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Showing papers in "Helvetica Chimica Acta in 2018"


Journal ArticleDOI
TL;DR: In this article, the design, synthesis, and evaluation of multifunctional dithieno[3,2,b;2′,3′d]thiophene (DTT) trimers is described.
Abstract: The design, synthesis, and evaluation of multifunctional dithieno[3,2‐b;2′,3′‐d]thiophene (DTT) trimers is described. Twisted push‐push‐pull or donor‐donor‐acceptor (DDA) trimers composed of one DTT acceptor and two DTT donors show strong mechanochromism in lipid bilayer membranes. Red shifts in excitation rather than emission and fluorescence recovery with increasing membrane order are consistent with planarization of the twisted, extra‐long mechanophores in the ground state. The complementary pull‐pull‐pull or AAA trimers with deep σ holes all along the scaffold are not mechanochromic in membranes but excel with submicromolar anion transport activity. Anion transport along membrane‐spanning strings of chalcogen‐bond donors is unprecedented and completes previous results on transmembrane cascades that operate with equally unorthodox interactions such as halogen bonds and anion‐π interactions.

39 citations


Journal ArticleDOI
TL;DR: In this paper, the authors report design, synthesis and evaluation of the necessary catalysts to confirm that bidentate BDS are more effective than their monodentate analogs, conformationally immobilized scaffolds are more efficient than more flexible ones, cationic BDS scaffolds were more effective, and in dicationic BDS, contributions from chalcogen bonding dominated possible contributions from ion-pairing catalysis.
Abstract: Benzodiselenazoles (BDS) are emerging as privileged structures for chalcogen‐bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Whereas much attention has been devoted to work out the advantages of selenium compared to the less polarizable sulfur donors, high expectations concerning bidentate, rigid, and neutral scaffolds have been generated with little experimental support. Here we report design, synthesis and evaluation of the necessary catalysts to confirm that i) bidentate BDS are more effective than their monodentate analogs, ii) conformationally immobilized scaffolds are more effective than more flexible ones, iii) cationic BDS scaffolds are more effective than neutral ones, and iv) in dicationic‐bidentate BDS, contributions from chalcogen‐bonding dominate possible contributions from ion‐pairing catalysis. These conclusions result from rate enhancements found for a Ritter‐type anion‐binding reaction and an X‐ray crystal structure of dicationic BDS with a triflate anion bound with highest precision in the focal point of the σ holes.

32 citations


Journal ArticleDOI
TL;DR: In this paper, a review of the self-assembly behavior of ABC triblock copolymers is presented, covering novel shapes of micelles but also polymersomes with an asymmetric membrane.
Abstract: The self-assembly of amphiphilic block copolymers has attracted the interest of a large number of research groups in the past two decades. Many examples have been reported using AB diblock copolymers, but the self-assembly becomes more complex and shows a greater variety if ABC triblock copolymers are used. However, the synthesis of the polymer becomes more demanding since end-group modifications or chain extensions become necessary. Using various kinds of polymerization techniques, pure triblock copolymers have been reported and their synthesis is covered in this review. Following the synthesis, a detailed and thorough analysis of the self-assembly behaviour is the next step. We have selected promising and well characterized examples to show the range of self-assembled structures possible, covering novel shapes of micelles but also polymersomes with an asymmetric membrane. Our selection of current examples in literature show the challenges and chances associated with amphiphilic ABC triblock copolymers.

31 citations



Journal ArticleDOI
TL;DR: Double‐stranded RNA‐specific templated reaction resulting from PNA‐reagent conjugates that are brought within reactive distance through the formation of sequence‐specific triplexes onto double‐Stranded RNA is reported.
Abstract: RNA, originally perceived as a simple information transfer biopolymer, is emerging as an important regulator in cellular processes. A number of non‐coding RNAs are double‐stranded and there is a need for technologies to reliably detect and image such RNAs for biological and biomedical research. Herein we report double‐stranded RNA‐specific templated reaction resulting from PNA‐reagent conjugates that are brought within reactive distance through the formation of sequence‐specific triplexes onto double‐stranded RNA. The reaction makes use of a ruthenium‐based photocatalyst that reduces a pyridinium‐based immolative linker, unmasking a profluorophore. The reaction was shown to proceed with signal amplification and to be selective for double‐stranded RNA over DNA as well as single‐stranded RNA. The generality of the triplex formation was enabled by non‐canonical nucleobases that extend the Hoogsteen base‐pairing repertoire. The technology was applied to a templated reaction using pre‐microRNA 31.

28 citations


Journal ArticleDOI
TL;DR: In this paper, a fullerene-functionalized macrocycle with an axle bearing a porphyrin stopper was used to obtain a photoactive molecular device in which the porphrin emission is efficiently quenched by the fullerenes moiety.
Abstract: Transformation of a methylene group of the pillar[5]arene scaffold into a ketone has been achieved by treatment with N-bromosuccinimide followed by hydrolysis of the bromide intermediate and oxidation of the resulting secondary benzylic alcohol with BaMnO4. Condensation of the resulting macrocycle including a ketone function with p-toluenesulfonyl hydrazide followed by reaction of the corresponding tosylhydrazone with C60 under modified Bamford–Stevens conditions gave a fulleropillar[5]arene derivative. This building block has been used to prepare a rotaxane. The resulting molecule combining the fullerene-functionalized macrocycle with an axle bearing a porphyrin stopper is a photoactive molecular device in which the porphyrin emission is efficiently quenched by the fullerene moiety.

23 citations


Journal ArticleDOI
TL;DR: Insensitivity toward l-glucose and d-galactose and insensitivity of conventional CPDs toward d- glucose supported that glucose-mediated uptake of the multifunctional Glu-CPDs involves selective recognition by glucose receptors at the cell surface.
Abstract: The glycosylation of cell-penetrating poly(disulfide)s (CPDs) is introduced to increase the solubility of classical CPDs and to achieve multifunctional cellular uptake. With the recently developed sidechain engineering, CPDs decorated with α-d-glucose (Glu), β-d-galactose (Gal), d-trehalose (Tre), and triethyleneglycol (TEG) were readily accessible. Confocal laser scanning microscopy images of HeLa Kyoto cells incubated with the new CPDs at 2.5 μm revealed efficient uptake into cytosol and nucleoli of all glycosylated CPDs, whereas the original CPDs and TEGylated CPDs showed much precipitation into fluorescent aggregates at these high concentrations. Flow cytometry analysis identified Glu-CPDs as most active, closely followed by Gal-CPDs and Tre-CPDs, and all clearly more active than non-glycosylated CPDs. In the MTT assay, all glyco-CPDs were non-toxic at concentrations as high as 2.5 μm. Consistent with thiol-mediated uptake, glycosylated CPDs remained dependent on thiols on the cell surface for dynamic covalent exchange, their removal with Ellman's reagent DTNB efficiently inhibited uptake. Multifunctionality was demonstrated by inhibition of Glu-CPDs with d-glucose (IC50 ca. 20 mm). Insensitivity toward l-glucose and d-galactose and insensitivity of conventional CPDs toward d-glucose supported that glucose-mediated uptake of the multifunctional Glu-CPDs involves selective recognition by glucose receptors at the cell surface. Weaker but significant sensitivity of Gal-CPDs toward d-galactose but not d-glucose was noted (IC50 ca. 110 mm). Biotinylation of Glu-CPDs resulted in the efficient delivery of streptavidin together with a fluorescent model substrate. Protein delivery with Glu-CPDs was more efficient than with conventional CPDs and remained sensitive to DTNB and d-glucose, i.e., multifunctional.

23 citations




Journal ArticleDOI
TL;DR: In this article, a new tool built upon molecular volcano plots was used to quickly predict the activity of molecular catalysts as well as estimate the intrinsic ability of each species to form one regioisomer over the other with striking accuracy.
Abstract: The discovery of new homogeneous catalysts that preferentially form one product over another in regio- or enantioselective chemical reactions has traditionally been the province of experimental chemists. Today, computational-based approaches have carved an increasingly important role, which, for computational catalytic designs, often rely on highly inefficient combinatorial-based screening methods. To increase the pace of discovery, tools capable of rapidly assessing large numbers of prospective species and identify those possessing desirable properties, such as activity and selectivity, are vital. Here, through the examination of the hydroformylation of 2-methylpropene, we demonstrate how a new tool built upon molecular volcano plots can be used to quickly predict the activity of molecular catalysts as well as estimate the intrinsic ability of each species to form one regioisomer over the other with striking accuracy. Following training and validation, these regioselective molecular volcanoes are employed to predict catalysts that preferentially form the branched product (2,2-dimethylpropanal) in violation of Keulemans’ 70-year-old law. Eighteen species (out of a total of 68 predicted) were computationally predicted to have regiomeric excess (r.e.) values > 90. Overall, these tools can be used to quickly screen the activity and selectivity of potential catalysis based on two easily computed descriptor variables.

18 citations


Journal ArticleDOI
TL;DR: The first asymmetric anion-π catalysis of cascade reactions that afford nonadjacent stereocenters was reported in this paper, where the authors showed that anionπ catalysts can increase the diastereoselectivity of the reaction beyond the maximal 1:4.0 dr with conventional catalysts to maximal 5.3:1 dr on the large fullerene surfaces.
Abstract: Anion-π interactions have been recently introduced to catalysis with the idea to stabilize anionic intermediates on π-acidic surfaces. Realized examples include enolate, enamine and iminium chemistry, domino processes and Diels–Alder reactions. Moving on from the formation of contiguous stereogenic centers on π-acidic surfaces, herein we report the first asymmetric anion-π catalysis of cascade reactions that afford nonadjacent stereocenters. Conjugate addition-protonation of achiral disubstituted enolate donors to 2-chloroacrylonitrile generates 1,3-nonadjacent stereocenters with moderate enantioselectivity and diastereoselectivity. The explored catalysts operate with complementary naphthalenediimide and fullerene surfaces with highly positive quadrupole moments and high polarizability, respectively, and proximal amine bases. We find that anion-π catalysts can increase the diastereoselectivity of the reaction beyond the maximal 1:4.0 dr with conventional catalysts to maximal 5.3:1 dr on the large fullerene surfaces. The enantioselectivity of anion-π catalysts, best on the confined naphthalenediimide surfaces with strong quadrupole moment, exceed the performance of conventional catalysts except for comparable results with a new, most compact, surprisingly powerful bifunctional control catalyst. Simultaneously increased rates and stereoselectivities compared to control catalysts without π-acidic surface support that contributions of anion-π interactions to the catalytic cascade process are significant.

Journal ArticleDOI
TL;DR: Flow cytometry analysis of the uptake of MOP 5 RGD Ad-FITC toward U87 cells demonstrated improved uptake relative to control MOP lacking c-RGD ligands, suggesting a broad applicability of orthogonally functionalizable MOPs in targeted drug delivery and imaging applications.
Abstract: Mixed self-assembly of ligands 1 and 2, PXDA (3), and Pd(NO3)2 afforded metal organic polyhedra (MOP 1 - MOP 3) which bear 24 covalently attached CB[7] and cyclooctyne moieties. Post assembly modification (PAM) of MOP 3 by covalent strain promoted alkyne azide click reaction provided MOP 4R bearing covalently attached functionality (PEG, sulfonate, biotin, c-RGD, fluorescein and cyanine). Orthogonal CB[7] guest mediated non-covalent PAM of MOP 4R with Ad-FITC afforded MOP 5RGDAd-FITC and MOP 5biotin0020Ad-FITC. Flow cytometry analysis of the uptake of MOP 5RGDAd-FITC toward U87 cells demonstrated improved uptake relative to control MOP lacking c-RGD ligands. These results suggest a broad applicability of orthogonally functionalizable (covalent and non-covalent) MOPs in targeted drug delivery and imaging applications.

Journal ArticleDOI
TL;DR: Fluorescent flippers that selectively recognize gangliosides on the surface of lipid bilayer membranes by formation of dynamic covalent boronate esters are reported.
Abstract: The development of fluorescent probes to image forces in cells is an important challenge in chemistry and biology. Planarizable push‐pull probes have been introduced recently for this purpose. To provide most valuable information on forces in complex systems, these mechanosensitive ‘flipper' probes will have to be localized by molecular recognition of targets of interest. Here we report fluorescent flippers that selectively recognize gangliosides on the surface of lipid bilayer membranes by formation of dynamic covalent boronate esters. The original flipper probes were equipped with 2‐fluorophenyl boronic acids and benzoboroxoles using consecutive triazole and oxime ligation. Evaluation was done in large unilamellar vesicles composed of EYPC/SM/CL/GM 40:40‐x:20:x to obtain mixed membranes with separate liquid‐disordered (Ld) and ganglioside (GM) containing liquid‐ordered (Lo) domains. With increasing GM concentration, fluorescence intensities increased and excitation maximum shifted to the red. Deconvolution of the spectra confirmed that these changes originate from a migration of the flipper probes from Ld to Lo domains upon binding to the gangliosides and thus the planarization in the more ordered environment. Control mechanophores without boronic acids failed to show the same response, and fructose partially inhibited the ganglioside sensitivity. These results demonstrate that it is possible to selectively accumulate mechanosensitive flipper probes in Lo domains and, more generally, that probe localization in complex membranes is possible and matters.


Journal ArticleDOI
TL;DR: The results show that use of CPPs for drug delivery, for instance to cancer cells and tissues, must be considered with due care, as well as showing a pronounced difference between in-vitro and in- vivo activity.
Abstract: Oligo-arginines are thoroughly studied cell-penetrating peptides (CPPs, Figures 1 and 2). Previous in-vitro investigations with the octaarginine salt of the phosphonate fosmidomycin (herbicide and anti-malaria drug) have shown a 40-fold parasitaemia inhibition with P. falciparum, compared to fosmidomycin alone (Figure 3). We have now tested this salt, as well as the corresponding phosphinate salt of the herbicide glufosinate, for herbicidal activity with whole plants by spray application, hoping for increased activities, i.e. decreased doses. However, both salts showed low herbicidal activity, indicating poor foliar uptake (Table 1). Another pronounced difference between in-vitro and in-vivo activity was demonstrated with various cell-penetrating octaarginine salts of fosmidomycin: intravenous injection to mice caused exitus of the animals within minutes, even at doses as low as 1.4 μmol/kg (Table 2). The results show that use of CPPs for drug delivery, for instance to cancer cells and tissues, must be considered with due care. The biopolymer cyanophycin is a poly-aspartic acid containing argininylated side chains (Figure 4); its building block is the dipeptide H-βAsp-αArg-OH (H-Adp-OH). To test and compare the biological properties with those of octaarginines we synthesized Adp8-derivatives (Figure 5). Intravenouse injection of H-Adp8-NH2 into the tail vein of mice with doses as high as 45 μmol/kg causes no symptoms whatsoever (Table 3), but H-Adp8-NH2 is not cell penetrating (HEK293 and MCF-7 cells, Figure 6). On the other hand, the fluorescently labeled octamers FAM-(Adp(OMe))8-NH2 and FAM-(Adp(NMe2))8-NH2 with ester and amide groups in the side chains exhibit mediocre to high cell-wall permeability (Figure 6), and are toxic (Table 3). Possible reasons for this behavior are discussed (Figure 7) and corresponding NMR spectra are presented (Figure 8).

Journal ArticleDOI
TL;DR: A series of bis(pyreneamide) macrocycles, synthesized in two steps from THF, THP, oxepane and 1,4-dioxane, are tested as chemosensors for a large range of mono-, di- and trivalent cations as discussed by the authors.
Abstract: A series of bis(pyreneamide) macrocycles, synthesized in two steps from THF, THP, oxepane and 1,4-dioxane, are tested as chemosensors for a large range of mono-, di- and trivalent cations. In their native states, these macrocycles exhibit a strong excimer fluorescence that is quenched upon the addition of the metal ions (alkaline, alkaline earth, p-, d-, and f-block metals). UV-Vis spectrophotometric titrations, cyclic voltammetry, excimer fluorescence quenching, and transient absorption spectroscopy experiments helped characterize the On-Off changes occurring upon binding and demonstrate that the highest stability constants are obtained with divalent cations Ca2+ and Ba2+ specifically.



Journal ArticleDOI
TL;DR: All material supplied via JYX is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of the repository collections is not permitted, except that material may be duplicated by you for your research use or educational purposes in electronic or print form.
Abstract: All material supplied via JYX is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of the repository collections is not permitted, except that material may be duplicated by you for your research use or educational purposes in electronic or print form. You must obtain permission for any other use. Electronic or print copies may not be offered, whether for sale or otherwise to anyone who is not an authorised user. Selective encapsulation and enhancement of the emission properties of a luminescent Cu(I) complex in mesoporous silica Donato, Loïc; Atoini, Youssef; Prasetyanto, Eko Adi; Chen, Pengkun; Rosticher, Céline; Bizzarri, Claudia; Rissanen, Kari; De Cola, Luisa


Journal ArticleDOI
TL;DR: In this paper, the authors describe the synthesis and characterization of a novel liquid crystalline hydrogen-bonding hepta(dimethylsiloxane) azobenzene carboxylic acid dimer, which forms sub-5nm lamellar features in the bulk and at the liquid solid interface.
Abstract: The self-assembly of molecular inorganic/organic hybrid building blocks into ordered hierarchical nanomaterials with a tunable morphology is an enormous challenge. Here, we describe the synthesis and characterization of a novel liquid crystalline hydrogen-bonding hepta(dimethylsiloxane) azobenzene carboxylic acid dimer. This inorganic/organic hybrid dimer forms sub-5 nm lamellar features in the bulk and at the liquid solid interface. When mixed with a complementary hydrogen-bonding disk-shaped small molecule, a columnar hexagonal phase is formed. When adding a block copolymer containing hydrogen bond-accepting moieties, a hierarchical nanostructured material is obtained with a hexagonal columnar arrangement perpendicular to lamellae super structure. Our supramolecular approach shows that hierarchical hybrid nanomaterials can be fabricated with controlled properties which is appealing for applications such as nanoporous materials, organic electronics, and nanolithography.

Journal ArticleDOI
TL;DR: It is suggested that streptavidin is a versatile host protein for the assembly of artificial hydrogenases and their activity can be fine-tuned via mutagenesis and the hydrogen evolution mechanism proceeds via a single Co centre.
Abstract: Photocatalytic hydrogen evolution by an artificial hydrogenase based on the biotin-streptavidin technology is reported. A biotinylated cobalt pentapyridyl-based hydrogen evolution catalyst (HEC) was incorporated into different mutants of streptavidin. Catalysis with [Ru(bpy)(3)]Cl-2 as a photosensitizer (PS) and ascorbate as sacrificial electron donor (SED) at different pH values highlighted the impact of close lying amino acids that may act as a proton relay under the reaction conditions (Asp, Arg, Lys). In the presence of a close-lying lysine residue, both, the rates were improved, and the reaction was initiated much faster. The X-ray crystal structure of the artificial hydrogenase reveals a distance of 8.8 angstrom between the closest lying Co-moieties. We thus suggest that the hydrogen evolution mechanism proceeds via a single Co centre. Our findings highlight that streptavidin is a versatile host protein for the assembly of artificial hydrogenases and their activity can be fine-tuned via mutagenesis.




Journal ArticleDOI
TL;DR: In this article, the usefulness of DMT/NMM/TsO− for peptide synthesis in solution, starting from Z-, Fmoc-, and Boc-protected substrates as well as unnatural building blocks was confirmed.
Abstract: 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO−), a representative member of the inexpensive and environmentally-friendly N-triazinylammonium family of sulfonates, has been found to be a very effective coupling reagent for the synthesis of amides, esters and peptides in solution. This study confirms the usefulness of DMT/NMM/TsO− for peptide synthesis in solution, starting from Z-, Fmoc-, and Boc-protected substrates as well as unnatural building blocks. Peptide synthesis with DMT/NMM/TsO− produced high yields, with high crude product purity and low risk of racemization. In all cases, stoichiometric amounts of reagents were used and the standard synthetic procedure, without the need for time-consuming optimization stages or expensive chromatographic purification. DMT/NMM/TsO− was also found to be very useful for the synthesis of oligopeptides using a fragment coupling strategy.