Chemistry Reference
In-Depth Information
Figure 9.17 Two components bearing complementary H bonding sequences can reversibly
form disulfide cross-linked products. A-B represents the most stable product because of the
stabilization from its fully matched, interstrand (now intramolecular) H bonds.
sequence-matched product A-B represents the most stable combination. The rever-
sibility of the dynamic covalent cross-linking allows the equilibria shown in
Figure 9.17 to shift toward the formation of the most stable A-B. Therefore, the
observed sequence specificity in the formation of the cross-linked pairs was due to
the extra stabilization from the H bonding interactions that in turn were the result
of the disulfide bond formation.
By examining pairs with four and two interstrand H bonds, it was found that as few
as two H bonds were sufficient to shift the equilibria toward the formation of sequence-
matched products in aqueous solutions. This discovery has opened a new avenue to the
design of a variety of highly specific, dynamic covalent associating units.
The presence of intramolecular H bonds in the cross-linked products was probed
by carrying out 2-D NMR (NOESY) experiments on cross-linked 26-27, which con-
tains two interstrand intramolecular H bonds. It was found that the same cross-strand
NOEs were detected in CDCl
3
(Fig. 9.18a) and in H
2
O/THF-d
8
(80/20, v/v;
Fig. 9.18b). Furthermore, diluting 26-27 from 9 to 0.2 mM in the same aqueous
solvent led to no shift in the two aninline NH signals, which remained at 9.75
ppm. These results suggest the persistence of an intramolecular H bonded confor-
mation for 26-27 in aqueous media, which is consistent with the thermodynamic
mechanism shown in Figure 9.17.
Thus, similar to the olefin cross-metathesis reactions, the symmetrical disulfide
formation under reversible conditions has also been directed into an unsymmetrical
process by a duplex consisting of two different strands. This result represents signifi-
cant progress in specifying molecular association by H bonding in water, which thus
far remains a major, largely unsolved problem. The availability of sequence-specific
linking units in water should greatly facilitate the ligation of various structural units.
For example, di-, tri-, and multiblock copolymers can be constructed based on the
sequence-specific pairing and subsequent covalent cross-linking of the duplexes,
which allows the incorporation of otherwise incompatible oligomer and polymer
