Effect of addition of trifluoroacetic acid on the photophysical properties and photoreactions of aromatic imides

Article abstract of DOI:10.1016/j.tet.2010.09.022

The UV and IR spectra of N-methyl-1,8-naphthalimide in benzene showed a two-step consecutive complexation (hydrogen bond formation) with trifluoroacetic acid (TFA). The equilibrium constant K₁ for the first complexation in benzene was determined from the UV spectrum to be 48 M^-1. The fluorescence intensities of the imide in benzene were found to be remarkably enhanced by the addition of TFA. Furthermore, photochemical cyclobutane formation of the imide with styrene in benzene was enhanced by the addition of TFA. Enhancement of the fluorescence intensity and the photoreaction of the imide by complexation with TFA was explained by a decrease of the efficiency of the intersystem crossing from ¹(ππ^*) to ³(nπ^*), that results from an increase in the energy of the ³(nπ^*) level due to the complexation.

Full text of DOI:10.1016/j.tet.2010.09.022

Tetrahedron 66 (2010) 9291e9296
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Effect of addition of trifluoroacetic acid on the photophysical properties
and photoreactions of aromatic imides
*
Kazuhiko Matsubayashi, Hideo Shiratori, Yasuo Kubo
Department of Materials Science, Faculty of Science and Engineering, Shimane University, 1060 Nishikawatsu, Matsue, Shimane 690-8504, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 May 2010
Received in revised form 5 September 2010
Accepted 7 September 2010
Available online 21 September 2010
The UV and IR spectra of N-methyl-1,8-naphthalimide in benzene showed a two-step consecutive
complexation (hydrogen bond formation) with trifluoroacetic acid (TFA). The equilibrium constant K1 for
the first complexation in benzene was determined from the UV spectrum to be 48 Mꢀ1. The fluorescence
intensities of the imide in benzene were found to be remarkably enhanced by the addition of TFA.
Furthermore, photochemical cyclobutane formation of the imide with styrene in benzene was enhanced
by the addition of TFA. Enhancement of the fluorescence intensity and the photoreaction of the imide by
Keywords:
complexation with TFA was explained by a decrease of the efficiency of the intersystem crossing from
Photochemistry
Aromatic imides
Hydrogen bonding
Fluorescence
1
(
pp p p ) level due to the complexation.
) to 3(n ), that results from an increase in the energy of the 3(n
* * *
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
that the fluorescence intensity and photoreactivity of N-methyl-
1,8-naphthalimide (2) are remarkably increased by intermolecular
hydrogen bonding with 2,2,2-trifluoroethanol (TFE), possibly
Naphthalimides are known to be promising anticancer agents,
showing broad-spectrum activity against a variety of human solid
tumor cells.1 Some naphthalimides have reached the phase of
clinical trials.2 Their DNA binding or enzyme inhibitory activity is
believed to be pivotal in exerting antitumor effects. 1,8-Naph-
thalimide derivatives with intramolecular dialkylammonium moi-
eties exhibit much stronger association to oligodeoxynucleotides
than the corresponding neutral molecules due to electrostatic in-
teractions with the phosphate groups.3
through a decrease in the efficiency of intersystem crossing from
1
(pp
*
) to 3(n
p
*
), because the energy of the 3(n
*
p ) level increases as
a result of the hydrogen bonding.14 In this paper, we report the
effect of the addition of trifluoroacetic acid (TFA) on the photo-
physical properties and photoreactions of aromatic imide com-
pounds in expectation of a more pronounced effect than that which
arose from hydrogen bond formation with TFE.
Photoinduced processes of naphthalimides are also of particular
interest because of their broad-ranging applications in fundamen-
tal studies and advanced technology as well as in biological and
medical areas. Naphthalimides are capable of initiating the pho-
tocleavage of DNA4 and photochemical crosslinking of proteins.5
Additionally, investigations on the photophysical behavior of
naphthalimides have contributed to the development of new
fluorescent probes6 and optical sensors.7 Dual fluorescence has
been reported for several substituted N-phenylnaphthalimides8
and the relative intensity of the two fluorescence bands has
been shown to be sensitive to solvent polarity, temperature,9
viscosity,10 and pressure.11 Some substituted N-phenyl-1,8-naph-
thalimides have been reported to show remarkable sensitivity and
selectivity for saccharides.12
2. Results and discussion
Five aromatic imide compounds, N-methylphthalimide (1),
N-methyl-1,8-, -2,3-, and -1,2-naphthalimides (2e4), and N-
methyl-9,10-phenanthrenedicarboximide (5), were chosen in this
investigation, because of differing energies of their pp
excited states (Scheme 1). The lowest singlet excited state of
phthalimide 1 has been reported to be an n
state.15 On the other
hand, the lowest singlet excited states of naphthalimides 2e4
and phenanthrenedicarboximide 5 have been reported to be pp
states, though the energy of the singlet states vary, namely,
80.6 kcal molꢀ1 for 2, 79.4 kcal molꢀ1 for 3, 72.7 kcal molꢀ1 for 4,
and 68.6 kcal molꢀ1 for 5.15 The second excited singlet states of
naphthalimides 2e4 and phenanthrenedicarboximide 5 may have
*
and n
p
*
p
*
*
The photoreactions of naphthalimides have been investigated
for the past decade in our laboratory.13 We have recently shown
np
*
characters with similar energies, since the n
localized mainly on the carbonyl group.
Since hydrogen bond formation has been known to affect the
energy levels of n states compared to those of pp states,
p
*
excitation is
* Corresponding author. Tel.: þ81 852 32 6422; fax: þ81 852 32 6429; e-mail
address: kubo@riko.shimane-u.ac.jp (Y. Kubo).
p
*
*
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.022

9292
K. Matsubayashi et al. / Tetrahedron 66 (2010) 9291e9296
ππ*
nπ*
S2
S1
nπ*
ππ*
nπ*
ππ*
nπ*
ππ*
(Es = 72.7
kcal / mol)
nπ*
ππ*
S2
S1
S2
S1
S2
S1
S2
S1
(Es = 80.6
kcal / mol)
(Es = 79.4
kcal / mol)
(Es = 68.6
kcal / mol)
S0
S0
S0
S0
S0
Me
N
Me
N
O
O
O
O
O
O
O
N Me
N Me
N Me
O
O
O
1
2
3
4
5
Scheme 1.
hydrogen bond formation is predicted to have a different effect on
the photophysical properties and photoreactions of aromatic im-
ides 1e5. Thus, we examined the photophysical properties and the
photoreactions of 1e5 in the presence of TFA in expectation of
a more pronounced effect. Indeed, we found that the photophysical
consecutive complexation (hydrogen bond formation) of 2 and TFA
shown in Eqs. 1 and 2, while there is no evidence for the stepwise
complexation of 2 and alcohols in the UV spectra.14 In the low con-
centration range (0e30 mM) of TFA, an isosbestic point is observed
around 336 nm. On the other hand, in the high concentration range
(30e150mM)ofTFA, thereisanotherisosbesticpointaround339nm.
In the low concentration range of TFA, the presence of the iso-
sbestic point suggests that the first complexation step shown in
Eq. 1 is dominant and the equilibrium constant K1 for the first
complexation in benzene is determined to be 48 Mꢀ1 from a linear
BenesieHildebrand plot using the absorbance at 360 nm (Fig. 2 and
Eq. 3).
properties and the photoreactions of 2, in which the pp
*
and n
p
*
levels were close together in energy, were remarkably affected by
hydrogen bond formation with TFA.
2.1. UV spectra
To clarify the effect of the addition of TFA in the ground state, UV
spectra of 2 in the absence and presence of various concentrations of
TFA were measured in benzene (Fig. 1). Fig. 1 shows a two-step
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
0
10
20
30
40
[TFA]-1 / L mol-1
Fig. 2. BenesieHildebrand plot for the protonation of 2 by TFA in benzene.
Me
N
Me
N
O
O
O
O
HOCOCF3
K1
(1)
+
CF3CO2H
HOCOCF3
2
6
Me
O
N
O
K2
+
CF3CO2H
6
Me
CF3CO 2H
O
N
O
HOCOCF3
(2)
Fig. 1. Absorption spectra of 2 (0.075 mM) with various concentrations of TFA in
benzene.
7

K. Matsubayashi et al. / Tetrahedron 66 (2010) 9291e9296
9293
½Imꢁl=Abs þ 1=K1eð1=½TFAꢁÞ þ 1=
e
(3)
Here, [Im] and [TFA] are the concentrations of imide 2 and TFA,
respectively, l is optical path length, is molar extinction co-
e
efficient of the 1:1 complex 6, and K1 is the equilibrium constant
for the first complexation. The value of K1 is considerably larger
compared to that of 1.5 Mꢀ1 for the corresponding complexation
of 2 and TFE.14
Similar spectral changes were observed in dichloromethane. In
nonpolar hexane, well-defined spectral changes for the two-step
consecutive complexation were observed (Fig. 3). A new absorption
maximum appeared around 355 nm in the low concentration range
(0e6 mM) of TFA and a new absorption around 362 nm developed
in the high concentration range (30e150 mM). On the other hand,
no clear evidence for the complexation was observed in polar
acetonitrile (Fig. 4).
Fig. 4. Absorption spectra of 2 (0.075 mM) with various concentrations of TFA in
acetonitrile.
2.2. IR spectra
IR spectra of 2 in the absence and presence of various concen-
trations of TFA were measured in benzene (Fig. 5). Fig. 5 shows the
decrease of the intensity of the 1669 cmꢀ1 band attributed to
n C]O
of 2 and the simultaneous increase of new 1642 and 1617 cmꢀ1
bands of the complexed species of 2 by the addition of TFA. These
results indicate that the complexation with TFA occurs at the car-
bonyl group of 2.
Fig. 5. IR spectra of the n C]O region of 2 (20 mM) with various concentrations of TFA
Fig. 3. Absorption spectra of 2 (0.075 mM) with various concentrations of TFA in hexane.
in benzene.

9294
K. Matsubayashi et al. / Tetrahedron 66 (2010) 9291e9296
2.3. Fluorescence spectra
of TFA. In contrast, in benzene, the fluorescence of 2 was enhanced
in the low concentration range (0e30 mM) of TFA and then de-
creased in the high concentration range (30e150 mM) of TFA. These
results indicate that the fluorescence intensity of the doubly com-
plexed species 7 (Eq. 2) in benzene is small compared with those in
dichloromethane and hexane.
Furthermore, the effect of the addition of benzene on the fluo-
rescence of 2 in dichloromethane was examined. While the fluo-
rescence of 2 was only slightly affected by the addition of benzene
in the presence of 30 mM of TFA (Fig. 8), in the presence of 150 mM
of TFA, the fluorescence intensity of 2 was remarkably decreased by
the addition of benzene and a weak emission appeared around
500 nm (Fig. 9). These results indicate that the fluorescence in-
tensity of the doubly complexed species 7 is markedly decreased by
the addition of a small amount of benzene, possibly through the
formation of an exciplex of 7 and benzene as indicated by the weak
emission.
To clarify the effect of the addition of TFA in the excited singlet
state, fluorescence spectra of 2 in the absence and presence of
various concentrations of TFA were measured in benzene (Fig. 6).
The fluorescence intensity of 2 was enhanced in the low concen-
tration range (0e30 mM) of TFA, in which the first complexation
shown in Eq. 1 was dominant, and then markedly decreased in the
high concentration range (30e150 mM) of TFA, in which the second
complexation shown in Eq. 2 was dominant.
Fig. 8. Fluorescence spectra of 2 in the presence of 30 mM of TFA and various con-
centrations of benzene in dichloromethane.
Fig. 6. Fluorescence spectra of 2 (0.075 mM) with various concentrations of TFA in
benzene.
Fig. 7 shows the effect of the addition of TFA on the fluorescence
quantum yield Fflu of 2 in various solvents. In polar acetonitrile, the
fluorescence of 2 was little enhanced by the addition of TFA. In less
polar dichloromethane and in nonpolar hexane, the fluorescence of
2 was remarkably enhanced in the low concentration range of TFA,
and then increased more gradually in the high concentration range
Fig. 7. Fluorescence quantum yield Fflu of 2 with various concentration of TFA in
Fig. 9. Fluorescence spectra of 2 in the presence of 150 mM of TFA and various con-
various solvents.
centrations of benzene in dichloromethane.

K. Matsubayashi et al. / Tetrahedron 66 (2010) 9291e9296
9295
2.4. UV and fluorescence spectra of other aromatic imides
Me
N
Me
N
Me
N
O
O
O
O
O
O
Ph
The effect of the addition of TFA on the absorption spectra of
aromatic imides 1, 3, 4, and 5, in benzene are shown in Figs. S1, S3,
S5, and S7, respectively, in the Supplementary data. The equilibrium
constants K1 for the first complexation of 1, 3, 4, and 5 with TFA
were determined to be 21, 43, 15, and 9.6 Mꢀ1, respectively.
The effect of the addition of TFA on the fluorescence spectra of 1, 3,
4, and 5 in benzene are shown in Figs. S2, S4, S6, and S8, respectively,
in the Supplementary data. These results indicate that the fluores-
cence of 1 is enhanced by the addition of TFA in benzene, while the
fluorescence of 3e5 is little enhanced by the addition of TFA. Fig. 10
shows the effect of addition of TFA on the relative fluorescence in-
tensity of 1e5 in benzene. Moderate and remarkable enhancement
hν
+
+
Ph
Ph
2
8
9
10
hν
hν
2
+
8
2
+
8
Scheme 2.
Table 1 shows that the addition of TFA accelerates the photoreaction
of 2 and 8 in a similar way as the fluorescence quantum yield. Fig. 11
shows the effect of the concentration of TFA on the relative fluo-
rescence quantum yield and the relative reactivity. These results
show that the complexation with TFA increases both the photo-
reactivity of 2 and the fluorescence quantum yield in a similar way.
effects were observed for 1 and 2, respectively, in which the pp
*
and
np
*
levels were close together in energy. The fluorescence of 2 in the
presence of 30 mM of TFA was thus most remarkably enhanced by
a factor of more than 5 compared with that in the absence of TFA.
7
Relative Reactivity
6
5
4
Relative Fluorescence
Quantum Yield
3
2
1
0
0
50
100
150
[CF3CO2H] / mM
Fig. 11. Effect of addition of TFA on relative fluorescence quantum yield and relative
reactivity of 2 in benzene.
2.6. Mechanism to account for the effect of the complexation
Wintgens et al. have reported that the rate of the intersystem
crossing from 12
*
to 32
*
is faster than those of other naph-
thalimides 3 and 4, and the intersystem crossing of 2 accounts for
more than 90% of the deactivation processes of 12 15 This suggests
that the 1(pp ) and 3(n
) levels of 2 are close together in energy.
Fig. 10. Relative fluorescence quantum yield of 1e5 with various concentrations of TFA
in benzene.
*
.
*
p
*
2.5. Effect of complexation on the photoreaction of 2 with
styrene
As mentioned above, the fluorescence quantum yield Fflu and
photoreactivity of 2 toward 8 in benzene was remarkably enhanced
by the addition of TFA. As the 1(pp
*
) and 3(n
p
*
) levels of 2 are close
together in energy and the complexation (hydrogen bond forma-
tion) is known to increase the energy of n states compared with
those of pp states, the complexation with TFA may increase the
energy of the 3(n ) compared with that of 1(pp
), and decrease the
rate of the intersystem crossing from the 1(pp ) to the 3(n
), thus
flu and photoreactivity
To clarify the effect of the addition of TFA on the photoreactions of
aromatic imides, photoreactions of 2 and styrene (8) in benzene
were examined in the absence of TFA and in the presence of 30 mM
of TFA, and the results are shown in Table 1. In the photoreactions of
2 and 8, two regioisomers of cyclobutanes 9 and 10 were formed
p
*
*
p
*
*
*
p
*
from the reaction of 12
with 8, 9, and 10 were decomposed to
*
increasing the fluorescence quantum yield
F
starting materials 2 and 8 upon prolonged irradiation (Scheme 2).13
of the singlet excited state (Scheme 3).
Table 1
nπ*
S2
S1
Yield of adducts 9 and 10 in the photoreactions of 2 and 8 in the absence and the
nπ*
ΔE
presence of TFAa
Tn
T1
nπ*
ππ*
ΔE
S2
S1
isc
isc
nπ*
ππ*
Yieldb (%)
Tn
T1
Additive
None
Irradiation
time (min)
Conversion (%)
ππ*
9
10
ππ*
1
2
3
4
5
7
9
14
16
18
27
42
35
35
35
19
35
30
29
31
hν
hν
S0
S0
Me
N
Me
N
TFA (CF3CO2H, 30 mM)
1
2
3
4
5
13
26
34
38
45
42
30
36
38
35
12
9
9
10
9
O
O
O
O
HOCOCF3
a
Irradiation was carried out at room temperature under N2 in benzene. [2]¼
2.0 mM. [8]¼100 mM.
6
2
b
Yield was based on consumed 2.
Scheme 3.

9296
K. Matsubayashi et al. / Tetrahedron 66 (2010) 9291e9296
3. Conclusion
Supplementary data
To our knowledge, there have been few systematic in-
vestigations on the effect of the addition of TFA on the photo-
physical properties of aromatic imides, even though TFA has
frequently been used as a chemical switch of the fluorescence in-
tensity of aromatic imides with an intramolecular amino group,
which can quench the fluorescence of the imides by electron
transfer in the neutral state.16 Our results show that the com-
UV and fluorescence spectra of 1, 3, 4, and 5 in the presence of
various concentrations of TFA in benzene. Supplementary data as-
sociated with this article can be found in the online version, at
doi:10.1016/j.tet.2010.09.022. These data include MOL files and
InChIKeys of the most important compounds described in this
article.
plexation of 1 and 2 with TFA in the ground state decreases the rate
References and notes
1
of the intersystem crossing from the
(pp
*
) to the 3(n
*
p ) levels,
1. (a) Bailly, C.; Carrasco, C.; Joubert, A.; Bal, C.; Wattez, N.; Hildebrand, M.-P.; Lansiaux,
A.; Colson, P.; Houssier, C.; Cacho, M.; Ramos, A.; Brana, M. F. Biochemistry 2003, 42,
4136; (b) Brana, M. F.; Ramos, A. Curr. Med. Chem.: Anti-Cancer Agents 2001, 1, 237.
2. Malvyiya, V. K.; Liu, P. Y.; Alberts, D. S.; Surwitt, E. A.; Craig, J. B.; Hanningan, E.
V. Am. J. Clin. Oncol. 1992, 15, 41.
3. Takada, T.; Kawai, K.; Tojo, S.; Majima, T. J. Phys. Chem. B 2004, 108, 761.
4. (a) Rogers, J. E.; Rostkowski, B. A.; Kelly, L. A. Photochem. Photobiol. 2001, 74, 521;
(b) Rogers, J. E.; Weiss, S. J.; Kelly, L. A. J. Am. Chem. Soc. 2000,122, 427; (c) Aveline,
B. M.; Matsugo, S.; Redmond, R. W. J. Am. Chem. Soc. 1997, 119, 11785; (d) Saito,
I.; Takayama, M.; Sugiyama, H.; Nakatani, K. J. Am. Chem. Soc. 1995, 117, 6406;
(e) Saito, I.; Takayama, M.; Kawanishi, S. J. Am. Chem. Soc. 1995, 117, 5590.
5. (a) Zhang, J.; Woods, J.; Brown, P. B.; Lee, K. D.; Kane, R. R. Bioorg. Med. Chem.
Lett. 2002, 12, 853; (b) Brana, M. F.; Castellano, J. M.; Moran, M.; Perez de Vega,
M. J.; Qian, X. D.; Romerdahl, C. A.; Kelhauer, G. Eur. J. Med. Chem. 1995, 30, 235;
(c) Abraham, B.; Kelly, L. A. J. Phys. Chem. B 2003, 107, 12534.
whose energy is selectively increased by the complexation, and
thus increases the fluorescence quantum yield Fflu and photo-
reactivity of the singlet excited state of 2. The effect of the com-
plexation of 2 and TFA on the photophysical properties and
photoreactivity is more remarkable than those with complexation
of TFE.14 It is interesting that the simple addition of a small amount
of acid can markedly control the photophysical properties and
photoreactivity of aromatic imides widely used in numerous
applications.
6. Cosnard, F.; Wintgens, V. Tetrahedron Lett. 1998, 39, 2751.
7. Niu, C. G.; Li, Z. Z.; Zhang, X. B.; Lin, W. Q.; Shen, G. L.; Yu, R. Q. Anal. Bioanal.
Chem. 2002, 372, 519.
4. Experimental section
4.1. General
8. (a) Nandhikonda, P.; Begaye, M. P.; Cao, Z.; Heagy, M. D. Chem. Commun. 2009,
4941; (b)Paudel, S.;Nandhikonda, P.; Heagy, M. D. J. Fluoresc. 2009,19, 681; (c) Cao,
H.; Chang, V.; Hernandez, R.; Heagy, M. D. J. Org. Chem. 2005, 70, 4929;(d) Demeter,
A.; Bérces, T.; Biczók, L.; Wintgens, V.; Valat, P.; Kossanyi, J. J. Phys. Chem.1996, 100,
2001; (e) Wintgens, V.; Valat, P.; Kossanyi, J.; Demeter, A.; Biczók, L.; Berces, T. J.
Photochem. Photobiol., A 1996, 93, 109; (f) Demerter, A.; Berces, T.; Biczók, L.;
Wintgens, V.; Valat, P.; Kossanyi, J. J. Chem. Soc., Faraday Trans. 1994, 90, 2635.
9. Valat, P.; Wintgens, V.; Kossanyi, J.; Biczók, L.; Demeter, A.; Bérces, T. Helv. Chim.
Acta 2001, 84, 2813.
UV spectra were measured by use of a JASCO UVIDEC-650
spectrometer. Fluorescence spectra were obtained on a Hitachi 850
spectrophotometer. NMR spectra were recorded on a JEOL JNM-AL-
400 (400 MHz) instrument.
Fluorescence spectra were measured under aerated conditions.
Fluorescence quantum yields were determined relative to that of
N-methyl-1,8-naphthalimide (2) in MeCN (Ff¼0.027).15 The fluo-
rescence quantum yields in benzene were determined to be
0.00026, 0.014, 0.22, 0.82, and 0.48 for imides 1, 2, 3, 4, and 5,
respectively.
̃
10. Valat, P.; Wintgens, V.; Kossanyi, J.; Biczók, L.; Demeter, A.; Bérces, T. J. Am.
̃
Chem. Soc. 1992, 114, 946.
11. Bon Hoa, G. H.; Kossanyi, J.; Demeter, A.; Biczók, L.; Bérces, T. Photochem. Pho-
tobiol. Sci. 2004, 3, 473.
12. Cao, H.; McGill, T.; Heagy, M. D. J. Org. Chem. 2004, 69, 2959.
13. Kubo, Y.; Suto, M.; Tojo, S.; Araki, T. J. Chem. Soc., Perkin Trans. 1 1986, 771.
14. Matsubayashi, K.; Kubo, Y. J. Org. Chem. 2008, 73, 4915.
15. Wintgens, V.; Valat, P.; Kossanyi, J.; Biczók, L.; Demerter, A.; Bérces, T. J. Chem.
Soc., Faraday Trans. 1994, 90, 411.
The preparation, purification, and characterization of imides 1,17
2,18 3,19 4,15 and 520 have been described elsewhere. Solvents, TFA,
and styrene (8) were commercially available.
Photoreactions of 2 and 8 were carried out under N2 by using an
Eikosha EHB-W-300 high-pressure Hg-lamp through an aq CuSO4
16. Abad, S.; Kluciar, M.; Miranda, M. A.; Pischel, U. J. Org. Chem. 2005, 52, 3614.
17. Sachs, F. Chem. Ber. 1898, 31, 1228.
̃
18. Somich, C.; Mazzocchi, P. H.; Ammon, H. L. J. Org. Chem. 1987, 70, 10565.
19. Kubo, Y.; Suto, M.; Araki, T. J. Org. Chem. 1986, 51, 4404.
filter (l>320 nm).
20. Kubo, Y.; Asai, N.; Araki, T. J. Org. Chem. 1985, 50, 5484.