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

• glass substrates. Hasegawa et al. [15] were the first to develop rhodamine labeled CDs for biological purposes. They synthesized two different fluorescent β-CDs and showed their utility as new fluorogenic probes for monitoring pH of HeLa cells. The synthetic strategy was based first on the modification

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• triarylmethane motif are ubiquitous and found mainly in technologically and medicinally relevant molecules like dyes [6][7][8][9], pH indicators [10][11][12], fluorescent probes [13][14][15][16][17][18] and antibacterial drugs [19]. For example, malachite green (1) is a dye, cresol red (2) is a pH indicator and

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

• to answer these questions where mechanistically interesting, there was a question – “How many people really care about such subtle details?” Thus, while mechanistic pursuits remain a constant in our group’s work, we switched from using synthetic receptors as mechanistic probes to using such receptors

• Molecular Probes. The directions that Vincent Rotello is taking the field of differential sensing, toward that of biological applications, is one clear future. We are similarly moving to biological applications with kinase and lipid analysis, and cellular classification. But, even beverage analysis, complex

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• macrocycle and the act of reading the polymer sequence would have to be performed sequentially rather than random access. Macrocycles make an appearance: macrocyclic bisintercalators and our early efforts to develop DNA probes As just illustrated, one of the major advantages of the molecular tweezer approach

• consistent with much of the data [45]. Beyond the novelty of the binding mode, we thought these macrocyclic bisintercalators might serve as probes of DNA breathing and further might have particularly slow dissociation kinetics, thereby improving their ability to inhibit enzymatic DNA processing. However

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• it is hard” [11]. We realized that most of the targeted fluorescent molecular probes for phospholipids were derivatives of large protein systems and we felt that we could devise small synthetic mimics of the binding pockets. Our primary phospholipid target was phosphatidylserine, which gets exposed

• selectively recognize the anionic head group of phosphatidylserine [12]. Furthermore, binding strength is amplified by electrostatic attraction of the cationic receptor to the apoptotic cell membrane with a negative surface potential. We developed a family of fluorescent ZnDPA probes for fluorescence

• microscopy and flow cytometry methods for preclinical research [13][14][15][16] (Figure 2). Many of these fluorescent probes are used as imaging reagents to quantify the level of cell death in a range of biomedical samples [17]. We also developed some nuclear isotopic labeled probes for in vivo imaging of

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• was to develop a toolbox of different dyads for further coordination of different types of metals, the easy and fast assembly of two polyazamacrocycles providing easy access to new bimodal probes. Depending upon the desired application, it could allow choosing one paramagnetic metal for MRI and one

• [16][17] and porphyrins as PET probes. Cu–NOTA is significantly more inert in acidic conditions compared to Cu–DOTA, which usually decomplexed within few minutes. 64Cu2+-NOTA is considered as better PET agent, with regard to its in vivo stability [18]. Porphyrins are also excellent macrocyclic ligands

• ]. Gallium-68. NOTA [22] and DOTA [23] have been reported to form a stable complex with gallium(III) and those two ligands are widely used in the preparation of 68Ga-based PET probes. Advantageously, Ga complexes of porphyrins and corroles are known to be very stable allowing possible PET imaging

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• which has attracted much attention due to the applications in various molecular probes and luminescent materials because of the remarkable photophysical properties of the ESIPT (excited state intramolecular proton transfer) chromophores [33][34]. UV-irradiation of solutions of these compounds in

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• regulator of cellular cholesterol [8]. Synthetic BODIPY–cholesterol conjugates were reported as probes for visualization of intracellular cholesterol pools and for monitoring cholesterol efflux from cells to extracellular receptors [9]. ABCA1 plays an inevitable role in the resistance against tumorgenesis

• under the same conditions and compound 32 also could not be obtained [44][45]. To investigate, whether the triazole or the cholesterol entities are not compatible with these debenzylation conditions, probes 36 and 38 (Scheme 7) were prepared by CuAAC of derivative 34 with compounds 35 and 9b

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

• fluorescent probes have been developed that react to different chemical stimuli [14]. Although previous work on the development of fluorescent olefin metathesis catalysts [15][16] exists, to our knowledge, the concept of fluorescent probes based on ring-closing metathesis is new and could be of value to

Adsorption mechanism and valency of catechol-functionalized hyperbranched polyglycerols

• Stefanie Krysiak,
• Qiang Wei,
• Klaus Rischka,
• Andreas Hartwig,
• Rainer Haag and
• Thorsten Hugel

Beilstein J. Org. Chem. 2015, 11, 828–836, doi:10.3762/bjoc.11.92

• GMBH, Kirchheim, Germany) and afterwards rinsed with ultrapure water. Tip functionalization The molecule is functionalized to the tip through covalent bonds in a similar manner as previously described [2]. Silicon nitride cantilevers (MLCT, Bruker SPM probes, Camarillo, USA) were first activated in an

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• gold coated SFM cantilever probes and surfaces using thiol chemistry (for details see Experimental section below). The interaction between gold and SH-groups is known to withstand rupture forces in the range of 1 to 2 nN [38], followed by the formation of a monoatomic gold nanowire that finally leads

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• scaffolds as well as NCAAs to provide multiple distinct probes for the generation of individually designed protein binders. An important parameter in the future will be the combination with protein modelling as well as the implementation of different linker lengths between the protein and the binding units

Glycodendrimers: tools to explore multivalent galectin-1 interactions

• Jonathan M. Cousin and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2015, 11, 739–747, doi:10.3762/bjoc.11.84

• concentration of the dendrimer (220:1, 9:1, or 3:1 ratio of galectin-1 to dendrimer, respectively). Fluorescent microsphere standards (FluoSpheres Fluorescent Microspheres, Molecular Probes) and image analysis software (Pixcavator 6.0) were used for size quantifications. The results from the fluorescence

• characterized according to the reported procedure [32]. Fluorescence microscopy Reagents for fluorescence microscopy were purchased from Molecular Probes. To measure galectin-1 nanoparticles formed using glycodendrimers with fluorescence microscopy, both species were fluorescently labeled. Galectin-1 was

• labeled with Alexa Fluor A555 NHS Ester (succinimidyl ester) (Molecular Probes) [42]. Fluorescent images were captured on an Olympus BX-61 motorized microscope with MicroSuite software with a 100× oil immersion objective at an exposure time of 2 ms. Size quantification was achieved using fluorescent

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• a concanavalin A (ConA) layer via poly(ethylene glycol)-(PEG)-based soft colloidal probes (SCPs). Special emphasis is on the dependence of multivalent presentation and density of carbohydrate units on specific adhesion. Consequently, we first present a synthetic strategy that allows for controlled

• of surface anchored carbohydrate ligands with a receptor surface, we developed a new method using carbohydrate coated hydrogel particles, also called soft colloidal probes (SCPs) that undergo mechanical deformation when coming into contact a with receptor surface [8][9][10][11]. The mechanical

• Recently, we introduced micrometer-sized SCPs composed of crosslinked PEG-diacrylamide hydrogels as probes [15]. Here, we used the ability of PEG-diacrylamide to phase separate from an aqueous solution to form microscopic droplets by means of precipitation using sodium sulfate as a kosmotrope. At

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

• molecular probes and synthesized by way of Cu(I)-catalysed azide–alkyne cycloadditions are fluorescent analogues of potent pharmacological chaperones/correctors recently reported in the field of Gaucher disease and cystic fibrosis, two rare genetic diseases caused by protein misfolding. Keywords: BODIPY

• ; fluorescent probes; iminosugars; 4-methylumbelliferone; multivalency; pyrene; Introduction Since the isolation in the 1970’s of 1-deoxynojirimycin (DNJ) from natural sources and the finding of its biological activity as an α-glucosidase inhibitor, thousands of sugar mimetics with a nitrogen atom replacing

• Discussion Synthetic design The fluorescent probes were designed as analogues of the best multivalent pharmacological chaperones/correctors reported so far that typically display three to four copies of a DNJ ligand linked to a central core via an alkyl chain spacer (Figure 1) [24][25][26]. The choice of the

Fluoride-driven ‘turn on’ ESPT in the binding with a novel benzimidazole-based sensor

• Kai Liu,
• Xiaojun Zhao,
• Qingxiang Liu,
• Jianzhong Huo,
• Bolin Zhu and
• Shihua Diao

Beilstein J. Org. Chem. 2015, 11, 563–567, doi:10.3762/bjoc.11.61

• ]. However, to OH-based anion sensors it has been paid less attention [25][26]. In fact, we have succeeded in designing and synthesizing the anion fluorescent probes, based on ESPT [15][16], containing phenolic OH as H-bond donor. In these systems, the probe displayed a narrower linear range for fluoride

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• to develop oligonucleotide-based drug candidates or biomedical chemical probes [5][6]. Native nucleic acids are connected by phosphate diesters as linking units, thus leading to a polyanionic backbone structure. Implications of this characteristic feature of nucleic acid architecture have been

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• ; Findings Compounds incorporating the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (F-BODIPY) motif 1 have found widespread use in fluorescent molecular probes [1][2], photovoltaic devices [3][4] and photodynamic therapy agents [5][6][7][8]. Accordingly, there is considerable interest in extending and

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

• ligand-ILPR complexes are different from the ones observed with other native quadruplex-forming DNA sequences. Keywords: DNA ligands; fluorescent probes; ILPR; nucleic acids; quadruplex DNA; Introduction The “insulin-linked polymorphic region” (ILPR) is a physiologically relevant G-rich DNA sequence

• show high selectivity towards quadruplex as compared to double stranded DNA [20]. Therefore, these ligands may be used as probes for the detection of quadruplex DNA. Although the CD-spectroscopic analysis only provides qualitative information about the binding between the ligand and the DNA, they may

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• - and RNA-fluorescent markers (ethidium bromide), probes for cell viability (propidium iodide), but also “ill-famed” for various toxic (genotoxic) and mutagenic effects. After two decades of low interest, the discovery of phenanthridine alkaloids and new studies of antiparasitic/antitumor properties of

Nucleic acid chemistry

• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2014, 10, 2928–2929, doi:10.3762/bjoc.10.311

• runs automatically on machines, so-called DNA synthesizers. With special care during each synthesis step, even longer oligonucleotides can be prepared in a similar, almost routine fashion. The field of nucleic acid chemistry has exploded: natural and artificial functionalities, as well as probes

• cases, postsynthetic strategies can allow for the desired oligonucleotides modification. This becomes an even more important issue for functionalities, probes or biologically relevant molecules that are incompatible with routine phosphoramidite chemistry. Although nucleic acid chemistry appears to be a

• mature part of organic and bioorganic chemistry, the many questions that are still being raised by research in biology and chemical biology give sufficient motivation to continue to synthesize new nucleic acid probes and thereby further develop nucleic acid chemistry. Moreover, in addition to their

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

• Michail Syrpas,
• Ewout Ruysbergh,
• Christian V. Stevens,
• Norbert De Kimpe and
• Sven Mangelinckx

Beilstein J. Org. Chem. 2014, 10, 2539–2549, doi:10.3762/bjoc.10.265

• . Most of the α-haloacylated analogues did not exhibit a significant reduction when tested in the QS inhibition test. Therefore, these novel analogues could be utilized as chemical probes for QS structure–activity studies. Keywords: halogenated fatty acids; halogenation; N-acylated homoserine lactones

• , inhibition of bacterial QS was recently demonstrated by a set of electrophilic probes (which included halogenated analogues of AHLs) that could covalently bind in the LasR binding pocket of Pseudomonas aeruginosa [15]. Therefore, designing analogues with small reactive moieties, such as halogenated carbon

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• Macromolecular Chemistry, Friedrich Schiller University, Humboldtstr. 10, 07743 Jena, Germany Institute for Physical Chemistry, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany 10.3762/bjoc.10.258 Abstract Molecular probes are widely used tools in chemical biology that allow tracing of

• bioactive metabolites and selective labeling of proteins and other biomacromolecules. A common structural motif for such probes consists of a reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation between terminal alkynes and azides to a reactive headgroup. Here we introduce the

• -Hydroxythiazoles are now becoming commercially available but are also easily accessible by synthesis with a broad range of substitution patterns. Substantial manipulations of the UV–vis excitation and emission wavelengths of these compounds are thus possible [6]. The design of molecular probes based on

Multivalent glycosystems for nanoscience

• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2014, 10, 2345–2347, doi:10.3762/bjoc.10.244

• nanoscience”. Bruce Turnbull (United Kingdom) has amassed contributions dedicated to “Synthetic methods to make multivalent glycosystems”, Alessandro Casnati (Italy) has delivered manuscripts regarding “Glycoconjugates for the delivery of drugs and diagnostic probes” for review, Roland Pieters (The

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• shows several unique properties [26][27][28]. Its potential applications as a probe for DNA sensing are well-established. For example, we have developed singly labeled acpcPNA probes that can give a fluorescence change in response to hybridization to DNA [29][30][31]. Due to its solvatochromic