Cao et al.
TABLE 1. Chart Showing R1 Substituent Groups on the
Naphthalimide Ring Along with R2 π-Deficient
Substrates a-g and π-Excessive Substrates h-n
on 4-(N,N-dimethylamino)benzonitrile (DMABN) and its
analogues.6,7 Molecular Probes’ SNARF displays particu-
larly good separation of its two emission bands and has
been widely used as a ratiometric probe for intracellular
pH.8 Recently, two-color emission band separation has
been improved by exploring the initial and phototautomer
states of the 3-hydroxyflavone (3HF) family of com-
pounds.9 Conversely, dyes which operate under the TICT
mechanism tend to undergo fluorescence quenching in
protic solvents. While these systems have been utilized
as molecular probes for a number of analytes, solvent
conditions remain limited to polar aprotic solvents such
as acetonitrile in order to promote the longer wavelength
emission.10
N-Arylnaphthalimdes, specifically 1,2-, 2,3- ,and 1,8-
naphthalimides, appear to be a class of fluorescent dyes
unlike either category and represent one of the few
exceptions to the well-established model of TICT com-
pounds.11 By comparison, the photophysics of N-aryl-
naphthalimides more closely resemble the excited state
properties of azulene where emission from its low-lying
S2 state is typically observed.12 Two emissive states (S1
and S2) capable of yielding both short wavelength (SW)
and long wavelength (LW) fluorescence are thought to
be present in the excited state of N-arylnaphthalimides.
Whereas the geometry of the SW state is similar to the
canted geometry of the ground state, a coplanar confor-
mation, which results from interannular twisting in the
excited state, appears to be responsible for the LW
emission. Because of this conformational dependence on
LW emission, electronic and steric factors intrinsic to the
N-arene play a significant role in their fluorescence.
Our interest in these compounds stems from their
successful use as a ratiometric probe for carbohydrates
in aqueous conditions.13 Because naphthalimides are
inherently more polar than polycyclic aromatic hydro-
carbons such as pyrene, additional functional groups
enhance their water solubility. Since these compounds
can potentially display discrete dual fluorescence in
either protic or aprotic solvents, our attention focused on
the mechanism responsible for this unique property.
Reports by Berces et al. on N-phenyl-2,3-naphthalimides
highlighted the role of solvent and rotational relaxation
by examining several naphthalimides with N-aryl groups
substituted at ortho, meta, and para positions.10 Their
findings revealed the importance of steric effects on the
two emission bands and provided a general model that
describes the influence that electron-withdrawing or
electron-releasing groups have on SW and LW emission.14
Because certain N-phenyl-1,8-naphthalimides were found
to exhibit dual emission when substituted with methoxy
at the naphthalene ring,15 we prepared a matrix library
that focuses on this synthetically less versatile compo-
nent. In addition to probing the effects of substituents,
heterocyles were also included to investigate how their
more subtle π-excessive and π-deficient properties (as
discussed by Marks and Ratner16) affect the emission
wavelengths of these compounds.
(6) Grabowski, Z.; Rotkiewicz, K.; Rettig, W. Chem. Rev. 2003, 103,
3899-4031. A notable exception includes: (a) Bettermann, H.; Bien-
ioschek, M.; Ippendorf, H.; Martin, H.-D. Angew. Chem., Int. Ed. Engl.
1992, 31, 1042-1043.
(7) Inoue has classified 11 distinct dual fluorescent systems. With
the exclusion of excimer/exciplex formation, these systems may also
be simplied to either tautomeric or conformational changes. Inoue, Y.;
Jiang, P.; Tsukada, E.; Wada, T.; Shimizu, H.; Tai, A.; Ishikawa, M.
J. Am. Chem. Soc. 2002, 124, 6942-6949.
(8) Handbook of Fluorescent Probes and Research; Molecular Probes
Inc.: Eugene, OR.
(9) (a) Klymchenko, A. S.; Demchenko, A. P. J. Am. Chem. Soc. 2002,
124, 12372-12379. (b) Klymchenko, A. S.; Ozturk, T.; Demchenko, A.
P. Tetrahedron Lett. 2002, 43, 7079-7082. (c) Klymchenko, A. S.;
Ozurk, T.; Pivovarenko, V. G.; Demchenko, A. P. Tetrahedron Lett.
2001, 42, 7967-7970.
(10) (a) Rurack, K.; Danel, A.; Rotkiewicz, K.; Grabka, D.; Spieles,
M.; Rettig, W. Org. Lett. 2002, 26, 4647-4650. (b) Kobiro, K.; Inoue,
Y. J. Am. Chem. Soc. 2003, 125, 421-427. (c) Rurack, K.; Resch-
Genger, U. Chem. Soc. Rev. 2002, 31, 116-127.
(11) (a) Demeter, A.; Berces, T.; Biczok, L.; Wintgens, V.; Valat, P.;
Kossanyi, J. J. Phys. Chem. 1996, 100, 2001-2011. (b) Demeter, A.;
Berces, T.; Biczok, L.; Wintgens, V.; Valat, P.; Kossanyi, J. J. Chem.
Soc., Faraday Trans. 1994, 90, 2635-2641.
(12) Shevyakov, S. V.; Li, H.; Muthyala, R.; Asato, A. E.; Croney, J.
C.; Jameson, D. M.; Liu, R. S. H. J. Phys. Chem. A 2003, 107, 3295-
3299.
To observe the effects that electron-withdrawing groups
have on the naphthalene ring component, we chose
commercially available 4-bromo-1,8-naphthalic anhydride
as a starting material that could be readily converted to
an electron-releasing system such as 4-methoxynaph-
thalic anhydride. Although the bromo group is a well-
known fluorescence quencher, these compounds provide
(14) Wintgens, V.; Valat, P.; Kossanyi, J.; Demeter, A.; Biczok, L.;
Berces, T. J. Photochem. Photobiol. A: Chem. 1996, 93, 109-117.
(15) Demeter, A.; Berces, T.; Biczok, L.; Wintgens, V.; Valat, P.;
Kossanyi, J. New J. Chem. 1996, 20, 1149-1158.
(16) Albert, I. D.; Marks, T. J.; Ratner, M. A. J. Am. Chem. Soc.
1997, 119, 6575-6582.
(13) (a) Cao, H.; McGill, T.; Heagy, M. D. J. Org. Chem. 2004, 69,
2959-2966. Cao, H.; Diaz, D. I.; DiCesare, N.; Lakowicz, J. R.; Heagy,
M. D. Org. Lett. 2002, 4, 1503-1505. (b) Cao, H.; Heagy, M. D. J.
Fluoresc. 2004, 14, 569-584.
4930 J. Org. Chem., Vol. 70, No. 13, 2005