Krzysztof K. Krawczyk

Modulation of antibiotic resistance and induction of a stress response in Pseudomonas aeruginosa by silver nanoparticles

The objective of this study was to characterize the effects of silver nanoparticles on Pseudomonas aeruginosa. Their interactions with several conventional antibiotics and ability to induce a stress response were examined. Interactions between silver nanoparticles (AgNPs) and antibiotics against free-living cells and biofilm of P. aeruginosa were studied using the chequerboard method and time-kill assays. The ability of AgNPs to induce a stress response was determined by evaluation of cellular levels of the DnaK and HtpG chaperones using SDS-PAGE and Western blot analysis. Synergistic activity against free-living P. aeruginosa between AgNPs and ampicillin, streptomycin, rifampicin and tetracycline, but not oxacillin, ciprofloxacin, meropenem or ceftazidime, was demonstrated by the chequerboard method. No such interactions were observed against P. aeruginosa biofilm. The results of time-kill assays confirmed synergy only for the AgNPs-streptomycin combination. AgNPs induced the expression of chaperone DnaK. No induction of the HtpG chaperone was detected. In conclusion, AgNPs not only display potent bactericidal activity against P. aeruginosa, but also act synergistically with several conventional antibiotics to enhance their effect against free-living bacteria as determined by the chequerboard method. The time-kill assay proved synergy between AgNPs and streptomycin only. The ability of AgNPs to induce the major chaperone protein DnaK may influence bacterial resistance to antimicrobials.

Formal synthesis of (−)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester – a flow photochemistry approach

We have developed a strategy for the stereoselective synthesis of cyclolignans related to podophyllotoxin and its derivatives. The crucial step of the synthesis is the photocyclization of a chiral atropoisomeric 1,2-bisbenzylidenesuccinate amide ester, which can be prepared from suitable aromatic aldehydes, diethyl succinate and l-prolinol. The photocyclization was found to be more efficient when irradiation was performed in a home-built continuous flow photochemical reactor. The in-flow irradiation also allowed us to perform the reaction on a multigram scale. The chiral auxiliary was removed by reductive cleavage with the Schwartzs reagent to give the cytotoxic 1R,2R-cis-podophyllic aldehyde, which in turn could be easily reduced to the corresponding alcohol, completing the formal synthesis of (-)-podophyllotoxin.

Characteristics of therapists working with people experiencing psychosis: A nation-wide survey in Poland

Objective: To characterise how psychotherapy with people who expereince psychosis is conducted in Poland, and by whom. Method: A nation-wide online survey and paper and pencil enquiry comprised of 40 questions and addressed mainly to the members of psychological, psychiatric and psychotherapeutic associations was administered to a sample of 1196 people who provide psychotherapy. Results: Of the 1196 therapists surveyed, 30.8% reported working with people experiencing psychosis. Therapists working with psychotic people were more likely than the rest of the therapists to have graduated in medicine, worked in a psychiatric hospital or public counselling centre and trained in psychoanalytic or psychodynamic psychotherapy. No difference in gender and age or years of experience was found between the two groups. Conclusions: The percentage of therapists working with psychotic patients in Poland is similar to the international average, but lower than in Austria. Psychoanalytic and psychodynamic psychotherapists play an important role in the psychological treatment of people experiencing psychosis in Poland.

On the mechanisms of the reactions between some perfluorinated compounds and CH5+—experimental and theoretical approaches†

Five perfluorocompounds [perfluoropentane, 4-(perfluoroethoxy)-perfluorobutane, 5-(perfluoroethyl)-perfluorotetrahydrofuran, 2-(trifluoromethyl)-perfluorotetrahydropyran, and 4-(trifluoromethyl)-perfluorotetrahydropyran] were analyzed by electron ionization (EI) and chemical ionization (CI), using methane and isobutane as reagent gases. Under CI conditions, isobutane does not lead to significative results whereas methane leads to high ionic yields [with respect to both CI (isobutane) and EI]. Under EI conditions, practically only fragment ions are observed, with the complete loss of molecular weight. In contrast under CI(CH(4) ) conditions, [M-F](+) ions are produced. Under these conditions, the behavior of oxygen-containing molecules is strongly different from that of perfluoropentane. This is because oxygen can greatly stabilize the formation of the [M-F](+) carbocation by a π-electron donor effect, especially in the case of cyclic structures. Moreover, π-stabilization can be considered a useful tool to rationalize the position of tertiary carbon atom in trifluoromethyl-perfluoro-pyrane isomeric ions. The experimental data formed the starting point for the theoretical calculation, which allowed us to explore the mechanisms of the reactions of CH(5) (+) ions with selected perfluorocompounds. The computational methods used show that a direct protonation of the perfluoroethers (PFEs) by CH(5) (+) as well as iBu(+) is very unlikely. In the theoretical calculations, the PFE molecule served rather as the F(-) donor, and the elimination of HF molecule occurred when the PFE molecule was placed close to H(+) or CH(5) (+) ions. The fact that the latter is very unstable and decomposes to a proton and methane molecule explains why the use of methane in CI is so successful in the generation of [M-F](+) ion. In contrast, the isobutonium cation rearranges to an isopropyl cation/methane complex rather than that it abstracts F(-) from the PFE molecule. Similar results can be expected for other PFEs and perfluoroalkanes (PFAs) because both CH(5) (+) and H(+) were able to abstract the HF molecule also by attacking along the perfluoroalkyl chain of the PFE.

Tetra­methyl 1,1,2-triphenyl-2H-1λ5-phosphole-2,3,4,5-tetra­carboxyl­ate

The title compound, C30H27O8P (1), was formed as one of two products {(1) and (2) [Krawczyk et al. (2010 ▶). Acta Cryst. E66 (cv2753)]} in the reaction of dimethyl acetylenedicarboxylate with triphenylphosphine. The molecule of (1) consists of a five-membered ring, in which the P atom is incorporated. One of the phenyl groups of the triphenylphosphine migrated to a vicinal C atom during the reaction. The five-membered ring of (1) is corrugated [r.m.s. deviation = 0.0719 (8) Å], whereas that in compound (2) is planar, the r.m.s. deviation being only 0.009 (2) Å.