Excited-state double proton transfer in 7-azaindole analogues: Observation of molecular-based tuning proton-transfer tautomerism [2]

Full text of DOI:10.1021/ja9917619

12186
J. Am. Chem. Soc. 1999, 121, 12186-12187
Excited-State Double Proton Transfer in 7-Azaindole
Analogues: Observation of Molecular-Based Tuning
Proton-Transfer Tautomerism
Pi-Tai Chou,* Ching-Yen Wei, Go-Ray Wu, and
Wen-Sin Chen
Department of Chemistry
The National Chung-Cheng UniVersity
Chia-Yi, Taiwan, R.O.C.
ReceiVed May 27, 1999
ReVised Manuscript ReceiVed August 21, 1999
Self-dimerization of 7AI has long been recognized for under-
going the excited-state double proton transfer (ESDPT) resulting
in a large Stokes shifted emission.1
a-m
Such a simple ESDPT
Figure 1. Structures of 7AI, 4ABI, 6IBP, and their methylated
derivatives.
process provides one possible mechanism for the mutation due
to a “misprint” of a specific DNA base pair.1 Further focus on
the ESDPT reaction relevant to the molecular nature of mutation
requires the study of the proton-transfer reaction in 7AI analogues
of biological importance, among which, purines possessing a
similar structural moiety are particularly crucial.
b,h
Scheme 1
Purine has been found to exist predominantly as an N(9)H
tautomeric form in the gas phase as well as isolated inert matrices,2
while there exists an equilibrium mixture of N(7)H and N(9)H
tautomers in protic solvents3 (see Figure 1). However, the
tautomeric reaction regarding the proton migration to the N(3)
position has not yet been reported. Our approach is to systemati-
cally investigate the ESDPT reaction on a molecular basis in
which a nitrogen atom is first added to the five-membered ring
of 7AI, forming 4-azabenzimidazole (4ABI). Subsequently,
4
6
-isobutylpurine (6IBP, Figure 1) was synthesized to study the
6
comparative proton-transfer tautomerism.
Significant concentration-dependent absorption spectra were
6
observed for both 4ABI and 6IBP (see Figure 2). For the case of
7
4
ABI, the 287 nm peak characterized for the monomer gradually
disappears upon increasing the concentration, accompanied by a
red shift of the overall spectrum and an appearance of a shoulder
at 292 nm. In comparison, N(9)-methyl-4-azabenzimidazole
*
To whom correspondence should be addressed.
8
(
9MABI), which is treated as a non-proton transfer model, shows
(
1) (a) Taylor, C. A.; El-Bayoumi, A. M.; Kasha, M. Proc. Natl. Acad.
concentration-independent absorption profiles (see Table 1). The
Sci. U.S.A. 1969, 65, 253. (b) Ingham, K. C.; El-Bayoumi, M. A. J. Am. Chem.
Soc. 1974, 96, 1674. (c) Fuke, K.; Yoshiuchi, H.; Kaya, K. J. Phys. Chem.
results unambiguously conclude the occurrence of self-aggregation
1
984, 88, 58402. (d) Tokumura, K.; Watanabe, Y.; Udagawa, M.; Itoh, M. J.
1/2 9
for 4ABI. A straight-line plot for C/A300 vs (1/A)
(see insert
Am. Chem. Soc. 1987, 109, 1346. (e) Chapman, C. F.; Maroncelli, M. J. Phys.
Chem. 1992, 96, 8430. (f) Chen, Y.; Gai, F.; Petrich, J. W. J. Am. Chem. Soc.
of Figure 2A) supports a dominant dimeric formation. Similar
behavior was also observed for 6IBP (see insert of Figure 2B).
1
993, 115, 10158. (g) Chou, P. T.; Wei, C. Y.; Chang, C. P.; Kuo, M. S. J.
Phys. Chem. 1995, 99, 11994. (h) Douhal, A.; Kim, S. K.; Zewail, A. H.
Nature (London) 1995, 378, 260. (i) Smirnov, A. V.; English, D. S.; Rich, R.
L.; Lane, J. Teyton, L.; Schwabacher, A. W.; Luo, S.; Thornburg, R. W.;
Petrich, J. W. J. Phys. Chem. B 1997, 101, 2758. (j) Chachisvillis, M.; Fiebig,
T.; Douhal, A.; Zewail, A. H. J. Phys. Chem. A 1998, 102, 669. (k) Chou, P.
T.; Yu, W. S.; Chen, Y. C.; Wei, C. Y.; Martinez, S. S. J. Am. Chem. Soc.
Accordingly, the association constant, K
a
, was calculated to be
3.0 × 10 and 4.2 × 10 M for 4ABI and 6IBP, respectively,
in CCl (305 K).
3
3
-1
∼
4
At sufficiently low concentrations so that only 4ABI monomer
exists, a normal Stokes-shifted emission was observed with a peak
maximized at 308 nm. Dual fluorescence was observed upon
increasing the concentration, consisting of a 308 nm emission
1
7
1
998, 120, 12927. (l) Takeuchi, S.; Tahara, T. J. Phys. Chem. A 1998, 102,
740. (m) Catalan, J.; Del Valle, J. C.; Kasha, M. Proc. Natl. Acad. Sci. U.S.A.
999, 96, 8338.
(2) (a) Lin, J.; Yu, S.; Peng, S.; Akiyama, I.; Li, K.; Lee, L. K.; LeBreton,
(
the F
emission maximum at 380 nm (the F
excitation maximum (∼292 nm) monitored at the F
red-shifted by ∼5 nm with respect to that monitored at the F
band. The results in combination with the system-response rise
1
band, τ
f
≈ 0.32 ns) followed by a large Stokes-shifted
band, τ ) 2.04 ns). The
band was
P. R. J. Am. Chem. Soc. 1980, 102, 4627. (b) Wiorkiewicz-Kuczera, J.;
Karplus, M. J. Am. Chem. Soc. 1990, 112, 5324. (c) Nowak, M. J.;
Rostkowska, H.; Lapinski, L.; Kwiatkowski, J. S.; Leszczynski, J. J. Phys.
Chem. 1994, 98, 281326.
2
f
2
(
3) (a) Pugmire, R. J.; Grant, D. M. J. Am. Chem. Soc. 1971, 93, 1880. (b)
Dryefus, M.; Dodin, G.; Bensaude, O.; Dubois, J. E. J. Am. Chem. Soc. 1975,
7, 2369. (c) Chenon, M. T.; Pugmire, R. J.; Grant, D. M.; Panzica, R. P.;
1
9
-10
time (<3 × 10
s) for both components lead us to conclude
Townsend, L. B. J. Am. Chem. Soc. 1975, 97, 4636. (d) Gonnela, N. C.;
Roberts, J. D. J. Am. Chem. Soc. 1982, 104, 3162. (e) Holmen, A.; Broo, A.;
Albinsson, B.; Norden, B. J. Am. Chem. Soc. 1997, 119, 12240.
the two emitting bands originate from two distinct ground-state
(
4) 6IBP was used due to its high solubility in nonpolar solvents and the
3
(8) 9MABI was synthesized by treating 4ABI with NaH and CH I in a
1
feasibility of synthesizing the N(3) tautomer. 6IBP was synthesized according
2
ratio of 1:2:2 in dry THF at 0 °C. H NMR(D O, 400 MHz) δ 3.87(s, 3H);
to ref 5.5 1H NMR (CDCl
m, 1H); 3.13 (d, 2H, J ) 7.2 Hz); 8.25 (s, 1H); 8.96 (s, 1H).
3
, 200 MHz) δ 1.01 (d, 6H, J ) 6.6 Hz); 2.27-2.54
7.31(m, 1H); 8.03(d, J ) 8.0 Hz, 1H); 8.23(s, 1H), 8.29(d, J ) 4.0 Hz, 1H).
(
(9) Equation 1
1
/2
1 1/2
A
(
5) Dvorakova, H.; Dvorak, D.; Holy, A. Tetrahedron Lett. 1996, 37, 1285.
C
A
1
ꢀ
1
2ꢀKa
)
+
(1)
(
6) Steady-state absorption and emission spectra were recorded by a Cary
(
) ( )
3
E (Varian) spectrophotometer and a Hitachi (SF4500) fluorimeter, respec-
1b,g,l
tively.
(
has been derived for the monomer-dimer association
where C denotes
7) Similar to the predominant N(9) form of various purines in inert
the prepared concentration, A is the absorbance of the dimer at a selective
2
matrices both 4ABI and 6IBP exist predominantly in their N(9)H forms in
nonpolar solvents.
a
wavelength, ꢀ is the molar extinction coefficient of the dimer, and K is
the association constant.
1
0.1021/ja9917619 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/14/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 51, 1999 12187
a
Table 1. Thermodynamic and Photophysical Properties of 7AI, 4ABI, 6IBP, and Their Methylated Derivatives in Cyclohexane and CCl
4
absorption (nm)
emission (nm)
Φ
f
τ
f
(ns)
K
a
(M-1)
sh
0.22c
0.016
b
c
7AI
7AI dimer
(287, 293 )
320
480
1.68 , 1.72
b d
sh
e
3 f
(292, 305 )
2.82 , 3.0
2.2 ×10
2
b,g
5
.2 × 10
(390, 458sh)
(463 ,495,510)
sh
0.0066
b
1.54, 1.67c
7
4
4
4
9
MAI
0
.0073c
ABI
(281, 287)
306b
308
0.038
0.012
0.05
0.44b
0.32
1.19
b
b
(
282, 287)
e
ABI dimer
MABI
MABI
(285, 292)
380
b,e
380b
0.06b
b
3 b
(
285, 292)
2.04
3.0 × 10
sh
sh
sh
(292, 329,368 )
(372 , 400)
0.031b
0.053
0.014
0.020b
1.80
b
sh
b
b
(
292,330,368 )
(372 , 400)
2.60
0.48
(284, 290)
305b
308
-
b
0.50b
(
284, 292)
b
6
6
3
IBP
IBP dimer
MIBP
263, 263
-
-
sh
b
3 b
(267, 275 )
(266, 275, 287 )
-
-
-
4.2 × 10
sh
sh
(290 , 310)
0.018
0.025
0.63
0.70
sh
b
sh
(268, 312, 290 )
(290 , 315)*
a
b
c
d
e
f
g
sh: shoulder. In CCl
4
. Reference 1e. Reference 1d. Obtained from the fluorescence excitation spectrum. Reference 1g. Reference 1b.
mum, lifetime, etc.) between 4MABI and the F
the occurrence of ESDPT in the 4ABI dimer. On the contrary,
although K for the 6IBP dimer determined from the absorption
2
band supports
a
spectroscopy is the greatest among the three 7AI analogues, no
emission is detectable throughout 280-600 nm. For comparison,
the N(3) methylated tautomeric form of 6IBP, N(3)-methyl-6-
isobutylpurine (3MIBP)11 exhibits an emission maximum at 325
nm with a spectral onset at ∼290 nm (see Figure 2B).
The photophysical properties shown in Table 1 reveal an
interesting correlation between the energy gap and the corre-
sponding number of nitrogen atoms in the methylated tautomers
of 7AI, 4ABI, and 6IBP, in which a significant blue shift of the
first peak on the order of N(7)-methyl-7azaindole (7MAI, 21 834
-
1
-1
-1
cm ) < 4MABI(27 200 cm ) < 3MIBP (30 770 cm ) was
observed. Thus, adding electron-rich nitrogen atoms in either a
five- or six-membered ring of 7AI alters the tautomeric form
toward an increase of the π f π* energy gap. Conversely, the
differences in 0-0 onsets among normal dimers are relatively
-
1
much smaller, being only 1460 and 3570 cm higher in energy
than that of the 7AI dimer for 4ABI and 6IBP dimeric forms,
respectively.13 Using a 6-31G(d,p) basis set with the inclusion of
1
4
solvation free energy (the PM3-SM4 method) for each species,
the formation free energy of 7AI, 4ABI, and 6IBP tautomer
dimeric forms are calculated to be 22.3, 15.6, and 16.8 kcal/mol,
respectively, relative to their corresponding normal dimers. It is
rather difficult to assign the S
0
-S (0-0) transition of the tautomer
1
dimer due to either spectral overlap (in 4ABI) or the lack of the
tautomer emission (in 6IBP). Simply, we took the absorption onset
of their corresponding methylated tautomers shown in Table 1.
Accordingly, ESDPT is calculated to be -9.0 and -4.7 kcal/
mol exergonically for 7AI and 4ABI dimers, respectively. In
contrast, a large endergonic value of 11.4 kcal/mol was obtained
for the 6IBP dimer, indicating that the ESDPT reaction is
thermally unfavorable.
Figure 2. A. The absorption (normalized at 276 nm) and emission spectra
-
5
-4
-4
of (λex ) 280 nm) 4ABI at 1. 1.5 × 10 , 2. 1.3 × 10 , 3. 2.5 × 10
,
-
4
-3
4
. 5.0 × 10 , 5. 1.2 × 10 M in CCl
4
(305 K). Insert: Plot of C/A300
1/2
values versus (1/A300
)
and a best least-squares fitting curve using eq
0 1
In conclusion, the energy gap between S′ and S′ states of the
9
1
.
To avoid spectral complexity only four curves were depicted in
tautomeric form plays an important role to determine the
molecular-based tuning ESDPT. Therefore, it is of great impor-
tance to probe the proton-transfer tautomerism as a function of
the relative excited-state thermodynamics for purine derivatives
of which the electronic properties, depending on the functional
group as well as substituted position, are altered.
absorption spectra. B. The absorption spectra (normalized at 263 nm) of
-
5
-4
-4
6
IBP at (a) 1.2 × 10 , (b) 1.0 × 10 , and (c) 3.0 × 10 M. Insert:
1/2
Plot of C/A285 values versus (1/A285
)
and a best least-squares fitting
curve. (d) The absorption and emission spectra (λex ) 270 nm) of 3MIBP.
species in which the F
bonded monomer. Consequently, the F
1
band originates from the non-hydrogen-
band can be ascribed to
2
Acknowledgment. This work was supported by National Science
Council, Taiwan CNS (87-2119-M-194-002).
the N(4)H tautomer emission resulting from ESDPT. To further
verify this viewpoint N(4)-methyl-4azabenzaimidazole (4MABI)
was synthesized,10 which exhibits absorption onset and fluores-
JA9917619
cence maximum at 368 and 400 nm (φ
f
≈ 0.053, τ ) 2.60 ns in
11) 3MIBP was synthesized according to ref 12.12 1H NMR(CDCl
(
3
, 200
CCl ), respectively. The spectral resemblance (i.e., peak maxi-
4
MHz) δ 1.03 (d, 6H, J ) 6.8 Hz); 2.30-2.56 (m, 1H); 3.15 (d, 2H, J ) 7.0
Hz); 8.19 (s, 1H); 8.91 (s, 1H).
(12) Barlin, G. B.; Fenn, M. D. Aust. J. Chem. 1983, 36, 633.
(10) 4MABI was synthesized by forming the 4-methyl-4ABI salt with CH
3
I
1
followed by deprotonation in strong basic conditions. H NMR (D
MHz) δ 4.23 (s, 3H); 7.28 (t, J ) 7.1 Hz, 1H); 8.07(d, J ) 6.2 Hz, 1H);
.28(d, J ) 5.2 Hz, 1H); 8.29(s, 1H).
2
O, 400
(13) S
0
1
-S (ππ*) absorption onsets of the 7AI, 4ABI, and 6IBP dimers
are taken to be 305, 292, and 275 nm, respectively (see Table 1).
8
(14) Cramer, C. J.; Truhlar, D. G. J. Am. Chem. Soc. 1993, 115, 8810.