Direct Evidence for Base-Mediated Decomposition
of Alkyl Hydroperoxides (ROOH) in the Gas Phase
Stephen J. Blanksby, G. Barney Ellison, Veronica M. Bierbaum, and Shuji Kato*
Department of Chemistry and Biochemistry, UniVersity of Colorado, Boulder Colorado, 80309
Received November 30, 2001
Alkyl hydroperoxides (ROOH) are attributed a key role in the
biochemical oxidation of lipids during oxidative stress.1In this
chemistry ROOH compounds, where the R groups are unsaturated
fatty acids, are viewed as transient intermediates which are readily
degraded, due to the lability of the RO-OH bond, to yield
potentially genotoxic aldehydes and ketones.2Generally, the
decomposition of alkyl hydroperoxides is thought to be mediated
by radical abstraction or electron transfer processes usually involv-
ing enzymes, transition metals, or recently, Vitamin C.3In this paper
we present the first unambiguous experimental and computational
evidence for base-mediated heterolytic decomposition of simple
alkyl hydroperoxides by the mechanism outlined in Scheme 1.
Mass-selected anion bases were allowed to react with simple
alkyl hydroperoxides in a flow of helium buffer gas (0.5 Torr, 300
K) using a tandem flowing afterglow-selected ion flow tube
(FA-SIFT) mass spectrometer.4Kinetics for the reaction of mass-
selected F-with CH3OOH5are typical of these systems and the
kinetics plot of this reaction is shown in Figure 1. The reaction is
rapid (k ) 1.23 × 10-9cm3s-1, 49% efficiency)6and the major
primary product is HO-(Scheme 2b), which produces CH3OO-
by a secondary reaction (Scheme 2c). To examine the secondary
ion chemistry of HO-, we allowed it to react with CH3OOH in a
separate experiment. Using these data we can quantitatively account
for the decay of HO-and formation of CH3OO-at longer reaction
times in Figure 1. Direct proton transfer to form CH3OO-(Scheme
2a) thus appears to be a minor process (∆acidH298[CH3OO-H] )
374.6 ( 1.0 kcal mol-1).7A numerical analysis based on Scheme
2 shows that the reaction of F-with CH3OOH proceeds mainly
via the formation of HO-(∼85%) whereas direct proton transfer
is only about 10%.8,9The inefficient proton transfer between F-
and CH3OOH is consistent with thermochemistry which predicts
the process to be endothermic7by about 3 kcal mol-1.
We attribute the efficient formation of HO-ions in this reaction
(Scheme 2b) to an elimination mechanism (Scheme 1) analogous
to that proposed for solution reactions by Kornblum and De La
Mare.11Interestingly, the formation of aldehydes and ketones
observed by these authors under basic conditions was later attributed
by others to decomposition of the peroxides by trace amounts of
transition metals.12Such metal-mediated redox chemistry has since
been observed in the gas phase.13Nevertheless, the Kornblum-
De La Mare mechanism is still favored for solution reactions where
R (Scheme 1) is electron withdrawing.12,14The proposed mechanism
is similar to the gas-phase ECO2 reaction15for the elimination of
NO-from alkyl nitrites (e.g. CH3ONO). In both reactions, depro-
tonation from the R-carbon leads to carbon-oxygen double bond
formation with concerted elimination of the anionic leaving group.
To probe the mechanism of this reaction in the gas phase, we
allowed F-to react with CD3OOH. HO-is found to be the major
primary product (HO-:DO-∼6:1), consistent with the proposed
*To whom correspondence should be addressed. E-mail: email@example.com.
mechanism involving base attack on an R-deuteron. The minor
amount of DO-is possibly due to H/D scrambling that involves
DF and HO-in the complex prior to dissociation. The observed
ratio also rules out possible decomposition of CD3OO-within a
hot ion-dipole complex, [HF‚‚‚CD3OO-]* f HF + CD2O +
DO-.16Further, no anion was observed at m/z 49, thus excluding
the possible elimination-addition reaction, F-+ CD3OOH f DF
+ HOCD2O-. The reactions of other alkyl hydroperoxides were
also investigated. The reaction F-+ CH3CH2OOH produced HO-
as a major product. In contrast the reaction F-+ (CH3)3COOH
produced negligible amounts of hydroxide while adduct formation
was the major pathway. These observations demonstrate the
importance of the R-hydrogen to the base-mediated decomposition
(cf. Scheme 1).
Supporting evidence for the efficiency of the ECO2 mechanism
comes from observing the reverse reaction, CH3OO-+ HF. This
reaction proceeds at nearly every collision with a rate coefficient6
of k ) 2.43 × 10-9cm3s-1and yields HO-as the major primary
reaction product (Scheme 3b, 81%) despite the possibility for
exothermic proton transfer (Scheme 3a). The primary fraction for
F-formation is only 19% after correction for secondary product
ion formation via HO-+ HF f H2O + F-. The predominance of
HO-formation suggests a reaction pathway whereby proton transfer
occurs within the initial ion-dipole complex followed by a
rearrangement of the complex to facilitate the ECO2 reaction and
Figure 1. Kinetics plot for the reaction of F-with CH3OOH at 300 K.
Ion counts have been corrected for mass discrimination and the reaction
time is computed using a standard approach.10The solid lines are the best
fits using Scheme 2; the broken line represents the yield of CH3OO-due
to direct proton transfer (Scheme 2a) extracted from the analysis.
Published on Web 03/06/2002
3196 9 J. AM. CHEM. SOC. 2002, 124, 3196-3197
10.1021/ja017658c CCC: $22.00 © 2002 American Chemical Society
regenerate HF (Scheme 3b). The HF provides an alternative
chemical pathway for CH3OO-decomposition that effectively
lowers the activation barrier. As far as we are aware, this reaction
represents the first reported example of a neutral-catalyzed
decomposition of an anion in the gas phase.
Computational studies were conducted for F-+ CH3OOH at
the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31+G(d) level of theory17
using GAUSSIAN98.18Figure 2 shows a transition state, TS1, 14.6
kcal mol-1below the entrance channel. TS1 has an antiperiplanar
structure with C-H and O-O bonds elongated by about 0.2 Å
relative to free CH3OOH. Atomic motion in the imaginary
frequency (647i cm-1) shows concerted (i) H-F bond formation,
(ii) C-O bond contraction, and (iii) O-O bond rupture. These
observations suggest TS1 is part of a synchronous E2 reaction
mechanism. Intrinsic reaction coordinate19calculations on TS1 show
this saddle point connects (i) the ion-dipole complex [F-‚‚‚CH3-
OOH]complexand (ii) the major observable product channel HF +
CH2O + HO-, which is 35.8 kcal mol-1below the entrance channel.
Formation of a product complex, [HF‚‚‚CH2O‚‚‚HO-]complex, fol-
lowed by proton transfer within the complex prior to dissociation
would result in the ensemble F-+ CH2O + H2O, which is a further
19.7 kcal mol-1more negative in energy. Although it would be
difficult to detect this experimentally, perhaps regeneration of F-
produces an artificially low reaction efficiency (49%, see earlier)
for this exothermic reaction. Such regeneration of the anionic base
would suggest base-catalyzed decomposition of the alkyl hydro-
peroxide in the gas phase.
OOH‚‚‚F-]complexand [F-‚‚‚CH3OOH]complex. Following the reaction
coordinate from HF + CH3OO-, the calculations predict (i) initial
proton transfer may be followed by (ii) rearrangement of the nascent
ion-dipole complex via TS2 and finally (iii) ECO2 reaction to
produce HO-. This scheme is entirely consistent with the experi-
mental assignment of a neutral-catalyzed decomposition of CH3OO-.
The ECO2 reaction pathway was also calculated for NC-+ CH3-
OOH. NC-is a significantly weaker gas-phase base than F-(i.e.
∆acidH298[HCN] , ∆acidH298[HF]) so, although the ECO2 reaction
is still exothermic by 22 kcal mol-1, the critical transition state,
TS1(NC-), is calculated to be 6.5 kcal mol-1above the entrance
channel (Figure 2). Experimentally, we observed no reaction
between NC-and CH3OOH. Both theory and experiment demon-
strate that NC-cannot decompose CH3OOH via the ECO2 pathway
at thermal energies. However, if the acidities of the R-hydrogens
were increased, as for example in allyl hydroperoxide (CH2dCHCH2-
OOH), then TS1 may be lowered relative to the entrance channel
and even weak gas-phase bases such as NC-may facilitate
decomposition of the alkyl hydroperoxide. We intend to investigate
such systems, as they are good models for endogenous lipid
Acknowledgment. S.J.B. and G.B.E. acknowledge support by
the Chemical Physics Program, United States Department of Energy
(DE-FG02-87ER13695). S.K. and V.M.B. gratefully acknowledge
support from the National Science Foundation (CHE 0100664). We
also thank Professor Charles DePuy for helpful discussions.
Supporting Information Available: Geometries, electronic ener-
gies, zero-point energies, and imaginary frequencies used for Figure 2
(PDF). This material is available free of charge via the Internet at http://
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Figure 2. Relative energetics (kcal mol-1) on the [F-, CH3OOH] potential
energy surface (electronic energy + ZPE). The TS1(NC-) energy has been
scaled to the energy of the reactants NC-+ CH3OOH.
C O MMU NI C A T I O NS
J. AM. CHEM. SOC. 9 VOL. 124, NO. 13, 2002 3197