Published on the web September 5, 2011
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Spectral Shifts of the Environment-sensitive Fluorophore POLARIC·
in Heterogeneous Interfaces
Sang-Hyun Son, Yutaka Yamagishi, Michiko Tani, Maiko Yuasa, and Koji Yamada*
Section of Materials Science, Faculty of Environmental Earth Science, Hokkaido University,
Kita-ku, Sapporo, Hokkaido 060-0810
(Received May 31, 2011; CL-110462; E-mail: yamada@ees.hokudai.ac.jp)
We have designed and synthesized amphiphilic environ-
ment-sensitive fluorophore, POLARIC·, from four building
blocks using Suzuki-Miyaura cross-coupling. The absorption
and fluorescence spectra were measured in various micelles and
vesicles. The results show that the emission wavelengths of
these probes respond to the surface charge and stability of the
self-assemblies.
Lipid membranes are functionally important in enclosing
and separating specific regions in many chemical and biological
systems.1 Furthermore, cell membranes play important roles in
cell-cell interactions, material transport, and signal transduc-
tion.2 However, the details of these mechanisms are poorly
understood. Among the analytical methods used to clarify the
membrane structure and dynamics, fluorescence techniques have
particular advantages due to their relatively high sensitivity and
high resolution under physiological conditions.3 Membrane
probes with environment-sensitive spectral shifts, such as
laurdan,4 Dapoxyl sulfonic acid,5 1,8-ANS (1-anilinonaphtha-
lene-8-sulfonic acid),6 and DCVJ (4-(dicyanovinyl)julolidine),7
enable the discrimination of membrane compositions. Since the
lipid membranes have a hydrophobic core and hydrophilic
surfaces, we expected that fluorescent solvatochromic dyes, the
emission wavelengths of which shift with solvent polarity, could
act as a potential backbone for novel membrane probes.
Figure 1. Synthetic strategy of POLARIC·.
Recently, we designed and synthesized a series of fluores-
cent solvatochromic dyes with four different heterocyclic rings
(thiophene, furan, bithiophene, and 3,4-ethylenedioxythio-
phene).8 All of these dyes were efficiently prepared from
electron-donating, aromatic, and electron-withdrawing building
blocks using Suzuki-Miyaura cross-coupling reactions. Bearing
this synthetic strategy in mind, we have designed amphi-
phile membrane probes that resemble lipid molecules. The
POLARIC· (named from POLARity Indicating Chromophore)
probe contains a pyridinium ring as the hydrophilic moiety and
the others as the hydrophobic moiety (Figure 1). Hydrophobicity
can be altered by substituting the electron-donating building
blocks (R1 and R2). Moreover, hydrophilicity may easily be
Scheme 1. Synthesis of 1a-1e.
The pyridine derivatives 2a-2e showed a broad absorbance
around 400 nm and fluorescence solvatochromism equivalent to
the previous fluorophores in various organic solvents (Support-
ing Information; SI13). However, little fluorescence was shown
by the pyridinium derivatives 1a-1e in the solvents. This
phenomenon could be explained by aggregation of 1a-1e due to
their amphiphilicity, so that the fluorescence was probably self-
quenched. When surfactant or cyclodextrin was added to the
aqueous solutions, the fluorescence shown by 1a-1e was
significantly stronger than that in the homogeneous solutions.
The addition of the surfactants above the critical micelle
concentration (CMC) led to a blue shift of the emission
spectrum (SI13). Hence, it is likely that 1a-1e localized in a
certain area of the micelle and emitted a specific signal in
response to the microenvironment. We, therefore, studied the
photophysical properties of 1a-1e in micelles and lipid vesicles
to visualize the self-assembly dynamics. As an additional
advantage, micelles and lipid vesicles serve as a simple model
system for the cell membrane due to their ease of formation via
¹
modified by exchanging the counter anion (X ) using anion-
exchange resin. As only the electron-withdrawing moiety is
displaced in the dye structure, the same electron-donating and
aromatic building blocks can be used for the membrane probes.
The intermediate pyridine derivatives 2a-2e were synthesized
from 4-bromopyridine in the same manner as described in
previous work (Scheme 1). The target fluorophores 1a-1e were
obtained by methylation of the pyridine derivatives using methyl
triflate. The synthetic route was quite simple, and the products
were obtained in moderate yields after three reaction steps
starting from commercially available materials.
Chem. Lett. 2011, 40, 989-991
© 2011 The Chemical Society of Japan
Son, Sang-Hyun
