Equilibrium dialysis experiments with a highly purified preparation of labeled tiamulin, a semisynthetic derivative of the antibiotic pleuromutilin, and Escherichia coli ribosomes allowed the determination of two binding sites for the drug. The binding reaction showed a cooperative effect. Of the two subunits, the 50S particle was able to bind the antibiotic in a 1:1 stoichiometry. Hence, the 50S subunit contributed predominantly to the binding energy which held the antibiotic to the ribosomes. The 30S subunit, showing no strong affinity for the drug, may be needed for the generation of the second binding site in the 70S particle. If depleted of ammonium ions, 70S ribosomes lost their binding capacity for the antibiotic. The attachment sites for tiamulin could be restored by heating the ribosomes to 40°C in the presence of either ammonium ions or the antibiotic. Other pleuromutilin derivatives displaced labeled tiamulin from its ribosomal binding sites. By quantifying this competition, the relative affinity of various pleuromutilin derivatives for E. coli ribosomes was determined. The binding correlated with the minimal inhibitory concentrations of these compounds against E. coli. When compared with the minimal inhibitory concentrations against Staphylococcus aureus, the correlation was less strict, but the same trend prevailed. These results suggest that the antibacterial activities of various pleuromutilin derivatives on a given test organism are mainly determined by the strength of binding to the ribosomes within the bacterial cell.

Reaction of an alkylating pleuromutilin derivative with E. coli ribosomes led to the binding of the compound to both proteins and RNA. If ribosomes of the E. coli strain MRE600 were used, mainly S18 and L2 became labeled. Ribosomes from E. coli D10 bound the reagent to S18 and frequently to L27 instead of L2. Possibly at slight difference in the structure of these ribosomes exposes different, although closely neighboring, L proteins to the reagent. The simultaneous labeling of L and S proteins seems to reflect the presence of two binding sites for the antibiotic and indicates that the binding sites are located at the interphase region between large and small ribosomal subunits. Analysis of the RNA showed that the affinity label is mainly attached to the 23S species. These data are in good agreement with the known effects of pleuromutilin derivatives on ribosomal functions.

Die Strukturen von [Re(CO)5(NSX)]AsF6 (X = F (1), Cl (3a) und Br (3b)) wurden durch Röntgenstrukturanalyse bestimmt. Aus den ermittelten ReN‐ bzw. ReC‐Bindungslängen wird π‐Akzeptor‐Verhalten für die Thiazylhalogenidliganden abgeleitet.

From the reactions of tr~ns-[Re(C0)~(MeCN)(NS)l [AsF& with CsCl, ~~~~S-[R~(CO)~C~(NS)][ASF~].M~CN 2 is formed, and with CsF [(Re(C0)~)~(C&I~N~S4)][AsF6]~ 3 is isolated; the X-ray crystal structures of 2 and 3 are reported.