Seven prospective biological indicators of systemic toxicity were examined at time points ranging from 15 minutes to 24 hours using male Sprague-Dawley rats, B6C3F1 mice, Golden-Syrian hamsters and Hartley guinea pigs following intraperitoneal dosing with 0.1 mg/kg and 1.0 mg/kg sodium arsenite. Rats and mice were also dosed with 1.0 mg/kg sodium arsenate. Pyruvate dehydrogenase (PDH) activity was significantly depressed at early time points in mice, hamsters and guinea pigs and at later time points in rats dosed with arsenic (III). Rats and mice dosed with arsenic (V) also exhibited PDH depression at early time points. Uroporphyrin and coproporphyrin excretion was elevated in mice following arsenic (III) dosing. Coproporphyrin excretion was elevated in rats following arsenic (V) dosing. Blood glucose, creatinine, urea nitrogen and creatinine were unchanged by arsenic dosing. Based upon the amount and types of biological responses observed, the mouse appears to be the most sensitive animal model for the further study of arsenic toxicity.

No description available.

Solid-liquid phase diagrams have been determined for binary systems of hexafluorobenzene + naphthalene-type compounds, and indicate strong 1:1 congruently melting point complexes. Hexafluorobenzene + cis- and + trans-deca1in were found to give simple eutectic phase diagrams. Excess enthalpies, excess volumes and excess Gibbs functions have been measured for the same hexaf1uorobenzene + naphthalene-type compound mixtures and are large and negative, which is characteristic of systems where specific interactions take place. This contrasts with the large positive excess functions found with hexafluorobenzene + decalin systems, where only dispersion forces are assumed present. The excess Gibbs function for hexafluorobenzene + trans- and cis-decalin have been determined theoretically from freezing point data as well as directly from vapour pressure measurements. A batch calorimeter, besides being used for excess enthalpy measurememts, has been employed in determining heats of solution, which lead to a value for the enthalpy change for the process, solid + solid ? complex. The possibility of charge-transfer interactions occuring in hexafluorobenzene + naphthalene-type compound systems has been discussed in terms of HOMO/LUMO overlap considerations and is supported by the observation that pentafluorocyanobenzene forms stronger (higher melting point) complexes with 1- and 2-methylnaphthalene, than hexafluorobenzene does.

No description available.

N-carboxy-α-amino acid anhydrides (NCAs) are amino acid derivatives discovered by Leuch in 1906. Ever since, they have found invaluable use in the preparation of peptide drugs and polypeptides. NCAs are generally synthesised using phosgene; however, due to the hazardous nature of this chemical, safer method of synthesis using protected amino acids in the presence of activating reagents such as P2O4, T3P, HBTU and BOP-Cl were investigated, where a protonated oxazolone intermediate is dealkylated to generate the corresponding amino acid NCA. After the successful synthesis of a variety of NCAs, starting from Boc-protected amino acids and using T3P, we attempted to work out a new method of sequential peptide synthesis using NCAs in a controlled way. The challenge involved in the use of NCAs in the synthesis of peptides is to prevent decarboxylation of the intermediate products, which lead to the generation of unwanted peptide oligomers. An elegant way to prevent the decarboxylation was studied in this work, which consists of the stabilisation of the carbamate intermediates using an appropriate receptor. We prepared several carbamate receptors and tested them in model reactions using amines and NCAs under various conditions. Despites partial success in limiting the amount of oligomerisation, we were never able to prevent it completely, and could not established conditions to prepare peptides in good purity.

No description available.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy