Synthetic Chemical Systems Involving Self-Catalytic Reactions of Helicene Oligomer Foldamers.

Self-catalysis is defined as catalysis by a product of a chemical reaction, that causes a significant increase in reaction rate in terms of the progress of the reaction. When a self-catalytic reaction is involved in a reversible nonequilibrium-to-equilibrium chemical reaction, notable kinetic phenomena appear including sigmoidal kinetics, the seeding effect, thermal hysteresis, and chiral symmetry breaking. The nature of self-catalytic reactions is characterized by microscopic mechanisms involving pathways of molecular structural changes and by macroscopic mechanisms involving molecular flux. Reversible self-catalytic reactions, which exhibit notably high sensitivity to environmental changes, are also observed. In this Review, reversible self-catalytic reactions of helicene oligomer foldamers during formation of homo- and hetero-double-helices are discussed, which exhibit the properties outlined above.

Sequential self-catalytic reactions in the formation of hetero-double-helix and their self-assembled gels by pseudoenantiomer mixtures of ethynylhelicene oligomers.

A 1:1 mixture of pseudoenantiomer ethynylhelicene (P)-pentamer and (M)-tetramer in toluene formed hetero-double-helix and their self-assembled gels. Kinetic analysis under isothermal conditions showed a complex nonlinear nature with regard to temperature changes. At 60°C, sigmoidal kinetics were observed, which disappeared after seeding with the self-assembled gels. These findings indicate the involvement of self-catalytic reaction I, in which a hetero-double-helix catalyzes the reaction to form a hetero-double-helix from random-coils. At 20°C, stairwise biphasic kinetics were observed, which disappeared after seeding. This phenomenon was explained by the involvement of two reactions with sigmoidal kinetics, namely, the formation of self-assembled gel I from hetero-double-helix by self-catalytic reaction II and the formation of self-assembled gel II by self-catalytic reaction III. Constant-rate temperature change experiments between 90 and 5°C showed nonsigmoidal thermal hysteresis in accordance with the involvement of sequential self-catalytic reactions with different reaction rates.

Figure-eight thermal hysteresis of aminomethylenehelicene oligomers with terminal C16 alkyl groups during hetero-double-helix formation.

1 : 1 mixtures of aminomethylenehelicene (P)-tetramer and (M)-pentamer with terminal C16 alkyl groups in fluorobenzene showed structural changes between hetero-double-helices B and C and random-coils 2A. Figure-eight thermal hysteresis appeared when the solution was cooled and heated at a constant rate and involved the crossing of cooling and heating curves in Δε/temperature profiles. This unusual thermal hysteresis emerged in the intermediate state between counterclockwise and clockwise thermal hystereses. This phenomenon arose from the competition between self-catalytic reactions to form B and C from 2A. Significant effects of terminal C16 alkyl groups on the thermodynamic and kinetic phenomena are also described.

Proximate stochastic chiral symmetry breaking is mechanically tunable: formation of enantiomeric hetero-double-helices and aggregates from racemic oxymethylenehelicene oligomers.

A mixture of oxymethylenehelicene (P)-hexamer and (M)-hexamer in solution exhibited chiral symmetry breaking, which was induced by mechanical stirring, during the formation of enantiomeric hetero-double-helices and their aggregates. A racemic 50 : 50 mixture was heated to 90 °C to form a dissociated state, and then cooled to 25 °C. Mechanical stirring with a magnetic stirrer at 2000 rpm for 100 h resulted in the exhibition of a strong negative Cotton effect at 322 nm. Repeated experiments provided negative Cotton effects, which is due to the deterministic chiral symmetry breaking. No change in the Cotton effect occurred in the absence of stirring. The (P)-hexamer to (M)-hexamer mixing molar fraction was varied, and a positive Cotton effect appeared at molar fractions between 40 : 60 and 46 : 54 and a negative Cotton effect at molar fractions between 48 : 52 and 60 : 40, which was reversed at 47 : 53. The slight deviation of symmetry from that at 50 : 50 was termed proximate stochastic chiral symmetry breaking. The process of chiral symmetry breaking could be tuned by varying the procedures of mechanical stirring and mixing procedures for solutions of (P)-hexamer and/or (M)-hexamer.

Chemical Systems Involving Two Competitive Self-Catalytic Reactions.

Self-catalytic reactions are chemical phenomena, in which a product catalyzes the reactions of substrates further to yield products. A significant amplification of product concentration occurs during the reactions in a dilute solution, which exhibit notable properties such as sigmoidal kinetics, seeding effects, and thermal hysteresis. Chemical systems involving two competitive self-catalytic reactions can be considered, in which the competitive formation of two products occurs, which is affected by environmental changes, subtle perturbations, and fluctuations, and notable chemical phenomena appear such as formation of different structures in response to slow/fast temperature changes, chiral symmetry breaking, shortcut in reaction time, homogeneous-heterogeneous transitions, and mechanical responses. Studies on such chemical systems provide understanding on biological systems and can also be extended to the development of novel functional materials.

Chemical CD oscillation and chemical resonance phenomena in a competitive self-catalytic reaction system: a single temperature oscillation induces CD oscillations twice.

Chemical CD oscillation and chemical resonance phenomena appear in a competitive chemical reaction system involving amplification. A pseudoenantiomeric mixture of an aminomethylenehelicene (P)-tetramer and an (M)-hexamer in toluene forms three states, namely hetero-double-helix B, hetero-double-helix C, and dissociated random-coil 2A. When the temperature of the solution is oscillated between -5 and 38 °C at a rate of 2 K min-1, Δε reaches maxima twice during a single temperature oscillation, which is called a chemical CD oscillation phenomenon. The phenomenon arises from the sharp competition between the two self-catalytic 2A + C-to-2C and 2A + B-to-2B reactions. In addition, the chemical CD oscillation appears, when temperature oscillation occurs at a rate of 2 K min-1, and higher and lower rates provide a single maximum, a process referred to as the chemical resonance phenomenon. The changes in concentration induced by temperature oscillation repeatedly crossed equilibrium.

Formation and dissociation of synthetic hetero-double-helix complex in aqueous solutions: significant effect of water content on dynamics of structural change.

A 1 : 1 mixture of the ethynylhelicene pseudoenantiomers (M)-tetramer and (P)-pentamer, which possess hydrophilic terminal tri(ethyleneglycol) (TEG) groups, changes their structures in the water-THF (10 µM) solvent system between dissociated random-coils and an associated hetero-double-helix upon heating and cooling. A small change in water content between 30 and 33% significantly affects the dynamics of structural changes. At 30% water content, heating to 60 °C causes rapid formation of random-coil and cooling to 10 °C causes the rapid formation of hetero-double-helix, accompanied by repeated changes in Δε at 369 nm between 0 and -2000 cm-1 M-1. Heating and cooling experiments at constant rates between 60 and 10 °C resulted in sigmoidal curves in Δε/temperature profiles, which indicate rapid structural changes. Different phenomena occurred at 33% water content. Heating to 60 °C and cooling to 0 °C initially induced changes in Δε between 0 and -2000 cm-1 M-1, and repeated cycles gradually reduced the range between 0 and -500 cm-1 M-1. Heating and cooling experiments at constant rates between 60 and 10 °C caused small changes in Δε, and repeated cycles at 10 °C gradually increased Δε to -500 cm-1 M-1. These phenomena involved rapid changes in molecular structure and slow structural changes in the water-THF solvent system. The sharp switching of the dynamics of structural changes at water content between 30 and 33% indicated discontinuous structural changes in the hydration of TEG and/or in water clusters in the vicinity of oligomer molecules.

Optically active iodohelicene derivatives exhibit histamine N-methyl transferase inhibitory activity.

Optically active helicene derivatives inhibit the activity on histamine N-methyl transferase (HNMT). Specifically, methyl (P)-1,12-dimethylbenzo[c]phenanthrene-8-carboxylate with 6-iodo and 5-trifluoromethanesulfonyloxy groups inhibits HNMT activity on the µM order of IC50. Chirality is important, and (M)-isomers exhibits substantially reduced activity. The 6-iodo group is also essential, which suggests the involvement of halogen bonds in protein binding. Substituents on the sulfonate moiety also affect the inhibitory activity.

Pendant-Type Helicene Oligomers with p-Phenylene Ethynylene Main Chains: Synthesis, Reversible Formation of Ladderlike Bimolecular Aggregates, and Control of Intramolecular and Intermolecular Aggregation.

Pendant-type (P)-helicene oligomers with p-phenylene ethynylene main chains up to a tetramer were synthesized by a building block method. The (P)-tetramer reversibly formed a ladderlike bimolecular aggregate upon cooling and disaggregated upon heating in (trifluoromethyl)benzene. Two bis(tetramer)s, in which two (P)-tetramers were connected by hexadecamethylene linkers, were also synthesized. The head-to-tail bis(tetramer) formed an intramolecular aggregate, and the head-to-head bis(tetramer) formed an intermolecular aggregate in toluene. The results suggest the antiparallel aggregation structure of the pendant-type (P)-tetramers. The structure of the linker was proven to be effective in controlling intramolecular and intermolecular aggregations.

Deterministic and Stochastic Chiral Symmetry Breaking Exhibited by Racemic Aminomethylenehelicene Oligomers.

Racemic mixtures of aminomethylenehelicene (P)- and (M)-pentamers exhibited deterministic and stochastic chiral symmetry breaking during hetero-double-helix formation and self-assembly in solution. Heating a 50:50 mixture of (P)- and (M)-pentamers at 90 °C, and then cooling the mixture to 70 °C resulted in hetero-double-helix formation; a Cotton effect with negative Δε at λ=315 nm appeared. Chiral self-assembly occurred when the mixture was cooled to 25 °C. A strong tendency of deterministic chiral symmetry breaking appeared at the molecular and self-assembled levels, which was indicated by the negative Δε at λ=315 nm that appeared in most cases in repeated experiments. Mixtures containing 60:40 and 40:60 (P)-/(M)-pentamers also self-assembled with the same chirality. When a homo-double-helix (P)-/(M)-pentamer and a random coil (M)-/(P)-pentamer were mixed, the chiral self-assembly formed stochastically, and heating and cooling resulted in deterministic chiral symmetry breaking.

Spatially Heterogeneous Nature of Self-Catalytic Reaction in Hetero-Double Helix Formation of Helicene Oligomers.

A 1:1 mixture of pseudoenantiomeric aminomethylenehelicene oligomers, (P)-tetramer and (M)-pentamer, in fluorobenzene show a self-catalytic phenomenon in the formation of hetero-double helices from random coils. This study visualizes the spatially heterogeneous nature of the self-catalytic reaction in dilute solution. UV/Vis imaging analysis of the mixture at 70 °C, containing random coils, exhibits a homogeneous bright area. When the solution is cooled from 70 to 30 °C and held at that temperature, dark domains of approximately 1 mm in size appear, which move approximately at a rate of 1 mm min-1 . The dark domains indicate that weaker UV/Vis absorption results from the formation of hetero-double helices, which is supported by circular dichroism (CD) imaging experiments. Then a homogeneous mixture is regenerated upon heating to 55 °C, as shown by CD imaging. Under self-catalytic conditions, a homogeneous solution spontaneously changed to a heterogeneous solution in the process of hetero-double-helix formation.

Fibril Film Formation of Pseudoenantiomeric Oxymethylenehelicene Oligomers at the Liquid-Solid Interface: Structural Changes, Aggregation, and Discontinuous Heterogeneous Nucleation.

Oxymethylenehelicene (P)- and (M)-oligomers up to a nonamer were synthesized by a building block method. The oligomers formed dimeric homoaggregates in trifluoromethylbenzene. A mixture of the pseudoenantiomeric (P)-pentamer and (M)-hexamer formed a heteroaggregate, which self-assembled into one-dimensional fibril films at the liquid-solid interface. Discontinuous heterogeneous nucleation occurred, which involved the formation of particles that were 50 nm in diameter and subsequent fibril growth from these particles. The fibril film was formed on the solid surface and the molecules remained dissociated in solution. The fibril film formation was affected by seeding and the solid surface materials.