provided 7-hydroxyquinaldine (6),13 whose hydroxy group
was subsequently protected as the tert-butyldiphenylsilyl
(TBDPS) ether. The 2-methyl group was oxidized with
selenium dioxide, and the resulting aldehyde 7 was reduced
to the alcohol 9 using sodium borohydride in ethanol.
Treatment with acetic anhydride in pyridine provided acetate
9, which, like other 7-hydroxy quinolines,14 was brominated
in the 8-position.15 Removal of the TBDPS protecting group
using tetrabutylammonium fluoride in THF provided BHQ-
OAc (12). Bhc-OAc (13) was synthesized according to the
published procedure.6
Upon photolysis with 365 nm light under simulated
physiological conditions in KMOPS (100 mM KCl, 10 mM
MOPS, pH 7.2), Bhc-OAc (13) and BHQ-OAc (12) are each
converted to their respective hydroxy derivative, Bhc-OH
(14) or BHQ-OH (15), and acetate (Scheme 2). A comparison
Figure 3. Time course of single photon photolysis of BHQ-OAc
(12) and Bhc-OAc (13) at 365 nm. Concentrations of BHQ-OAc
and Bhc-OAc were determined by HPLC and are the average of 4
runs (see the Supporting Information). Solid lines are least-squares
fits of simple decaying exponentials, which gave time constants τ
) 11.7 and 16.6 s and coefficients of determination R2 ) 0.99 and
1.00, for BHQ-OAc and Bhc-OAc, respectively.
Scheme 2. Photolysis of Bhc-OAc and BHQ-OAc18
These data are summarized in Table 1 along with selected
absorption data.
Table 1. Photochemical Properties of DMNB-OAc, Bhc-OAc,
and BHQ-OAc
λmax ꢀ (M-1
‚
ꢀ365 (M-1
cm-1)
‚
Qu1
δu
δu
of the time courses for these reactions, obtained from HPLC
analysis of aliquots taken at periodic intervals, shows that
BHQ-OAc photodecomposes more rapidly than Bhc-OAc
(Figure 3). From these data, single-photon uncaging quantum
efficiencies, Qu1, were determined from the relationship Qu1
) (Iσt90%)-1,16 where I is the irradiation intensity in
ein‚cm-2‚s-1 (determined by potassium ferrioxalate actin-
ometry17), σ is the decadic extinction coefficient (103 times
ꢀ, molar extinction coefficient) in cm2‚mol-1, and t90% is the
irradiation time in seconds for 90% conversion to product.
(nm) cm-1)
(mol/ein) (740 nm) (780 nm)
1a 346
6100
2600
5200
2580
14 800a
0.005
0.29
0.036
0.03
0.59
0.72
0.01
0.087
0.21
12
13
369
370 15 000a
a Values taken from ref 6.
The sensitivity to two-photon photolysis of potential caged
compounds is quantified as the uncaging action cross-section
δu. This value is the product of the two-photon absorbance
cross-section δa and the uncaging quantum yield Qu2, and to
be biologically useful, δu should exceed 0.1 Goeppert-Mayer
(GM), where 1 GM is defined as 10-50 cm4‚s/photon.6 Two-
photon uncaging cross-sections were measured using a fs-
pulsed, mode-locked Ti:sapphire laser with fluorescein as
an external standard because its two-photon fluorescence
cross-section has been well-characterized.19 The progress of
the uncaging reaction was measured by HPLC and graphed
as a function of time (Figure 4). The initial rate of photolysis
was used to determine Np, the number of molecules formed
per second, which is related to δu by the equation
(10) Matsuzaki, M.; Ellis-Davies, G. C. R.; Nemoto, T.; Miyashita, Y.;
Iino, Y.; Kasai, H. Nature Neurosci. 2001, 4, 1086-1092.
(11) Pearce, D. A.; Jotterand, N.; Carrico, I. S.; Imperiali, B. J. Am.
Chem. Soc. 2001, 123, 5160-5161. Prodi, L.; Bargossi, C.; Montalti, M.;
Zaccheroni, N.; Su, N.; Bradshaw, J. S.; Izatt, R. M.; Savage, P. B. J. Am.
Chem. Soc. 2000, 122, 6769-6770. Budde, T.; Minta, A.; White, J. A.;
Kay, A. R. Neuroscience 1997, 79, 347-358. Geddes, C. D.; Apperson,
K.; Karolin, J.; Birch, D. J. S. Dyes Pigments 2001, 48, 227-231.
(12) Douhal, A.; Dabrio, J.; Sastre, R. J. Phys. Chem. 1996, 100, 194-
154. Nakagawa, T.; Kohtani, S.; Itoh, M. J. Am. Chem. Soc. 1995, 117,
7952-7957.
(13) Song, Z.; Mertzman, M.; Hughes, D. L. J. Heterocycl. Chem. 1993,
30, 17-21.
(14) Jones, G., Ed. Quinolines; Wiley: London, 1977; Vol. 32.
(15) The 1H NMR spectrum of 11 confirmed the regiochemistry; the
C-6 proton signal condensed to a doublet (J ) 8.8 Hz), and the C-8 proton
signal disappeared.
NpφQf2δaFCF
δu )
(16) Adams, S. R.; Kao, J. P. Y.; Grynkiewicz, G.; Minta, A.; Tsien, R.
Y. J. Am. Chem. Soc. 1988, 110, 3212-3220.
(17) Hatchard, C. G.; Parker, C. A. Proc. R. Acad. London A 1956, 235,
518-536.
F(t) Cs
where φ is the collection efficiency of the detector, Qf2 is
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