On-line storage and retrieval of chemical information. II. Substructure and biological activity searching

An improved interactive system for searching substructure and biological activity data has been developed. Features of the system include a two-level substructure search (fragment screen and atom by atom) and an expanded biological activity data base. The system operates on a file of about 150 000 compounds.     

Directional fluorescence spectra of laser dye in opal and inverse opal photonic crystals

We have investigated the fluorescence from R6G dye molecules embedded in fcc photonic crystals with a large range of lattice parameters. Both polystyrene opals and alumina inverse opals are studied, allowing us to compare direct and inverted structures. We observe clear stop bands in the fluorescence spectra, whose center positions, widths, and depths are analyzed and compared to stop bands from reflectivity measurements. In the frequency range of first-order stop gaps, the measured stop band centers and widths agree well with theoretical predictions. The depths are interpreted in terms of the mean free path (disorder) and the Bragg attenuation length (order). We observe intriguing enhanced emission at the blue side of the stop bands, which is attributed to the escape of diffuse light from the photonic crystal (related to both order and disorder). We perform the first experiments in the range of second-order stop gaps, which is the regime where the photonic band gap is anticipated. We observe complex multiple-Bragg features that correlate favorably with reflectivity peaks.     

Versuche mit markierten Atomen über den Mechanismus der Vermehrung von Tabakmosaikvirus in Nicotiana tabacum

Zusammenfassung Tabakmosaikvirus hoher spezifischer Aktivität, das am Phosphor und/oder Kohlenstoff markiert war, wurde biosynthetisch hergestellt. Damit wurde jeweils ein Blatt einer Pflanze von Nicotiana tabacum infiziert und der etwaige Transport von intaktem Virus durch das Leitungssystem der Pflanzen dadurch weitgehend unterbunden, daß die Leitgefäße des behandelten Blattes durchtrennt wurden.Das aus den unbehandelten Blättern der Pflanze nach 17 1/2, 48 und 72 Stdn. isolierte Virus wies im Vergleich zum eingesetzten TMV einen viel geringeren Anteil an Gesamtradiokohlenstoff im Protein auf. Dies deutet darauf hin, daß das Virus der unbehandelten Blätter höchstens zu einem sehr geringen Teil aus intakt transportiertem TMV bestehen könnte.Die nicht im TMV enthaltenen Polynukleotide der unbehandelten Blätter enthalten 7 Stdn. nach der Infektion verhältnismäßig viel³²P, doch tritt derselbe innerhalb 70 Stdn. zum allergrößten Teil in niedermolekulare Verbindungen über.Die in Puffer unlöslichen Polynukleotide der unbehandelten Blätter (Blattnukleinsäure) weisen ein mit der Zeit abnehmendes Verhältnis von³²P/¹⁴C auf. Auch innerhalb der Nukleinsäure (NS) des TMV dieser Blätter nimmt dieses Verhältnis zunächst ab, steigt aber später wieder an.Die angeführten Ergebnisse stehen mit der Vorstellung im Einklang, daß das Virus NS abspaltet und sowohl die systemische Infektion der Pflanze wie auch die Virusvermehrung mindestens zum Teil durch diese freie NS bewirkt wird. Die aus dem Virus stammende freie NS unterliegt zum großen Teil lebhaftem Abbau, wobei ihre Komponenten wahrscheinlich dem Aufbau normaler Blattbestandteile dienen.Mit 3 Abbildungen     

Shielded alkyl-functionalised rotaxane host cavities for improved anion recognition

The synthesis and anion recognition properties of four novel [2]rotaxane host architectures containing additional alkyl functionality integrated within macrocyclic and axle components to shield the binding cavity from the solvent are described. The rotaxane species containing a tetra(methyl)-functionalised macrocycle component is found to be a weaker anion complexant than the equivalent unfunctionalised receptor, which is likely due to steric hindrance restricting the anion's access to the interlocked cavity. Rotaxane molecules containing tetra(methyl)-functionalised axle components are also investigated, and the additional alkyl functionality serves to enhance anion binding affinity and selectivity when incorporated within the axle's flexible ethylene linkages. Moreover, the equivalent unfunctionalised rotaxane displays a rare preference for oxoanions over chloride guest species.     

Structure Elucidation and Activity of Kolossin A,the D‐/L‐Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D ‐/ L ‐peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness.     

Fluoroquinolone Antimicrobials: Singlet Oxygen, Superoxide and Phototoxicity

The fluoroquinolone antibacterial agents possess photo-sensitizing properties that lead to phototoxic responses in both human and animal subjects. The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin > ciprofloxacin ? enoxacin, norfloxacin and ofloxacin. Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical. We determined the quantum yields of singlet oxygen generation (φ_Δ,) by detection of the singlet oxygen (¹O₂) luminescence at 1270 tun for several fluoroquinolones, naphthyridines and other structurally related compounds. All the fluoroquinolones examined have low φ_Δ values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5. We also determined the ¹O₂ quenching constants for these compounds and their values were on the order of 10⁶M^?1 s¹, except for lomefloxacin whose rate constant was 1.8 × 10⁷M^?1 s^?1. The φ_Δ values were significantly decreased in a solvent of lower polarity such as methanol (0.007 ≤φ_Δ≤ 0.02). The production of ¹O₂ by these antibiotics did not correlate with the order reported for their phototoxicity. We also measured the photogeneration (λ > 300 nm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-l-pyrroiine N-oxide. Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate. Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular. For these latter drugs the photoinduced loss of the F₈ atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties.