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Can. J. Chem. Vol. 84, 2006
Cysteamine and its disulfide, cystamine, can also be used in
topical eye drops to dissolve corneal cystine crystals (10).
Cysteamine is an excellent scavenger of OH and HOCl; it
did not contain enough metal ions to affect the overall reac-
tion kinetics and mechanism (21). The highest metal ion
concentration was cadmium at 1.5 ppb, followed by lead at
0.43 ppb.
·
also reacts with H2O2 and other oxygen-based toxic metabo-
lites (11). In addition to protection against radical damage in
DNA, cysteamine can also act as a repair agent for DNA
through the formation of the protective RSSR·–, which reacts
with the DNA·+ radical ion to regenerate DNA and form
cystamine (12). It has been shown that cysteamine and its
metabolite hypotaurine are far more likely to act as antioxi-
dants in vivo than is taurine, provided that they are present
in sufficient concentration at sites of oxidant generation (13).
Cysteamine is oxidized to the sulfinic derivative (hypotaurine)
only in the presence of cofactorlike compounds such as sul-
fide, methylene blue, and hydroxyalamine (14). Most meta-
bolic pathways give hypotaurine as a precursor to taurine
(15, 16).
In some of our recent work, we examined the reactivity of
the cysteamine metabolites: hypotaurine (cysteamine sulfinic
acid) and taurine (cysteamine sulfonic acid) (17). Oxidation
of hypotaurine by chlorite and chlorine dioxide occurred si-
multaneously at the sulfur center (giving taurine) and at the
nitrogen center (to give the chloramines) (18). On the other
hand, taurine is relatively inert to oxidation by chlorine di-
oxide, a reactive radical species, and acidified bromate (19).
When subjected to the strong oxidizing agent HOCl, the C—
S bond is not cleaved, and reaction occurs exclusively at the
nitrogen center, giving chlorotaurine (17).
The key to understanding the physiological role of
cysteamine is through its oxidation pathway: its reactive in-
termediates and oxidation products. In this manuscript we
report on the oxidation of cysteamine by the mild oxidizing
agents acidic iodate and aqueous iodine. In a nonenzymatic
pathway, could the oxidation of cysteamine yield hypo-
taurine or go all the way to taurine? Specifically, we are
aware that the action of most goitrogenic mechanisms in-
volves the consumption of the iodine atom, which is needed
for thyroid activity (20). What then, is the rate and mecha-
nism by which cysteamine reacts with molecular iodine?
Methods
All experiments were carried out at 25.0 0.5 °C and at a
constant ionic strength of 1.0 mol L–1 (NaClO4). CA, so-
dium perchlorate, and perchloric acid solutions were mixed
in one reactant vessel and iodate (or iodine) solutions in an-
other. All kinetics measurements were performed on a Hi-
Tech Scientific SF61–DX2 double mixing stopped-flow
spectrophotometer. Spectrophotometric determinations were
performed on a PerkinElmer Lambda 25 UV–vis spectro-
photometer.
Stoichiometric determinations
–
The stoichiometry for the CA–IO3 was determined both
in excess iodate and in excess CA. In excess iodate the total
oxidizing power was determined by titration. Excess acidi-
fied iodide was added to the reaction solution, and the re-
leased iodine was titrated against standard thiosulfate.
Spectrophotometry was also used to determine the amount
of iodine formed in excess iodate by its absorbance at
460 nm. In the I2–CA reaction the stoichiometry was deter-
mined by titrating standardized iodine solution from a bu-
rette into a solution of CA of known strength. The end point,
which was enhanced by starch indicator, was detected as the
point where the blue-black color lingered.
Results
Stoichiometry
The stoichiometry of the reaction was strictly 1:6, with
6 mol of cysteamine reacting with 1 mol iodate. This sug-
gested a one-electron oxidation of the sulfur center, and the
only product possible after one-electron oxidation of an
organosulfur center was the disulfide (H2NCH2CH2S-
SCH2CH2NH2, RSSR). Both spectrophotometric and
titrimetric techniques were used to deduce the following
stoichiometry:
Experimental
–
Materials
[R1] IO3 + 6H2NCH2CH2SH → I–
Cysteamine hydrochloride (CA, 2-aminoethanethiol hy-
drochloride) (98%), iodine, potassium iodide (Aldrich), so-
dium perchlorate (98%) (Acros), cystamine dihydrochloride
(MP Biomedical), potassium iodate, perchloric acid (72%),
soluble starch, sodium thiosulfate, and hydrochloric acid
(Fisher) were used without further purification. The concen-
tration of iodine was determined by standardization against
thiosulfate with starch as indicator. This standardization
allowed us to evaluate the absorptivity coefficient of iodine
at its isosbestic point of 460 nm with triiodide as
770 (mol L–1)–1 cm–1. This standardization was carried out
before each series of kinetic experiments were performed
because of the volatile nature of iodine. CA solutions were
prepared just before use and not kept for more than 24 h. All
solutions were prepared using distilled–deionized water
from a Barnstead Sybron Corporation water purification
unit. Inductively coupled plasma mass spectrometry
(ICPMS) was used to show that our aqueous reaction media
+ 3H2NCH2CH2S-SCH2CH2NH2 + 3H2O
Stoichiometry [R1] was obtained only at the stoichio-
metric ratio of 1:6. In lower concentrations of iodate, the re-
action mixture produced a mixture of both cysteamine and
cystamine. These products were confirmed by the NMR
spectrum of the mixture. In stoichiometric excess of iodate,
the reaction products included iodine, which was then spec-
trophotometrically examined to deduce the overall
stoichiometry of [R2]:
–
[R2] 2IO3 + 10H2NCH2CH2SH + 2H+ → I2
+ 5H2NCH2CH2S-SCH2CH2NH2 + 6H2O
If the iodate-to-substrate ratio was greater than 1:5, then
the amount of iodine produced was determined by the
amount of cysteamine as the limiting reagent. There was an
increase in the amount of iodine produced as the ratio was
© 2006 NRC Canada