pair; no dithiane is detected after photolysis at concentrations
below 1 mM. In contrast, the I/C ratio stays relatively
constant for the {1c‚5} pair in the wide range of concentra-
tions, decreasing considerably only in the vicinity of KD. The
fitted dashed line in Figure 2b represents a simulation
obtained with KD ) 0.48 mM. At low concentrations, only
the bonded pairs produce dithiane upon photolysis.
this effect to be of significance in the studied systems. In a
control experiment (Scheme 2) barbiturate 4 is only one-
Scheme 2
For more tightly bound complexes, such as {2‚4} (KD )
86 µM), the I/C curve stays relatively level at concentrations
high enough for the subsequent detection of the released
dithiane, i.e., above the dithiane detection limit by GCMS
(Figure 3). This effectively extends the dynamic range of
third less efficient than the unsubstituted benzophenone as
a sensitizer in a fragmentation reaction of a model benzal-
dehyde-dithiane adduct 6 that, unlike 2, is not capable of
complexation with 4.
Finally, an alternative proof of concept for the conditional
(i.e., molecular recognition dependent) photoinduced release
of dithiane at higher concentrations is to quench the
bimolecular sensitization channel with an external quencher,
for which we chose diethyl sulfide. The dithiane-bearing
receptor 2 (5 mM) was sensitized, in the presence of 1 M
diethyl sulfide, by free benzophenone or the guest 4. All
photolyses were run in a Rayonet carousel reactor with RPR
3500 lamps (∼350 nm). At this range of wavelengths there
was no self (non-sensitized) cleavage observed in the dithiane
adducts. GCMS analysis of irradiated samples showed no
traces of released dithiane in the case when free benzophe-
none was used as the sensitizer. On the contrary, sensitization
with the benzophenone-barbiturate conjugate 4 produced
dithiane in amounts comparable to the amounts released in
the absence of the quencher. Same observations were made
for pairs {5‚1a} (forms complex) and {5‚BP} (does not form
complex) in the presence of diethyl sulfide as the external
quencher.
To conclude, using isophthaloyl bis-aminopyridines as
barbiturate recognition elements, we designed binary pho-
tolabile systems capable of conditional fragmentation and
release of dithiane tags. Photoinduced fragmentation in such
binary systems is only possible when a molecular recognition
event arms the system, making it light-sensitive. Although
a number of useful applications can utilize this concept, we
believe that it can be most beneficial for bioanalytical
applications, where a molecular recognition event is detected
and reported via photoinduced dithiane release in a bulk
solution or in a spatially addressable manner on the surface
of a chip. We are currently pursuing these directions.
Figure 3. Normalized dithiane peak intensity I/C as a function of
the initial concentrations: host 2 sensitized by barbiturate 4 (b) or
by free benzophenone (BP) (2).
concentrations at which the fragmentation in the bound state
is overwhelmingly more efficient than the one caused by
bimolecular collisional quenching. We hypothesize that the
observed slight decline of the dithiane peak intensity at higher
concentrations (dashed line) is due to secondary photooxi-
dation of dithiane.2g The slow photodegradation of the
dithiane markers affects the reactions of both the bound and
the free sensitizers.
Expectedly, complexation does not guarantee quantum
yields of fragmentation better than those of free collisional
quenching at higher concentrations. In fact, at 5 mM,
benzophenone releases more dithiane from receptor 2 than
does the benzophenone-tethered barbiturate 4. Depending on
the structural features and conformational flexibility in the
bound complex, its quantum efficiency of fragmentation can
be both greater than the benzophenone-sensitized (as was
observed for {5‚1c} versus {5‚BP}) or smaller, as is the case
for {2‚4} versus {2‚BP} at 5 mM (not shown in Figure 3).
The complexation, while increasing the initial ET rate, also
makes back electron transfer more efficient. In some
complexes this can lower the yield of the triplet charge-
separated species, needed for the productive channel, i.e.,
the fragmentation. At a higher concentration bimolecular
quenching of the triplet benzophenone can be very efficient,
and yet the radical ion pairs have a chance of escaping the
cage and diffusing apart to slow the wasteful back electron
transfer. Another factor is the intramolecular quenching of
the sensitizer in the tethered modules, which makes the
sensitizer inherently less efficient, although we did not find
Acknowledgment. We thank the NSF (CHE-314344) and
the NIH (GM 67655) for financial support of this work.
Supporting Information Available: Synthetic procedures
and spectra. This material is available free of charge via the
OL0700153
Org. Lett., Vol. 9, No. 6, 2007
1079