Interest of Homodialkyl Neamine Derivatives against Resistant P. aeruginosa, E. coli and β-lactamases-Producing Bacteria—Effect of Alkyl Chain Length on the Interaction with LPS

Development of novel therapeutics to treat antibiotic-resistant infections, especially those caused by ESKAPE pathogens, is urgent. One of the most critical pathogens is P. aeruginosa, which is able to develop a large number of factors associated with antibiotic resistance, including high level of impermeability. Gram-negative bacteria are protected from the environment by an asymmetric Outer Membrane primarily composed of lipopolysaccharides (LPS) at the outer leaflet and phospholipids in the inner leaflet. Based on a large hemi-synthesis program focusing on amphiphilic aminoglycoside derivatives, we extend the antimicrobial activity of 3′,6-dinonyl neamine and its branched isomer, 3′,6-di(dimethyloctyl) neamine on clinical P. aeruginosa, ESBL, and carbapenemase strains. We also investigated the capacity of 3′,6-homodialkyl neamine derivatives carrying different alkyl chains (C7–C11) to interact with LPS and alter membrane permeability. 3′,6-Dinonyl neamine and its branched isomer, 3′,6-di(dimethyloctyl) neamine showed low MICs on clinical P. aeruginosa, ESBL, and carbapenemase strains with no MIC increase for long-duration incubation. In contrast from what was observed for membrane permeability, length of alkyl chains was critical for the capacity of 3′,6-homodialkyl neamine derivatives to bind to LPS. We demonstrated the high antibacterial potential of the amphiphilic neamine derivatives in the fight against ESKAPE pathogens and pointed out some particular characteristics making the 3′,6-dinonyl- and 3′,6-di(dimethyloctyl)-neamine derivatives the best candidates for further development.

Ortho-para spin conversion of Ps by paramagnetic O2 dissolved in organic compounds

The o-Ps mean lifetime value in liquids decreases in the presence of the paramagnetic oxygen molecules via the ortho-para conversion process. This effect was observed for several organic samples composed of carbon and hydrogen atoms differing in the arrangement of atoms forming the molecule, e.g. n-alkanes, alcohols, branched isomer of alkane, cycloalkane. The usually observed tendency of the o-Ps lifetime value to be an increasing function of temperature (in the case of measurements performed in vacuum) changes to a decreasing one in the presence of O2 dissolved in the sample. The difference between the o-Ps lifetimes measured in samples in vacuum and in the presence of O2 increases with the distance from the melting point. The ortho-para constant rate λconv was estimated to be ~130 μs−1 at 300 K for three compounds investigated.

Synthesis, structure determination, and hydroformylation activity of N-heterocyclic carbene complexes of rhodium

The effect of ancillary phosphine ligands on the structure and hydroformylation activity of Rh-N-heterocyclic carbene complexes of type [Rh(IMes)(PR3)(CO)Cl] and [Rh(SIMes)(PR3)(CO)Cl] is described. Very high selectivities for the branched isomer (>95:5) were obtained in the hydroformylation of vinylarenes in all cases except for R = OPh. The new complexes were characterized spectroscopically and by X-ray crystallography.Key words: hydroformylation, rhodium, N-heterocyclic carbene, IMes.

Microbial degradation of a single branched isomer of nonylphenol by Sphingomonas TTNP3

The endocrine disrupting chemical nonylphenol (NP) is a technical product which consists of a complex mixture of nonylphenols with different alkyl side-chain isomers. Since the bio-degradation of each NP isomer may lead to its own range of metabolites, the isolation and identification of transformation products is very difficult. In order to overcome this difficulty, the nonylphenol isomer 4(3′,5′-dimethyl-3′-heptyl)-phenol (p353NP) was synthesized, and its degradation by an axenic culture of Sphingomonas TTNP3 was investigated with [ring-U-14C]-labelled and non-labelled p353NP including a time-course study. Radioactive mass balancing resulted in different polar soluble fractions, in insoluble radioactivity associated with biomass, and volatile radioactivity in the form of the mineralization product 14CO2. In the extracellular media, the presence of nonanol corresponding to the nonyl chain of the NP isomer was confirmed and its concentration was determined during the course of fermentation. No other radioactive compounds were detected beside the parent isomer. Radioactive metabolites were only found in the intracellular fraction of S. TTNP3.

Heats and free energies of mixing of tridodecylamine with nine heptane isomers, two octanes, and one hexane. Disorder and steric hindrance contributions

Heats and free energies of mixing have been measured at 298 K for tridodecylamine in n-C7, and eight branched isomers, n-C8 and one branched isomer, and a branched hexane. Heats of mixing are such that these systems can be divided in three classes. Class A [Formula: see text] includes n-C7, and n-C8. Class B [Formula: see text] includes isomers which do not have two substituents on neighbouring carbon atoms, i.e. 2-MeC6 2,2-diMeC5, 2,4-diMeC5, 2,2,4-triMeC5. Class C which includes isomers having substituents on neighbouring carbon atoms; 2,3-diMeC5, 2,2,3-triMeC4, 3-MeC6, 3,3-diMeC5, 3-EtC5, has smaller values of heats of mixing [Formula: see text]. These results are interpreted as not showing an extensive destruction of the correlations of orientations of the dodecyl chains by the linear alkanes of class A. The larger heats of class B are indicative of more disorientations of the long chains by the globular isomers. The smaller values of the heats for class C are seen as the balance of a positive disordering contribution and a negative one. The negative contribution is associated with a sterically hindered character of the compounds having substituents on neighbouring atoms. Free energies of mixing do not separate in the same three classes. This is thought to be due to an enthalpy–entropy compensation in the disordering and steric hindrance contributions. The Xl2S1−l parameter of the Flory theory shows the same variation as HE.