Enantioselective Reduction
of Noncovalent Complexes
of Amino Acids with CuII via Resonant Collision-Induced
Dissociation: Collision Energy, Activation Duration Effects, and RRKM
Modeling
Formation of noncovalent complexes is one of the approaches
to
perform chiral analysis with mass spectrometry. Enantiomeric distinction
of amino acids (AAs) based on the relative rate constants of competitive
fragmentations of quaternary copper complexes is an efficient method
for chiral differentiation. Here, we studied the complex [CuII,(Phe,PhG,Pro-H)]+ (m/z 493) under resonant collision-induced dissociation conditions while
varying the activation time. The precursor ion can yield two main
fragments through the loss of the non-natural AA phenylglycine (PhG):
the expected product ion [CuII,(Phe,Pro-H)]+ (m/z 342) and the reduced product
ion [CuI,(Phe,Pro)]+ (m/z 343). Enantioselective reduction describes the difference
in relative abundance of these ions, which depends on the chirality
of the precursor ion: the formation of the reduced ion m/z 343 is favored in homochiral complexes (DDD)
compared to heterochiral complexes (such as LDD). Energy-resolved
mass spectrometry data show that reduction, which arises from rearrangement,
is favored at a low collision energy (CE) and long activation time
(ActT), whereas direct cleavage preferentially occurs at a high CE
and short ActT. These results were confirmed with kinetic modeling
based on RRKM theory. For this modeling, it was necessary to set a
pre-exponential factor as a reference, so that the E0 values obtained are relative values. Interestingly,
these simulations showed that the critical energy E0 required to form the reduced ion is comparable in both
homochiral and heterochiral complexes. However, the formation of
product ion m/z 342 through direct
cleavage is associated with a lower E0 in heterochiral complexes. Consequently, enantioselectivity would
not be caused by enhanced reduction in homochiral complexes but rather
by direct cleavage being favored in heterochiral complexes.