Helical Molecular Programming: Supramolecular Double Helices by Dimerization of Helical Oligopyridine-dicarboxamide Strands

Abstract

Helically preorganized oligopyridine-dicarboxamide strands are found to undergo dimerization into double helical supramolecular architectures. Dimerization of single helical strands with five or seven pyridine rings has been characterized by NMR and mass spectrometry in various solvent/ temperature conditions. Solution studies and stochastic dynamic simulations consistently show an increasing duplex stability with increasing strand length. The double helical structures of three different dimers was characterized in the solid phase by X-ray diffraction analysis. Both aromatic stacking and hydrogen bonding contribute the double helical arrangement of the oligopyridinedicarboxamide strand. Inter-strand interactions involve extensive face-to-face overlap between aromatic rings, which is not possible in the single helical monomers. Most hydrogen bonds occur within each strand of the duplex and stabilize its helical shape. Some inter-strand hydrogen bonds are found in the crystal structures. Dynamic studies by NMR as well as by molecular modeling computations yield structural and kinetic information on the double helices and on monomer-dimer interconversion. In addition, they reveal the presence of a spring-like extension/compression as well as rotational displacement motions.

Hybridization of Long Pyridine‐Dicarboxamide Oligomers into Multi‐Turn Double Helices: Slow Strand Association and Dissociation, Solvent Dependence, and Solid State Structures

“…In the case of pyridine oligoamides, we have initially reported the unexpected trend that double stranded hybrid stability tends to drop when oligomer length increases 9c. We have also shown that short sequences (5 to 9 monomers) are able to form several types of duplex architectures in which the two strands may be offset by zero,9d one,9b, k or two9a, f monomers, consistent with the dynamics observed in solution9a and with calculations 18. Recently, we demonstrated that hybridization is a mostly enthalpically driven process in which the high cost of spring‐like extension of single helical monomers observed during hybridization is compensated by the large enthalpy gain that results from interstrand π–π stacking in the duplex 9i.…”

“…They also strongly influence the hybridization process: oligomers that carry alkoxy groups on every residue hybridize into double helices possess K dim values that are several orders of magnitude larger than oligomers with no such substituents 9a. b However, it was also shown that the effect of alkoxy residues on hybridization does not depend on the nature of the alkyl group, and so n ‐decyloxychains have the same effect as methoxy groups 9k. It was thus assumed that isobutoxy groups would result in a similar propensity towards hybridization.…”

“…However, it has not been established whether these interactions ultimately stabilize double helical architectures. Indeed, water is also bound in the channel of single helical conformers,23 and water has been shown to promote duplex dissociation in solution 9b…”

Synthetic Molecular Motors and Mechanical Machines

“…Interconversion of two equivalent forms occurs by a rotational corkscrew motion of one strand relative to the other. Significant heating is required to cause the much larger conformational changes required to bring the system into the single‐helix regime (Figure 16 b) 129a,c…”

Molecular Recognition with Linear Molecules as Receptors

“…Oligopyridine-dicarboxamide strands represents another family of linear molecules that fold into helical structures driven by intramolecular N H-N hydrogen bonding as well as aromatic stacking interaction [66]. This class of oligomers has a great tendency of forming double, triple, and even quadruple helicates [30].…”