Reversible positioning at submicrometre scale of carbon nanotubes mediated by pH-sensitive poly(amino-methacrylate) patterns

The selective adsorption of carbon nanotubes (CNTs) on a pH-reversible PDMAEMA patterned gold surface is presented. In acidic conditions, a selective CNTs adsorption onto the polymer brushes is obtained due to ammonium-π interactions. The reversible behavior was shown by successive treatments in both alkaline and acidic solutions with CNTs.     

A rapid and environmental friendly determination of the dithiocarbamate metabolites ethylenethiourea and propylenethiourea in fruit and vegetables by ultra high performance liquid chromatography tandem mass spectrometry

Previous published methods for the analysis of ETU and PTU are time-consuming and furthermore use dichloromethane (DCM) for extraction or clean-up. This study details the development and validation of a rapid method that combines a simple extraction step with UHPLC-ESI(+)-MS/MS. This is the first application of UHPLC-MS/MS to analyse these compounds. Besides that, we replaced DCM with a more environmental-friendly solvent. The analytical performance was evaluated with the analysis of spiked celery samples at 50 μg kg(-1) (LOQ) and 300 μg kg(-1). The recoveries were between 65% and 90% for ETU and between 71% and 127% for PTU with RSDs in repeatability and reproducibility conditions below 10% for ETU. This method is rapid (a chromatographic run time of 2 min) and can easily be performed (no laborious clean-up). The presented method is environmental friendly with significant reduction in solvent consumption.     

Tridentate N-donor palladium(II) complexes as efficient coordinating quadruplex DNA binders

Fifteen complexes of palladium, platinum, and copper, featuring five different N‐donor tridentate (terpyridine‐like) ligands, were prepared with the aim of testing their G‐quadruplex–DNA binding properties. The fluorescence resonance energy transfer melting assay indicated a striking positive effect of palladium on G‐quadruplex DNA stabilization compared with platinum and copper, as well as an influence of the structure of the organic ligand. Putative binding modes (noncoordinative π stacking and base coordination) of palladium and platinum complexes were investigated by ESI‐MS and UV/Vis spectroscopy experiments, which all revealed a greater ability of palladium complexes to coordinate DNA bases. In contrast, platinum compounds tend to predominantly bind to quadruplex DNA in their aqua form by noncoordinative interactions. Remarkably, complexes of [Pd(ttpy)] and [Pd(tMebip)] (ttpy=tolylterpyridine, tMebip=2,2′‐(4‐p‐tolylpyridine‐2,6‐diyl)bis(1‐methyl‐1H‐benzo[d]imidazole)) coordinate efficiently G‐quadruplex structures at room temperature in less than 1 h, and are more efficient than their platinum counterparts for inhibiting the growth of cancer cells. Altogether, these results demonstrate that both the affinity for G‐quadruplex DNA and the binding mode of metal complexes can be modulated by modifying either the metal or the organic ligand.     

Recognition of G-quadruplex DNA by triangular star-shaped compounds: with or without side chains?

We report the synthesis of two new series of triangular aromatic platforms, either with three aminoalkyl side chains (triazatrinaphthylene series, TrisK: six compounds), or without side chains (triazoniatrinaphthylene, TrisQ). The quadruplex-DNA binding behavior of the two series, which differ essentially by the localization of the cationic charges, was evaluated by means of FRET-melting and G4-FID assays. For the trisubstituted triazatrinaphthylenes (TrisK), the length of the substituents and the presence of terminal hydrogen-bond-donor groups (NH(2)) were shown to be crucial for ensuring a high quadruplex affinity (ΔT(1/2) values of up to 20 °C at 1 μM for the best candidate, TrisK3-NH) and selectivity versus duplex DNA. Subsequently, comparison of data collected on both the telomeric- and c-myc-quadruplex showed that the nonsubstituted TrisQ is even more efficient than TrisK3-NH, both in terms of quadruplex affinity (ΔT(1/2)=26 °C in K(+) buffer) and selectivity versus duplex DNA. Structural considerations conducted with the c-myc quadruplex indicate that both TrisK3-NH and TrisQ stack well onto the G-quartet but in an offset position, which might be influenced by the formation of multiple hydrogen bonds with the target in the former case. Finally, the nonsubstituted TrisQ displays a binding profile very similar to some of the best quadruplex binders, BRACO-19 and bisquinolinium 360A, used herein as references, and thereby represents a highly promising novel molecular design for quadruplex recognition.     

A Three-Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two-Photon Excitation with Near-Infrared Light

A supramolecular nanoassembly, of about 30 nm in diameter, that consists of a green-fluorescent, β-cyclodextrin-based, branched polymer co-encapsulating a red-emitting singlet oxygen (¹O₂) photosensitizer and a nitric oxide (NO) photoreleaser, which comprises a blue fluorescent reporter, is here reported. The system exhibits “five-in-one” photofunctionalities. All components can be simultaneously excited in the phototherapeutic window with two-photons by using near-infrared light at 740 nm and despite their close proximity, behave as independent units. This allows for their in vitro visualization in carcinoma cancer cells, due to their distinct green, red, and blue fluorescence, and for the production of both cytotoxic ¹O₂ and biofunctional NO.     

Isolation and Biomass Production of a <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> Strain Binding Copper and Zinc Ions

Copper and zinc are essential trace elements participating in many physiological functions, notably immunity and protection against oxidative stress. Yeasts and the yeast Saccharomyces cerevisiae, in particular, possess in their genome tandem repeats of the CUP1 gene coding for a protein (a metallothionein) capable of capturing and binding toxic elements such as copper ions. The number of copies of this gene in a cell determines its physiological level of resistance to these ions. This paper describes the selection, characterization, and production of a new copper-resistant yeast strain that can bind large quantities of copper and zinc. This approach should lead to increasing the bioavailability of these trace elements and hence to reducing their emission into the environment.     

α,α-Difluorophosphonohydroxamic Acid Derivatives among the Best Antibacterial Fosmidomycin Analogues

Three α,α-difluorophosphonate derivatives of fosmidomycin were synthesized from diethyl 1,1-difluorobut-3-enylphosphonate and were evaluated on Escherichia coli. Two of them are among the best 1-deoxy-d-xylulose 5-phosphate reductoisomerase inhibitors, with IC₅₀ in the nM range, much better than fosmidomycin, the reference compound. They also showed an enhanced antimicrobial activity against E. coli on Petri dishes in comparison with the corresponding phosphates and the non-fluorinated phosphonate.     

Productive Syntheses of Privileged Scaffolds Inspired by the Recognition of a Diels–Alder Pattern Common to Three Classes of Natural Products

Identification of a common Diels–Alder pattern in three classes of bioactive natural products led us to study the synthesis and cycloaddition of a new class of cyclic dienes readily available from β,γ-unsaturated lactams. A practical and readily scalable route to the parent p-methoxybenzyl-protected 6- and 7-membered β,γ-unsaturated lactams was developed. These were readily transformed into the corresponding O-silylated dienes, which were reacted with dimethyl and diethyl fumarate to yield stereoselectively highly functionalized bicyclic adducts. These exhibited unexpected and versatile transformations upon acid hydrolysis depending on the nature of the dienophile substituents and the acid catalyst. All reactions have been performed on multigram quantities. These transformations provide a convenient, economical, and easily scalable pathway for the rapid construction of functionally and stereochemically dense privileged scaffolds for the construction of libraries of natural products-inspired molecules of pharmacological relevance.     

1H‐NMR relaxometric studies of interaction between apoptosis specific MRI paramagnetic contrast agents and micellar models of apoptotic cells

¹H‐NMR was previously used to analyze the interaction between peptides (E3 and R826) selected by phage display to target apoptotic cells and phospholipidic models of these cells. In order to avoid the use of apoptotic cells and to obtain a fast evaluation of the efficiency of the potential MRI contrast agents obtained by grafting these peptides and their scramble analogs on a paramagnetic gadolinium complex, their proton relaxometric behavior was investigated in the presence of micelles mimicking healthy and apoptotic cells. Their preferential interaction with 1,2‐dipalmitoyl‐sn‐glycero‐3‐phospho‐l ‐serine micelles mimicking apoptotic cells as compared with 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine micelles modeling healthy cells was shown by nuclear magnetic relaxation dispersion profiles and the enhancement of the transverse proton relaxation rates at 60 MHz. The association constant values confirm the stronger interaction of the selected conjugated peptides (K_a Gd‐PMN‐E3(gadolinium 2,2′,2′′,2′′′‐[((4‐carboxy)pyridine‐2,6‐diyl)bis(methylenenitrilo)]‐tetrakis acetate) grafted with E3 peptide): 2.43 10⁴ m ^?1; K_a Gd‐DTPA‐R826(gadolinium ((1‐p‐isothiocyanatobenzyl)‐diethylenetriaminepentaacetate) grafted with R826 peptide): 2.91 10⁴ m ^?1) as compared with their conjugated scrambles (K_a Gd‐PMN‐E3sc(gadolinium 2,2′,2′′,2′′′‐[((4‐carboxy)pyridine‐2,6‐diyl)bis(methylenenitrilo)]‐tetrakis acetate) grafted with E3 scramble peptide): 0.18 10⁴ m ^?1; K_a Gd‐DTPA‐R826sc(gadolinium ((1‐p‐isothiocyanatobenzyl)‐diethylenetriaminepentaacetate) grafted with R826 scramble peptide): 0.32 10⁴ m ^?1) even if the conjugation of E3 and R826 seems to decrease their interaction. Copyright © 2015 John Wiley & Sons, Ltd.