counts is obtained and an apparent increase in CL intensities
is expected. On the basis of the above concepts, we selected
bisindolylmaleimides (BIM) as candidates of a new probe.
BIM have been developed as protein kinase inhibitors.7 A
little was studied about the FL and CL properties of BIM.
BIM as red electroluminescence materials have been devel-
oped.8 However, the CL properties of BIM were not
evaluated. Recently, we found that 3,4-bis(3-indolyl)-1H-
pyrrole-2,5-dione (1, Scheme 1) had a large Stokes shift and
Indolocarbazole 2 was synthesized via electrocyclization
followed by aromaization with DDQ, and was converted into
phthalhydrazide 3. The N-alkylation of 1 and 2 with alkyl
iodides in acetone rapidly proceeded to yield 4-12 and 13-
15, respectively. 16 was synthesized by the hydrogenation
of 1 with 10% Pd-C catalyst (Scheme 1).11
The FL spectra of 1-3, 6, 13, and luminol (3-amino-
phthalhydrazide) are shown in Figure 1. The Stokes shifts
Scheme 1. Synthesis of 1-16
Figure 1. FL spectra of 1-3, 6, 13, and luminol. 0.1 µM 1-3, 6,
13, and luminol in DMF. The excitation wavelengths of 1-3, 6,
13, and luminol were 452, 315, 316, 471, 323, and 357 nm,
respectively.
of 1-3 were 148, 192, and 201 nm, respectively. The FL
quantum yields of 2 and 13 were 0.42 and 0.58, respec-
tively.12 The FL intensity of 2 was 7-fold higher than that
of 1 in DMF (Table 1).
The FL emission maximum wavelength of 3 was 517 nm.
This wavelength is approximately 120 nm longer than that
for luminol. The FL intensities of 4-12 were 0.25-1.4-fold
compared to that of 1. In contrast, the FL intensities of 13-
15 apparently did not decrease compared to that of 2. The
FL emission maxima wavelengths of 4-12 were 615-630
nm and were longer than that (600 nm) of 1. In the FL
properties of 13-15, similar results were observed. These
results indicated that the FL emission maxima wavelengths
shifted to longer wavelengths due to the N-alkylation of the
maleimide and indole moieties. The FL lifetime of 13 was
the longest among 1-3, 6, 13, 16, and luminol. According
to Table 1, the FL lifetimes of 2 and 3 are similar but the
FL quantum yield is very different. This means the difference
of the quantum yield is not due to the contribution of the
nonradiative path, but due to the difference of the real
fluorescence rate constant.
strong CL intensity when compared to those of indole.9 Thus
we synthesized various BIM and evaluated their FL and CL
properties.
BIM 1, which was synthesized from methyl 2-(3-indolyl)-
glyoxylate and 2-(3-indolyl)acetamide in the presence of
potassium tert-butoxide,10 can be converted to the indolo-
carbazole, phtahlhydrazide, and N-alkyl substituted structures.
(6) (a) Schaap, A. P.; Sandison, M. D.; Handley, R. S. Tetrahedron Lett.
1987, 28, 1159-1162. (b) MacManus-Spencer, L. A.; McNeill, K. J. Am.
Chem. Soc. 2005, 127, 8954-8955.
(10) Zhu, G.; Conner, S. E.; Zhou, X.; Shih, C.; Li, T.; Anderson, B.
D.; Brooks, H. B.; Campbell, R. M.; Considine, E.; Dempsey, J. A.; Faul,
M. M.; Ogg, C.; Patel, B.; Schultz, R. M.; Spencer, C. D.; Teicher, B.;
Watkins, S. A. J. Med. Chem. 2003, 46, 2027-2030.
(7) (a) Bregman, H.; Carroll, P. J.; Meggers, E. J. Am. Chem. Soc. 2005,
128, 877-884. (b) Bartlett, S.; Beddard, G. S.; Jackson, R. M.; Kayser,
V.; Kilner, C.; Leach, A.; Nelson, A.; Oledzki, P. R.; Parker, P.; Reid, G.
D.; Warriner, S. L. J. Am. Chem. Soc. 2005, 127, 11699-11708.
(8) (a) Chiu, C.-W.; Chow, T. J.; Chuen, C.-H.; Lin, H.-M.; Tao, Y.-T.
Chem. Mater. 2003, 15, 4527-4532. (b) Yeh, T.-S.; Chow, T. J.; Tsai,
S.-H.; C.-W.; Chiu, C.-W.; Zhao, C.-X. Chem. Mater. 2006, 18, 832-839.
(9) Nakazono, M.; Zaitsu, K. Biolumin. Chemilumin. Prog. Perspect.
2005, 179-182.
(11) Davis, P. D.; Hill, C. H.; Lawton, G.; Nixon, J. S.; Wilkinson, S.
E.; Hurst, S. A.; Keech, E.; Turner, S. E. J. Med. Chem. 1992, 35, 177-
184.
(12) Velapoldi, R. A.; Tφnnesen, H. H. J. Fluorescence 2004, 14, 465-
472. The FL quantum yield of each compound was determined in DMF
with reference to quinine bisulfate in 0.05 M H2SO4 aqueous solution (Φf
) 0.51). Emissions are corrected.
3584
Org. Lett., Vol. 9, No. 18, 2007