The autoxidation of glutathione (GSH) is catalyzed by [Cl(NH
3)
5Ru
III]
2+ yielding only [OH(NH
3)
5Ru
III]
2+ and GSSG according to the rate law d[GSSG]/d
t =
k[Ru][GSH], where
k = 3
M-1 s
-1. The anaerobicreaction of GSH with [Cl(NH
3)
5Ru
III]
2+ yields first [OH(NH
3)
5Ru
III]
2+ and then [GS(NH
3)
5Ru
III]
+ at neutralpH, both through redox catalysis. The reaction appears to proceed through reduction of Ru
III by GSH to give[H
2O(NH
3)
5Ru
II]
2+, followed by coordination to produce [GSH(NH
3)
5Ru
II]
2+ and then oxidation of the latterion by [OH(NH
3)
5Ru
III]
2+ or GSSG to yield [GS(NH
3)
5Ru
III]
+. [GS(NH
3)
5Ru
III]
+ is also produced by the reactionof GSH with [(NH
3)
6Ru]
3+ or [py(NH
3)
5Ru]
3+. Glutathione reduces [OH(NH
3)
5Ru
III]
2+ through a pre-equilibriu
mmechanis
m according to the following rate law: d[Ru
II]/d
t = k[Ru
III][GSH]/(
Ki + [GSH]), where
Ki = 2.0 ×10
-3 M
-1 and
k = 2.3 × 10
-3 s
-1. The reduction potential of [(GS)(NH
3)
5Ru
III,] is pH-dependent accordingto the Nernstian equation:
E =
E![](/i<font color=)
mages/entities/deg.gif"> - 0.59log {
Ka/([H
+] +
Ka)}, where
E![](/i<font color=)
mages/entities/deg.gif"> = -440
mV, p
Ka = 7.1. While[GS(NH
3)
5Ru
III] is stable for extended periods under inert at
mosphere, it changes in air, eventually yielding[HO(NH
3)
5Ru
III] a
mong other products at high pH with
kobs (s
-1) = (
k1Ka +
k2[H
+])/([H
+] +
Ka), where
k1= 9 × 10
-6 s
-1,
k2 = 1.2 × 10
-4 s
-1 M
-1, and p
Ka = 12. At [GSH]/[Ru
III]
![](/i<font color=)
mages/entities/le.gif"> 1, the coordination of [Cl(NH
3)
5Ru
III]
2+ to DNA is facilitated by GSH reduction to the
more substitution-labile [H
2O(NH
3)
5Ru
II]
2+.However, at [GSH]/[Ru
III]
![](/i<font color=)
mages/entities/ge.gif"> 1, guanine binding on DNA is inhibited by GSH, which coordinates Ru
II andfacilitates oxidation back to Ru
III because of the low
E![](/i<font color=)
mages/entities/deg.gif"> of [GS(NH
3)
5Ru
III]
+. Consistent with this is the increasedtoxicity of [Cl(NH
3)
5Ru
III]
2+ to Jurkat T-cells, when GSH levels are suppressed. High [GSH]/[Ru] alters theDNA binding of [H
2O(NH
3)
5Ru
II]
2+ to essentially eli
minate G
7 coordination and lower C
4 binding, but leavingA
6 binding relatively unaffected, which
may have i
mplications for the
mechanis
m of rutheniu
m antitu
moragents.