A Structural View on Medicinal Chemistry Strategies against Drug Resistance

The natural phenomenon of drug resistance is a widespread issue that hampers the performance of drugs in many major clinical indications. Antibacterial and antifungal drugs are affected, as well as compounds for the treatment of cancer, viral infections, or parasitic diseases. Despite the very diverse set of biological targets and organisms involved in the development of drug resistance, the underlying molecular mechanisms have been identified to understand the emergence of resistance and to overcome this detrimental process. Detailed structural information on the root causes for drug resistance is nowadays frequently available, so next‐generation drugs can be designed that are anticipated to suffer less from resistance. This knowledge‐based approach is essential for fighting the inevitable occurrence of drug resistance.     

Stable and soluble oligo(3,4-ethylenedioxythiophene)s end-capped with alkyl chains

The synthesis of a new series of stable and soluble EDOT oligomers end-capped with n-hexyl groups is described. Optical and electrochemical results indicate that the synergy between the direct electron-releasing effects of the ethylenedioxy groups and the self-rigidification resulting from intramolecular interactions controls to a large extent the HOMO-LUMO gap.     

Elimination of Listeria inoculated in ready-to-eat carrots by combination of antimicrobial coating and γ-irradiation

A combined treatment of an edible coating composed of trans-cinnamaldehyde (TCN; 0.5% p/p) with γ-irradiation was investigated against Listeria inoculated in peeled mini-carrots. First, the D₁₀ value (γ-irradiation dose required to eliminate 90% of the bacterial population) of TCN was evaluated under air. This treatment resulted in a 3.66-fold increase in relative bacterial radiosensitivity (RBR) as compared to the control without antimicrobial coating. Secondly, the shelf life of mini-carrots during 21 day of storage at 4 °C was studied. Antimicrobial coating containing TCN was assayed in combination with two irradiation doses (0.25 and 0.5 kGy). Results suggested that the inactive coating did not have any antimicrobial effect against Listeria while the coating containing TCN resulted in a 1.29 log reduction in carrots packed under air after 21 days of storage. Hence, these observations indicated that the combination of irradiation with antimicrobial coating played an important role in enhancing the radiosensitization of Listeria to γ-irradiation.     

An Easy Route to (Hetero)arylboronic Acids

An unprecedented spontaneous reactivity between diazonium salts and diboronic acid has been unveiled, leading to a versatile arylboronic acid synthesis directly from (hetero)arylamines. This fast reaction (35 min overall) tolerates a wide range of functional groups and is carried out under very mild conditions. The radical nature of the reaction mechanism has been investigated.     

On nonlinear gauge theories

In this note, we study non-linear gauge theories for principal bundles, where the structure group is replaced by a Lie groupoid. We follow the approach of Moerdijk–Mr?un and establish its relation with the existing physics literature. In particular, we derive a new formula for the gauge transformation which closely resembles and generalizes the classical formulas found in Yang Mills gauge theories.     

The di-iron subsite of all-iron hydrogenase: mechanism of cyanation of a synthetic [2Fe3S]-carbonyl assembly

This paper describes the kinetics and intimate mechanisms associated with cyanation of [2Fe3S] assemblies to give species structurally related to the subsite of all-iron hydrogenase. Stopped-flow FTIR spectroscopy has enabled the quantitation of the dynamics of five well-defined steps that experimentally illustrate the role of bridging carbonyls in the assembly of the dicyanide species, how on-off sulfur ligation can have a dramatic effect on cyanation kinetics and how the [2Fe3S] core stabilises bridging carbonyl species.     

Transient FTIR spectroelectrochemical and stopped-flow detection of a mixed valence (Fe(I)-Fe(II)) bridging carbonyl intermediate with structural elements and spectroscopic characteristics of the di-iron sub-site of all-iron hydrogenase

Iron(I) in biology?: one-electron oxidation of an (Fe(I)-Fe(I)) carbonyl cyanide precursor bearing a proximal thioether group leads to an (Fe(I)-Fe(II)) bridging carbonyl transient with spectral features similar to the di-iron sub-site of the CO inhibited paramagnetic centre of all-iron hydrogenase.     

Über die Erzeugung der 2. harmonischen Frequenz der Strahlung eines Nd-Lasers in KDP

Ohne Zusammenfassung