good selectivity characteristics. PET thermodynamics were matched by the use of a 4-aminonaphthalimide fluorophore [38][39][40], which, in the presence of

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• biosensors to transduce the presence of a target molecule into a dose-dependent fluorescence output [20]. In this sensor format, a short quencher-labeled complementary strand is hybridized to the fluorophore-labeled aptamer, and equilibrium favors duplex formation in the absence of the target. However

• these enantiomeric biosensors with orthogonal fluorophores (Figure 5). In our initial experiments, we utilized fluorescein (FAM) and cyanine 3 (Cy3), however, we observed that the difference in fluorophore structure resulted in an approximately two-fold difference in the equilibrium constants for the

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• photodecomposition in this solvent [32], we found that this did not happen in the case of the compounds investigated here). Electronic absorption and emission spectra of 3a in various solvents are shown in Figure 2. The introduction of a phosphonato group into the N-alkyl chain of the pyrene carboxamide fluorophore

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• -methoxynaphthalene-1-sulfonamide moiety that is connected by an internal double bond to a 2,4-dinitroaniline core, acting as a fluorescence quencher [17]. Both the sulfonamide of the fluorophore and the aniline group of the quencher bear another allyl group. Upon relay ring-closing metathesis, the fluorophore and

• substrates The synthesis of profluorescent substrate 8 leading to umbelliferone after ring-closing metathesis was carried out according to a published, four-step procedure starting from 2,4-dihydroxybenzaldehyde (10) with an overall yield of 50% [23][24]. The synthesis of the fluorophore–quencher substrate 5

• was achieved relying on two converging synthons (Scheme 2). The fluorophore part of the molecule was synthesized starting from sodium 5-methoxynaphthalene-1-sulfonate (11), which was prepared according to a known procedure [25]. It was then transformed to the corresponding allyl sulfonamide 12 by

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• shows the energy-minimized 3D structures of the lipophilic nucleoside headgroups 4a–9a. The reactive building blocks 4b–9b were subsequently used to synthesize the following lipo-oligonucleotides (LONs), which have an identical nucleotide sequence in common as well as a cyanine-5 (Cy5) fluorophore at

• , where one pixel equals 1 kHz or 1 µm. All devices used as well as the general techniques used in this paper have been described in detail in preceding manuscripts as well as in an mp4 video [18]. General structure of the fluorophore-labeled lipo-oligonucleotides and positions of lipophilization of the

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• obtained by hybridization of PNA-tagged libraries, Chevolot and co-workers first reported the use of glycan–DNA conjugates to display glycans in a spatially addressable array format [27]. A fluorophore (Cy3) was used to quantify the immobilized conjugate on the array. In a pilot experiment, a galactose

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• fluorophore core is naturally primordial for the design of photostable, water-soluble and biocompatible probes with the required photophysical properties. An additional challenge is that, as the central core of a multivalent system, the fluorophore structure defines also its valency, size and shape

• adequate tailoring, including fluorescence amplification [50], and ratiometric pH reporter for imaging protein–dye conjugates in living cells [51], or display physiological binding of D-glucose [52]. The pyrene nucleus was also selected as an alternative fluorophore since it may be easily

• tetrafunctionalized at the 1, 3, 6 and 8 positions to give a suitable core for the synthesis of tetravalent clusters [53]. In addition, this fluorophore was chosen for its biological/chemical stability and its photophysical properties including high extinction coefficient with reliable fluorescence [54][55]. Another

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• synthesized the s2s construct with a terminal rhodamine fluorophore. This compound was mixed with DOPC giant unilamellar vesicles (GUV) or human erythrocytes. In both cases clear membrane labeling could be detected (Figure 6). To assess how strong membrane incorporation of these peptides can perturb membranes