Stability Enhancement of a π-Stacked Helical Structure Using Substituents of an Amino Acid Side Chain: Helix Formation via a Nucleation-Elongation Mechanism

Molecular design involving the incorporation of an alpha-amino acid residue into the side chain or main chain of apolymer is often used to stabilize artificial molecular architecturesthrough intramolecular hydrogen bonding. However, this molec-ular design strategy rarely considers the importance of interactionsbetween substituents at the alpha-position of amino acid moieties, asfound in nature. Herein, we report the synthesis of a novel series of pi-stacked helical poly(quinolylene-2,3-methylene) with amino acidderivatives bearing different substituents at the alpha-position. Wefound that the thermal stability of pi-stacked helical poly-(quinolylene-2,3-methylene) is significantly improved by packingthe substituents in the empty spaces between the side chains. Inparticular, when a bulky cyclohexyl alanine derivative was used asthe side chain, the pi-stacked helical structure maintained its stability even in dimethylsulfoxide, a hydrogen bond competitor. Thestabilization of the pi-stacked structure by the amino acid substituents resulted in a unique polymerization behavior involvingnucleation-elongation steps. In the case of derivatives with leucine and cyclohexyl alanine, which form stable pi-stacked helicalstructures, metastable structures with entangled main chains were formed in the initial polymerization stage. These structuressubsequently underwent an irreversible structural change to achieve a thermodynamically stable helical pi-stacked conformation as anucleus for subsequent polymerization. Thereafter, the polymerization reaction proceeded with the elongation of the pi-stackedhelical structure. Differences in the stability of these systems indicated that the amino acid substituents on the side chains determinethe most thermodynamically stable pi-stacked helical structure.

Automated summary

By packing the substituents in the empty spaces between the side chains, the thermal stability of pi-stacked helical poly(quinolylene-2,3-methylene) is significantly improved. The amino acid substituents stabilize the pi-stacked structure and also affect the polymerization behavior.