Design and synthesis of fluorescent pilicides and curlicides: bioactive tools to study bacterial virulence mechanisms.

Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores. Several of the resulting fluorescent compounds had improved activities as measured in pili- and curli-dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated with the bacteria with a heterogeneous distribution.

Locations and reorientations of multi-ring-fused 2-pyridones in ganglioside G(M1) micelles.

Fluorescent multi-ring-fused 2-pyridones, with chemical resemblance to other biologically active 2-pyridone systems, were solubilized in spherical micelles formed by the ganglioside G(M1) and studied with respect to their spatial localization and rotational mobility. For this, electronic energy transfer between the multi-ring-fused 2-pyridone (donor) and BODIPY-FL-labeled G(M1) was determined, as well as their fluorescence depolarization. From the obtained efficiency of energy transfer to the acceptor group (BODIPY-FL), either localized in the polar or in the nonpolar part of the ganglioside, it has been possible to estimate the most likely localization of the multi-ring-fused 2-pyridones. The center of mass of the studied multi-ring-fused 2-pyridones are located at approximately 33 Å from the micellar center of mass, which corresponds to the internal hydrophobic-hydrophilic interfacial region. At this location, the reorienting rates of the multi-ring-fused 2-pyridones are surprisingly slow with typical correlation times of 35-55 ns. No evidence was found for the formation of ground and excited state dimers, even when two monomers were forced to be near each other via a short covalent linker.

A versatile standard for bathochromic fluorescence based on intramolecular FRET.

A perylene and a terrylene tetracarboxylic bisimide dyad was prepared in which an efficient energy transfer from the former to the latter is observed. The absorption spectrum of this compound covers a broad range. Bathochromic fluorescence with a high quantum yield was obtained independent of excitation wavelengths (λ < 655 nm). The dyad can be recommended for the use of calibrating fluorescence spectrometers, as well as a fluorescence standard in the bathochromic region.

Unusual light spectroscopic properties of a 2-pyridone-based multi-ring-fused fluorescent scaffold.

UV-VIS absorption and fluorescence spectroscopic properties of six related polyaromatic 2-pyridones have been studied. Excitation of the lowest and rather weak and structure-less transition [ε (max) (430 nm) ≈ 3,000 mol(-1)dm(3)cm(-1)] gives rise to a broad fluorescence band in the visible region, for these compounds. These S (0) ↔ S (1) transitions are compatible with symmetrically forbidden transitions, promoted by intensity borrowing, as is revealed by fluorescence depolarisation data. With one exception, all compounds exhibit strong fluorescence, with quantum yields in glycerol varying between 40% and 70%. The corresponding fluorescence lifetimes range from 11 ns to 17 ns, while the radiative lifetimes are very similar (≈26 ns), for all compounds. Interestingly and rarely observed, the calculated radiative lifetimes for the weak absorption band are significantly longer, i.e. between 37 and 40 ns.

Influence of water matrix and hydrochar properties on removal of organic and inorganic contaminants.

The removal of contaminants from water using low-cost adsorbents has been widely studied, yet studies employing a realistic water matrix are still lacking. This study investigated the removal of organic compounds (trimethoprim, fluconazole, and perfluorooctanoic acid (PFOA)) and metals (As, Zn, and Cu) from landfill leachate. Additionally, tests in pure water, humic acid, and ion matrices were carried out to better understand how the water matrix affects adsorption. The hydrochars were produced from four feedstocks at three carbonization temperatures. The results show that the removal efficiencies for organic pollutants were low and metal removal by hydrochars was comparable with commercial activated carbon. The removal of all compounds from pure water was substantially lower. Tests with humic acid and ion-containing matrices could not fully explain the increased removal in the landfill leachate, which may be due to the combination of the water matrix and presence of soluble species from the hydrochars.

A characterisation study on the application of inverted lyotropic phases for subcutaneous drug release.

An experimental characterisation of lipid mixtures consisting of inverted hexagonal and inverted cubic phases composed of soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) was performed. The release of five chromophores of varying lipophilicity, used as model drugs, was investigated. Two experimental setups were applied: one based on maintaining sink condition, while a constant volume release medium was employed for the other. For neither setup, no correlation between the model drug lipophilicity and the polarity of the carrier matrix was found. However, the lipid phases showed a prolonged release, spanning weeks, of the model drugs, which exhibit lipophilicity values ranging by four orders of magnitude.