Design and synthesis of a new chromophore, 2-(4-nitrophenyl)benzofuran, for two-photon uncaging using near-IR light

Article abstract of DOI:10.1039/c5cc07664a

A new chromophore, 2-(4-nitrophenyl)benzofuran (NPBF), was designed for two-photon (TP) uncaging using near-IR light. The TP absorption (TPA) cross-sections of the newly designed NPBF chromophore were determined to be 18 GM at 720 nm and 54 GM at 740 nm in DMSO. The TP uncaging reaction of a caged benzoate with the NPBF chromophore quantitatively produced benzoic acid with an efficiency (δ_u) of ～5.0 GM at 740 nm. The TP fragmentation of an EGTA unit was observed with δ_u = 16 GM. This behavior makes the new chromophore a promising TP photoremovable protecting group for physiological studies.

Full text of DOI:10.1039/c5cc07664a

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Design and synthesis of
a
new chromophore, 2-(4-
nitrophenyl)benzofuran, for two-photon uncaging using near-IR
light†
Received 00th January 20xx,
Accepted 00th January 20xx
Naomitsu Komori,a Satish Jakkampudi,a,b Ryusei Motoishi,a Manabu Abe,*a,b,c Kenji Kamada,*d Ko
Furukawa,e Claudine Katan,*f Wakako Sawada, g Noriko Takahashi, g Haruo Kasai,b,g Bing Xue,b,h
and Takayoshi Kobayashib,h
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new chromophore, 2-(4-nitrophenyl)benzofuran (NPBF), was designed
for two-photon (TP) uncaging using near-IR light. The TP absorption (TPA)
cross-sections of the newly designed NPBF chromophore were determined
to be 18 GM at 720 nm and 54 GM at 740 nm in DMSO. The TP uncaging
reaction of a caged benzoate with the NPBF chromophore quantitatively
PPG
hν
uncaging
biologically active
compound
inactivated compound
( = caged compound)
caging
produced benzoic acid with an efficiency (
δu) of ~5.0 GM at 740 nm. The TP
fragmentation of a EGTA unit was observed with
δu = 16 GM. This behavior
photolabile protecting group (PPG)
makes the new chromophore a promising TP photoremovable protecting
group for physiological studies.
Fig 1. Caging and uncaging of biologically active compounds upon photolysis.
Caged compounds1 have attracted considerable interest in
physiological studies, e.g. in neuroscience, due to their many
applications.2-5 These compounds, in which biologically active
molecules are inactivated by photoremovable protecting
groups (PPGs)6, can uncage (= release) the bioactive molecules
upon photolysis (Fig. 1).4 Spatial and temporal control of the
uncaging process allows detailed investigation of the role of
bioactive molecules in vivo.
deeper penetration depth than one-photon (OP) excitation
processes.5,7 However, to work under the physiological
conditions, a high uncaging efficiency is required. This
efficiency is defined as the uncaging quantum yield (φu
multiplied by excitation probability.8 The excitation probability
can be expressed with the molar extinction coefficient ( ) for
2) for TP excitation.
φu 2) has the
)
ε
OP excitation or with TPA cross-section (
σ
From this convention, TP-efficiency (δu
=
σ
Two-photon absorption (TPA) by near-IR irradiation of light
(approximately 700-1300 nm) is increasingly used for
photolysis in biological studies because most living tissues
have low absorption and scattering in this wavelength
region.5,7 In addition, TPA enables spatial selective excitation
of the small volume near the focal point of the laser beams.
Thus two-photon (TP) excitation affords uncaging with higher
spatial resolution, less photodamage to cells and tissues, and
same unit as the TPA cross section (GM). For biological
applications, the minimum δu threshold value currently
accepted is
3
GM.9,10 This calls for development of
biocompatible caged compounds with sizeable δu to ensure
efficient release with tissue-permeable near-IR irradiation,
providing valuable targets for applications in in vivo
physiological studies.
Several PPGs with TPA character (TP-PPGs) have been
reported so far.11,12 For instance, in 2006, Ellis-Davis and co-
workers reported a nitro-dibenzofuran (NDBF) skeleton with a
planar biphenyl structure (Fig. 2). A caged calcium with the
NDBF chromophore has high ε (18,400 M-1cm-1) and φu (0.7) in
the OP excitation process,12 but a low δu (~0.6 GM) in an
aqueous buffer solution at 720 nm photolysis. Such a small δu
is not surprising, given that NDBF has a dipolar character with
an OPA maximum at 331 nm,13 that predicts the lowest energy
TPA maximum near 660 nm, far away from 720 nm.14a This
prompted us to design a new chromophore having a red-
shifted absorption band.
a.Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1
Kagamiyama, Higashi-hiroshima, Hiroshima 739-8526, Japan.
b.JST-CREST, K’s Gobancho, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.
c. Research Centre for Smart Materials, Hiroshima University, 1-3-1 Kagamiyama,
Higashi-hiroshima, Hiroshima 739-8526, Japan.
d.IFMRI, National Institute of Advanced Industrial Science and Technology (AIST), 1-
8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.
e. Centre for Instrumental Analysis, Niigata University, 8050 Ikarashi 2-no-cho, Nishi-
ku, Niigata 950-2181, Japan.
f. Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite Rennes 1,
35042 Rennes, France.
g.Laboratory of Structural Physiology, CDBIM, Graduate School of Medicine, The
University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
h.Advanced Ultrafast Laser Research Center, The University of Electro-
Communications, Chofugaoka 1-5-1,Chofu,Tokyo 182-8585, Japan.
The extension of the π-conjugation system is an efficient
way to bathochromically shift the absorption maximum and
†
Electronic Supplementary Information (ESI) available: Experimental section,
compound characterizations and computational details. See
DOI: 10.1039/x0xx00000x
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also improve the TP properties of chromophores.15 At the phenone
Journal Name
16
1
.
Next, 1-(5-(benzofuran-2-yl)-2-nitrophenyl)-
, a compound exhibiting a rigid stilbene structure,
same time, one may want to retain a simple synthetic scheme. ethane-1-ol
4
NO2
NO2
a
b
Br
Br
Br
1
2
3
O
O
OH
O
O
NO2
O
NO2
NO2
NDBF
c
d
5
4
O
O
HO
Ph
O
O
O
O
e
f
NO2
6
8
7
NO2
NO2
NO2
NPBF
O
HO
O
Ph
O
Scheme 1 Synthesis of
5 and 8. a) KNO3, H2SO4, 0 °C to RT, 2h, 68%. b) NaBH4,
MeOH, 0 °C to RT, 1 h, 95%. c) Pd(PPh3)4, K2CO3, 2-benzofuranboronic acid,
THF/water (1:1), 80 oC, 15 h, 95%. d) Benzoic acid, DCC, DMAP, CH2Cl2, RT, 16 h,
64%. e) NaBH4, CH2Cl2/MeOH (1:1), 0 oC to RT, 1 h, 76%. f) Benzoic acid, DMAP,
DCC, CH2Cl2, RT, 23 h, 56%. THF
=
tetrahydrofuran, DMAP
=
4-
dimethylaminopyridine, DCC = N,N’-dicyclohexylcarbodiimide.
was synthesized in 95% yield by reacting
3 with commercially
Fig. 2 Calculated OPA (dashed lines) and TPA (solid lines) spectra of NDBF (top
panel) and NPBF chromophores (bottom panel).
available 2-benzofuranboronic acid through a Suzuki-Miyaura
cross-coupling.20 1-(3-Nitrodibenzo[b,d] furan-2-yl)ethane-1-
In our previous study,16 a stilbene skeleton was chosen for its
inherently high TPA cross-section of 12 GM at 514 nm, in spite
of its small π-conjugated portion.17,18 To avoid cis-trans
isomerization in the excited state, the 1,2-dihydronaphthalene
cyclic structure was chosen for the TP-uncaging reaction.16
We report herein the design and synthesis of a new TP-PPG
with a 2-(4-nitrophenyl)benzofuran (NPBF) chromophore. The
dipolar character of the donor-π-acceptor skeleton with a
cyclic stilbene structure is promising to increase the TPA cross-
section (Fig. 2).14,15 For the comparison, the TP uncaging
one
synthetic method,12 and was then rapidly reduced with NaBH4
to provide the corresponding alcohol , exhibiting an NDBF
core. Finally, the benzoic acid (BA) moiety was introduced to
alcohols and to provide the caged benzoates NPBF-BA
and NDBF-BA
in 64% and 56% yields, respectively.21
6 was prepared according to a previously reported
7
4
7
5
8
The absorption spectra of 5 and 8 were measured in DMSO (Fig.
S14, ESI). The absorbance maxima of 5 and 8 are found at 364 nm (ε
= 12000 M-1cm-1) and 320 nm (ε = 9000 M-1cm-1), respectively. The
red shift and increased absorbance of 5 were found and consistent
with the theoretical predictions.
reaction of a caged benzoate
5 with NPBF is also investigated
The photolytic release of carboxylic acid22 from compounds 5
and 8 was investigated by irradiation with a Xe-lamp at 360 ± 10 nm
in DMSO-d6 (Figs. 3 and 4). The reaction was monitored using 1H
NMR (400 MHz). The NMR signals of benzoic acid in the aromatic
region are shown in Figs. 3e and 4e, with the overall time evolution
of the reaction demonstrating a quantitative uncaging, larger than
90%. The uncaging quantum yields φu were determined in DMSO
using the photochemical actinometer ferrioxalate coupled with
high-performance liquid chromatography (HPLC), which led to 0.09
and 0.21 for 5 and 8, respectively. Although the reported uncaging
quantum yield of NDBF-EGTA12 is 0.7, that of the measured NDBF-
BA species is 0.21, despite having the same core. This indicates
substituent effects on the benzyl position of the o-nitrobenzyl
under irradiation in the 700-760 nm range.
First, the OPA and TPA spectra of the parent NPBF were
computed at the TD-B3LYP/6-31G*//HF/6-31G* level of theory
and compared with those of the NDBF core (Fig. 2). This level
of theory has been shown to provide good predictions for
structure-TPA relationships.14a A detailed discussion of the
accuracy of calculated TPA cross sections can be found in the
ESI. As expected, the extended π-conjugation system of the
NPBF chromophore led to a sizable TPA cross-section of about
150 GM at longer wavelength of approximately 700 nm in gas
phase.19 On the other hand, the NDBF chromophore showed a
relatively small TPA cross-section of about 50 GM at a shorter
wavelength of about 600 nm. The NPBF calculations prompted
caging groups.4 The OP photochemical efficiency (ε360
uncaging reaction of 5 (ε360 = 12000) at 360 nm was 1080, which
x φu) of the
us to synthesize the caged benzoate
5 and investigate its TP
photochemical reactivity. To compare the TP uncaging reaction
of the NPBF chromophore with the NDBF chromophore, the
was nearly the same as the value of 1071 obtained for 8 (ε360
=
caged benzoate
The syntheses of the caged benzoates
summarized in Scheme 1. The key intermediate 1-(5-bromo-2-
nitrophenyl)ethane-1-ol was prepared using a modified
8 was also prepared.
5100).
5
and 8 are
The TPA cross-sections of the parent cores of NPBF and NDBF
were measured at 720 nm by the Z-scan method, in which the
sample was moved along the path of the laser beam and the light
intensity was measured by a detector as a function of its position on
3
method from our previous work, starting with 3-bromoaceto-
2 | J. Name., 2012, 00, 1-3
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the Z-axis.23 Values of 18 ± 3 and 6 ± 1 GM were obtained for the
The new TP-PPG, NPBF chromophore, was successfully
NPBF and NDBF cores, respectively, at 720 nm in DMSO. Detailed applied for the photochemical decomposition of ethylene
e)
d)
c)
b)
a)
hν
8.5
8.0
7.5
7.0
6.5
δ / ppm
Fig. 3 1H NMR spectra of compound
5 in DMSO-d6 (a) initially and after (b) 6, (c)
12, (d) and 24 h of irradiation at 360 nm; (e) the 1H NMR spectrum of benzoic
acid in DMSO-d6.
e)
d)
c)
b)
hν
Fig. 5 Time profile of TP uncaging of (a)
irradiation time at wavelengths of 700, 710, 720, 730, 740, 750, and 760 nm and
at a power of 700 mW.
5 and (b) 8, ln([sub]/[sub]0) versus
a)
8.5
8.0
7.5
7.0
6.5
δ / ppm
Fig. 4 1H NMR spectra of compound
8
in DMSO-d6 (a) initially and after (b) 1, (c)
4, (d) and 6 h of irradiation at 360 nm; (e) the 1H NMR spectrum of benzoic acid
in DMSO-d6
.
information for the determination of the values can be found in the
ESI.
TP photolysis of
5 and 8 was carried out in DMSO using 700,
710, 720, 730, 740, 750, and 760 nm light from a Ti:sapphire
laser (pulse width 100 fs, 80 MHz) emitting at the average of
700 mW. The consumption of
5 and 8 and the production of
benzoic acid upon photolysis were monitored by HPLC (Fig. 5).
As shown in Figure 5, the TP-uncaging rates were found to
vary depending on the excitation wavelength. The fastest rate
of
was at 700 nm (k700 = 8.0 x 10-6 s-1). The data shows the
improved performance of the NPBF structure in for the new
chromophore. The other rate constants of TP uncaging
reaction of and were measured in similar ways using the
near-IR photolyses (Fig. 5).
The rate constant of
at 720 nm was 3.1 x 10-6 s-1 (Fig. 5a),
5 ( 8
k740 = 9.4 x 10-6 s-1) was found at 740 nm while that of
5
Fig. 6 (a) TPA spectra of
relative rate constants of the corresponding uncaging reactions; (b) TP reaction
of at 740 nm, u = ~16 GM, u = 0.3.
5 (red line) and 8 (blue line), as determined by the
5
8
9
δ
φ
glycol tetraacetic acid (EGTA) derivative NPBF-EGTA 9 (Figure
6b). The EGTA unit is important for caging Ca2+.12,24 The TP-
5
about one third of the value that was observed at 740 nm.
Since the absolute value of the TPA cross-section of the NPBF
core was 18 GM at 720 nm, the corresponding value at 740 nm
can be extrapolated to be about 54 GM. This would give a δu
value of 5.0 GM (54 GM x 0.09), which is higher than the
threshold value of δu > 3 GM.9,10
induced fragmentation of the EGTA unit was observed with δu
= 16 GM (φu = 0.3) at 740 nm in benzene (Figures S17,18).
In conclusion, a new NPBF chromophore with TPA capability
was designed and synthesized. The simple increase in the π-
conjugation length and donating ability led to a bathochromic
shift and a significant increase in TP sensitivity. The OP
The TPA spectra of
5 and 8 over a wavelength range of 700-
photolysis of
with a high uncaging efficiency
Meanwhile, TP uncaging of using near-IR light quantitatively
5
showed the quantitative release of benzoic acid
760 nm were extrapolated based on the TPA cross-section
values at 720 nm of the two species (Fig. 6). The new NPBF
species clearly shows highly improved TPA in the near-IR
region when compared to the previously reported NDBF
derivatives.
ε
φu = 1080 at 360 ± 10 nm.
5
produced benzoic acid with an efficiency of 5.0 GM at 740 nm,
corresponding to a TPA cross-section of 54 GM. Furthermore,
TP photolysis of
9
was found to induce the decomposition of
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photon molecule) with the uncaging quantum yield
σ2 x u. OP uncaging efficiency, ε x u, is expressed by the
multiplication of an extinction coefficient ε in M-1cm-1 with
φu, δu =
EGTA structure. This behaviour is superior to that of the NDBF
derivatives, and makes it a promising TP-PPG, suggesting
potential applications in physiology and neuroscience.
φ
φ
uncaging quantum yield φu
.
We thank N-BARD, Hiroshima University, for NMR and MS
measurements. M.A. and K.K. gratefully acknowledge financial
support from the Grant-in-Aid for Science Research on
Innovative Areas “Stimuli-responsive Chemical Species” (No.
24109008 (MA); 25109544(KK)) from the MEXT, Japan. C.K.
acknowledges the HPC resources of CINES and of IDRIS under
the allocations 2014-[x2014080649] made by GENCI (Grand
Equipement National de Calcul Intensif).
9
Goeppert-Mayer (GM) unit: 1 GM = 10-50 cm4 s photon-1
molecule-1; named in honor of Maria Goeppert-Mayer, who
set the theoretical basis of the TPA process, see: M.
Goeppert-Mayer, Ann. Phys., 1931, 401, 273-294.
10 N. I. Kiskin, R. Chillingworth, J. A. McCray, D. Piston and D.
Ogden, Eur. Biophys. J., 2002, 30, 588-604.
11 (a) L. Donato, A. Mourot, C. M. Davenport, C. Herbivo, D.
Warther, J. Leonard, F. Bolze, J. F. Nicoud, R. H. Kramer, M.
Goeldner and A. Specht, Angew. Chem. Int. Ed., 2012, 51
,
1840-1843. (b) A. Specht, F. Bolze, L. Donato, C. Herbivo, S.
Charon, D. Warther, S. Gug, J. F. Nicoud and M. Goeldner,
Photochem. Photobiol. Sci., 2012, 11, 578-586. (c) C. Tran, T.
Gallavardin, M. Petit, R. Slimi, H. Dhimane, M. Blanchard-
Desce, F. C. Acher, D. Ogden and P. I. Dalko, Org. Lett., 2015,
17, 402-405. (d) H. J. Yin, B. C. Zhang, H. Z. Yu, L. Zhu, Y. Feng,
Notes and references
1
(a) J. Engels, E-J. Schlaeger, J. Med. Chem. 1977, 20, 907–911.
(b) H. Kaplan, B. Forbush and J. F. Hoffmann, Biochemistry,
1978, 17, 1929-1935.
2
(a) W. J. McEntee and T. H. Crook, Psychopharmacology,
1993, 111, 391-401. (b) V. Parpura, T. A. Basarsky, F. Liu, K.
M. Z. Zhu, Q. X. Guo and X. M. Meng, J. Org. Chem., 2015, 80
,
4306-4312. (e) K. A. Korzycka, P. M. Bennett, E. J. Cueto-Diaz,
G. Wicks, M. Drobizhev, M. Blanchard-Desce, A. Rebane and
Jeftinija, S. Jeftinija and P. G. Haydon, Nature, 1994, 369
744-747.
,
H. L. Anderson, Chem. Sci., 2015,
12 A. Momotake, N. Lindegger, E. Niggli, R. J. Barsotti and G. C.
R. Ellis-Davies, Nat. Methods, 2006, , 35-40.
6, 2419-2426.
3
(a) H. Mohler, Cell Tissue Res., 2006, 326, 505-516. (b) P.
Somogyi and T. Klausberger, J. Physiol., 2005, 562, 9-26. (c)
G. A. Ascoli, L. Alonso-Nanclares, S. A. Anderson, G.
Barrionuevo, R. Benavides-Piccione, A. Burkhalter, G.
Buzsaki, B. Cauli, J. DeFelipe, A. Fairen, D. Feldmeyer, G.
Fishell, Y. Fregnac, T. F. Freund, D. Gardner, E. P. Gardner, J.
H. Goldberg, M. Helmstaedter, S. Hestrin, F. Karube, Z. F.
Kisvarday, B. Lambolez, D. A. Lewis, O. Marin, H. Markram, A.
Munoz, A. Packer, C. C. H. Petersen, K. S. Rockland, J. Rossier,
B. Rudy, P. Somogyi, J. F. Staiger, G. Tamas, A. M. Thomson,
M. Toledo-Rodriguez, Y. Wang, D. C. West, R. Yuste, Nat. Rev.
3
13 The absorption maximum of NDBF was observed at 331 nm
(ε = 18945 M-1cm-1) in DMSO, see the UV-vis spectrum of
NDBF in Supporting Information (Fig. S11a, ESI).
14 (a) F. Terenziani, C. Katan, E. Badaeva, S. Tretiak and M.
Blanchard-Desce, Adv. Mater., 2008, 20, 4641-4678. (b) H.
M. Kim and B. R. Cho, Chem. Commun., 2009, 153-164. (c) S.
Gug, F. Bolze, A. Specht, C. Bourgogne, M. Goeldner and J. F.
Nicoud, Angew. Chem. Int. Ed., 2008, 47, 9525-9529.
15 G. S. He, L. S. Tan, Q. Zheng and P. N. Prasad, Chem. Rev.,
2008, 108, 1245-1330.
16 S. Boinapally, B. Huang, M. Abe, C. Katan, J. Noguchi, S.
Watanabe, H. Kasai, B. Xue and T. Kobayashi, J. Org. Chem.,
2014, 79, 7822-7830.
17 M. Albota, D. Beljonne, J. L. Bredas, J. E. Ehrlich, J. Y. Fu, A. A.
Heikal, S. E. Hess, T. Kogej, M. D. Levin, S. R. Marder, D.
McCord-Maughon, J. W. Perry, H. Rockel, M. Rumi, C.
Subramaniam, W. W. Webb, X. L. Wu and C. Xu, Science,
1998, 281, 1653-1656.
18 R. J. M. Anderson, G. R. Holtom and W. M. McClain, J. Chem.
Phys., 1979, 70, 4310-4315.
19 The absorption maximum of NPBF was observed at 371 nm
(ε = 23260 M-1cm-1) nm in DMSO, see the UV-vis spectrum of
NPBF in Supporting Information (Fig. S13b, ESI).
20 H. J. Lee, S. H. Kim, Y. R. Lee, X. Wang and W. S. Lyoo, Bull.
Korean Chem. Soc., 2010, 31, 3027-3030.
21 A. K. Singh and P. K. Khade, Tetrahedron, 2005, 61, 10007-
10012.
Neurosci., 2008, 9, 557-568.
4
5
6
(a) P. Klan, T. Solomek, C. G. Bochet, A. Blanc, R. Givens, M.
Rubina, V. Popik, A. Kostikov and J. Wirz, Chem. Rev., 2013,
113, 119-191. (b) C. G. Bochet, A. Blanc, in Handbook of
Synthetic Photochemistry, ed. A. Albini, M. Fagnoni, Wiley-
VCH, Weinheim, 2010, 417-447.
(a) C. Brieke, F. Rohrbach, A. Gottschalk, G. Mayer and A.
Heckel, Angew. Chem. Int. Ed., 2012, 51, 8446-8476. (b) G.
Bort, T. Gallavardin, D. Ogden and P. I. Dalko, Angew. Chem.
Int. Ed., 2013, 52, 4526-4537. (c) H. M. Kim, B. R. Cho, Chem.
Rev., 2015, 115, 5014-5055.
(a) J. A. Barltrop, P. Schofield, Tetrahedron Lett., 1962,
697-699. (b) D. H. R. Barton, Y. L. Chow, A. Cox, G. W. Kirby,
Tetrahedron Lett., 1962, , 1055-1057. (c) J. C. Sheehan, R.
3,
3
M. Wilson, J. Am. Chem. Soc., 1964, 86, 5277-5281. (d) J. A.
Barltrop, P. J. Plant and P. Schofield, Chem. Commun., 1966,
822-823. (e) A. Patchornik, B. Amit and R. B. Woodward, J.
Am. Chem. Soc., 1970, 92, 6333-6335.
7
(a) M. Matsuzaki, G. C. R. Ellis-Davis, T. Nemoto, Y. Miyashita,
22 Photo-release of carboxylic acid derivatives, see: (a) B. Amit,
A. Patchornik, Tetrahedron Lett., 1973, 14, 2205-2208. (b) B.
Amit, D. A. Ben-Efraim and A. Patchornik, J. Am. Chem. Soc.,
1976, 98, 843-844. (c) J. Morrison, P. Wan, J. E. T. Corrie, G.
M. Iino, H. Kasai, Nature. Neurosci. 2001,
Svoboda and R. Yasuda, Neuron, 2006, 50, 823-839. (c) G. C.
R. Ellis-Davies, Nat. Methods, 2007, , 619-628. (d) A. Specht,
F. Bolze, Z. Omran, J. F. Nicoud and M. Goeldner, HFSP J.,
2009, , 255-264. (e) M. Pawlicki, H. A. Collins, R. G. Denning
4, 1086-1092. (b) K.
4
Papageorgiou, Photochem. Photobiol. Sci., 2002,
(d) A. D. Cohen, C. Helgen, C. G. Bochet, J. P. Tpscano, Org.
Lett., 2005, , 2845-2848. (e) M. Matsuzaki, T. Hayama, H.
Kasai, G. C. Ellis-Davies, Nat. Chem. Biol., 2010, , 255-257.
1, 960-969.
3
and H. L. Anderson, Angew. Chem. Int. Ed., 2009, 48, 3244-
3266. (f) D. Warther, S. Gug, A. Specht, F. Bolze, J. F. Nicoud,
7
6
A. Mourot and M. Goeldner, Bioorg. Med. Chem., 2010, 18
7753-7758. (g) G. C. R. Ellis-Davies, ACS Chem. Neurosci.,
2011, , 185-197. (h) J. P. Olson, H. B. Kwon, K. T. Takasaki, C.
,
23 M. Sheik-Bahae, A. A. Said, T. H. Wei, D. J. Hagan and E. W.
Van Stryland, IEEE J. Quant. Electron., 1990, 26, 760-769.
24 G. C. R. Ellis-Davies, Chem. Rev., 2008, 108, 1603-1613.
2
Y. Q. Chiu, M. J. Higley, B. L. Sabatini and G. C. R. Ellis-Davies,
J. Am. Chem. Soc., 2013, 135, 5954-5957. (i) J. M. Amatrudo,
J. P. Olson, G. Lur, C. Q. Chiu, M. J. Higley and G. C. R. Ellis-
Davies, ACS Chem. Neurosci., 2014, 5, 64-70.
TP uncaging efficiency (δu) is expressed by the multiplication
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of a TPA cross-section (σu in GM, 1 GM = 10-50 cm4s per
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