Double-Helical Complexes

All the discussions so far have centered on linear hydrogen bond arrays. Most of the issues such as unwanted tautomerizations, isomerization conformations are serious considerations when designing a synthetic array for complementary complexation. In an attempt to overcome these hurdles, various attempts have been made by supramolecular chemists to understand some of nature‟s best complementary systems. The knowledge gained through these studies has enabled them to apply the underlying principles they have uncovered to build artificial double helical complexes.60

Helical oligopyridine‐dicarboxamide strands61 (Figure 1-37) were reported by Lehn and coworkers demonstrating the ability of the oligomers to form both single helical foldamers and double helical complexes. The conformations leading to the helical shape of the array result from intramolecular hydrogen bonding within 2'-pyridyl-2-

pyridinecarboxamide units. Extensive intermolecular aromatic stacking was observed stabilizing the double-stranded helices that form through dimerization.

Figure 1-37 Structure of an oligopyridinecarboxamide and the crystal structures of its

single helix foldamer and double helix dimer.

A number of complexes have been studied by Yashima and coworkers who have reported double helical oligoresorcinols that specifically recognize oligosaccharides by forming heteroduplexes through noncovalent interactions in water. It is quite difficult to accomplish saccharide recognition in water using artificial receptors because water molecules are such good competitors for the hydrogen bonds. An exception to this is the receptor system relying on covalent sugar-boronate formation, which is truly effective in water.62 _{The oligoresorcinol forms a double helix in water, which unravels and entwines} upon complexation with specific oligosaccharides having a particular chain length and glucosidic linkage pattern, thus generating the heteroduplex with an excess one-handed

helical conformation that can be readily monitored and further quantified by absorption, circular dichroism and NMR spectroscopies.

Figure 1-38 Schematic illustration of the heteroduplex formation of 9merH with

oligosaccharides63 _{and structure of 9merH (on right).}

The oligoresorcinol nonamer 9merH (Figure 1-28) is long enough to form a

double helix as the major species in water, but it dissociates into individual strands in the presence of an increasing volume of organic polar solvents such as methanol at more than 28 vol %, indicating that the double helix formation is highly sensitive to its environment. It starts to unwind as oligosaccharides or polysaccharides are introduced in to the aqueous layer to form the corresponding heterodimer complex whose affinities are measured to be in the range of 3.5 x 103 _M-1 _{in water despite the competition.}

The same group has reported an entirely different kind of double helical formation of sequence and chain length specific complementary complexes that are built via amidinium-carboxylate salt bridges (Figure 1-39).64 _{The helical strands consisting of two,} three, or four m-terphenyl groups attached by diacetylene linkers with complementary

binding sites, either the chiral amidine A or achiral carboxyl C group, were employed.

When three dimeric molecular strands (AA, CC, and AC) or six trimeric molecular strands (AAA, CCC, AAC, CCA, ACA, and CAC) were mixed in solution, the

complementary strands were sequence-specifically hybridized to form one-handed double-helical dimers AACC and (AC)2 or trimers AAACCC, AACCCA, and ACACAC, respectively, through complementary amidinium-carboxylate salt bridges.

Figure 1-39 Structures of m-terphenyl-based molecular strands bearing amidine and/or

carboxyl groups and an illustration of double-helical oligomers consisting of complementary molecular strands stabilized by amidinium-carboxylate salt bridges. A

and C denote the monomer units bearing the chiral amidine and achiral carboxyl groups,

respectively.

Upon the addition of CCA to a mixture of AAA, AAC, and ACA, the AACCCA double

helix was selectively formed. Moreover, the homo-oligomer mixtures of amidine or carboxylic acid from the monomers to tetramers (A, AA, AAAA, C, CC, and CCCC) assembled with a precise chain length specificity to form AC, AACC, and

AAAACCCC, which indicated an extremely specific and well behaved complementary

dimerization of carboxylic acid (~ 102 _M-1_{) is much less than binding constant of} amidinium carboxylate salt bridges (> 106 M-1). Based on the success of the salt bridge arrays the group has extended the design to make platinum coordinated polymers65 _{or by} incorporating phosphoric acid diesters.66

Heteromeric double helices formed by cross-hybridization of chloro and fluoro- substitured quinolone oligoamides have been reported by Huc and coworkers,67 _whose handedness can be controlled by the chiral substituents on the strands (Figure 1-40). These strands are stabilized by intramolecular N-H…_{F hydrogen bonds and C=O}…_F repulsions of the consecutive quinolone units of the sequence.

Figure 1-40 Fluoro-substituted quinoline oligoamide that forms cross-hybridized double

helical complex. Towards it‟s right is the crystal structure of the chloro analogue.

Several examples of double helical complexes have been reported from our group that are both self-complementary and complementary arrays built based on pyridyl, thiazine dioxide and indole heterocycles. These examples have demonstrated the importance of considerations of secondary interactions in this context. More will be discussed in detail about these complementary AAADDD and self-complementary

1.3.3.1 Design of Double-Helical Arrays

Figure 1-41 (i) A and D subunits form components of a supramolecular “toolbox” which

can be used to construct arrays that undergo hydrogen bonding to form complementary complexes; (ii) X-ray crystal structure and schematic representation of a self- complementary double helical ADADA complex developed previously in our research group.

The design of the hydrogen bonding motifs consists of heterocycles such as pyridine, thiazine dioxide and indole derivatives that will form components of our supramolecular „toolbox‟. The pyridyl moieties form the acceptor or A units (represented in blue, Figure 1-40) and indole and thiazine dioxides form the donor or D units (represented in red). Pyridine, being easily derivatized, will incorporate methyl groups to enhance the design where required. They serve as electron donating as well as providing steric bias to induce “kink” in the molecule so as to give it a helical geometry. Thiazine dioxide bearing a strong electron withdrawing sulfone group in conjugation with the

amine group, usually forms the central or inner D component. On the other hand, indole being a relatively poor hydrogen donor requires electron withdrawing substituents such as halogens, esters and nitro functional groups (at 5-position) for increased hydrogen bond donor ability and usually forms the terminal or outer D components while designing a complex. Keeping these factors in mind the design is extendable to construction of different arrays merely by changing the sequence of the omponents. An alternating self- associating pentamer ADADA complex has been reported from our research group serves as an example.