Net demethoxylation of dimethoxy viologen might occur by
a b-elimination pathway where a pyridine leaving group is
ejected and the methoxyl group is oxidized to formaldehyde.
1
0
An interesting possibility to explore is the preparation of a
stable analog of dimethoxy viologen lacking this b-elimination
decomposition pathway.
In summary, a-aminoalkyl radicals can be generated under
acidic conditions. The reduction potential of a-carbon radicals
was found to be pH dependent, and it shows a linear correla-
tion between the reduction potential and pH for Hcy. The pH
profiles of Cys and Hcy have been established for six
viologens. Most of the viologens can be used to selectively
detect Hcy and Cys under acidic conditons. The determination
of standard reduction potentials of a-carbon radicals is
currently underway in our lab.
Fig. 2 Reduction potential vs. whole pH range.
The absence of a pH endpoint for entries 1 and 2 is
consistent with pH(calc.) r 0 for these two entries.
It seems that there are two color change ranges for Cys and
alkyl viologens. Both of the two alkyl viologens, methyl and
heptyl viologens (entry 8 and entry 7), showed two color
change ranges when mixed with Cys (Table 1). The reason is
unclear.
Support from the National Institutes of Health
R01 EB002044) is gratefully acknowledged.
(
Notes and references
1
(a) O. Nekrassova, N. S. Lawrence and R. G. Compton, Talanta,
003, 60, 1085; (b) H. Refsum, A. D. Smith, P. M. Ueland,
E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek,
0
We also prepared dimethoxy viologen (E = ꢁ651 mV,
2
pH(calc.) = 8.4) and found that no color formation occurred
in the pH range 8–11. A tempting interpretation of this data is
that the reduction potential of dimethoxy viologen is more
J. Schneede, C. McPartlin and J. M. Scott, Clin. Chem., 2004,
5
0, 3; (c) A. De Bree, W. M. M. Verschuren, D. Kromhout,
L. A. J. Kluijtmans and H. J. Blom, Pharmacol. Rev., 2002, 54,
99.
0
+
ꢀ
negative than E (RC /RC ), and therefore there is no pH at
which the mid-point potential E
5
+
(RC /RC ) is negative
ꢀ
2 (a) W. H. Wang, O. Rusin, X. Y. Xu, K. K. Kim, J. O. Escobedo,
S. O. Fakayode, K. A. Fletcher, M. Lowry, C. M. Schowalter,
C. M. Lawrence, F. R. Fronczek, I. M. Warner and
R. M. Strongin, J. Am. Chem. Soc., 2005, 127, 15949;
(b) W. H. Wang, J. O. Escobedo, C. M. Lawrence and
R. M. Strongin, J. Am. Chem. Soc., 2004, 126, 3400.
m
enough for dimethoxy viologen reduction to occur. This
interpretation is represented graphically in Fig. 2.
This interpretation would allow us to bracket the standard
potential of the homocysteine-derived a-carbon radical as:
0
+
ꢀ
3 R. Zhao, J. Lind, G. Merenyi and T. E. Eriksen, J. Am. Chem.
Soc., 1994, 116, 12010.
ꢁ
651 mV o E (RC /RC ) o ꢁ446 mV. While the upper
2+
value of this bracketing is certainly valid (ꢁ446 mV for MV
4
5
6
R. Zhao, J. Lind, G. Merenyi and T. E. Eriksen, J. Chem. Soc.,
Perkin Trans. 2, 1997, 569.
See, for example: P. Wardman, J. Phys. Chem. Ref. Data, 1989, 18,
+
falls on the linear part of the E (RC /RC ) vs. pH curve),
ꢀ
m
the lower value is uncertain. At pH = 11 there should be
color formation associated with formation of the disulfide
1
637.
Components of buffer solutions were as follows: pH 0.0–2.2: HCl +
KCl; pH 2.3–6.9: citric acid + Na HPO , pH 7.0–9.0: Tris + HCl;
ꢀ
ꢁ
0
E
radical anion ([HcyS–SHcy]
ꢁ
,
E
ꢁ1700 mV for
2
4
ꢀ
[
CysS–SCys] ).
3
pH 10.0–11.0: NaHCO + NaOH; pH 12.0–13.0: NaOH + KCl.
7
While viologens in entries 1, 4, 5, 7 and 8 are commercially
available, others were prepared by nucleophilic alkylation of
Lack of color formation at pH = 11 probably suggests that
dimethoxy viologen is not stable at this pH. Indeed, gently
refluxing a solution of dimethoxy viologen at pH 11 leads
to complete conversion of the viologen to a mixture of
0
8
,4 -bipyridine as described in the literature. Dimethoxy viologen
4
was prepared by alkylation of N-oxide according to a known
9
process .
8
9
J. Bruinink, C. G. A. Kregting and J. J. Ponjee, J. Electrochem.
Soc., 1977, 124, 1854.
E. D. Lorance, W. H. Kramer and I. R. Gould, J. Am. Chem. Soc.,
0
decomposition products from which 4,4 -bipyridine can be
isolated in 80–85% yield.
2
002, 124, 15225.
0 W. Feely, W. L. Lehn and V. Boekelheide, J. Org. Chem., 1957, 22,
135.
1
1
1
878 | Chem. Commun., 2009, 1876–1878
This journal is ꢃc The Royal Society of Chemistry 2009