Correlation of surface pressure and hue of planarizable push–pull chromophores at the air/water interface

• Frederik Neuhaus,
• Fabio Zobi,
• Gerald Brezesinski,
• Marta Dal Molin,
• Stefan Matile and
• Andreas Zumbuehl

Beilstein J. Org. Chem. 2017, 13, 1099–1105, doi:10.3762/bjoc.13.109

• fluorescent probes are an elegant solution to this problem but it requires first the establishment of a direct correlation between the membrane surface pressure and the induced color change of the probe. Here, we analyze planarizable dithienothiophene push–pull probes in a monolayer at the air/water interface

• using fluorescence microscopy, grazing-incidence angle X-ray diffraction, and infrared reflection–absorption spectroscopy. An increase of the lateral membrane pressure leads to a well-packed layer of the ‘flipper’ mechanophores and a clear change in hue above 18 mN/m. The fluorescent probes had no

• influence on the measured isotherm of the natural phospholipid DPPC suggesting that the flippers probe the lateral membrane pressure without physically changing it. This makes the flipper probes a truly useful addition to the membrane probe toolbox. Keywords: fluorescent probes; membrane biophysics

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• ][9]. In many cases, total synthesis is of critical importance to enhance the supply of these often scarce metabolites and even complex polyketides have been prepared on an industrial scale [10][11]. These natural products are also valuable molecular probes for the discovery and evaluation of novel

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• probing biological interactions and in biomedical applications [2][3][4][5][6]. Among these novel type of probes, luminescent semiconductors, quantum dots (QDs), which possess a narrow emission spectra and common excitation, superior photostability and electron density when compared to organic

• -octadecene) that could subsequently be functionalised with hydrophilic PEG-diamine, providing an amine functionality for conjugation with glucosamine, histidine, arginine and folate. The yellow/red emissive loaded-CDs were shown to be viable bioimaging probes in live cells, since their emission did not

• where found to localise in the cytoplasm and particularly around the nucleus. Due to the large amounts of internalisation a receptor-mediated endocytosis was proposed. The particles were used as fluorescent probes to target CD44 high expression in tumour cells, opening the door for these types of

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

• -yl)-4-methylmorpholinium chloride (DMTMMCl), a coupling reagent frequently used in peptide synthesis. Malanga et al. recently reported on the preparation of xanthene-dye-appended CDs with the most commonly used fluorescent probes rhodamine and fluorescein (Flu, 1). The conjugation of the 6-monoamino

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

• -synthesising enzymes ARTD1, ARTD2, ARTD5 and ARTD6. By varying the site and size of the NAD+ modification, suitable probes were identified for each enzyme. This report provides guidelines for choosing analogues for studying poly(ADP-ribose)-synthesising enzymes. Keywords: ARTD; click chemistry; NAD+; poly(ADP

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• 10.3762/bjoc.13.31 Abstract Recent advances in the use of flow chemistry with in-line and on-line analysis by NMR are presented. The use of macro- and microreactors, coupled with standard and custom made NMR probes involving microcoils, incorporated into high resolution and benchtop NMR instruments is

• optimization is discussed. Keywords: expert systems; flow chemistry; microcoil; NMR probes; Introduction New enabling technologies have facilitated the transition from traditional chemistry to a more automated approach that will be the chemistry of the 21st century [1][2]. The objective is that the reaction

• systems for the rapid analysis and optimization of reaction parameters and conditions. The use of this technique in mechanistic studies is also discussed. Review Commercial flow probes NMR spectroscopy is based on the absorption of radiofrequency radiation to produce absorption on the nuclear spin level

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• reduction of radical probes (no rearranged products formed from 25d,l,m) and deuterium-labelling experiments (no deuterium incorporation using THF-d8 and quenching with D2O) discard the possibility of a single-electron transfer pathway. Other reductions suggest a hydride addition with formation of an iminyl

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• as well as in the design of chemical probes to dissect glorin-mediated signaling pathways. Keywords: Dictyostelium; glorin; multicellularity; Polysphondylium; signaling molecules; social amoebae; Introduction The emergence of multicellularity from unicellular ancestors is considered a major

• is known about glorin’s biosynthesis, signaling pathways, or degradation. To facilitate further studies, our chemical route allows for a facile synthesis of glorin derivatives and glorin-based chemical probes. Here, we report the synthesis of glorin (1), as well as the novel synthetic analog

• allow for facile access to glorin derivatives required for structure–activity relationship studies. Eventually, these studies can lead to the construction of various chemical probes to identify the unknown glorin receptor. Syntheses of glorin and glorinamide (Scheme 1) started from commercially

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications

• Srikala Pangannaya,
• Neethu Padinchare Purayil,
• Shweta Dabhi,
• Venu Mankad,
• Prafulla K. Jha,
• Satyam Shinde and
• Darshak R. Trivedi

Beilstein J. Org. Chem. 2017, 13, 222–238, doi:10.3762/bjoc.13.25

• ][24][25][26]. The choice of the appropriate detection technique is highly essential as it directly dictates the efficacy of the sensor. Anion binding through colorimetric probes comprising of a binding site and a signaling unit works in a coordinative way yielding an optical output visible to the

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• ]. Notably, the chromophore of the oxyanion-substituted quinolizinium derivative 2cB resembles the well-established solvatochromic pyridinium-N-phenolate betaine dyes that are employed as polarity probes [53]. Correspondingly, the derivative 2cB shows a similar positive solvatochromism, i.e., a blue shift of

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

• traffic lights” [17][19][25] that are energy transfer-based nucleic acid probes that can be used in molecular beacons [26], especially for vesicular microRNA imaging in living cancer cells [27], and for siRNA transport imaging [28]. Donor and acceptor dyes are combined in an interstrand and diagonal

• /or fluorescence quantum yields. Thereby, improved fluorescent nucleic acid probes were elucidated that are suitable not only for nucleic acid imaging of living cells but additionally allow a two-color readout. Experimental Materials and methods. Chemicals and dry solvents were purchased from Aldrich

• energy transfer-based nucleic acid probes. Melting temperatures (Tm) and fluorescence quantum yields (ΦF) of singly modified DNA2aD1–DNA2rD4. Fluorescence intensity ratios (color contrast) C = IAc/IDo and fluorescence quantum yields ΦF of energy transfer pairs between dyes D1–D4 in DNA2a and DNA2r and

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• ) contrast agents and positron emission tomography (PET) probes for in vivo studies. Conclusion In this study, we described a novel preparation method for end-reactive PRXs using 3 as an axle polymer for the PRXs. The terminal 2-amino-3-phenylpropyl groups of 3 prevent the dethreading of α-CDs after end

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• -atom probes for O-alkyl carbohydrate binding lectins. Results and Discussion The first synthetic approach towards O-methylated selenofucoside 3 was based on the reported syntheses of unmodified methyl α-L-selenofucoside (1) [23] and of the reported tectonin ligand allyl 2-O-methyl-α-L-fucoside (2) [28

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

• developed a library of cysteine reactive chemical probes with an alkyne handle for fluorescence tagging and report the selective and highly sensitive in vitro labelling of the active site cysteine of this important enzyme. Interestingly, only one type of probe, with a reactive α-chloroacetamide was capable

• of covalently reacting with the active site. We demonstrated the potential of our probes in a competitive labelling platform where we screened a library of synthetic HHQ and PQS analogues with heteroatom replacements and found several inhibitors of probe binding that may represent promising scaffolds

• for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme. Keywords: activity-based probes; PqsD; protein labelling; Pseudomonas aeruginosa; quinolones; Introduction The emergence of multi-drug resistant

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

• with very similar geometrical parameters differing only in their absorption and emission wavelengths. The grade of unsaturation as the sole geometrical difference thus provides a set of probes to study the effect of rigidified ethene moieties as straight-chain alkane surrogates within biological

• , but spectroscopically different fluorescent probes we believe that these fatty acids might find interest as useful candidates to study the sensitive hydrophobic area of membranes in terms of domain formation or as labeling agents in general. Experimental General. All solvents for column chromatography

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• -based methods [90]. In Q-SiteFinder a van der Waals probe is used and the interaction energy between the probe and the protein is found in order to identify binding sites of the protein [91]. The SiteHound program is another energy-based method that uses two kinds of probes; a carbon probe and a

• protease. Another energy-based method, FTMAP, uses 16 probes in identifying hot spots in structures and was more recently extended to include any user provided small molecule as an additional probe [93][94]. Many other binding pocket finding programs exist. PEP-SiteFinder [95], SiteMap available through

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• resulting complexes [2]. These systems typically exhibit high thermodynamic and kinetic stability and have found application within biomimetic systems [1][7][8][9][10], in biomedicine [3][6][11][12][13][14][15][16], as catalysts [17][18][19][20][21][22], and as fluorescent probes [5][23][24][25][26][27][28

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• nanostructures in cellulo [12][13]. The precursor of D-aminoluciferin, 6-amino-2-cyanobenzothiazole (ACBT, 8), is an attractive building block for BLI probes and for handles for CBT ligations, because of the ease of derivatisation of its amino group. Like other functionalised CBTs, ACBT is available from

• plug to give the desired product in 60–71% yield. Pure product 8 was recrystallised from hot ethanol for melting point determination. Conclusion We have developed a straight-forward, practical and readily scalable synthesis of ACBT 8, a valuable intermediate in the development of chemical probes for

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

• , so they were successfully used for both gene expression regulation and the synthesis of fluorescent probes for DNA imaging in fixed and live cells [1][2][3][8][9]. However, the length of the sequence recognized by the classical hairpin polyamides (5–6 base pairs) is much shorter than that for TFOs

• transformations. So, this reaction is suitable for the synthesis of different biologically important conjugates including polyamide-TFO conjugates and fluorescent probes based on these components. Several methods avoiding the presence of cytotoxic copper ions have been also described [27][28][29]. Baskin et al

• because of the low concentration of integrated viral DNA in the genome. That is why for the synthesis of the fluorescent probes by "click chemistry" we decided to use a polyamide F1-NH2 that targets the tandem repeats of murine pericentromeres abundant in the murine genome [2][3]. The polyamide structure

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

• derivatives were then selected and their biological and photophysical properties were studied. Luminescent properties of pyrenyl aminophosphonates The widespread use of pyrene derivatives as luminescent probes in biological research [24][25][26][27] prompted us to study emissive properties of the synthesized

• 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 of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• fulfill this task, radioactive labeling or fluorescent probes have been thoroughly used. For example, the subcellular localization of the 3H-radiolabeled GemSQ conjugate has been evaluated by micro-autoradiography coupled to confocal imaging of fluorescently labeled cellular structures [21]. A dual

• , the use of fluorescent probes requires the covalent binding of large dye molecules (bodipy, cyanine, rhodamine etc, ...) to the drug conjugate, thus potentially modifying its physicochemical profile as well as the in vivo fate and the pharmacological activity. A simple encapsulation of an amphiphilic

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

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

• states. Keywords: fluorescence; heterocycles; quinolizinium; solvatochromism; Introduction Dyes that change their absorption and emission properties, especially their color, in different media are considered as helpful optical probes, because they may be applied for the characterization and

• identification of either bulk media or microscopic environments with relatively simple spectrometric analyses [1][2][3]. For example, distinct solvent properties, such as hydrogen-bonding ability, polarity or polarizability can be determined even quantitatively by means of solvatochromic optical probes [4][5][6

• ][7]. In this context, fluorosolvatochromic probes appear to be especially attractive as indicators for the surrounding medium, because emission spectroscopy is a highly sensitive method that allows to determine three different physical quantities, namely emission quantum yield, emission energy and

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• chromophores are valuable candidates for the fabrication of OLEDs [21][22], dye lasers [23], sensors [24], dye-sensitized solar cells, fluorescent probes [25] or logic gates [26]. Recently [27], 6-CF3-2H-pyran-2-ones have been reported as potential building blocks for the preparation of novel

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• Background: Derivatives of D-glucosamine and D-galactosamine represent an important family of the cell surface glycan components and their fluorinated analogs found use as metabolic inhibitors of complex glycan biosynthesis, or as probes for the study of protein–carbohydrate interactions. This work is