position and the kinetics of binding was investigated by
tracking the CD signal at 315 nm vs time at various
compositions of water containing 4 µM dodecamer 2 and
2
0 equiv of (-)-R-pinene. To determine the half-life of the
process, the CD signal at 315 nm was normalized by its final
value and fit to a psuedo-first-order kinetics model.
In the case of 60 and 70% water in acetonitrile, the CD
signal reached its maximum before the first measurement
could be taken or within a minute of mixing. The half-lives
of the process in 80, 90, and 100% water were on the order
of seconds, minutes, and hours, respectively. It is evident
that the rate of the process was highly dependent on the
composition of the solution. The role of the longer side chains
is difficult to determine because mPE oliogmers with shorter
triethylene glycol side chains are not soluble at these solvent
compositions. However, the strong dependence on water
composition would seem to support a higher energy, unfolded
intermediate that slows the evolution of the preferred helical
handedness of binding.
Figure 5. Plot of association constant for dodecamer 2 at 4 µM
with (-)-R-pinene against the percentage of water in acetonitrile.
Note that the association constant for 100% water was collected at
2
µM due to the relative insolubility of (-)-R-pinene in water.
In conclusion, water-soluble mPE dodecamer 2 was
achieved by replacing triethylene glycol side chains of
dodecamer 1 used in previous studies with longer hexa-
ethylene glycol side chains. The UV spectra of dodecamer
content of the solution was changed from 70 to 80% (Figure
1
5
). The association constant peaked at 90% water in
6
-1
acetonitrile with a value of 1.4 ( 0.090 × 10 M , which
is significantly higher than the maximum value predicted
by extrapolation to 100% water in the previous study (6 ×
2
showed a large hypochromic effect that increased with
4
-1
1
increasing water composition. This hypochromic effect was
attributed to close stacking of the backbone chromophores
possibly through the tightening of the helical conformation
and/or aggregation of the folded dodecamer 2. Varying the
water composition of the solvent allowed access to a large
10 M ). In pure water, the association constant was an
order of magnitude lower than the maximum value, sug-
gesting that some impedance to binding exists. It is possible
that the helical conformation in 100% water is tighter and
has a smaller interior cavity, which disfavors binding with
4
6
-1
range of association constants (10 -10 M ). The maximum
association constant of dodecamer 2 with (-)-R-pinene was
(-)-R-pinene. This hypothesis is consistent with the differ-
ences observed in the UV spectrum collected in 100% water,
6
-1
1
.4 ( 0.090 × 10 M at a solvent composition of 90%
which may also be attributed to a tighter helical conforma-
4
6
-1
water in acetonitrile, which is the largest association constant
measured for a mPE foldamer with a guest molecule. Finally,
the evolution of the induced CD signal upon mixing was
also found to be highly dependent on solvent composition,
and the rate at which equilibrium was reached decreased
dramatically as the solvent composition approached pure
water. Thus, increasing the solubility range of mPE oligomers
provides an opportunity to express considerable control over
the host-guest binding event through the modulation of
solvent composition.
tion. The wide range of association constants (10 -10 M )
demonstrates the tremendous sensitivity of binding affini-
ties based on nonspecific, noncovalent interactions to sol-
vent composition. The association constants measured for
dodecamer 2 with (-)-R-pinene are similar in magnitude to
those exhibited by enzymes binding their substrates, sug-
gesting that mPE oligomers might have potential as scaffolds
for engineering artificial enzymes.17,18
In addition to the strength of the association constant, the
approach of the host/guest system to equilibrium was found
to be significantly different for water-soluble dodecamer 2
in comparison with previous guest binding studies. In prior
investigations at lower percentages of water, the induced CD
signal reached equilibrium nearly instantaneously upon
mixing with a chiral guest; however, at higher compositions
of water, the CD signal of 2 was much slower to reach a
Acknowledgment. This material is based upon work
supported by the U.S. Department of Energy, Division of
Materials Sciences, under Award No. DEFG02-91ER45439
through the Frederick Seitz Materials Research Laboratory
at the University of Illinois at Urbana-Champaign.
1
9,20
Supporting Information Available: Detailed descrip-
tions of all experimental procedures and results. This material
is available free of charge via the Internet at http://pubs.acs.org.
constant value.
The relationship between solvent com-
(17) Wilchek, M.; Bayer, E. A. Biomol. Eng. 1999, 16, 1-4.
(18) Sanders, J. K. M. Chem.sEur. J. 1998, 4, 1378-1383.
(19) Slower kinetics of binding were also observed for a dumbbell-shaped
OL036238K
guest in a solution of 40% water in acetonitrile where the host-guest
complex that formed resembled a rotaxane-like structure. The slower rate
was attributed to the large conformational distortion required of the host.
(20) Tanatani, A.; Hughes, T. S.; Moore, J. S. Angew. Chem., Int. Ed
2002, 41, 325-328.
472
Org. Lett., Vol. 6, No. 4, 2004