(~10
3 M
À1
) in methanol. Not surprisingly, PC4A4C could also bind tightly with Argand/or Lys-rich proteins. Because of the amphiphilic structure, the addition
of PC4A4C to the stearic acid monolayer on water resulted in the incorporation
of increasing amounts of PC4A4C in the monolayer. The following addition of
basic proteins would produce moderate but distinct additional expansions of pressure/area diagrams. After this work, a cationic calixarene containing quaternary
ammonium was introduced, and the sensing of acid proteins was realized using the
same strategy [35]. On the basis of the above work, Schrader co-assembled phospholipids with polydiacetylene, which showed a blue color and changed to red by various
stimuli [36]. The stimulus could be heat, ionic strength, or mechanical pressure. Then,
the addition of proteins caused obvious color changes and enabled the detection of
proteins by the naked eye. Schrader’s work cleverly took advantage of multivalence
and assembly behavior, greatly simplifying the sensing of proteins. Although the work
was done more than 10 years ago, it still provides valuable lessons.
8.6
Calixarenes for Bioimaging
When Wilhelm Roentgen filmed the first X-ray of his wife’s hand in 1896, medical
diagnosis entered a new era. Since X-rays have been applied to bioimaging,
various noninvasive imaging methods have been developed and applied to clinical
imaging and research in vivo or in vitro. Calixarene-Gd complexes or their
derivatives have been used in magnetic resonance imaging as a tool in medical
diagnostics [37–41]. In the field of optical imaging of macrocyclic molecules, Nau et
al. detailed and systematically summarized the changes of fluorescence properties
when the host-guest complex formed between the fluorescent dyes and the macrocyclic molecules in an aqueous environment [42]. Host-guest complexes between
calixarenes and fluorescence dyes or calixarenes directly modified by dyes have been
utilized for bioimaging in vitro and in vivo, showing tuneable or targeted florescence
response, physiochemical shielding, and enhanced biocompatibility provided by
macrocyclic host molecules [43–57].
As mentioned above, one of the advantages of IDA is that it has a broad spectrum
of analytes, eliminating the need to design specific receptors for specific analytes.
Our group collaborated with Nau’s group to develop a host-guest sensing system
using sulfonated calixarene-LCG pairs and applied it to detect enzyme activity,
quantify bioactive molecules, and screen drugs [23, 31]. However, the broad spectrum of the IDA method also results in a response to nontarget analytes, which is
widespread when testing biological samples. Nau and co-workers used artificial
receptors to transfer probes to living cells, and IDA method was used to monitor
cellular uptake of biomolecular analytes [43]. The fluorescent dye LCG was
quenched by the macrocycle p-sulfonato-calix[4]arene to form a stable host-guest
complex. The LCG/calixarene sensing pairs were incubated with V79 and CHO
cells. After adding choline, acetylcholine, or protamine to the cell culture medium,
they were uptaken into the cells, and formed complexes with calixarenes replaced
LCG to achieve fluorescence switch-on response (Fig. 10). This response can be
214
J. Gao and D.-S. Guo
3 M
À1
) in methanol. Not surprisingly, PC4A4C could also bind tightly with Argand/or Lys-rich proteins. Because of the amphiphilic structure, the addition
of PC4A4C to the stearic acid monolayer on water resulted in the incorporation
of increasing amounts of PC4A4C in the monolayer. The following addition of
basic proteins would produce moderate but distinct additional expansions of pressure/area diagrams. After this work, a cationic calixarene containing quaternary
ammonium was introduced, and the sensing of acid proteins was realized using the
same strategy [35]. On the basis of the above work, Schrader co-assembled phospholipids with polydiacetylene, which showed a blue color and changed to red by various
stimuli [36]. The stimulus could be heat, ionic strength, or mechanical pressure. Then,
the addition of proteins caused obvious color changes and enabled the detection of
proteins by the naked eye. Schrader’s work cleverly took advantage of multivalence
and assembly behavior, greatly simplifying the sensing of proteins. Although the work
was done more than 10 years ago, it still provides valuable lessons.
8.6
Calixarenes for Bioimaging
When Wilhelm Roentgen filmed the first X-ray of his wife’s hand in 1896, medical
diagnosis entered a new era. Since X-rays have been applied to bioimaging,
various noninvasive imaging methods have been developed and applied to clinical
imaging and research in vivo or in vitro. Calixarene-Gd complexes or their
derivatives have been used in magnetic resonance imaging as a tool in medical
diagnostics [37–41]. In the field of optical imaging of macrocyclic molecules, Nau et
al. detailed and systematically summarized the changes of fluorescence properties
when the host-guest complex formed between the fluorescent dyes and the macrocyclic molecules in an aqueous environment [42]. Host-guest complexes between
calixarenes and fluorescence dyes or calixarenes directly modified by dyes have been
utilized for bioimaging in vitro and in vivo, showing tuneable or targeted florescence
response, physiochemical shielding, and enhanced biocompatibility provided by
macrocyclic host molecules [43–57].
As mentioned above, one of the advantages of IDA is that it has a broad spectrum
of analytes, eliminating the need to design specific receptors for specific analytes.
Our group collaborated with Nau’s group to develop a host-guest sensing system
using sulfonated calixarene-LCG pairs and applied it to detect enzyme activity,
quantify bioactive molecules, and screen drugs [23, 31]. However, the broad spectrum of the IDA method also results in a response to nontarget analytes, which is
widespread when testing biological samples. Nau and co-workers used artificial
receptors to transfer probes to living cells, and IDA method was used to monitor
cellular uptake of biomolecular analytes [43]. The fluorescent dye LCG was
quenched by the macrocycle p-sulfonato-calix[4]arene to form a stable host-guest
complex. The LCG/calixarene sensing pairs were incubated with V79 and CHO
cells. After adding choline, acetylcholine, or protamine to the cell culture medium,
they were uptaken into the cells, and formed complexes with calixarenes replaced
LCG to achieve fluorescence switch-on response (Fig. 10). This response can be
214
J. Gao and D.-S. Guo