Reduction of trans-dichloro- and
trans-dibromo-tetracyanoplatinate(IV) by
L-methionine
Abstract
Reduction of
trans-[Pt(CN)
4
X
2
]
2-
(X = Cl or Br) [as model compounds for antitumour-active
platinum(IV) pro-drugs] to
[Pt(CN)
4
]
2-
by L-methionine,
MeSR, has been studied at 25 °C in the range
0 < pH < 12 (X = Cl) and
0 < pH < 6 (X = Br) by
use of stopped-flow spectrophotometry. The stoichiometry is
[Pt
IV
]:[MeSR] ≈ 1:
1; the reaction products are methionine S-oxide and
[Pt(CN)
4
]
2-
as identified by NMR and UV
spectroscopies, respectively. The kinetics is first order with respect
to the platinum(IV) and methionine concentrations and the
second-order rate constants have a small pH dependence. In analogy with
reduction of platinum(IV) complexes by thioglycolic acid,
cysteine, penicillamine and glutathione, a mechanism is postulated in
which [Pt(CN)
4
X
2
]
2-
is reduced by
the various protolytic species of methionine in parallel reactions. In
the transition state the thioether group of methionine is assumed to
interact with co-ordinated halide, mediating the electron transfer to
the platinum(IV) centre. The transition states for previously
studied reactions between
[Pt(CN)
4
X
2
]
2-
and thiols are
discussed in view of these results. It is concluded that
methionine-containing biomolecules may compete with thiol compounds for
reduction of platinum(IV) pro-drugs under acidic conditions,
and also in neutral solutions with low concentrations of
thiol-containing biomolecules.
:[MeSR] ≈ 1:
1; the reaction products are methionine S-oxide and
[Pt(CN)
4
]
2-
as identified by NMR and UV
spectroscopies, respectively. The kinetics is first order with respect
to the platinum(IV) and methionine concentrations and the
second-order rate constants have a small pH dependence. In analogy with
reduction of platinum(IV) complexes by thioglycolic acid,
cysteine, penicillamine and glutathione, a mechanism is postulated in
which [Pt(CN)
4
X
2
]
2-
is reduced by
the various protolytic species of methionine in parallel reactions. In
the transition state the thioether group of methionine is assumed to
interact with co-ordinated halide, mediating the electron transfer to
the platinum(IV) centre. The transition states for previously
studied reactions between
[Pt(CN)
4
X
2
]
2-
and thiols are
discussed in view of these results. It is concluded that
methionine-containing biomolecules may compete with thiol compounds for
reduction of platinum(IV) pro-drugs under acidic conditions,
and also in neutral solutions with low concentrations of
thiol-containing biomolecules.
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