Energy Aspects of Thermal Molecular Switching: Molecular Thermal Hysteresis of Helicene Oligomers

Molecular switching is a phenomenon by which a molecule reversibly changes its structure and state in response to external stimuli or energy. Herein, molecular switching is discussed from thermodynamic and kinetic aspects in terms of energy supply with an emphasis on the thermal switching exhibited by helicene oligomers. It includes the inversion of relative thermodynamic stability induced by temperature changes and molecular thermal hysteresis in a closed system. The thermal phenomenon associated with the oligomers involves population/concentration changes between metastable states under nonequilibrium thermodynamic control.     

Concentration Threshold and Amplification Exhibited by a Helicene Oligomer during Helix‐Dimer Formation: A Proposal on How a Cell Senses Concentration Changes of a Chemical

Sulfonamidohelicene tetramer (M)‐ 1 exhibits a concentration threshold and amplification phenomena in solution during helix‐dimer formation from a random‐coil. The (M)‐tetramer is a random‐coil below a threshold concentration, and the concentration of the helix‐dimer is irreversibly amplified once the threshold concentration is exceeded. For example, a 15 % increase in (M)‐tetramer total concentration from 0.6 to 0.7 mM induces an 8‐fold increase in the concentration of the helix‐dimer, being 8:0.15=53‐fold amplification, under temperature oscillation conditions between 47 and 49 °C. Experiments without oscillation also exhibit concentration amplification. The threshold and amplification phenomenon involves concentration hysteresis, being away from equilibrium, and self‐catalysis. On the basis of this study, a proposal on how a biological cell senses concentration changes of a chemical substance is provided.     

Kinetics of Helix‐Handedness Inversion: Folding and Unfolding in Aromatic Amide Oligomers

A series of helically folded oligoamides of 8‐amino‐2‐quinoline carboxylic acid possessing 6, 7, 8, 9, 10 or 16 units are prepared following convergent synthetic schemes. The right‐handed (P) and the left‐handed (M) helical conformers of these oligomers undergo an exchange slow enough to allow their chromatographic separation on a chiral stationary phase. Thus, the M conformer is isolated for each of these oligomers and its slow racemization in hexane/CHCl₃ solutions is monitored at various temperatures using chiral HPLC. The kinetics of racemization at different temperatures in hexane/CHCl₃ (75:25 vol/vol) are fitted to a first order kinetic model to yield the kinetic constant and the Gibbs energy of activation for oligomers having 6, 7, 8, 9, 10 or 16 quinoline units. This energy gives the first quantitative measure of the exceptional stability of the helical conformers of an aromatic amide foldamer with respect to its partly unfolded conformations that occur between an M helix and a P helix. The trend of the Gibbs energy as a function of oligomer length suggests that helix‐handedness inversion does not require a complete unfolding of a helical strand and may instead occur through the propagation of a local unfolding separating two segments of opposite handedness.     

Crosslinked Aspartic Acids as Helix‐Nucleating Templates

Described is a facile helix‐nucleating template based on a tethered aspartic acid at the N‐terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side‐chain‐end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N‐terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix‐stabilizing methods.     

On the Helical Motif of the Complexes Created by Association of Helix‐Forming Schizophyllan (SPG) and Helix‐Forming Polythiophene Derivatives

π‐Conjugated polymers can finely tune their electrical and optical properties in response to their conformational changes. We believe that a deeper understanding of their higher‐order structures will stimulate further development of their applications. We had revealed that one helix‐forming natural polysaccharide (SPG) and one polythiophene derivative (PT‐1) formed a stable one‐dimensional complex and in the polythiophene main chain a helical conformation was induced through the dynamic conformational changes. The objective of our present research is to obtain a better mechanistic understanding on the interaction between SPG and polythiophenes. Here we have used particular left‐ and right‐handed helix‐forming polythiophene derivatives (D ‐ and L ‐POWTs, respectively) and studied their influence on the helical motif of the complexes. We observed that SPG interacts with both D ‐ and L ‐POWTs through their dynamic conformational changes and both D ‐ and L ‐POWTs form the right‐handed co‐helical complexes with SPG according to the inherent helical motif of SPG. In addition, it was confirmed that 1) the complexes do not coagulate in aqueous solution, and 2) the exchange in the helical motif can occur only when the polymers experience the denature–renature process. We believe, therefore, that the mechanism of the helical induction of the SPG/POWT complexes is very unique, being different from conventional equilibrium reactions.     

Formation of a Dimer of Trinuclear Helicates which Encapsulates an Array of Six Hydrogen‐Bonded Anions

The amine‐containing ligand L, composed of two bidentate pyridyl‐thiazole moieties linked by a 1,3‐diaminophenylene unit, reacts with copper(II) ions to form a dinuclear double helicate [Cu₂L₂]⁴⁺. Reaction of [Cu₂L₂]⁴⁺ with dihydrogen phosphate (0.5 equivalents) gives the unsaturated dinuclear double helicate [Cu₂L₂(OPO₃H₂)]³⁺. [Cu₂L₂(OPO₃H₂)]³⁺ further reacts with another 0.5 equivalents of dihydrogen phosphate to give a trinuclear circular helicate which then self‐assembles into a hexameric cluster [{Cu₃L₃(OPO₃H₂)₃}]²⁶⁺.     

Chain Folding Controlled by an Isomeric Repeat Unit: Helix Formation versus Random Aggregation in Acetylene‐Bridged Carbazole–Bipyridine Co‐Oligomers

An unprecedented, positional effect of the isomeric repeat unit on chain folding in donor–acceptor‐linked oligomers, which contain alternating bipyridine and carbazole moieties that are connected through an acetylinic linkage, is reported. 4,4′‐Linked oligomer 1 adopts an intrachain helical conformation (CD‐active) in CHCl₃/MeCN (20:80 v/v), whereas oligomer 2 , which contains an isomeric 6,6′‐linkage, forms interchain randomly coiled aggregates (CD‐inactive). The substitution position plays a significant role in controlling the variations in electronic effects and dipole moments around the bipyridyl moiety, which are responsible for this observed phenomenon. Two model compounds of oligomers 1 and 2 ( 3 and 4 , respectively) were prepared and their properties were compared. A systematic investigation of the photophysical and CD properties of these structures, as well as theoretical studies, support our conclusions.     

Glycosyl‐Templated Chiral Helix Stapling of Ethynylpyridine Oligomers by Alkene Metathesis between Inter‐Pitch Side Chains

Ethynylpyridine polymers and oligomers consisting of 4‐substituted pyridine rings linked by acetylene bonds at the 2‐ and 6‐positions have been investigated. Ethynylpyridine oligomers covalently linked with a glycosyl chiral template form chiral helical complexes by intramolecular hydrogen bonding, in which the chirality of the template is translated to the helix. With a view to fixation of the chiral architecture, D /L ‐galactosyl‐ and D /L ‐mannosyl‐linked ethynylpyridine oligomers have been developed with 4‐(3‐butenyloxy)pyridine units having alkene side chains. The helical structures are successfully stapled by alkene metathesis of the side chains. Subsequent removal of the chiral templates by acidolysis produces template‐free stapled oligomers. The chiral, template‐free, stapled oligomers show chiral helicity, which is resistant to polar solvents and heating.     

Construction of a Triangle‐Shaped Trimer and a Tetrahedron Using an α‐Helix‐Inserted Circular Permutant of Cytochrome c555

Highly‐ordered protein structures have gained interest for future uses for biomaterials. Herein, we constructed a building block protein (BBP) by the circular permutation of the hyperthermostable Aquifex aeolicus cytochrome (cyt) c₅₅₅, and assembled BBP into a triangle‐shaped trimer and a tetrahedron. The angle of the intermolecular interactions of BBP was controlled by cleaving the domain‐swapping hinge loop of cyt c₅₅₅ and connecting the original N‐ and C‐terminal α‐helices with an α‐helical linker. We obtained BBP oligomers up to ≈40 mers, with a relatively large amount of trimers. According to the X‐ray crystallographic analysis of the BBP trimer, the N‐terminal region of one BBP molecule interacted intermolecularly with the C‐terminal region of another BBP molecule, resulting in a triangle‐shaped structure with an edge length of 68 Å. Additionally, four trimers assembled into a unique tetrahedron in the crystal. These results demonstrate that the circular permutation connecting the original N‐ and C‐terminal α‐helices with an α‐helical linker may be useful for constructing organized protein structures.     

Self‐Assembly of Aniline Oligomers

A great number of nano/microscaled morphologies have recently been prepared during the oxidation of aniline. At the early stage of oxidation, aniline oligomers are obtained, often in spectacular morphologies depending on reaction conditions. Herein, the flower‐like hierarchical architectures assembled from aniline oligomers by a template‐free method are reported. Their formation process is ascribed to the self‐assembly of oligoanilines through non‐covalent interactions, such as hydrogen bonding, hydrophobic forces, and π–π stacking. The model of directional growth is offered to explain the formation of petal‐like objects and, subsequently, flowers. In order to investigate the chemical structure of the oligomers, a series of characterizations have been carried out, such as matrix‐assisted laser desorption ionization, time‐of‐flight mass spectrometry, gas chromatography coupled with mass spectrometry analysis, X‐ray diffraction, and UV/Vis, Fourier‐transform infrared, and Raman spectroscopies. Based on the results of characterization methods, a formation mechanism for aniline oligomers and their self‐assembly is proposed.     

Molecular Function of Counting the Numbers 1 and 2 Exhibited by a Sulfoneamidohelicene Tetramer

The sulfoneamidohelicene tetramer in solution exhibits different molecular responses to the same cooling stimulus delivered once and twice under thermal hysteresis conditions. Its random‐coil state at a high temperature was cooled and maintained at a given temperature for which its molecules remained in a random coil (first cooling); the resulting solution was heated and cooled, after which a helix dimer formed (second cooling). Such a property can be regarded as a molecular function of counting the numbers 1 and 2.     

Double‐Stranded Helical Oligomers Covalently Bridged by Rotary Cyclic Boronate Esters

Novel double helices covalently bridged by cyclic boronate esters were synthesized from complementary dimers with an m ‐terphenyl backbone joined by a chiral or achiral phenylene linker bearing diethyl boronates and diols, respectively. The X‐ray crystallographic analysis and variable‐temperature NMR and circular dichroism measurements, along with theoretical calculations, revealed that the double helices function as a “molecular rotor” in which the cyclic boronate ester units rotate, yielding two stable rotamers at low temperatures. Moreover, our data indicates that the covalently bonded double helices can undergo a unique helix‐inversion simultaneously with a rotational motion of the boronate esters.     

Two‐Component Fibers/Gels and Vesicles Formed from Hetero‐Double‐Helices of Pseudoenantiomeric Ethynylhelicene Oligomers with Branched Side Chains

A methodology for the formation of fibers/gels and vesicles by molecular assembly and for controlling their properties is presented. Two‐component systems of pentamer (P)‐ 5 and tetramer (M)‐ 4 pseudoenantiomeric ethynylhelicenes with decyloxycarbonyl (D) and 4‐methyl‐2‐(2‐methylpropyl)‐1‐pentyloxycarbonyl (bD) side‐chains have been examined. Distinct aggregates were formed by changing the solvent for the three combinations of (P)‐bD‐ 5 /(M)‐bD‐ 4 , (P)‐D‐ 5 /(M)‐bD‐ 4 , and (P)‐D‐ 5 /(M)‐D‐ 4 . In toluene, (P)‐bD‐ 5 /(M)‐bD‐ 4 , (P)‐D‐ 5 /(M)‐bD‐ 4 , and (P)‐D‐ 5 /(M)‐D‐ 4 all formed gels and fibrous assemblies were observed by AFM. The minimum gel‐forming concentration (MGC) decreased in the order (P)‐bD‐ 5 /(M)‐bD‐ 4 >(P)‐D‐ 5 /(M)‐bD‐ 4 >(P)‐D‐ 5 /(M)‐D‐ 4 . In diethyl ether, vesicular formation was observed by dynamic light scattering (DLS), AFM, and TEM, and the size of the vesicles decreased in the order (P)‐bD‐ 5 /(M)‐bD‐ 4 >(P)‐D ‐ 5 /(M)‐bD‐ 4 >(P)‐D ‐ 5 /(M)‐D ‐ 4 . Both fiber/gel and vesicle formation were accompanied by enhanced CDs and redshifted UV/Vis absorption bands with a change in color to deep yellow. These are novel two‐component oligomeric systems that form assemblies of fibers/gels or vesicles depending on the solvent, and the structures and properties of the assemblies can be fine‐tuned by changing the combination of oligomers. In m‐difluorobenzene, a homogeneous solution was obtained with (P)‐D‐ 5 /(M)‐bD‐ 4 , which again exhibits enhanced CDs and redshifted UV/Vis absorptions. Vapor pressure osmometry analysis showed the formation of a bimolecular heteroaggregate. The study has indicated that pseudoenantiomeric oligomers form hetero‐double‐helices that hierarchically assemble to form fibers/gels and vesicles.     

Self‐assembly of supramolecular polymers into tunable helical structures

There is growing interest in the design of synthetic molecules that are able to self‐assemble into a polymeric chain with compact helical conformations, which is analogous to the folded state of natural proteins. Herein, we highlight supramolecular approach to the formation of helical architectures and their conformational changes driven by external stimuli. Helical organization in synthetic self‐assembling systems can be achieved by the various types of noncovalent interactions, which include hydrogen bonding, solvophobic effects, and metal‐ligand interactions. Since the external environment can have a large influence on the strength and configuration of noncovalent interactions between the individual components, stimulus‐induced alterations in the intramolecular noncovalent interactions can result in dynamic conformational change of the supramolecular helical structure thus, driving significant changes in the properties of the materials. Therefore, these supramolecular helices hold great promise as stimuli‐responsive materials. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1925–1935, 2008     

Synthesis and Surface Morphology of Tetraaniline‐block‐Poly(L‐lactate) Diblock Oligomers

Summary: Tetraaniline‐block‐poly(L ‐lactide) diblock oligomers are synthesized via ring‐opening polymerization. The diblock oligomers cast from an L ‐lactide selective solvent (chloroform) show spherical aggregates for the leucoemeraldine state, and ring‐like structures that are composed of much smaller spherical aggregates for the emeraldine state. The formation mechanisms of the two different surface morphologies are discussed in detail.

Surface morphology changes induced by oxidation of the aniline segment of tetraaniline‐block‐poly(L ‐lactate) and drying effects.     

Inversion of Supramolecular Helicity in Oligo‐p‐phenylene‐Based Supramolecular Polymers: Influence of Molecular Atropisomerism

The helical organization of oligo‐p‐phenylene‐based organogelators has been investigated by atomic force microscopy, circular and vibrational circular dichroism, and Raman techniques. Whilst OPPs with more than two phenyl rings in the core self‐assemble into left‐handed helices, that with a biphenyl core shows an inversion of the supramolecular helicity depending on the formation conditions through the atropisomerism of the biphenyl central unit. The results presented herein outline a new example of kinetically controlled modulation of supramolecular helicity.