Chemistry Reference
In-Depth Information
5.0
TNB
4.0
3.0
Pen
2.0
Cys MeE
Cys
Cysteamine
NAC
1.0
0.0
GSH
5
6
7
8
9
10
Thiol p
K
a
Figure 3.10.
The relationship between the rate constants (
k
, /M/s) and p
K
a
for the
reactions of thiols with HOSCN at pH 7.4 and 22°C. TNB, 5-thio-2-nitrobenzoic acid;
Pen, penicillamine; Cys Me E, l-cysteine methyl ester; NAC,
N
-acetylcysteine (adapted
from Skaff et al. [84] with the permission of the Biochemical Society).
The seleno-containing amino acids react rapidly with HOSCN, and the
determined rate constants,
k
, were in the range from 2.8 × 10
3
/M/s to
5.8 × 10
6
/M/s for selenomethionine and selenocystamine, respectively [86].
These rate constants are much higher than the reactions of thiols with HOSCN.
The selenium atom has more nucleophilicity than the sulfur atom and seleno-
compounds would be more easily oxidized by HOSCN. Significantly, the rate
constants are ∼6000 times higher than the corresponding reactions of H
2
O
2
with selenium-containing amino acids. These results have significance in the
inhibition of TrxR and gPx enzyme activities [86].
3.1.3.2 Products of HOSCN Oxidation.
HOSCN reacted with low-molecular-
mass and protein thiols in different cell types, isolated proteins, and biological
fluids, such as plasma, to yield unstable sulfenyl thiocyanate (RS-SCN) (Eq.
3.11) [87-90]. The adducts of RS-SCN showed pH dependence stability, and
sulfenyl thiocyanates of Cys, gSH, and pencillamine were isolated [91-93].
However, the adducts showed reactivity with other thiols at the physiological
pH resulted in the formation of disulfide via possible intermediates such as
thiosulfinate esters and sulfenic acids (Eqs. 3.12 and 3.13):
HOSCN R-SH RS-SCN H O
+
→
+
(3.11)
2
RS-SCN H O RS-OH SCN H
+
→
+
−
+
+
(3.12)
2
−
+
.
RS-SCN R -SH RS-SR SCN H
+ ′
→
+
+
(3.13)
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