Table 1. Photophysical Properties of Chromophores 10, 14, 21 and 25
a
a,b
a,b
nm)
b,c
b
max
max
λmax
εmax
ε(366
Qu
(%)
εQu
δu,730
(GM)
λTPA
(nm)
σ2
σ2,(730
(GM)
σ2Qu
(GM)
nm
nm)
(nm)
(MÀ1cmÀ1
)
(MÀ1cmÀ1
)
(MÀ1cmÀ1
)
(GM)
5-DMAQ-OAc (21) 340
6-DMAQ-OAc (14) 369
7-DMAQ-OAc (10) 371
8-DMAQ-OAc (25) 347
4900
3380
4790
4800
2770
3330
4670
4090
0
0
0
0
0
e700
740
e1.5
3.0
2.8
10
0.8
2.0
2.2
3
0
0
0
3.0
140
708
0.05
0.67
760
0.07
0.52
17.3
700
a Measured in acetonitrile/TRIS buffer (20 mM) 1/1 at 293 K. b Measured at 366 nm. c Samples were prepared in 0.1 mM concentration in
acetonitrile/TRIS buffer 1/1 solvent mixture (pH 7.4). For full experimental protocol, see Supporting Information.
a similar strategy (Scheme 1). The condensation of 4-(N,N
dimethylamino)aniline 11 and crotonaldehyde 7 in HCl
(cc) afforded the 6-(N,N-dimethylamino)quinaldine 12, in
considerably higher yield (70%) than by using parafor-
maldehyde. Quinaldine 12 was transformed to the acetox-
ymethylene derivative 14 by SeO2 oxidation (58%),
reduction by NaBH4 (13, 80%) and acetylation (87%).
The 5- and 8-(N,N-dimethylamino) acetates, (5-DMAQ-
OAc, 21 and 8-DMAQ-OAc, 25) were prepared from
quinaldine 15 as starting material (Scheme 2). Nitration of
15 in a 1:4 mixture of HNO3 (cc) and H2SO4 (cc) afforded a
mixture of a roughly equivalent amounts of C(5), and C(8)
mononitrated compounds 16 and 17, that were separated on
silica gel (39% and 44%). The structure of the position
isomer 23 and thus the structures of 16 and 17 were
Figure 3. Photolysis of 5-DMAQ-OAc (21), 6-DMAQ-OAc
(14), 7-DMAQ-OAc (10), and 8-DMAQ-OAc (25) at 366 nm
with the calculated time course of the photolyses of DMAQ
acetate samples determined by HPLC.
unambiguously attributed by chemical correlation (for
full experimental details see Supporting Information (SI)).
Isomers 16 and 17 were transformed to the corresponding
dimethylamino quinaldines respectively by using Bechamp
reduction followed by methylation under standard condi-
tions (NaH, MeI). The desired acetates 21 and 25 were
obtained after benzylic oxidation using SeO2 followed by
reduction and acetylation (Scheme 2).
DMAQ acetates 10, 14, 21 and 25 were practically
insoluble in 10 mM TRIS buffer; thus, all analyses were
performed in a 1/1 mixture of acetonitrile/TRIS buffer
(20 mM, pH 7.4). The absorption spectra of compounds
10, 14, 21 and 25 were recorded in a mixture of acetonitrile/
TRIS (1/1) solution (pH 7.4) at 293 K in the 200À600 nm
wavelength range and the calculated molar extinction spectra
are plotted in Figure 2. Compounds 10, 14, 21 and 25 have
qualitatively similar absorption spectra. The first absorption
maxima of compounds 10, 14, 21 and 25 are located between
340 and 371 nm having molar extinction at the absorption
maxima εmax between 3380 and 4900 MÀ1cmÀ1 (Figure 2,
Table 1).
shifted in addition to increased aqueous solubility con-
veyed by the free acid derivative.4j
DMAQ acetate samples 10, 14, 21 and 25 were photo-
lyzed by UV (366 nm: OPA) and near IR (730 nm: TPA)
irradiation. The time course of UV photolysis was moni-
tored by HPLC and the consumption of the starting materi-
als against the time is plotted in Figure 3. No quantitative
analysis of photoreleased acetic acid was made. The photo-
lysis at 366 nm of 5- and 6-DMAQ acetates 21 and 14 are too
slow to record photofragmentation within 2 h of irradiation
and these compounds are photochemically stable at this
wavelength. In contrast, 8-DMAQ-OAc (25) was photo-
lyzed 6-fold more efficiently at 366 nm than the reference
compound 7-DMAQ-OAc (10) (Table 1). Notably, com-
pound 25 showed a slow dark hydrolysis rate under these
condition with t1/2 = 192 h (pH 7.4). The two-photon
photolysis of DMAQ acetates 10, 14, 21 and 25 was then
performed by using 100 fs pulsed 730 nm laser light.
The two-photon uncaging cross section (δu) values
measured directly from the fractional conversion are col-
lected in Table 1. The irradiation did not afford detectable
As compared to 6- and 7-DMAQ acetates 14 and 10,
which absorb at 369 and 371 nm, respectively, 5- and
8-DMAQ acetates 21 and 25 are significantly blue-shifted
(by more than 20 and 30 nm, respectively). Interestingly,
when 6- and 7-DMAQ bear carboxylic ester/acid substi-
tuents in position 2 and 4, the absorption is further red-
(7) Holding potential À60 mV, Purkinje neuron in a cerebellar slice
from 20 day old rat. Experiments were in presence of 2 μM TTX, 10 μM
SR 95531, 50 μM D-AP5 and 1 μM Agatoxin IVA: Palma-Cerda, F.;
Auger, C.; Crawford, D. J.; Hodgson, A. C. C.; Reynolds, S. J.; Cowell,
J. K.; Swift, K. A. D.; Cais, O.; Vyklicky, L.; Corrie, J. E. T.; Ogden, D.
Neuropharm. 2012, 63, 624–634.
(6) 6-DMAQ acetate was prepared earlier by Liu et al. The photolysis
of this compound was not reported due to the low aqueous solubility of
14. See in: Li, Y.-M.; Shi, J.; Cai, R.; Chen, X.-Y.; Guo, Q.-X.; Liu, L.
Tetrahedron Lett. 2010, 51, 1609–1612.
6368
Org. Lett., Vol. 14, No. 24, 2012