9346
J. Am. Chem. Soc. 2000, 122, 9346-9347
from ∼30 µs to 80 ns in AN, and it was identified as the triplet
p-Hydroxyphenacyl Phototriggers: The Reactive
3
state of 4, 4, by energy transfer to naphthalene (ET ) 61 kcal
Excited State of Phosphate Photorelease
mol-1),5 ket ≈ 1 × 1010 M-1 s-1. Pump-probe spectroscopy of 4
in AN (248-nm excitation, 1 mJ per pulse, 0.8 ps pulse length)
Peter G. Conrad, II,‡ Richard S. Givens,*,‡ Bruno Hellrung,
Cheruvallil S. Rajesh, Markus Ramseier, and Jakob Wirz*
1
3
showed that intersystem crossing (ISC), 4 f 4, is very fast,
kISC ) (3.1 ( 0.2) × 1011 s-1
.
Replacement of the methoxy group by an ionizable hydroxy
group introduces new functionality (Scheme 1). The ionization
constant of 3 is pKa(3) ) 7.9 ( 0.1.6 The equilibrium constant
for the isomerization of 3 to its quinonoid enol tautomer 3′, pKE
) 16.4, was calculated using density functional theory (DFT).7
A thermodynamic cycle then defines the acidity of enol 3′ to be
very high, pKa(3′) ) -8.5.
Institut fu¨r Physikalische Chemie der UniVersita¨t Basel
Klingelbergstrasse 80, CH-4056 Basel, Switzerland
Department of Chemistry, UniVersity of Kansas
Lawrence, Kansas 66045
ReceiVed March 31, 2000
ReVised Manuscript ReceiVed July 11, 2000
Formation of 33 is equally fast in aqueous AN solvent mixtures
(kISC ) 2.7 × 1011 s-1, λmax ) 370 in dry AN, 395 nm with 50%
H2O). Energy transfer from 33 to naphthalene was again observed.5
The transient is acidic,8 but does not ionize in dry AN. Adiabatic
Fast release of biological stimulants is needed to monitor
physiological response in real time.1 p-Hydroxyphenacyl (pHP)
phototriggers meet this requirement. Moreover, the side products
are biologically compatible and transparent to excitation wave-
lengths >300 nm.2 Knowledge of the release rate is essential to
biophysical applications. Givens et al. identified a short-lived
triplet state as the reactive excited state of pHP phosphates and
carboxylates on the basis of quenching experiments.2 In a recent
study of pHP esters Zhang et al.3a questioned that evidence and
favored a singlet mechanism. Here, we prove that the reactive
excited state of pHP diethyl phosphate (1) is a very short-lived
triplet state and we provide direct evidence for adiabatic tau-
tomerization of p-hydroxyacetophenone and its derivatives in the
triplet state.
ionization, 3 f 3- + H+, takes place in aqueous AN (50%
H2O), kion ≈ 9 × 106 s-1, and is too fast for detection by LFP in
water, kion > 3 × 107 s-1. The spectra of 33 and 33- appear to be
quite similar; the absorption maximum of 33- is shifted to slightly
longer wavelength (405 nm) and the weaker band in the visible,
λmax ≈ 500 nm, is more pronounced. In a second process, k )
1.9 × 106 s-1, the intensity of the 405-nm band is reduced, and
a new strong band appears at 350 nm.3b Excitation of the anion
3- in aqueous NaOH (0.1 M) at 308 nm gave only the 405 and
500 nm bands, which shows that these are due to the triplet state
3
3
3
of the anion, 3-.
Apparently, 33- is re-protonated to form the 350-nm transient
in acidic solutions. The first-order rate coefficient for re-
protonation in dilute aqueous acid ([HClO4] ) 3-10 × 10-4 M)
was proportional to acid concentration, kH ≈ 4 × 1010 M-1 s-1
.
+
Spectrographic traces of the equilibrated triplet-triplet absorptions
(delay relative to excitation 200 ns) formed by excitation of 3 in
aqueous buffer solutions at pH 7.1 (phosphate, I ) 0.01 M), 5.32,
4.66, 4.38, 4.04 (acetate, I ) 0.01 M), and 2.0 (HClO4, 10-2 M)
are shown in Figure 1. Factor analysis indicated that two
components sufficed to reproduce all spectra within experimental
accuracy. Fitting of a titration function to the loading coefficients
gave pKa ) 4.6 ( 0.2.
p-Hydroxyphenylacetic acid (2) is the only product detected
by GC-MS after irradiation of 1 in wet acetonitrile (AN, H2O
g 5% by vol). Numerous products of higher molecular weight
are formed in dry AN. Relative quantum yields of the photore-
action in different media were determined by the permanent
bleaching of the absorption by 1 at 270 nm (pulsed laser excitation
at 308 nm). Water (5%) accelerated the reaction about 5-fold,
but saturation with air or addition of 0.5 mM piperylene slowed
the conversion about 4-fold in dry AN. The absolute quantum
yield in wet AN (5%) was determined as 0.94 (steady-state 313-
nm irradiation, azobenzene actinometry); it was reduced to 0.37
by addition of 10 mM piperylene. Still higher quencher concen-
trations were required to reduce the quantum yield in solutions
containing more water.2c,3a
We attribute the protonated species observed at low pH (λmax
3
3
≈ 350 nm) to the quinonoid enol triplet, 3′. Clearly, 3′ is an
3
excited tripletsit is in equilibrium with 3- and the lifetimes of
both are equally reduced by oxygensbut its properties are
3
distinctly different from those of 3. The triplet energy of 3 (ET
) 70.5 kcal mol-1 2c DFT calculation:7 ET ) 69.5 kcal mol-1) is
,
well above that of naphthalene. On the other hand, the excitation
Identification of the transients produced by nanosecond laser
flash photolysis (LFP)4 of 1 was aided by referring to p-
hydroxyacetophenone (3) and p-methoxyacetophenone (4) as
model compounds. Strong absorption was formed by LFP of 4
(1 × 10-4 M) in aqueous AN (50% H2O, λmax ≈ 395 nm) or AN
(385 nm). Admission of air reduced the lifetime of this transient
energy of the quinonoid enol 3′ is expected to be much lower
(5) Naphthalene concentrations e1 mM, selective excitation of the ketone
at 351 nm (XeF excimer laser). The formation of triplet naphthalene was
monitored at λmax ) 415 nm.
(6) Spectrophotometric titration in tris(hydroxymethyl)amine/HCl buffer
(ionic strength I ) 0.1 M). See also: Vandenbelt, J. M.; Henrich, C.;
Vandenberg, S. G. Anal. Chem. 1954, 26, 726-727.
(7) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.; Johnson,
B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G. A.;
Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski, V. G.;
Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov, B. B.; Nanayakkara,
A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.;
Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Binkley,
J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J. A. Gaussian 94, revision B.2; Gaussian, Inc.: Pittsburgh, PA,
1995. B3LYP functionals (unrestricted for the triplet states) with the 6-31G*
basis set. Zero-point and thermal free-energy corrections were included. This
method gives reliable values for keto-enol equilibria: Sklena´k, S.; Apeloig,
Y.; Rappoport, Z. J. Am. Chem. Soc. 1998, 120, 10359-10364.
(8) Bromophenol blue is protonated by 33 at a diffusion-controlled rate
(λobs ) 600 nm), but the proton transfer is largely suppressed when 33 is
quenched by oxygen (1 atm).
‡ University of Kansas.
(1) Methods in Enzymology; Marriott, G., Ed.; Caged Compounds, Vol.
291; Academic Press: New York, 1998.
(2) (a) Givens, R. S.; Park, C.-H. Tetrahedron Lett. 1996, 37, 6259-6262.
(b) Park, C.-H.; Givens, R. S. J. Am. Chem. Soc. 1997, 119, 2453-2463. (c)
Givens, R. S.; Weber, J. F. W.; Conrad, P. G.; Orosz, G.; Donahue, S. L.;
Thayer, S. A. J. Am. Chem. Soc. 2000, 122, 2687-2697.
(3) (a) Zhang, K.; Corrie, J. E. T.; Munasinghe, V. R. N.; Wan, P. J. Am.
Chem. Soc. 1999, 121, 5625-5632. (b) Brousmiche, D. W.; Wan, P. J.
Photochem. Photobiol., A 2000, 130, 113-118.
(4) Excimer laser operated on XeCl, 308 nm, ∼100 mJ per pulse, pulse
width 25 ns. Low concentrations of ketones 1, 3, and 4 were used to avoid
radical formation by intermolecular hydrogen abstraction: Das, P. K.; Encinas,
M. V.; Scaiano, J. C. J. Am. Chem. Soc. 1981, 103, 4154-4162. Canonica,
S.; Hellrung, B.; Wirz, J. J. Phys. Chem. A 2000, 104, 1226-1232.
10.1021/ja001134f CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/09/2000