Journal of the American Chemical Society
ARTICLE
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side chain). This is in sharp contrast to glycine whose R-carbon is
the predominant hydrogen atom donor site. The regioselectivity
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structure of the radical but dependent on the structure of the
amino acid.
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The mechanism of the previously reported NH2 abstraction
(proposed to occur via the nucleophilic additionꢀelimination
mechanism12b) was examined computationally. The relative
transition-state energies for addition of ammonia to different
positions in 3-dehydropyridinium cation revealed that addition
to the radical carbon is kinetically favored and hence the most
likely addition site for amino acids in charged phenyl radicals.
The calculated charge and spin densities in the ammonia adduct
of 3-dehydropyridinium cation support the Lewis structure
chosen to illustrate the amino acid adducts of the radicals.
Several unprecedented reaction pathways were also observed.
These include the abstraction of two hydrogen atoms from
proline and lysine by the nitro-substituted radical d. Further-
more, abstractions of C2H4N, C5H7NO, and OH groups by
radical c were observed for proline. These reactions are likely to
occur by nucleophilic additionꢀelimination pathways, similar to
that leading to NH2 abstraction from all the other amino acids
but proline, where the nitrogen atom is part of a ring structure.
Finally, both NH2 and 15NH2 groups were abstracted from lysine
labeled with 15N on the side chain, indicating that NH2 abstrac-
tion occurs both from the amino terminus and from the side
chain of lysine.
The electron affinity of the radical appears to be the major
factor in controlling the radical’s reaction rates with the amino
acids. Both the radical (hydrogen atom abstraction) and non-
radical (NH2 abstraction) reaction efficiencies were found to
depend on the electrophilicity of the radical, although the
nonradical reactions are influenced more strongly. However, in
contrast to an earlier report,12b the ionization energies of the
amino acids do not appear to have a general reactivity-
controlling role.
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’ ASSOCIATED CONTENT
S
Supporting Information. Absolute energies and coordi-
b
nates of atoms for all optimized structures and complete ref 23.
This material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
(16) Chen, L.; Wang, T.-C. L.; Ricca, T. L.; Marshall, A. G. Anal.
Chem. 1987, 59, 449–454.
(17) Gauthier, J. W.; Trautman, T. R.; Jacobson, D. B. Anal. Chem.
1991, 246, 211–225.
Corresponding Author
(18) Leeck, D. T.; Stirk, K. M.; Zeller, L. C.; Kiminkinen, L. K. M.;
Castro, L. M.; Vainiotalo, P.; Kentt€amaa, H. I. J. Am. Chem. Soc. 1994,
116, 3028–3030.
’ ACKNOWLEDGMENT
(19) Huang, Y.; Kentt€amaa, H. I. J. Am. Chem. Soc. 2005, 127,
7952–7960.
(20) Thoen, K. K.; Smith, R. L.; Nousiainen, J. J.; Nelson, E. D.;
Kentt€amaa, H. I. J. Am. Chem. Soc. 1996, 118, 8669–8676.
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(22) Mitulovi, G.; Lammerhofer, M.; Maier, N. M.; Linder, W.
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(23) Frisch, M. J.; et al. Gaussian 98, revision A.11.3; Gaussian, Inc.:
Pittsburgh, PA, 2002 (for complete reference, see the Supporting
Information).
Financial support for this work provided by Purdue University
and the National Institutes of Health is gratefully acknowledged.
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