Design of Photosensitizing Agents for Targeted Antimicrobial Photodynamic Therapy

Photodynamic inactivation of microorganisms has gained substantial attention due to its unique mode of action, in which pathogens are unable to generate resistance, and due to the fact that it can be applied in a minimally invasive manner. In photodynamic therapy (PDT), a non-toxic photosensitizer (PS) is activated by a specific wavelength of light and generates highly cytotoxic reactive oxygen species (ROS) such as superoxide (O²⁻, type-I mechanism) or singlet oxygen (¹O₂*, type-II mechanism). Although it offers many advantages over conventional treatment methods, ROS-mediated microbial killing is often faced with the issues of accessibility, poor selectivity and off-target damage. Thus, several strategies have been employed to develop target-specific antimicrobial PDT (aPDT). This includes conjugation of known PS building-blocks to either non-specific cationic moieties or target-specific antibiotics and antimicrobial peptides, or combining them with targeting nanomaterials. In this review, we summarise these general strategies and related challenges, and highlight recent developments in targeted aPDT.     

A unifying look at the Apostolico–Giancarlo string-matching algorithm

String matching is the problem of finding all the occurrences of a pattern in a text. We present a new method to compute the combinatorial shift function (“matching shift”) of the well-known Boyer–Moore string matching algorithm. This method implies the computation of the length of the longest suffixes of the pattern ending at each position in this pattern. These values constituted an extra-preprocessing for a variant of the Boyer–Moore algorithm designed by Apostolico and Giancarlo. We give here a new presentation of this algorithm that avoids extra preprocessing together with a tight bound of 1.5n character comparisons (where n is the length of the text).     

Site‐ and Enantioselective C−H Oxygenation Catalyzed by a Chiral Manganese Porphyrin Complex with a Remote Binding Site

A chiral manganese porphyrin complex with a two‐point hydrogen‐bonding site was prepared and probed in catalytic C?H oxygenation reactions of 3,4‐dihydroquinolones. The desired oxygenation occurred with perfect site selectivity at the C4 methylene group and with high enantioselectivity in favor of the respective 4S‐configured secondary alcohols (12 examples, 29–97 % conversion, 19–68 % yield, 87–99 % ee). Mechanistic studies support the hypothesis that the reaction proceeds through a rate‐ and selectivity‐determining attack of the reactive manganese oxo complex at the hydrogen‐bound substrate and an oxygen transfer by a rebound mechanism.     

First experimental evidence of potassium ordering in layered k4co7o14

The layered P2-K4Co7O14 oxide has been prepared and characterized by means of X-ray diffraction, electrical conductivity, thermopower, and magnetic measurements. The crystal structure of K4Co7O14 (P6(3)/m space group, Z=2, a=7.5171(1) A, and c=12.371(1) A) consists of a stacking of slabs of edge-shared CoO6 octahedra with K+ ions occupying ordered positions in the interslab space, leading to a a0 radical7xa0 radical7 supercell. Potential energy calculations at 0 K are in good agreement with the ordered distribution of potassium ions in the (ab) plane. This oxide is metallic, and the magnetic susceptibility is of Pauli-type, which contrasts with the Curie-Weiss behavior of the homologous NaxCoO2 (x approximately 0.6) oxide with close alkali content. The thermopower at room temperature is about one-third that of polycrystalline Na0.6CoO2.     

Rapid Synthesis of New 5‐Nitroimidazoles as Potential Antibacterial Drugs via VNS Procedure

Original 4‐arylsulfonylmethyl‐5‐nitroimidazoles were prepared by reacting four chloromethylaryl sulfones with 5‐nitroimidazole derivatives via a vicarious nucleophilic substitution (VNS) of hydrogen reaction.     

Search for a Strong,Virtually “No‐Shift” Hydrogen Bond: A Cage Molecule with an Exceptional OH⋅⋅⋅F Interaction

Reported herein is the synthesis of a molecule containing an unusually strong hydrogen bond between an OH donor and a covalent F acceptor, a heretofore somewhat ill‐defined if not controversial interaction. This unique hydrogen bond is to a large extent a product of the tight framework of the rigid caged system. Remarkably, the interaction shows little to no perceptible shift in the OH stretch of the IR spectrum relative to appropriate nonhydrogen‐bound standards in fairly non‐interactive solvents. This fascinating example of what has been termed a virtual “no‐shift” hydrogen bond is investigated through NMR (coupling constants, isotopic chemical shift perturbations, proton exchange rates) and IR studies which all tell a consistent story.     

Occurrence of betablockers in effluents of wastewater treatment plants from the Lyon area (France) and risk assessment for the downstream rivers

Five betablockers (oxprenolol, metoprolol, propranolol, bisoprolol, betaxolol) were analysed in effluents collected over a 3-month period from wastewater treatment plants (WTP) from the Lyon area in France. The analytical protocol consisted of solid phase extraction of the dissolved aqueous phase on HLB cartridges and analysis by gas chromatography coupled with mass detection (GC-MS) after derivatization. Concentrations of metoprolol, propranolol and bisoprolol varied from 45 to 2838 ng/L whereas oxprenolol and betaxolol were never detected in these effluent samples. A high variability of betablockers concentrations and fluxes was observed between WTP effluents and within each WTP over the time period studied. Considering a flux per person for a dry weather period, Fontaine plant was pointed out as the less efficient WTP, which might be explained by its type of treatment (biological aerated filters). But we need additional analysis of effluent and influent waters to confirm this hypothesis. A tentative approach of local environmental risk assessment of propranolol based on the calculation of PEC/PNEC (predicted environmental concentration/predicted non effect concentration) ratio approach lead us to conclude on a negligible risk for the downstream rivers (Rhône river at Ternay and Saône river at Couzon Mt d’Or).     

Built-in axial base binding on phenanthroline-strapped zinc(II) and iron(III) porphyrins

In addition to the need for functional models of cytochrome c oxidase, structural models are still required for a better understanding of the small reorganizations occurring during the catalytic cycle. An efficient synthetic approach has been designed to prepare several phenanthroline-strapped porphyrins, two of them bearing two pendant imidazoles. These built-in bases are both potentially able to act as axial bases for the metalloporphyrin and as complementary ligands for copper if necessary. Diamagnetic zinc(II) was used to demonstrate that the distal/proximal selectivity demonstrated by exogenic bases binding studies can be extended to the coordination of iron(III). Combination of EPR and paramagnetic 1H NMR shows that the imidazole binding on the zinc species can be further extended to the iron(III) species in dilute conditions.