Photochemical cleavage reaction of 8-quinolinyl sulfonates that are halogenated and nitrated at the 7-position

Article abstract of DOI:10.1248/cpb.59.1355

Photochemical bond-cleavage reactions are potentially useful in chemistry, bioorganic chemistry and medicinal chemistry. We previously reported on a photochemical cleavage reaction of 8-quinolinyl sulfonate (8-QS) derivatives in aqueous solution at neutra

Full text of DOI:10.1248/cpb.59.1355

November 2011
Regular Article
Chem. Pharm. Bull. 59(11) 1355—1362 (2011)
1355
Photochemical Cleavage Reaction of 8-Quinolinyl Sulfonates That Are
Halogenated and Nitrated at the 7-Position
a
b
b
a,b
a,c
Shinya ARIYASU, Kengo HANAYA, Megumi TSUNODA, Masanori KITAMURA, Masanori HAYASE,
Ryo ABE,
a,b,d
,a,b
and Shin AOKI*
a
b
Center for Technologies against Cancer, Tokyo University of Science; Faculty of Pharmaceutical Sciences, Tokyo
c
d
University of Science; Faculty of Science and Technology, Tokyo University of Science; and Research Institute for
Biological Science, Tokyo University of Science; 2641 Yamazaki, Noda 278–8510, Japan.
Received June 29, 2011; accepted August 15, 2011; published online August 23, 2011
Photochemical bond-cleavage reactions are potentially useful in chemistry, bioorganic chemistry and medic-
inal chemistry. We previously reported on a photochemical cleavage reaction of 8-quinolinyl sulfonate (8-QS) de-
rivatives in aqueous solution at neutral pH, which we proposed to proceed via an excited triplet state. In this re-
port, we report on the synthesis of some new photocleavable 8-QS derivatives, in which halogen atoms or a nitro
group was introduced at the 7-position, in an attempt to improve photoreactive properties and to produce a red-
shift in the irradiation wavelength. The introduction of bromine and iodine resulted in an acceleration in the
photoreaction by about 1.5 times, possibly due to a heavy atom effect. It was also found that 7-nitro-8-QS
absorbs at ꢁ360 nm, and, as a result, the S–O bond of this compound can be cleaved by photoirradiation with a
fluorescent lamp in aqueous solution and on silicon surface.
Key words photolysis; 8-quinolinol; sulfonate; nitration; halogenation
25,26)
Photochemical bond-cleavage reactions are potentially ciency and a red shift in the irradiation wavelength.
Fur-
useful in organic chemistry, biological chemistry and chemi- thermore, a mechanistic study implied that this photolysis
cal biology (e.g.; protection/deprotection in organic proceeds via homolytic cleavage of the S–O bond in the ex-
1
—4)
synthesis
and the uncaging of chemically masked or cited triplet state generated from the excited singlet state
5—14)
28)
caged biorelevant molecules).
For example, the photoly- through intersystem crossing (ISC).
15—18)
19—22)
sis of sulfonic esters,
sulfonamides,
and sul-
One of the advantages of the photoreaction of 8-QS is that
2
3,24)
16,20)
fones
tecting groups,
has been applied to photoresist materials,
pro- its photocleavage proceeds with negligible byproduct produc-
6
,17,21,22)
15,24,25)
and other chemical reactions.
tion. We recently reported on the design and synthesis of 8-
We previously reported that substituted 8-quinolinyl sul- QS-based photocleavable linkers 4 that consist (ꢀ)-biotin
fonates such as 1a, e and f undergo photochemical S–O bond and dopamine moieties at both ends of the molecules (Chart
30,31)
cleavage reactions to afford the corresponding 8-quinolinols 2).
This linker was fixed on an avidin-coated resin
(
2a, e, f) and sulfonate (3) by photoirradiation of aqueous so- through a strong avidin-biotin complex, and a dopamine moi-
26—28)
lutions at ca. 300 nm (Chart 1),
which was found during ety was introduced at the other molecular end to trap specific
2
ꢀ
a study of Zn -selective fluorescent probes having 8-quino- receptors such as an anti-dopamine antibody. Subsequently,
linol side chains.
26—29)
A comparison of the photoreactivity the 8-QS moieties were cleaved by photoirradiation at
of various 8-quinolinyl sulfonate (8-QS) derivatives sug- 313 nm, and the target complex of dopamine and the anti-
gested that the photoreaction efficiency is dependent on the dopamine antibody were isolated and identified.
nature of the substituent groups attached to the 8-quinolinol
Despite the aforementioned potential of this methodology,
moiety rather than those on the sulfonate unit. In particular, low quantum yields of photochemical S–O bond cleavage
the introduction of electron-withdrawing groups such as N,N- and the relatively short photoirradiation wavelength (300—
dialkylaminosulfonyl group contributes to an improved effi- 330 nm) may limit further applications. It is known that halo-
gen atoms such as chlorine, bromine and iodine exhibit a
heavy atom effect that facilitate ISC from the excited singlet
32)
state to the triplet state. On the other hand, the nitro group
is one of the strongest electron-withdrawing groups and fre-
quently seen in photosensitize protecting groups. For exam-
ple, the o-nitrobenzyl unit is often used as a photosensitive
33)
protecting groups in caged compounds and the nitro group
is known to induce a red-shift in the UV absorbance of the
molecules. In this paper, we report on the photochemical
properties of 8-QS derivatives having halogen atoms or a
nitro group at the 7-position that were synthesized in order to
improve the photoreactive efficiency and to produce a red
shift in the irradiation wavelength (Chart 1), as followed by
1
UV absorption spectrometry and H-NMR measurement.
The chemical modification of silicon (Si) wafers with 8-QS
derivatives, and the photoreactivity conferred by this modifi-
Chart 1. Photoreaction of 8-QS Derivatives (1a—g) in Aqueous Solution
To whom correspondence should be addressed. e-mail: shinaoki@rs.noda.tus.ac.jp
∗
© 2011 Pharmaceutical Society of Japan

1
356
Vol. 59, No. 11
Chart 2. 8-QS Based Photocleavable Linker 4
cation is also described.
Results and Discussion
Synthesis of 7-Haloganated and Nitrated 8-Quinolinyl
Sulfonates The synthesis of 7-halo-8-quinolinyl sulfonates
2
6—29)
1
a—d was carried out as shown in Chart 3.
The reac-
2
6,28,29)
tion of 5-chlorosulfonyl-8-hydroxyquinaldine (5)
with
N-tert-butoxycarbonyl (Boc)-N,Nꢂ-dimethylethylenediamine
7) gave 2a, reaction with N-chlorosuccinimide (NCS), N-
bromosuccinimide (NBS), or N-iodosuccinimide (NIS) gave
b, c, and d, respectively. 7-Haloganated 8-quinolinols 2b—
(
2
d were reacted with benzenesulfonyl chloride to yield 1b—d.
A conventional direct nitration of 2e to g (H SO , HNO )
2
4
3
was not successful (Chart 4). Therefore, a two step reaction
(
nitrosation with NaNO , HCl and oxidation with H O ) gave
2
2
2
2
1
g, which was treated with benzenesulfonyl chloride to yield
g.
Photoreaction of 7-Halo-8-quinolinyl Sulfonates The
photoreaction of 1b—d was conducted by irradiation using a
xenon (Xe) lamp at 290 nm in a 90/10 mixture of CH CN
3
and N-(2-hydroxyethyl)piperazine-Nꢂ-2-ethanesulfonic acid
Chart 3. Syntheses of 1a and 7-Halo-8-QS Derivatives 1b—d
(
HEPES) buffer (pH 7.4) and the reaction was monitored by
UV absorption spectrometer according to our previous report
26—28)
(Figs. 1, 2).
Figure 1 shows the UV absorption spectral
changes of 1c. The absorption at 290 nm of 1c was reduced
with increasing irradiation time with the isosbestic points at
267 nm and 315 nm. Similar results were obtained in the case
of 1b and d, while the photoreaction of 1b was slower than
that of 1d. As shown in Fig. 2, the half life of 1a—d were de-
termined to be 9.0 min, 55.2 min, 5.4 min and 5.6 min, re-
spectively, indicating that the photoreactivity of 1d and c is
ca. 1.5 times higher than that of 1a.
The photoreaction of 1b—d (irradiated at 290 nm) was
1
also followed by H-NMR (Figs. 3, 4). Figure 3 shows the Chart 4. Synthesis of 7-Nitro-8-QS 1g
1
change in the H-NMR spectrum of 1c upon photoirradiation
at 290 nm using a Xe lamp in a 90/10 mixture of CD CN and
3
1
D O (100 mM HEPES at pD 7.4). As shown in Fig. 3, the H
2
signals of 1c have nearly disappeared after 4 h and 1c is al-
most quantitatively converted into 2c with negligible byprod-
uct production. The time course for the photoreactions of
1
a—d are summarized in Fig. 4, indicating that the photore-
action of 7-Cl derivative 1b was slower than that of 1a and
that 1c and 1d are more reactive than 1a. These results sug-
gest that the introduction of heavy atoms such as bromine
and iodine at the 7-position of 1c and d somehow accelerates
photochemical cleavage reaction of 8-QS, possibly due to
their stronger heavy atom effect than that of chlorine in
Fig. 1. Change in UV Absorption Spectra of 50 mM 1c upon Photoirradia-
32,34)
1b.
We assume that the heavy atom effect and/or elec-
tion at 290 nm in 90/10 CH CN/10 mM HEPES (pH 7.4 with Iꢃ0.1
3
tron-withdrawing effect (inductive effect) of chlorine in 1b (NaNO )) at 25 °C
3

November 2011
1357
1
Fig. 4. Conversion of the Photoreaction Followed by H-NMR Spectra of
a (Plain Curve), 1b (Dashed Curve), 1c (Bold Curve) and 1d (Dashed Bold
1
Curve) against Irradiation Time
Fig. 2. Change in UV Absorbance of 1a (Plain Curve), 1b (Dashed
Curve), 1c (Bold Curve) and 1d (Dashed Bold Curve) against Photoirradia-
tion Time (Photoirradiation at 290 nm)
Photoirradiation was conducted at 290 nm in 90/10 CD CN/100 mM HEPES (pD 7.4
3
with Iꢃ0.1 (NaNO )) at 25 °C.
3
Fig. 5. UV Absorption Spectra of 50 mM 1e—g in 90/10 CH CN/20 mM
3
HEPES (pH 7.4 with Iꢃ0.1 (NaNO )) at 25 °C
3
Dashed, plain and bold lines indicate UV absorption spectra of 1e—g, respectively.
fonyl group (1f) induces a red-shift in the UV absorption
spectrum (plain curve in Fig. 5). Furthermore, the UV ab-
sorption spectrum of 7-nitro substrate 1g is extended to ca.
380 nm, as shown by the bold curve in Fig. 5.
Based on these observations, the photoreaction of 1g was
carried out by irradiation at 360 nm, at which the absorption
of 1e and f is very weak. Figure 6 shows the photoreaction of
1
g, as followed by UV absorption spectrometry. With in-
creasing irradiation time, the absorbance at 346 and 420 nm
is considerably increased, eventually reaching that of 2g. The
fact that isosbestic points around 298 nm and 321 nm were
observed strongly suggests that 1g was converted into 2g
with minimum byproduct production, when the photoirradia-
tion is conducted at 360 nm. For comparison, the photoreac-
1
tion of 1e (R ꢃH, dashed curve in Fig. 6b) and 1f
1
(
R ꢃSO NMe , plain curve in Fig. 6b) was very slow when
2
2
1
36)
Fig. 3. Change in H-NMR Spectra (Aromatic Region) of 1 mM 1c upon the photoirradiation was made at the same wavelength.
UV Irradiation at 290 nm in 90/10 CD CN/100 mM HEPES (pD 7.4 with
Iꢃ0.1 (NaNO )) at 25 °C
3
The photoreaction of 1g irradiated at 360 nm by a Xe lamp
was also analyzed by H-NMR in a 90/10 mixture of CD CN
and D O (100 mm HEPES at pD 7.4) at 25 °C. As shown in
1
3
3
1
Plain and hollow arrows indicate H signals of 2c and 3, respectively.
2
Fig. 7, 1g was converted into 2g after photoirradiation for
1
are compensated by its electron-donating effect (resonance 3 h. Considering the combined UV absorption and H-NMR
effect), resulting in the lower photoreactivity of 1b than 1a, c results, it can be concluded that 1g was converted into 2g
35)
and d.
with minimum byproduct production by photoirradiation at
Photoreaction of 7-Nitro-8-quinolinyl Sulfonates In 360 nm.
27,28)
our previous work,
we reported that the introduction of
Quantum Yields for Photolysis of 8-Quinolinyl Sul-
electron-withdrawing groups such as N,N-dialkylaminosul- fonate Derivatives The quantum yields (F) for the photol-

1
358
Vol. 59, No. 11
Fig. 6. (a) Change in UV Absorption Spectra of 10 mM 1g upon UV Irra-
diation at 360 nm in 90/10 CH CN/10 mM HEPES (pH 7.4 with Iꢃ0.1
3
(
NaNO )) at 25 °C
3
For comparison, UV absorption spectrum of 2g in indicated with a dashed curve.
(b) Conversion of the Photoreaction of 1e (Dashed Curve), 1f (Plain Curve),
and 1g (Bold Curve) against Irradiation Time under Xe Lamp at 360 nm
ysis of 8-QS derivatives were estimated by following changes
in their UV absorption spectra (Table 1). The F values of 1c
1
Fig. 7. Change in H-NMR Spectra (Aromatic Region) of 1 mM 1g upon
ꢅ4
ꢅ4
(
2.7ꢄ10 ) and 1d (3.2ꢄ10 ) were greater than that of 1a UV Irradiation at 360 nm in 90/10 CD CN/100 mM HEPES (pD 7.4 with
3
ꢅ4
(
1.5ꢄ10 ), suggesting that bromine and iodine at the 7-po- Iꢃ0.1 (NaNO
3
)) at 25 °C
1
Plain and hollow arrows indicate H signals of 2g and 3, respectively.
sition assist ISC, from the excited singlet state to the triplet
state due to the heavy atom effect alluded to above. The im-
provement in photoreactivity and the red shift of 1f and g can Table 1. Quantum Yields for Photolysis of 8-QS Derivatives 1a—g ([1a—
g]ꢃ10 mM in 90/10 CH CN/20 mM HEPES (pH 7.4 with Iꢃ0.1 (NaNO )) at
be attributed to the electron withdrawing effects of sulfon-
3
3
ꢅ5
25 °C)
amide or nitro groups. The smaller F value of 1g (7.6ꢄ10
at 366 nm) than those of other 8-QS derivatives allows us to
handle the solutions of 1g even in the daytime without strict
dark conditions.
Photoreaction of 7-Nitro-8-quinolinyl Sulfonate under
a Fluorescent Lamp During experiments, we noticed that
the photolysis of 1g proceeds under a fluorescent lamp in
aqueous solution, while 1g is relatively stable against light in
Irradiation wavelength
(mm)
Quantum yield for
photolysis (F)
Substrate
ꢅ4
1
a
313
313
313
313
328
330
366
1.5ꢄ10
0.9ꢄ10
2.7ꢄ10
3.2ꢄ10
2.5ꢄ10
6.9ꢄ10
ꢅ4
1b
ꢅ4
1c
ꢅ4
1d
ꢅ4
1e
3
7,38)
ꢅ4
1f
the solid state. To date, 2-nitroveratrole group,
phenacyl
ꢅ4
39)
14)
1g
7.6ꢄ10
group, substituted nitrophenyl group, and substituted
13,40)
coumarins
be removed by visible light. In our experiments, it was found
that the S–O bond of 1g was cleaved under a fluorescent known to be one of the most versatile materials for detection
have been reported as caging groups that can
41—43)
lamp (27 W) more effectively than 1e, as displayed in Fig. 8. or isolation of proteins, peptides and cells,
because it
Unexpectedly 1e and f undergo photolysis under the same can be easily fabricated to desired shapes and modified by
conditions, because emissions at shorter wavelength various silane-coupling reagents. Thus, we investigated
(
ꢆ350 nm) from the fluorescent lamp used in these experi- chemical modification of Si wafer with 1g and their photore-
ments promote the photolysis of 1e and f. action in order to evaluate photoreactivity of 1g on Si surface
Photolysis of 1g on Silicon Wafer Surface Our next ob- for application of photoreactive Si devices. As depicted in
ject is to develop photoreactive Si wafer devices modified Chart 5, Si wafers (150 mmꢄ150 mm) were first reacted
with photoclevable linkers for trap and isolation of target bio- with 10% 3-aminopropyltriethoxysilane (APTES)/anhydrous
molecules or cells with minimum damages. Si wafer is toluene at room temperature for 24 h and then at 100 °C for

November 2011
1359
Fig. 9. UV Absorption Spectra of the Aqueous Phase after Hydrolysis of
1
3 (Plain Curve) under Dark Condition in 50/50 CH CN/NaOH aq. Solution
3
(pH 13) at 25 °C for 6 h and Photolysis of 13 (Bold Curve) under Fluores-
cent Lamp (27 W) in 50/50 CH CN/10 mM HEPES (pH 7.4) at 25 °C for 6 h
3
3
The chemical yield of the photolysis was calculated based on the e value (8.5ꢄ10
ꢅ1
ꢅ1
M
cm ) at 425 nm of the photoproduct 2g.
24 h to obtain 10. The amino group was reacted with 4-
(chlorosulfonyl)phenylisocyanate (11) to give 12, whose sul-
fonylchloride groups was reacted with 2g to afford the 1g-
modified Si wafer 13.
The photoreaction of 13 was performed under a fluores-
cent lamp. The modified Si wafer plate 13 was placed on the
Fig. 8. Conversion of the Photoreaction of 10 mM of 1e (Dashed Curve), 1f
(
Plain Curve), and 1g (Bold Curve) in 90/10 CH CN/10 mM HEPES (pD 7.4
3
bottom of a vial containing a 50/50 mixture of CH CN and
3
with Iꢃ0.1 (NaNO )) against Irradiation Time under a Fluorescent Lamp
3
H O (10 mM HEPES at pH 7.4) and photoirradiated with a
(27 W)
2
fluorescent lamp (27 W) from nearly vertical direction
against Si wafer, so that all Si surface is exposed almost
2
equally to the light (25—30 mW/cm at Si surface). The reac-
tion was followed by UV absorption spectra of the solution
phase, to which the photoproduct 2g is released (Fig. 9). In
order to determine the total amount of 2g on 13, 13 was sub-
jected to hydrolysis using a 50/50 mixture of CH CN and
3
NaOH aq. (pH 13) and the UV absorption spectra of the
aqueous phase was obtained. As shown by the plain curve in
Fig. 9, the concentration of 2g released by alkaline hydrolysis
(13→2gꢀ14) was determined to be 0.23 mM based on the in-
crease in the absorption at 425 nm. Based on these values,
the photorelease yields of 2g from 13 (bold curve in Fig. 9)
was calculated to be 56ꢇ3% (0.13 mM) after photoirradiation
using the 27 W fluorescent lamp for 6 h at 25 °C. These re-
sults imply that the photoreaction of 1g proceeds on the Si
surface, as well, under a fluorescence lamp.
Conclusion
In this paper, we report on the design and synthesis of
photocleavable 8-QS derivatives having halogen atoms or a
nitro group at the 7-position of 8-quinolinols, in an attempt
to improve their photoreactive properties. The findings show
that the photoreaction of 1c (7-bromo-8-QS) and 1d (7-iodo-
8-QS) are accelerated in comparison to that of 1a (8-QS),
possibly due to the heavy atom effect of bromine or iodine,
which facilitates ISC. On the other hand, the introduction of
a nitro group contributed to a red shift in the absorbance of
1
g, so that it undergoes selective photoclevage reaction of its
S–O bond in aqueous solution upon photoirradiation at
360 nm. Moreover, it is demonstrated that the photolysis of
1
g undergoes in aqueous solution and on a Si wafer upon
photoirradiation by a fluorescent lamp. For the synthesis of
photoclevable linker (Chart 2), it is considered that the intro-
duction of nitro group at the 7-position of 5-aminosulfonyl-
Chart 5. Modification of Si Wafer with 2g

1
360
Vol. 59, No. 11
8
-QS would be easier than the discrimination of two duced pressure to give the crude product as a yellow amorphous solid 2b
(
91.4 mg, 71.4% yield), which was used without further purification in the
aminosulfonyl groups of 5,7-bis(aminosulfonyl)-8-QS. These
photochemical properties of 1g may be useful for the isola-
tion of UV-sensitive biological materials such as proteins,
oligo nucleotides and cells.
synthesis of 1b.
1
H-NMR (CDCl ) d: 1.43 (9H, s), 2.73 (3H, s), 2.83 (6H, br), 3.26 (2H,
br), 3.38 (2H, t), 7.47 (1H, d, Jꢃ8.6 Hz), 8.08 (1H, br), 8.83 (1H, br).
Benzenesulfonyl chloride (0.05 ml, 0.39 mmol) was added dropwise to a
3
solution of 2b (73.1 mg, 0.16 mmol) and Et N (0.1 ml, 0.72 mmol), DMAP
3
Experimental
(ca. 1—2 mg) in CH Cl (2 ml) at 0 °C under an argon atmosphere. The re-
2
2
General Information Reagents and solvents were purchased at the
highest commercial quality and used without further purification. All aque-
ous solutions were prepared using deionized and distilled water. Buffer solu-
tions (HEPES, pH 7.4) were used and the ionic strengths were adjusted with
action mixture was stirred for 30 min at 0 °C and then overnight at room
temperature. The reaction mixture was poured into water and the solution
was extracted with CHCl . The organic layer was washed with saturated
3
K CO aq., and brine. The combined organic layer was dried over Na SO ,
2
3
2
4
NaNO . The Good’s buffer reagents (Dojindo) were commercially available:
filtered, and concentrated under reduced pressure. The resulting residue was
3
HEPES (N-(2-hydroxyethyl)piperazine-Nꢂ-2-ethanesulfonic acid, pK ꢃ7.5). purified by silica gel column chromatography (hexane/AcOEt), to give 1b
a
Melting points were obtained on a Büchi 510 Melting Point Apparatus and
are uncorrected. UV absorption spectra were recorded on a Hitachi U-3500
spectrophotometer and JASCO UV–VIS spectrophotometer V-550, and fluo-
rescence (excitation and emission) spectra were recorded on a JASCO FP-
(87.3 mg, 65% yield for 2 steps) as a colorless solid.
IR (neat) cm : 3009, 2978, 2932, 1687, 1606, 1492, 1451, 1367, 1337,
1156, 1143, 1073, 955, 894, 809, 750, 725, 713, 684, 654, 600, 583. H-
ꢅ1
1
NMR (CDCl ) d: 1.46 (9H, s), 2.45 (3H, s), 2.88—2.95 (6H, br), 3.36 (2H,
3
6200 and FP-6500 spectrofluorometers at 25ꢇ0.1 °C. IR spectra were br), 3.43 (2H, br), 7.41 (1H, d, Jꢃ8.9 Hz), 7.60 (2H, t, Jꢃ7.9 Hz), 7.74 (1H,
1
3
recorded on Perkin-Elmer Fourier transform (FT)-IR spectrophotometer at t, Jꢃ7.5 Hz), 8.11 (3H, m), 8.86 (1H, br). C-NMR (CDCl ) d: 24.89,
3
1
13
room temperature. H- (300 MHz) and C- (75 MHz) NMR spectra were 28.34, 29.52, 34.88, 46.37, 47.05, 47.34, 122.65, 124.03, 127.88, 128.58,
recorded on a JEOL Always 300 spectrometer. Tetramethylsilane was used
128.77, 129.64, 131.34, 133.19, 134.04, 137.82, 142.69, 146.09, 155.19,
1
13
ꢀ
as an internal reference for H- and C-NMR measurements in CDCl . 3- 161.26. HR-ESI-MS m/z: 584.12865 (Calcd for C H ClN O S [MꢀH] :
3
25 31
3
7 2
(
Trimethylsilyl)propionic-2,2,3,3-d acid (TSP) sodium salt was used as an
584.12860).
4
1
13
external reference for H- and C-NMR measurements in D O. The pD val-
5-N-Boc-N,Nꢀ-dimethylethylenediaminosulfonyl-8-benzenesulfonyl-
oxy-7-bromoquinaldine (1c) 5-N-Boc-N,Nꢂ-dimethylethylenediamino-
sulfonyl-7-bromo-8-hydroxyquinaldine (2c) was prepared as a yellow amor-
phous solid (139.2 mg, 95% yield) from 2a (123.9 mg, 0.30 mmol) and NBS
2
ues in D O were corrected for a deuterium isotope effect using pDꢃ(pH-
2
meter reading)ꢀ0.40. MS measurements were performed on a JEOL JMS-
SX-102A and Agilent (Varian) 910-MS. Elemental analyses were performed
on a Perkin-Elmer CHN 2400 analyzer. Thin-layer (TLC) and silica gel col-
umn chromatographies were performed using a Merck Silica gel 60 F254
TLC plate and Fuji Silysia Chemical FL-100D, respectively.
(53.4 mg, 0.30 mmol) in a manner similar to that described for 2b.
1
H-NMR (CDCl ) d: 1.43 (9H, s), 2.77 (3H, s), 2.84 (6H, br), 3.29 (2H,
3
t), 3.40 (2H, t), 7.97 (1H, d, Jꢃ9.2 Hz), 8.23 (1H, br), 8.86 (1H, br).
Sulfonate 1c was prepared as a colorless solid (160.3 mg, 85% yield for 2
5
-N-Boc-N,Nꢀ-dimethylethylenediaminosulfonyl-8-hydroxyquinaldine
(
2a) Triethylamine (Et N) (0.8 ml, 5.7 mmol) was added to a solution of N- steps) from 2c and benzenesulfonyl chloride in a manner similar to that de-
3
44)
Boc-N,Nꢂ-dimethyl-ethylenediamine 7 in CH Cl (14 ml) at 0 °C under an scribed for 1b.
argon (Ar) atmosphere, to which sulfonyl chloride 5
2
2
2
7,29,45,46)
ꢅ1
(490 mg,
IR (neat) cm : 3008, 2977, 2931, 1690, 1606, 1586, 1491, 1451, 1367,
1
.90 mmol) was added in small portion over 1 h. The reaction mixture was
1337, 1146, 1141, 1073, 955, 895, 796, 746, 726, 714, 686, 650, 608, 584.
1
stirred for 30 min at 0 °C and overnight at room temperature. The solvent
was removed under reduced pressure and the remaining residue was purified
by silica gel column chromatography (hexane/ethyl acetate (AcOEt)) to
H-NMR (CDCl ) d: 1.45 (9H, s), 2.42 (3H, s), 2.87—2.94 (6H, br), 3.35
3
(2H, br), 3.43 (2H, br), 7.39 (1H, d, Jꢃ8.8 Hz), 7.60 (2H, t, Jꢃ7.7 Hz), 7.73
13
(1H, t, Jꢃ7.4 Hz), 8.08 (2H, d, Jꢃ7.3 Hz), 8.22 (1H, br), 8.81 (1H, br). C-
ꢅ1
yield 2a as a yellow amorphous solid (610.2 mg, 78% yield). IR (neat) cm
:
NMR (CDCl ) d: 24.89, 28.31, 29.63, 34.86, 46.41, 47.09, 47.30, 123.12,
3
3
9
2
008, 2977, 2931, 1686, 1600, 1567, 1503, 1394, 1366, 1324, 1140, 1117, 124.16, 126.90, 128.58, 128.80, 129.65, 133.38, 134.00, 135.20, 138.15,
60, 879, 835, 749, 713, 666, 559, 532. H-NMR (CDCl ) d: 1.42 (9H, s),
.76 (3H, s), 2.83 (6H, br), 3.25 (2H, t), 3.37 (2H, t), 7.13 (1H, d, C H BrN O S [MꢀH] : 628.0787).
1
142.66, 148.11, 155.76, 161.20. HR-FAB-MS m/z: 628.0790 (Calcd for
3
ꢀ
2
5
31
3
7 2
1
3
Jꢃ8.3 Hz), 7.47 (1H, d, Jꢃ8.8 Hz), 8.06 (1H, br), 8.87 (1H, br). C-NMR
CDCl ) d: 24.61, 28.25, 28.32, 34.61, 46.39, 46.91, 47.04, 107.89, 123.17,
5-N-Boc-N,Nꢀ-dimethylethylenediaminosulfonyl-8-benzenesulfon-
(
yloxy-7-iodequinaldine (1d) 5-N-Boc-N,Nꢂ-dimethylethylenediaminosul-
fonyl-7-iode-8-hydroxyquinaldine (2d) was prepared as a yellow amorphous
solid (152.6 mg, 95% yield) from 2a (123.9 mg, 0.30 mmol) and NIS
3
1
24.28, 131.23, 131.42, 134.12, 137.48, 155.67, 156.19, 157.87. HR-FAB-
ꢀ
MS m/z: 410.1750 (Calcd for C H N O S [MꢀH] : 410.1750).
1
9
28
3
5
5
-N-Boc-N,Nꢀ-dimethylethylenediaminosulfonyl-8-benzenesulfon-
yloxyquinaldine (1a) Benzenesulfonyl chloride (0.1 ml, 0.78 mmol) was
(67.5 mg, 0.30 mmol) in a manner similar to that described for 2b.
1
H-NMR (CDCl ) d: 1.43 (9H, s), 2.77 (3H, s), 2.85 (6H, br), 3.28 (2H,
3
added dropwise to a solution of 2a (131.0 mg, 0.32 mmol) and Et N (0.2 ml, t), 3.40 (2H, t), 7.50 (1H, d, Jꢃ9.2 Hz), 8.37 (1H, br), 8.85 (1H, br).
3
1
.44 mmol), 4-dimethylaminopyridine (DMAP) (ca. 1—2 mg) in CH Cl
Sulfonate 1d was prepared as a colorless solid (172.3 mg, 84% yield for 2
steps) from 2d and benzenesulfonyl chloride in a manner similar to that de-
scribed for 1b.
2
2
(4 ml) at 0 °C under an argon atmosphere. The reaction mixture was stirred
for 30 min at 0 °C and then 30 min at room temperature. The reaction mix-
ture was evaporated and was extracted with AcOEt. The combined organic
layer was dried over Na SO , filtered, and concentrated under reduced pres-
sure. The resulting residue was purified by silica gel column chromatogra-
phy (hexane/AcOEt), to give 1a (130.3 mg, 74% yield) as a colorless amor-
ꢅ1
IR(neat) cm : 3008, 2976, 2928, 1687, 1606, 1580, 1488, 1450, 1367,
1336, 1153, 1139, 1069, 954, 896, 794, 751, 734, 685, 646, 628, 603, 583.
2
4
1
H-NMR (CDCl ) d: 1.45 (9H, s), 2.39 (3H, s), 2.87—2.94 (6H, br), 3.34
3
(2H, br), 3.43 (2H, br), 7.41 (1H, d, Jꢃ8.8 Hz), 7.60 (2H, t, Jꢃ7.7 Hz), 7.73
(1H, t, Jꢃ7.4 Hz), 8.09 (2H, d, Jꢃ7.1 Hz), 8.40 (1H, br), 8.81 (1H, br). C-
13
phous solid.
ꢅ1
IR (neat) cm : 2977, 2931, 1690, 1601, 1498, 1451, 1367, 1332, 1188, NMR (CDCl ) d: 24.90, 28.37, 29.68, 35.01, 46.47, 47.18, 47.34, 123.85,
3
1
1
146, 1060, 951, 854, 797, 755, 717, 686, 648, 623, 590. H-NMR (CDCl ) 124.36, 128.61, 128.86, 128.92, 133.39, 133.97, 137.21, 137.53, 138.72,
3
d: 1.44 (9H, s), 2.54 (3H, s), 2.85—2.91 (6H, br), 3.33 (2H, br), 3.41 (2H, 141.99, 152.09, 155.78, 160.92. HR-FAB-MS m/z: 676.06426 (Calcd for
ꢀ
br), 7.37 (1H, d, Jꢃ9.0 Hz), 7.49 (2H, t, Jꢃ9.0 Hz), 7.62 (1H, t, Jꢃ7.3 Hz), C H BrN O S [MꢀH] : 676.06382).
2
5
31
3
7 2
1
3
7
2
1
1
.72 (1H, d, Jꢃ8.0 Hz), 8.01 (3H, m), 8.84 (1H, br). C-NMR (CDCl ) d:
5-N,N-Dimethylaminosulfonyl-8-hydroxy-7-nitroquinaldine (2g) To
3
4.33, 28.23, 34.51, 34.83, 46.34, 46.97, 47.19, 121.16, 124.13, 124.22, a cooled (0 °C) mixture of 5-N,N-dimethylaminosulfonyl-8-hydroxy-quinal-
2
6,32)
27.74, 127.94, 128.66, 133.11, 134.07, 135.96, 141.24, 148.43, 155.08, dine (2e)
55.63, 160.38. HR-FAB-MS m/z: 550.1684 (Calcd for C H N O S
(131.8 mg, 0.50 mmol) in 1 ml of conc. HCl was added NaNO2
(114 mg, 1.65 mmol) in 5 ml of water over a 10 min period. The reaction
mixture was stirred overnight at room temperature. The reaction mixture
was filtered and washed with excess cold water to give a yellow solid, the
2
5
32
3
7 2
ꢀ
[MꢀH] : 550.1682).
5
-N-Boc-N,Nꢀ-dimethylethylenediaminosulfonyl-8-benzenesulfon-
yloxy-7-chloroquinaldine (1b) To a stirred solution of 2a (119.8 mg, product which was dried under vacuum to give a yellow solid. The solid was
0
.29 mmol) in CH CN (1.5 ml) at 0 °C, a solution of NCS (41.4 mg,
suspended in an aqueous solution of 30% (w/v) H O for 12 h. The reaction
3
2 2
0
.30 mmol) in CH CN (5 ml) was added dropwise. The reaction mixture was
mixture was then extracted with CHCl . The combined organic layer was
3
3
allowed to warm to room temperature. After 3 h, the solution was dissolved
in AcOEt, and then washed with water, and brine. After drying the organic
dried over Na SO , filtered, and concentrated under reduced pressure to give
2
4
2g (122.4 mg, 84%) as a yellow solid: mp ꢁ250 °C.
ꢅ1
layer over Na SO4 and filtration, the solution was concentrated under re-
IR (neat) cm : 2938, 1596, 1585, 1521, 1356, 1313, 1272, 1213, 1173,
2

November 2011
1361
1
136, 1113, 1048, 963, 940, 870, 854, 769, 727, 719, 665, 576, 554, 516. Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
1
H-NMR (CDCl ) d: 2.82 (3H, s), 2.86 (6H, s), 7.66 (1H, d, Jꢃ8.8 Hz), 8.76
Japan (No. 23790023 for S. Ariyasu and No. 18390009, 19659026, and
3
1
3
(
1H, s), 8.99 (1H, d, Jꢃ8.8 Hz). C-NMR (CDCl ) d: 23.75, 37.02, 126.98, 22659005 for S. Aoki) and the “Academic Frontier” project for Private
3
1
27.18, 127.90, 130.76, 131.21, 135.50, 139.21, 140.33, 155.41. HR-FAB- Universities: matching fund subsidy from MEXT 2009—2013.
ꢀ
MS m/z: 296.0704 (Calcd for C H N O S [MꢀH] : 296.0705).
1
2
13
3
4
8
-Benzenesulfonyloxy-5-N,N-dimethylaminosulfonyl-7-nitroquinal-
References and Notes
dine (1g) A solution of benzenesulfonyl chloride (0.1 ml, 0.78 mmol) was
1) Turro N. J., “Modern Molecular Photochemistry,” University Science
Books, Sausalito, CA, 1991.
added dropwise to a solution of 2g (120.0 mg, 0.41 mmol) and Et N (0.1 ml,
3
0
.72 mmol), DMAP (ca. 1—2 mg) in CH Cl (2 ml) at 0 °C under an argon
2) Kagan J., “Organic Photochemistry: Principles and Applications,”
Academic Press, London, 1993.
3) Mattay J., Griesbeck A. G., “Photochemical Key Steps in Prganic Syn-
thesis: An Experimental Course Book,” VCH, Weinheim, 1994.
4) Wayne C. E., Wayne R. P., “Photochemistry,” Oxford University Press,
Oxford, 1996.
2
2
atmosphere. The reaction mixture was stirred for 30 min at 0 °C and then
overnight at room temperature. The reaction mixture was poured into water
and the solution was extracted with CHCl . The organic layer was washed
with saturated K CO aq., and brine. The combined organic layer was dried
over Na SO , filtered, and concentrated under reduced pressure. The remain-
3
2
3
2
4
ing residue was purified by silica gel column chromatography (hexane/
AcOEt), to give 1g (50.2 mg, 23% yield) as a colorless solid: mp 172.0—
5) “Methods in Enzymology,” ed. by Marriott G., Caged Compounds,
Vol. 291, Academic Press, New York, 1998.
1
74.5 °C.
6) McCray J. A., Trentham D. R., Annu. Rev. Biophys. Biophys. Chem.,
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ꢅ1
IR (neat) cm : 3097, 2975, 1595, 1569, 1537, 1452, 1383, 1347, 1213,
186, 1148, 1078, 955, 856, 834, 790, 757, 727, 702, 685, 640, 598, 583.
H-NMR (CDCl ) d: 2.51 (3H, s), 2.92 (6H, s), 7.51 (1H, d, Jꢃ8.8 Hz), 7.57
2H, t, Jꢃ7.7 Hz), 7.73 (1H, t, Jꢃ7.3 Hz), 7.99 (2H, d, Jꢃ7.3 Hz), 8.52 (1H,
1
1
3
(
1
3
s), 8.97 (1H, d, Jꢃ8.8 Hz). C-NMR (CDCl ) d: 25.09, 37.53, 122.89, 10) Shigeri Y., Tatsu Y., Yumoto N., Pharmacol. Ther., 91, 85—92 (2001).
26.16, 126.44, 128.63, 129.03, 133.29, 133.46, 134.50, 136.78, 140.99, 11) Bochet C. G., J. Chem. Soc., Perkin Trans. 1, 2002, 125—142 (2002).
3
1
1
42.20, 142.39, 162.57. HR-FAB-MS m/z: 451.0512 (Calcd for
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1935 (1978).
ꢀ
C H N O S [MꢀH] : 451.0508).
18
17
3
7 2
Modification of Si Wafer with 1g The modification of a Si wafer with
g was carried out as shown in Chart 5. The Si wafer (150 mmꢄ150 mm)
13) Shembekar V. R., Chen Y., Carpenter B. K., Hess G. P., Biochemistry,
44, 7107—7114 (2005).
1
cleaned by pretreatment with a piranha solution was reacted with 10%
APTES in anhydrous toluene at room temperature for 24 h to give 10. After
modification, 10 was sonicated with toluene and dried by a stream of Ar gas.
Then the 10 was incubated at 100 °C for 24 h to cure the APTES and the 10
14) Banerjee A., Grewer C., Ramakrishnan L., Jäger J., Gamerio A.,
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47)
was then sonicated with distilled water and dried under a stream of Ar gas.
Next, 10 was reacted with 5 mg/ml anhydrous CH CN solutions containing
3
4
1
-(chlorosulfonyl)phenylisocyanate (11) at room temperature for 6 h to give
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2. After the modification step, 12 was sonicated with anhydrous CH CN
3
solution and dried under a stream of Ar gas. Finally, 12 was treated with 17) Binkley R. W., Koholic D. J., J. Org. Chem., 54, 3577—3581 (1989).
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1
3
3
portion of DMAP to give 13. 13 was sonicated with anhydrous CH CN and
dried under a stream of Ar gas.
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3
Photoreactions of 1 in Aqueous Solution Followed by UV Absorption
Spectrometry In a typical experiment, a 10 mM or 50 mM solution of sub-
strate in a 9 : 1 mixture of CH CN and H O (10 mM HEPES at pH 7.4) was
3
2
irradiated with a 150 W Xe lamp equipped in a spectrofluorometer (JASCO 21) Hamada T., Nishida A., Yonemitsu O., J. Am. Chem. Soc., 108, 140—
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Photoreaction of 13 (on the Silicon Surface) Followed by UV Absorp-
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3
2
HEPES at pH 7.4) and photoirradiated with a fluorescent lamp (27 W) from
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2
UV light meter (UV-340 (CUSTOM Ltd.))). The reaction was followed by
UV absorption spectra of the solution phase, to which the photoproduct 2g
is released.
3933—3940 (2004).
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1
Photoreactions of 1 Followed by H-NMR In a typical experiment, a
1
mM solution of substrate in a 9 : 1 mixture of CD CN and D O (100 mM
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3
2
HEPES at pD 7.4) was irradiated with a 150 W Xe lamp equipped in a spec-
trofluorometer (JASCO FP-6500 with band-width 20 nm). The photoreaction
was follwed by H-NMR .
Determination of Quantum Yields of Photolysis Quantum yields for
the photocleavage of 1c were determined as follows: 10 mM solution of a
given substrate in CH CN and HEPES buffered water (20 mM, pH 7.4) (9 : 1)
1
3
was placed into a 1ꢄ1 cm quartz cell, and irradiated with a 150 W Xe lamp
in a spectrofluorometer (JASCO FP-6500 with a band-width of 5 nm). The
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i
trometry. The quantum yield was calculated using the equation Fꢃ
ꢅabs
v ꢄV/{I ꢄ(1ꢅ10 )}, where V is the volume of the reaction solution, I is
i
0
0
ꢅ6
the number of photon per second (2.83ꢄ10 mol/s at 313 nm, 3.59ꢄ
ꢅ6
ꢅ6
ꢅ6
1
0
mol/s at 328 nm, 3.67ꢄ10 mol/s at 330 nm, 6.48ꢄ10 mol/s at
366 nm), and abs is the initial absorbance (cell lengthꢃ1 cm) of 2c (0.06043
at 313 nm [2c]ꢃ10 mM). The I value was determined by means of ferrox-
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0
48)
alate actinometry.
35) DFT calculations (B3LYP/6-31ꢀG(d)) (ref. 28) of 1a—d implied that
Acknowledgements This study was supported by Grant-in-Aid from the
their shape and energy levels of their lowest unoccupied molecular

1
362
Vol. 59, No. 11
orbitals (LUMOs) are almost identical.
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3
6) The pKa values of 8-OH group of 2e—g, which are photoproducts
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this work). It is likely that the photolysis of 1g by irradiation at 360 nm
depends on its absorption at this wavelength rather than pK values of
these products.
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4