A synergic approach of X-ray powder diffraction and Raman spectroscopy for crystal structure determination of 2,3-thienoimide capped oligothiophenes.

This work presents a Raman based approach for the rapid identification of the molecular conformation in a series of new 2,3-thienoimide capped quaterthiophenes, whose crystal structures were determined by synchrotron radiation X-ray powder diffraction. These systems display two conformational polymorphs, known as forms A and B, as a result of the anti-anti-anti and syn-anti-syn arrangements of the quaterthiophene cores. In a micro-Raman and computational study, the spectroscopic differences between the conformers were detected and proved to be suitable markers for polymorph identification. Thus, the synergic employment of diffraction and Raman spectroscopy techniques yields a full and reliable characterization of 2,3-thienoimide capped quaterthiophene compounds in their solid state.

A third blind test of crystal structure prediction.

Following the interest generated by two previous blind tests of crystal structure prediction (CSP1999 and CSP2001), a third such collaborative project (CSP2004) was hosted by the Cambridge Crystallographic Data Centre. A range of methodologies used in searching for and ranking the likelihood of predicted crystal structures is represented amongst the 18 participating research groups, although most are based on the global minimization of the lattice energy. Initially the participants were given molecular diagrams of three molecules and asked to submit three predictions for the most likely crystal structure of each. Unlike earlier blind tests, no restriction was placed on the possible space group of the target crystal structures. Furthermore, Z' = 2 structures were allowed. Part-way through the test, a partial structure report was discovered for one of the molecules, which could no longer be considered a blind test. Hence, a second molecule from the same category (small, rigid with common atom types) was offered to the participants as a replacement. Success rates within the three submitted predictions were lower than in the previous tests - there was only one successful prediction for any of the three ;blind' molecules. For the ;simplest' rigid molecule, this lack of success is partly due to the observed structure crystallizing with two molecules in the asymmetric unit. As in the 2001 blind test, there was no success in predicting the structure of the flexible molecule. The results highlight the necessity for better energy models, capable of simultaneously describing conformational and packing energies with high accuracy. There is also a need for improvements in search procedures for crystals with more than one independent molecule, as well as for molecules with conformational flexibility. These are necessary requirements for the prediction of possible thermodynamically favoured polymorphs. Which of these are actually realised is also influenced by as yet insufficiently understood processes of nucleation and crystal growth.

A basal-defined medium for the study of proteolytic activity of Serratia marcescens.

A simple defined basal medium is presented for the study of proteolytic activity, induction and repression, and protease purification with Serratia marcescens. Since the medium contains no protein, it does not interfere with or present artifact to protein assays, column chromatography, or electrophoresis. The medium consists of the basal salts and buffer medium of Bromke and Hammel (1979) plus a carbon-energy source such as glycerol, calcium chloride for the cation requirement for protease activity, and an amino acid, preferably leucine. Growth parameters and proteolytic activities are presented for unsupplemented medium and for the medium supplemented with each of 18 amino acids. Unsupplemented medium completes the logarithmic phase in 12.5 h of incubation and has a constitutive level of proteolytic activity. Supplementation with any amino acid, except cysteine and tryptophan, increases significantly the proteolytic activity, but has a varied effect on growth parameters.

In vitro activity of novobiocin against multiresistant strains of Enterococcus faecium.

Sixty strains of vancomycin- and ampicillin-resistant Enterococcus faecium were evaluated for their susceptibilities to novobiocin in vitro. In Mueller-Hinton broth, novobiocin inhibited all strains when it was used at a concentration of < or = 2 microgram/ml and 40 of 60 strains when it was used at a concentration of < or = 0.5 micrograms/ml. MICs were 8- to 16-fold higher in 50% serum. Novobiocin alone resulted in 2-log-unit killing at 24 h. Combinations of novobiocin and a fluoroquinolone (either ciprofloxacin or ofloxacin) were additive and bactericidal for quinolone-susceptible strains in either broth or 50% serum. Gentamicin did not affect novobiocin activity, and rifampin and doxycycline were antagonistic.

Inconsistent bactericidal activity of triple-combination therapy with vancomycin, ampicillin, and gentamicin against vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium.

Combination therapy with ampicillin, vancomycin, and gentamicin in vitro against several clinical isolates of vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium, including VanA and VanB strains, was evaluated. The MICs of ampicillin were not significantly decreased by induction with vancomycin, and the combination of ampicillin and vancomycin was not inhibitory for any strain. Triple-combination therapy was least active against highly resistant VanA isolates, achieving a reduction of less than 1 log CFU at 24 h, but demonstrated slightly more activity against VanB strains.