Direct observation of an Acyl nitroso species in solution by time-resolved IR spectrocopy

Article abstract of DOI:10.1021/ja028978e

Benzoyl nitroside (5) was generated in solution by laser photolysis of 3,5-diphenyl-1,2,4-oxadiazole-4-oxide (4) and studied by time-resolved infrared spectroscopy. The second-order rate constantsfor reaction of 5 with diethylamine and 1,3-cyclohexadiene were determined to be (1.3 ± 0.5) × 10⁵ M^-1 s^-1 and (6.0 ± 0.5) × 10³ M^-1 s^-1, respectively. The formation of nitroxyl (HNO), a product of the reaction of 5 with diethylamine, was also observed. Copyright

Full text of DOI:10.1021/ja028978e

Published on Web 01/16/2003
Direct Observation of an Acyl Nitroso Species in Solution by Time-Resolved
IR Spectrocopy
Andrew D. Cohen,† Bu-Bing Zeng,‡ S. Bruce King,‡ and John P. Toscano*,†
Department of Chemistry, Johns Hopkins UniVersity, 3400 North Charles Street, Baltimore, Maryland 21218, and
Department of Chemistry, Wake Forest UniVersity, Salem Hall, Winston-Salem, North Carolina 27109
Received October 16, 2002 ; E-mail: jtoscano@jhu.edu
Scheme 1
The recent and resurgent interest in the biological chemistry of
nitrogen oxides has focused mainly on nitric oxide (NO).1 Much
of the fundamental chemistry of this natural free radical has been
worked out long ago. On the other hand, much less is known about
the nitroxyl system (NO-/HNO), the one-electron reduced congener
of NO.2,3 For instance, the uncertainty concerning the pKa of HNO4,5
has only recently been clarified. A value of approximately 11 has
been obtained by several methods.6,7 Direct observation of HNO
has been limited mainly to gas-phase8,9 and matrix10 studies.
Currently, studies use prodrugs of HNO (that decompose spontane-
ously under physiological conditions) to monitor its pharmacological
effects.11-13 Further knowledge of the fundamental solution-phase
chemistry of HNO will certainly be relevant to the understanding
of its physiological efficacy.
In addition to the bleaching of 4 at 1310 cm-1, we observe bands
due to both benzonitrile (2265 cm-1) and acyl nitroso 5 (1735, 1590,
1560, and 1235 cm-1). To corroborate this latter assignment, we
examined the B3LYP/6-31G* calculated frequencies of 5 (scaled
by 0.9627). These frequencies are in good agreement with the
The most common chemical precursor to the nitroxyl system is
observed IR spectra, as shown in Figure 1a. Laser photolysis (266
-
Angeli’s anion (1), which decomposes to NO- and NO2 both
nm, 5 ns, 2 mJ) of Diels-Alder adduct 3 (R ) Ph), a known thermal
thermally14 and photochemically.15 Other precursors include N-
precursor to 5,19 yields a similar IR band at 1735 cm-1, although
hydroxybenzenesulfonamide (Piloty’s acid)16 and the naturally
the photochemistry here appears to be substantially more compli-
occurring S-nitrosothiols.17 Recent attention has been given to acyl
cated and will require a more detailed study.
nitroso compounds (2), transient electrophiles that react with
Consistent with literature reports,25 we observe trapping of acyl
nitroso 5 when generated in the presence of both added DEA and
nucleophiles to yield HNO.18 Acyl nitroso compounds are most
commonly generated by either the periodate oxidation of hydrox-
CHD in either acetonitrile-d3 or dichloromethane (Scheme 1). The
amic acids or the thermal fragmentation of Diels-Alder adducts.19-21
observed decay rates of 5 (kobs) are obtained by monitoring the
King and co-workers have used dimethylanthracene-based Diels-
signal at 1735 cm-1 following excitation. Using the pseudo-first-
Alder adducts (3, R ) NR2) to produce urea derivatives of 2 (R )
order equation (kobs ) k0 + kq[Q]), the second-order rate constants
kDEA ) (1.3 ( 0.5) × 105 M-1 s-1 and kCHD ) (6.0 ( 0.5) × 103
M-1 s-1 are derived (Supporting Information). We estimate that
the lifetime of 5 at infinite dilution (1/k0) in organic solution is on
the order of 1 ms. At the high concentrations (>10 M) required to
observe trapping by water-d2, strong IR absorbance preclude
accurate monitoring of the 1735 cm-1 signal.
NR2) at biologically relevant temperatures.22 Nevertheless, the only
spectroscopic evidence for 2 has been provided in the gas phase
by Schwarz and co-workers using both charge reversal and
neutralization-reionization mass spectrometry.23,24 Herein, we
report the first direct detection of an acyl nitroso compound (2, R
) Ph) in solution by time-resolved infrared (TRIR) spectroscopy.
We have monitored its reactions with diethylamine (DEA) and with
1,3-cyclohexadiene (CHD). We also report the direct detection of
HNO, formed upon reaction with DEA.
Laser photolysis of a solution of 4 in acetonitrile-d3 with 0.15
M diethylamine produces the TRIR difference spectra shown in
Figure 1b. Analogous spectra are observed in dichloromethane.
Decay of the bands due to acylnitroso 5 are accompanied by the
growth of a new band at 1660 cm-1 with identical kinetics (Figures
1b, 2). The stable 1660 cm-1 signal is assigned to N,N-diethylben-
zamide (6) on the basis of comparison with authentic material.
Additionally, we observe a weak broad signal around 2650 cm-1
that also grows with identical kinetics (Figures 1b, 2). We tentatively
assign this signal to HNO on the basis of the following observations.
No signal is observed in the absence of added nucleophiles. The
band is broadened and red-shifted compared to the N-H vibrational
Caramella and co-workers initially reported the photochemical
fragmentation of 3,5-diphenyl-1,2,4-oxadiazole-4-oxide (4) to form
benzoyl nitroside (5) and benzonitrile (Scheme 1).25 Laser photolysis
(355 nm, 5 ns, 4 mJ) of a solution of 4 in acetonitrile-d3 produces
the TRIR difference spectra shown in Figure 1a.26 Analogous
spectra are observed in dichloromethane. The transients are formed
faster than the time-resolution of our instrument (kobs > 2.0 × 107
s-1) and are stable for at least 180 µs (Supporting Information).
frequency of matrix-isolated (2717 cm-1 10
and gas-phase (2684
)
cm-1)8 HNO, as expected in solution with a high concentration of
H-bond acceptors. We were unable to observe cleanly the NdO
stretch expected near 1550 cm-1 for HNO due to overlap with the
NdO stretch of 5 as well as with aromatic vibrational modes of
both 5 and 6.
† Johns Hopkins University.
‡ Wake Forest University.
9
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J. AM. CHEM. SOC. 2003, 125, 1444-1445
10.1021/ja028978e CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
preliminary evidence indicating direct IR detection of HNO. Water-
soluble analogues of 4, currently under development in our
laboratory, could prove useful for the study of both the fundamental
aqueous chemistry of nitroxyl as well as its potential applications
in biology and medicine.
Acknowledgment. We thank the National Institutes of Health
(GM58109 at Hopkins and HL62198 at Wake Forest) for financial
support. J.P.T. also acknowledges a Camille Dreyfus Teacher-
Scholar Award and an Alfred P. Sloan Research Fellowship.
Supporting Information Available: Details of the synthesis of
precursors 3 (R ) Ph) and 4, kinetic traces for the formation of 5 in
the absence of quencher, details of the derivation of second-order rate
constants, and B3LYP/6-31G* optimized geometry and frequencies of
5 (PDF). This material is available free of charge via the Internet at
http://pubs.acs.org.
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In summary, we provide the first direct detection and kinetic
study of an acyl nitroso compound. Additionally, we present
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