Synthesis of new antimicrobial 4-aminosubstituted 3-nitrocoumarins

A series of new coumarin derivatives has been synthesized by condensation of 4-chloro-3-nitrocoumarin and the appropriate arylamine and sulfonamide in ethyl acetate in the presence of triethylamine. The synthesized compounds were screened for their in vitro antimicrobial activity against thirteen strains of bacteria and three fungal/yeast strains using disk diffusion assays. They were shown to possess a wide range of activities from almost completely inactive compounds to medium active ones. (4-[(5-Chloropyridin-2-yl)amino]-3-nitro-2H-chromen-2-one) showed similar activity against Klebsiella pneumoniae as tetracycline.     

Double families of integrated evolution operators

A theory of double families of evolution operators, which involves mappings between different spaces, is presented. Causality is in a form analogous to that in integrated semi-groups, but involves an integrated relationship between members of both families. The approach is from a dynamic systems point of view, and focuses very much on the trajectories defined by the evolution operators and their relationship to the solutions of implicit evolution equations. Illustrative examples concerned with dynamic boundary conditions are provided.     

Divergence-Free Solutions of Poisson-Like Equations

It is shown that Poisson-like equations for 3-vector fields can have divergence-free solutions and desired boundary behaviour in bounded domains, provided the mean curvature of the boundary is nowhere too large positive. A-priori estimates for the solutions are given.     

The rippled β-sheet layer configuration—a novel supramolecular architecture based on predictions by Pauling and Corey

The rippled β-sheet is a peptidic structural motif related to but distinct from the pleated β-sheet. Both motifs were predicted in the 1950s by Pauling and Corey. The pleated β-sheet was since observed in countless proteins and peptides and is considered common textbook knowledge. Conversely, the rippled β-sheet only gained a meaningful experimental foundation in the past decade, and the first crystal structural study of rippled β-sheets was published as recently as this year. Noteworthy, the crystallized assembly stopped at the rippled β-dimer stage. It did not form the extended, periodic rippled β-sheet layer topography hypothesized by Pauling and Corey, thus calling the validity of their prediction into question. NMR work conducted since moreover shows that certain model peptides rather form pleated and not rippled β-sheets in solution. To determine whether the periodic rippled β-sheet layer configuration is viable, the field urgently needs crystal structures. Here we report on crystal structures of two racemic and one quasi-racemic aggregating peptide systems, all of which yield periodic rippled antiparallel β-sheet layers that are in excellent agreement with the predictions by Pauling and Corey. Our study establishes the rippled β-sheet layer configuration as a motif with general features and opens the road to structure-based design of unique supramolecular architectures.

The rippled sheet was proposed by Pauling and Corey in 1953, yet structural foundation remains extremely limited. Here we report on three X-ray crystal structures of rippled β-sheets, thus providing the long-sought structural basis for the field.     

Ferrocenylmethylation of estrone and estradiol: Structure,electrochemistry, and antiproliferative activity of new ferrocene–steroid conjugates

Conjugates of ferrocene with steroidal estrogens as selective antiproliferative agents against hormone-dependent breast cancer cells are believed to be limited by the inherent estrogenicity of the conjugates. Motivated by a significant cytotoxicity of the ester of ferrocenecarboxylic acid and the phenolic group of estradiol toward such a cell line, we decided to explore other a -ring-tethered ferrocene–estra-1,3,5(10)-triene conjugates; in this study, ferrocenylmethylation of estradiol and estrone with (ferrocenylmethyl)trimethylammonium iodide in the presence of potassium carbonate yielded five new compounds ( 1 – 5 ). In dimethylformamide, only O-alkylated products formed ( 1 and 3 ), while a mixture of O- and C-alkylated products was obtained when methanol was used ( 2 , 4 , and 5 in addition to 1 and 3 ). All compounds were characterized using 1D and 2D NMR, IR, UV–Vis, and high-resolution mass spectrometry. Two of the conjugates, a 3-O- and a 4-C-alkylated derivative of estrone ( 3 and 4 , respectively), were also analyzed using single-crystal X-ray diffraction. A cyclic voltammetric investigation of the electrochemical properties of 1 – 5 was performed. While some of the compounds were shown to have a slight-to-moderate antiproliferative activity against at least one of the six tested human tumor cell lines and were nontoxic to (the noncancerous) fetal human fibroblasts, compound 2 (4-(ferrocenylmethyl)estra-1,3,5(10)-triene-3,17β-diol) with an IC₅₀ value of 0.34 μM was found to be more active against the hormone-dependent breast cancer cell line MCF-7 than doxorubicin. These results suggest that a -ring substitution of steroidal estrogens is a plausible strategy for preparing other ferrocene–steroid conjugates acting against tumor cells.     

Direct detection of Δ9-tetrahydrocannabinol in aqueous samples using a homogeneous increasing fluorescence immunoassay (HiFi)

The detection of the major active component of cannabis, Δ9-tetrahydrocannabinol (THC), becomes increasingly relevant due to its widespread abuse. For control purposes, some easy-to-use, sensitive and inexpensive test methods are needed. We have developed a fluorescence immunoassay utilising THC–fluorescein conjugate as tracer. Fluorescence spectroscopy of the conjugate revealed an unusual property: The relatively weak fluorescence of a dilute tracer solution was increased by a factor of up to 5 after binding of a THC-specific antibody. Fluorescence lifetime measurements in aqueous solutions suggested two different tracer conformations both associated with quenching of fluorescein fluorescence by the intramolecular THC moiety. After antibody binding, the tracer enters a third conformation in which fluorescence quenching of fluorescein is completely suppressed. Utilising this property, we established a homogeneous competitive immunoassay (homogeneous increasing fluorescence immunoassay) with low detection limits. The test requires only two reagents, the new tracer molecule and an anti-THC antibody. A single test takes only 8 min. The dynamic detection range for THC is 0.5 to 20 ng/mL in buffer, with a limit of detection (LOD) of 0.5 ng/mL. The test also works in diluted saliva samples (1:10 dilution with buffer) with an LOD of 2 ng/mL and a dynamic range of 2–50 ng/mL.     

Lanthanides to quantum dots resonance energy transfer in time-resolved fluoro-immunoassays and luminescence microscopy

A time-resolved fluoro-immunoassay (TR-FIA) format is presented based on resonance energy transfer from visible emitting lanthanide complexes of europium and terbium, as energy donors, to semiconductor CdSe/ZnS core/shell nanocrystals (quantum dots, QD), as energy acceptors. The spatial proximity of the donor-acceptor pairs is obtained through the biological recognition process of biotin, coated at the surface of the dots (Biot-QD), and streptavidin labeled with the lanthanide markers (Ln-strep). The energy transfer phenomenon is evident from simultaneous lanthanide emission quenching and QD emission sensitization with a 1000-fold increase of the QD luminescence decay time reaching the hundred mus regime. Delayed emission detection allows for quantification of the recognition process and demonstrated a nearly quantitative association of the biotins to streptavidin with sensitivity limits reaching 1.2 pM of QD. Spectral characterization permits calculation of the energy transfer parameters. Extremely large F?rster radii (R(0)) values were obtained for Tb (104 A) and Eu (96 A) as a result of the relevant spectral overlap of donor emission and acceptor absorption. Special attention was paid to interactions with the varying constituents of the buffer for sensitivity and transfer efficiency optimization. The energy transfer phenomenon was also monitored by time-resolved luminescence microscopy experiments. At elevated concentration (>10(-)(5) M), Tb-strep precipitated in the form of pellets with long-lived green luminescence, whereas addition of Biot-QD led to red emitting pellets, with long excited-state decay times. The Ln-QD donor-acceptor hybrids appear as highly sensitive analytical tools both for TR-FIA and time-resolved luminescence microscopy experiments.     

Interface of nanoparticle-coated electropolished stents

Nanostructures entail a high potential for improving implant surfaces, for instance, in stent applications. The electrophoretic deposition of laser-generated colloidal nanoparticles is an appropriate tool for creating large-area nanostructures on surfaces. Until now, the bonding and characteristics of the interface between deposited nanoparticles and the substrate surface has not been known. It is investigated using X-ray photoelectron spectroscopy, Auger electron spectroscopy, and transmission electron microscopy to characterize an electropolished NiTi stent surface coated by laser-generated Au and Ti nanoparticles. The deposition of elemental Au and Ti nanoparticles is observed on the total 3D surface. Ti-coated samples are composed of Ti oxide and Ti carbide because of nanoparticle fabrication and the coating process carried out in 2-propanol. The interface between nanoparticles and the electropolished surface consists of a smooth, monotone elemental depth profile. The interface depth is higher for the Ti nanoparticle coating than for the Au nanoparticle coating. This smooth depth gradient of Ti across the coating-substrate intersection and the thicker interface layer indicate the hard bonding of Ti-based nanoparticles on the surface. Accordingly, electron microscopy reveals nanoparticles adsorbed on the surface without any sorption-blocking intermediate layer. The physicomechanical stability of the bond may benefit from such smooth depth gradients and direct, ligand-free contact. This would potentially increase the coating stability during stent application.