13C n.m.r. study of conformational equilibria in solutions of methyl N-benzoyl-l-leucyl-l-histidinate monohydrate

¹³C n.m.r. spectra for the title compound are reported in CDCl₃ and also in pure and acidified DMSO solutions. In all cases, cis/trans isomerization about the amide bond occurs. For the cis isomers, severe steric compression shifts the ortho phenyl and leucyl β-CH₂ resonances to higher field. In CDCl₃ solution, two imidazole conformations are present. In one, the imidazole group is freely rotating about the β-CH₂-C(ring) bond, whilst the nitrogen-bound proton participates in a dynamic tautomeric equilibrium, rapid on the n.m.r. time-scale, between the two ring nitrogen atoms. In the other, the imidazole ring is protonated at N1 and held in a relatively rigid conformation by hydrogen-bonding between N3, the water molecule, and the amide carbonyl group oxygen atom. The major imidazole species present in DMSO solution is the N1-protonated tautomer. Small amounts of the N3 tautomer are also present, but in this solvent proton exchange between the two sites is slow on the n.m.r. time-scale. In acidified DMSO, both nitrogen atoms are protonated.     

Micellar distribution equilibria: ultracentrifugal study of apparent partition coefficients.

Ultracentrifugation was used for the partial isolation of polysorbate 80 micelles in aqueous media to determine the apparent partition coefficients of various drug species between water and the micellar pseudophase. The ratio of solute concentration in the micelles to that in water was measured for procaine, salicylic acid, sulfapyridine, sulfisoxazole, and sodium 2-naphthalensulfonate over ranges of pH, surfactant concentration, drug concentration, and micelle sedimentation. Apparent partition coefficients for the systems investigated were independent of both drug concentration and surfactant concentration, indicating that the mode(s) of surfactant-drug interaction are essentially invariant over the ranges of systematic variables studied. The method provides a relatively simple and rapid means of quantitatively evaluating drug-surfactant interactions above the CMC, when surfactant and solute can be assayed in mixtures without interference.     

Effects of glutaraldehyde in a 2-year inhalation study in rats and mice.

Whole-body inhalation toxicology and carcinogenicity studies were performed with the widely used fixative and cold-sterilant glutaraldehyde. Groups of 50 male and female F344/N rats and B6C3F(1) mice were exposed to glutaraldehyde (rats: 0, 250, 500, or 750 ppb; mice: 0, 62.5, 125, or 250 ppb) 6 h/day, 5 days/week, for 104 weeks. Survival of 500- and 750-ppb female rats was less than that of controls. Mean body weights of all exposed groups of male rats, 500- and 750-ppb female rats, and 250-ppb female mice were generally less than those of controls. No exposure-related neoplastic lesions were observed in either rats or mice. Non-neoplastic lesions were limited primarily to the most anterior region of the nasal cavity. In rats, hyperplasia and inflammation of the squamous epithelium; hyperplasia, goblet cell hyperplasia, inflammation, and squamous metaplasia of the respiratory epithelium; and hyaline degeneration of the olfactory epithelium were observed. In mice, the nasal lesions were qualitatively similar to those in rats. Squamous metaplasia of the respiratory epithelium was observed in both sexes of mice while female mice also had inflammation and hyaline degeneration of the respiratory epithelium. In contrast to the nasal carcinogen formaldehyde, no neoplastic lesions were observed after inhalation exposure to glutaraldehyde. However, exposure to glutaraldehyde resulted in considerable non-neoplastic lesions in the noses of rats and mice.