- The first part of this thesis describes a study of the
characteristics of oxidation of a 1:2 iron(III):thiolate system in
methanolic solution and in water. This system was investigated as a
potential analog for the cysteine- and cysteamine-dioxygenase catalyzed
0₂-oxidation of cysteine and cysteamine, respectively, to the
corresponding sulfinic acids. In the neutral pH range, oxidation by 0₂
and H₂0₂ of a stoichiometric mixture of 1:2 iron(III):cysteine in
aqueous solution produced cysteinesulfinic acid, (CyS0₂H) and cysteic
acid, (CyS0₃H) , reported as CyS0x⁻ (with yields of 4.1-24.6%), in
addition to the principal product, cystine (CySSCy). All amino acid
material was separated by ion exchange chromatography and detected
quantitatively by standard ninhydrin colorimetric analysis or
gravimetric analysis. The primary mechanism pertaining to oxidation of
CyS⁻ to CyS0x⁻ involves the proposal of an initial four atom "cluster", [-(FeII)₂(SCy)₂-1]n, which on oxidation with 0₂ generates H₂0₂ and [-(FeIII)₂(SCy)₂-1]n⁺². The active oxidant would then in turn react with an available Fe(III)-thiolate bond forming the S-bonded sulfenate
ligand. An IR spectrum of the oxidized solid from the product mixture
supports this proposal. An alternative mechanism would be the direct
0₂-oxidation of an Fe(III) coordinated thiolate to (Fe-S(0)₂Cy]. This
oxidative mode seems to be active at low Fe(III) concentration in the
presence of excess thiolate in slightly alkaline medium.
Early iron-thiolate studies were carried out using the thiol,
penicillamine. Syntheses of penicillaminesulfinic acid were explored.
The syntheses of K₃[(S- PenS-N,S)₃] and of yellow K₃[(S-PenS0₂-N,S)₃] were performed. The ¹H nmr and UV-visible spectra are reported. The
decomposition of K₃[(S-PenS0₂-N,S)₃] with ethylenediamine provided the
best yield of the sodium salt of the penicillaminesulfinate ion. The
molecular acid was unstable in acidic or near neutral, aqueous
solution, and therefore was not isolated.
The second part of this thesis details the synthesis of
bis-penicillaminato-N,S,0-cobaltate(III) complex and its stoichiometric H₂0₂-oxidation resulting in isolation of Na[Co(S-PenS-N,S,0)-
(S-PenSO-N,S,0)] and Na[Co(S-PenSO-N,S,O)₂]. The UV-visible, IR and ¹H
nmr spectra of these cobalt(III) complexes are reported. Techniques
were developed and refined during the study which made possible the
separation and identification of the oxidation products, using anion
exchange chromatography and gel filtration. Determination of the
chirality of each sulfenato sulfur atom was made using applications of
circular dichroism. Structures for the several complexes are
postulated, based on the combined spectral results. The second-order
rate constants for oxidation of the thiolato and the sulfenato complexes were measured under pseudo-first-order conditions.
By analogy with the results of the oxidation of Fe(III) and
Co(III) complexes studied, proposals on the mechanism and stoichiometry
of the reaction at the active site of the cysteine and cysteamine
dioxygenases are suggested.