Chemistry Reference
In-Depth Information
9.8. INTEGRATING NONCOVALENT AND COVALENT INTERACTIONS:
DIRECTED OLEFIN METATHESIS AND DISULFIDE
BOND FORMATION
The previous examples demonstrate the power of H bonded duplexes as highly
specific supramolecular assemblers for ligating various structural units. However,
our H bonded duplexes, like most other H bonded complexes, are stable only in non-
polar solvents. Their intolerance to nonpolar media such as water hampers many
applications, particularly those involving biological conditions. Although several
systems with microenvironments that promote H bonding in polar media are
known (Nowick and Chen 1992; Fan et al. 1993; Kato et al. 1995; Torneiro and
Still 1995; Paleos and Tsiourvas 1997; Ariga and Kunitake 1998; Brunsveld et al.
2002), in competitive environments, including aqueous solutions, the association
of artificial molecular components based on H bonding still represents a largely
unsolved fundamental problem. In contrast to designed systems, all water-soluble
natural self-assembling systems are stabilized by the cooperative interaction of mul-
tiple noncovalent forces. DNA duplexes provide one of the best known examples that
are stabilized by H bonding, aromatic stacking, and other noncovalent interactions.
Using similar approaches adopted by Nature, one possible solution to constructing
stable and specific assemblies in competitive media involves the design of molecular
components capable of simultaneously specifying H bonding and other noncovalent
forces. However, the successful design of such molecular components still represents
a daunting challenge. Instead of contemplating the design of molecular structures that
can assemble based on different types of noncovalent forces, we decided to integrate
the superb specificity of H bond arrays and the strength of covalent interactions into
the same duplex. Although most covalent interactions are irreversible and can only
lead to structures that are formed under kinetically controlled conditions, a few revers-
ible (dynamic) covalent bond formation reactions (Furlan et al. 2002) do exist. In fact,
they have attracted intense interest in recent years in thermodynamically controlled
covalent synthesis and in the creation of dynamic combinatorial libraries (Swann
et al. 1996; Huc and Lehn 1997; Giger et al. 1998; Cousins et al. 1999; Lehn
1999; Polyakov et al. 1999; Rowan et al. 2002; Corbett et al. 2006; Saur et al.
2006). Therefore, the integration of H bonding and dynamic covalent interaction
may lead to a simplified, easily manageable system.
9.8.1. Templated Olefin Cross-Metathesis
The two most used reversible covalent reactions are disulfide exchange and
palladium-catalyzed olefin metathesis. We first probed the incorporation of olefin
units into the H bonded duplexes by subjecting the modified duplexes to a Pd
(Grubb's) catalyst. Based on a duplex template with the same unsymmetrical H
bonding sequence used for directing the formation of the b-sheet structures, we pre-
pared two groups (strands 17 and 18) of five olefins covalently linked to the two
template strands (Fig. 9.13). Mixing each one of components 17 with each one of
components 18 in a 1:1 fashion results in a small library of 25 (5
5) members.
