Conformational analysis of dipeptide‐derived polyisocyanides

The conformational properties of polymers derived from isocyanodipeptides have been investigated with a combination of model calculations, X‐ray diffraction, and circular dichroism spectroscopy. Depending on the configuration of the side chains, defined arrays of hydrogen bonds along the polymeric backbone are formed. This leads to a well‐defined conformation as, for example, expressed in the formation of lyotropic liquid‐crystalline phases and increased helical stability. Upon the disruption of the hydrogen bonds by a strong acid, a less well‐defined macromolecular conformation is observed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1725–1736, 2003     

STRUCTURE AND PHOTOBIOLOGICAL ACTIVITY OF 7-CHLORO-1,4-BENZODIAZEPINES. STUDIES ON THE PHOTOTOXIC EFFECTS OF CHLORDIAZEPOXIDE, DESMETHYLCHLORDIAZEPOXIDE AND DEMOXEPAM USING A BACTERIAL INDICATOR SYSTEM

The photobiological activity of chlordiazepoxide, an active ingredient of the drug Librium, which is known to induce phototoxic effects, and two of its metabolites, desmethylchlordiazepoxide and demoxepam, was investigated. Upon irradiation of these biologically active compounds with longwave UV light, the main decomposition product formed is an oxaziridine. Using a strain of Salmonella typhimurium as a test organism for cytotoxicity, it could be demonstrated that not only the drug itself, but also the major mammalian metabolites are phototoxic and, furthermore, that the respective oxaziridines are responsible for the toxic effects found upon irradiation. A close relationship appears to exist between the phototoxicity of the nitrones and the toxicity in the dark of their respective oxaziridines. Investigations of the photobiological activity of a few closely structurally related benzodiazepines could establish that a 4-oxide moiety in the benzodiazepine nucleus is the structural characteristic responsible for the appearance of phototoxicity; in those compounds which contain a 4-oxide in the benzodiazepine nucleus, photo-decomposition to a toxic oxaziridine is observed, while the analogues lacking the 4-oxide moiety do not show this characteristic and, therefore, no phototoxic effects can be observed. Finally, mutagenicity tests performed with the same bacterial indicator as used for phototoxic studies, and including chlorpromazine as a positive reference compound, indicate that under the present experimental conditions photoproducts formed upon irradiation of chlordiazepoxide and its metabolites with longwave UV light do not exert a mutagenic effect.