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

Abstract

Molecular design involving the incorporation of an α-amino acid residue into the side chain or main chain of a polymer is often used to stabilize artificial molecular architectures through intramolecular hydrogen bonding. However, this molecular design strategy rarely considers the importance of interactions between substituents at the α-position of amino acid moieties, as found in nature. Herein, we report the synthesis of a novel series of π-stacked helical poly­(quinolylene-2,3-methylene) with amino acid derivatives bearing different substituents at the α-position. We found that the thermal stability of π-stacked helical poly­(quinolylene-2,3-methylene) is significantly improved by packing the substituents in the empty spaces between the side chains. In particular, when a bulky cyclohexyl alanine derivative was used as the side chain, the π-stacked helical structure maintained its stability even in dimethylsulfoxide, a hydrogen bond competitor. The stabilization of the π-stacked structure by the amino acid substituents resulted in a unique polymerization behavior involving nucleation–elongation steps. In the case of derivatives with leucine and cyclohexyl alanine, which form stable π-stacked helical structures, metastable structures with entangled main chains were formed in the initial polymerization stage. These structures subsequently underwent an irreversible structural change to achieve a thermodynamically stable helical π-stacked conformation as a nucleus for subsequent polymerization. Thereafter, the polymerization reaction proceeded with the elongation of the π-stacked helical structure. Differences in the stability of these systems indicated that the amino acid substituents on the side chains determine the most thermodynamically stable π-stacked helical structure.

Synthesis Methodology of End-Functionalized Poly(quinolylene-2,3-methylene)s: Living Cyclocopolymerization Using Aryl Palladium Initiators Conveniently Prepared from Versatile Aryl Halide

“…Similarly, various types of end-functionalized polymers using 3wBr and 3xBr were synthesized (entries 4 and 5). The resulting end-functionalized polymers also exhibited a helical π-stacked structure, which was confirmed by comparison with the previously reported CD and UV spectra of poly-1c 20 -(Me) 25 (Figure 6).…”

“…Previously, we achieved the construction of a novel π-stacked helical polymer using poly­(quinolylene-2,3-methylene) as a scaffold by introducing an amino acid residue into the side chain. , End-functionalized π-stacked polymers were synthesized by cyclocopolymerization of 1b - and 1c -bearing amino acid residues through the one-pot polymerization method. When 3aI was used as the aryl halide, the desired polymers [ 2Cl-poly-1b 20 -(3a) and 2Cl-poly-1c 20 -(3a) ] were obtained (Table , entries 2 and 3).…”

“…Previously, we reported the living cyclocopolymerization of o -allenylaryl isocyanide ( 1 ) using the [1,3-bis­(diphenylphosphino)­propane­(dppp)]­PdMeCl [ 2Cl-(Me) ] complex as an initiator to yield a novel polymer architecture, poly­(quinolylene-2,3-methylene) [ 2Cl-poly-1 n -(Me) ], − which allows for controlled molar mass and narrow molar mass dispersity (Figure b). We recently developed our system to form a novel π-stacked helical polymer based on poly-1 n (Me) with an amino acid residue in the side chain, , and the resulting structures may be developed into functional polymers with π-stacked structures. − The resulting polymer, 2Cl-poly-1 n -(Me) , has well-defined chain ends (α- and ω-chain ends) derived from the initiator 2Cl-(Me) . In particular, a methyl group on 2Cl-(Me) was quantitatively introduced at the α-chain end, without a transfer reaction or deactivation at initiation.…”

Controlling the Transition of Nanospheres to Superhelices in Aqueous Media by Using a “Smart” Pyrazine Building Block

“…While we were compiling these results, an interesting study highlighting the role of the substituent at the α-carbon of the amino acid residue towards the generation of a stable π-stacked self-assembled helical structure was reported. [21] This study demonstrates the contribution of bulky groups in the side chain in enhancing the stability of the π-stacked structure in dimethyl sulfoxide (DMSO); however, the thermodynamic stability of the supramolecular assembled structure was not examined in aqueous media. Unprecedentedly, the present study reveals the control of the flexible side chain and stereocenter of the amino acid residue in the π-conjugated building block over guest selection, and eventually, over the supramolecular chirality of the co-assembled superhelices in aqueous media.…”

“…The guest selectivity exhibited by the Pyra‐Met:Au 3+ ensemble points to the ‘hidden’ control of building block over the guest‐induced co‐assembly. While we were compiling these results, an interesting study highlighting the role of the substituent at the α‐carbon of the amino acid residue towards the generation of a stable π‐stacked self‐assembled helical structure was reported [21] . This study demonstrates the contribution of bulky groups in the side chain in enhancing the stability of the π‐stacked structure in dimethyl sulfoxide (DMSO); however, the thermodynamic stability of the supramolecular assembled structure was not examined in aqueous media.…”