Theoretical Study of Photophysical Properties of Bisindolylmaleimide Derivatives :

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Theoretical Study of Photophysical Properties of Bisindolylmaleimide Derivatives
Kenichiro Saita,|,†,‡ Manabu Nakazono,§ Kiyoshi Zaitsu,§ Shinkoh Nanbu,|,*,‡ and
Hiroshi Sekiya*,†
Department of Chemistry, Faculty of Science, Graduate School of Molecular Chemistry, Kyushu UniVersity,
6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan, Research Institute for Information Technology,
Kyushu UniVersity, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan, and Graduate School of
Pharmaceutical Sciences, Kyushu UniVersity, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
ReceiVed: May 10, 2009; ReVised Manuscript ReceiVed: June 9, 2009
The photophysical properties of two bisindolylmaleimide derivatives, 3,4-bis(3-indolyl)-1-H-pyrrole-2,5-dione
(arcyriarubin A) and indolo[2,3-a]pyrrolo[3,4-c] carbazole-5,7-(6 H)-dione (arcyriaflavin A), are investigated
by using ab initio molecular orbital (MO) and multireference perturbation theory. These compounds are
suggested to exist as monovalent anions deprotonated from an indole NH group in aprotic polar solvents.
The analysis of MOs shows that the electronic structures of the S1 and S2 states are described by the singleor
double-electron excitation between the naturally localized MOs on an indole moiety and on the maleimide
part. This indicates that the intramolecular charge transfer (ICT) transfer may occur by photoexcitation. The
minimum-energy structure of the arcyriarubin A anion is twisted; the dihedral angles between the indole and
maleimide rings are 83.4° and 20.2° for the S1 and S0 states, respectively. The analysis of the minimum
energy path along the coordinate of the twist angle is performed to explore the emission process from the S1
state. It has been shown that the magnitude of the Stokes shift increases with increasing the twist angle, but
the oscillator strength decreases. It has been suggested that the experimentally observed fluorescence arises
on the way toward the energy minimum of the S1 state. The Stokes-shifted emission of arcyriaflavin A is
contributed by the S1-S0 electronic relaxation after the excitation in the S2 state.
Introduction
Bisindolylmaleimide derivatives such as arcyriarubin and
arcyriaflavin, which are isolated from the fruiting bodies of the
slime mold (Arcyria denudata),1 contain both two indole
subunits and a maleimide subunit. These compounds correspond
to a core structure of selective inhibitors of protein kinase C
(PKC) or DNA topoisomerase, as staurosporine,2 rebeccamycin,3
and ICP-1,4 which have a bisindolylmaleimide or indolocarbazole
skeleton with a C-N linkage to a sugar moiety. The ability
of selective inhibition or regulation of the metabolism of cells
makes them therapeutically important anticancer agents.5 The
PKC isoenzyme family members phosphorylate a wide variety
of protein targets, and they are involved in diverse cellular
signaling or signal transduction.6 Consequently the PKC inhibitors
such as these bisindolylmaleimide derivatives are promising
therapy agents for autoimmune diseases and tumors.4,7
On another matter, fluorescent, chemiluminescent, and bioluminescent
compounds have been developed for luminescence
assays,8-10 especially for specific detection of certain biomolecules.
11-13 Various indole derivatives were also synthesized,
and their luminescent characteristics were investigated.14,15 A
number of bisindolylmaleimide derivatives exhibit strong
fluorescence accompanying a large Stokes shift with respect to
the absorption wavelength, which leads to suitable luminescence
assays available for a specific detection.16,17 Most bisindolylmaleimides
are vivid red crystals1 and some of them exhibit
red luminescence in their solid phase; amorphous films of
N-methylated derivatives have been applied for fabrication of
red light-emitting diodes (LEDs).18