Stimuli-responsive synthetic helical polymers.

Synthetic dynamic helical polymers (supramolecular and covalent) and foldamers share the helix as a structural motif. Although the materials are different, these systems also share many structural properties, such as helix induction or conformational communication mechanisms. The introduction of stimuli responsive building blocks or monomer repeating units in these materials triggers conformational or structural changes, due to the presence/absence of the external stimulus, which are transmitted to the helix resulting in different effects, such as assymetry amplification, helix inversion or even changes in the helical scaffold (elongation, J/H helical aggregates). In this review, we show through selected examples how different stimuli (e.g., temperature, solvents, cations, anions, redox, chiral additives, pH or light) can alter the helical structures of dynamic helical polymers (covalent and supramolecular) and foldamers acting on the conformational composition or molecular structure of their components, which is also transmitted to the macromolecular helical structure.

P/M Macromolecular Switch Based on Conformational Control Exerted by an Achiral Side Chain within an Axially Chiral Locked Pendant.

Molecular switches, supramolecular chemistry, and polymers can be combined to create stimuli-responsive multichiral materials. Therefore, by acting on the extended/bent conformational composition of an achiral arm, it is possible to create a macromolecular gear, where different supramolecular interactions can be activated/deactivated to control the helical sense of a polymer containing up to five different chiral axial motifs. For this, a chiral allene with a flexible achiral arm was introduced as a pendant in poly(phenylacetylene). Through flexible arm control between extended and bent conformations, it is possible to selectively induce either a P or M helical sense in the polymer, while the relative spatial distribution of the substituents in the allene remains unaltered in two perpendicular planes (configurationally locked). These results show that complex dynamic multichiral materials can be obtained by the polymerization of appropriate monomers that combine chirality, switching properties, and the ability to generate chiral supramolecular assemblies.

Size Control of Chiral Nanospheres Obtained via Nanoprecipitation of Helical Poly(phenylacetylene)s in the Absence of Surfactants.

Nanostructuration of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) depends on the secondary structure adopted by the polymer and the functional group used to connect the chiral pendant to the PPA backbone. Thus, while PPAs with dynamic and flexible scaffolds (para- and meta-substituted, ω1< 165º) generate by nanoprecipitation low polydisperse nanospheres with controllable size at different acetone/water mixtures, those with a quasi-static behavior and the presence of an extended, almost planar structure (ortho-substituted, ω1> 165º), aggregate into a mixture of spherical and oval nanostructures whose size is not controlled. Photostability studies show that poly(phenylacetylene) particles are more stable to light irradiation than when dissolved macromolecularly. Moreover, the photostability of the particle depends on the secondary structure of the PPA and its screw sense excess. This fact, in combination with the encapsulation ability of these polymer particles, allows the creation of light stimuli-responsive nanocarriers, whose cargo can be delivered by light irradiation.

Metallo-Supramolecular Helical Fibres from Chiral Phenylacetylene Monomers: Cation Induced Self-Assembly.

Chiral metallo-supramolecular fibres can be easily obtained by mixing a chloroform solution of a phenylacetylene monomer (PA) that bears a chiral sulfoxide group as pendant, with different equivalents of a methanolic solution of AgClO4 . Thus, while the PA is found molecularly dissolved in chloroform, the addition of Ag+ ions induce its aggregation through the formation of an axially chiral metallo-supramolecular aggregate with high thermal stable properties. In this case, the ability of the metal ion to coordinate the PA triple bond, combined with the argentophilicity of the metal ion and the planarity of the phenylacetylene drives to the formation of a helical coordination polymer, whose P or M axial chirality is determined by the chirality of the sulfoxide used as substituent of the PA. Depending on the PA/Ag+ (mol/mol) ratio, it is possible to tune the morphology of the metallo-supramolecular aggregate from chiral fibers to chiral gel.

Diastereomeric multi-chiral pendant groups: Their key role in stimuli-responsive polymeric responses.

Chiral information transmission in helical polymers bearing multi-chiral pendant groups is usually determined by the absolute configuration of the first chiral center. The second chiral residue usually has low-to-null influence in the macromolecular handedness of the polymer, due to its remote position respect to the polyene main chain. Here, we demonstrate how the stimuli responsive properties of diastereomeric polymers, obtained by changing the absolute configuration of the second chiral center, are different due to the unlike properties of diastereoisomers.

Conformational Kinetics in Chiral Poly(diphenylacetylene)s: A Dynamic P/M Memory Effect.

Dynamic P/M (plus/minus) helical memory in chiral dissymmetric poly(diphenylacetylene)s (PDPA) is shown using a PDPA that bears the benzamide of (L)-alanine methyl ester as pendant. For a single chiral polymer, it is possible to obtain either P or M helical structures in a specific solvent without the presence of any chiral external stimuli. To do that, it is necessary to combine the conformational control at the pendant group with a high steric hindrance at the backbone. In this case, by thermal annealing in low-polar solvents, an anti-conformer is stabilized at the pendant which commands a P helix in the PDPA. Next, solvent removal followed by addition of a polar solvent such as dimethyl sulfoxide (DMSO), results in the kinetic conformationally trapped P helix. However, in this medium, the preferred handedness and the thermodynamic macromolecular helix for poly-(L)-1 is M. This process also occurs in the opposite way. Electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) studies show that the dynamic memory effect is present both in ground and excited states.

Dynamic Axial-to-Helical Communication Mechanism in Poly[(allenylethynylenephenylene)acetylene]s under External Stimuli.

Helix inversion in chiral dynamic helical polymers is usually achieved by conformational changes at the pendant groups induced through external stimuli. Herein, a different mechanism of helix inversion in poly(phenylacetylene)s (PPAs) is presented, based on the activation/deactivation of supramolecular interactions. We prepared poly[(allenylethynylenephenylene)acetylene]s (PAEPAs) in which the pendant groups are conformationally locked chiral allenes. Therefore, their substituents are placed in specific spatial orientations. As a result, the screw sense of a PAEPA is fixed by the allenyl substituent with the optimal size/distance relationship to the backbone. This helical sense command can be surpassed by supramolecular interactions between another substituent on the allene and appropriate external stimuli, such as amines. So, a helix inversion occurs through a novel axial-to-helical communication mechanism, opening a new scenario for taming the helices of chiral dynamic helical polymers.

Elucidating the Supramolecular Copolymerization of N- and C-Centered Benzene-1,3,5-Tricarboxamides: The Role of Parallel and Antiparallel Packing of Amide Groups in the Copolymer Microstructure.

An in-depth study of the supramolecular copolymerization behavior of N- and C-centered benzene-1,3,5-tricarboxamides (N- and C-BTAs) has been conducted in methylcyclohexane and in the solid state. The connectivity of the amide groups in the BTAs differs, and mixing N- and C-BTAs results in supramolecular copolymers with a blocky microstructure in solution. The blocky microstructure results from the formation of weaker and less organized, antiparallel hydrogen bonds between N- and C-BTAs. In methylcyclohexane, the helical threefold hydrogen-bonding network present in C- and N-BTAs is retained in the mixtures. In the solid state, in contrast, the hydrogen bonds of pure BTAs as well as their mixtures organize in a sheet-like pattern, and in the mixtures long-range order is lost. Drop-casting to kinetically trap the solution microstructures shows that C-BTAs retain the helical hydrogen bonds, but N-BTAs immediately adopt the sheet-like pattern, a direct consequence of the lower stabilization energy of the helical hydrogen bonds. In the copolymers, the stability of the helical aggregates depends on the copolymer composition, and helical aggregates are only preserved when a high amount of C-BTAs is present. The method outlined here is generally applicable to elucidate the copolymerization behavior of supramolecular monomers both in solution as well as in the solid state.

The Role of Polymer-AuNP Interaction in the Stimuli-Response Properties of PPA-AuNP Nanocomposites.

The helical sense control of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) is greatly affected when they are conjugated to AuNPs through a strong thiol-Au connection, which restricts conformational changes at the polymer. Thus, the classical thiol-MNP bonds must be replaced by weaker ones, such as supramolecular amide-Au interactions. A straightforward preparation of the PPA-Au nanocomposite by reduction of a preformed PPA-Au3+ complex cannot be used due to a redox reaction between the two components of the complex which degrades the polymer. To avoid the interaction between the PPA and the Au3+ ions before the reduction takes place, the metal ions are added to the polymer solution capped as a TOAB complex, which keeps the PPA stable due to the lack of PPA-Au3+ interactions. Ulterior reduction of the Au3+ ions by NaBH4 affords the desired nanocomposite, where the AuNPs are stabilized by supramolecular anilide-AuNPs interactions. By using this approach, 3.7 nm gold nanoparticles are generated and aligned along the polymer chain with a regular distance between particles of 6 nm that corresponds to two helical pitches. These nanocomposites show stimuli-responsive properties and are also able to form macroscopically chiral nanospheres with tunable size.

Dissymmetric Chiral Poly(diphenylacetylene)s: Secondary Structure Elucidation and Dynamic Luminescence.

The secondary structure of a dissymmetric and chiral poly(diphenylacetylene) (PDPA) is elucidated by combining the data from NMR experiments (regioregular head to tail structure), Raman and IR studies (E configuration of the polyene double bonds), and high-resolution AFM images (helical pitch, packing angle and orientation of the external helix). As a result, an E-transoidal polyene backbone describing three coaxial helices is obtained. Theoretical electronic circular dichroism (ECD) studies of the structure show a good correspondence between experimental and theoretical data and allow one to decipher that the first Cotton band is generated by the poly(diphenylacetylene) core and not only by the polyene backbone. The dynamic behavior of poly-(S)-2 is also demonstrated by a helix inversion effect produced by conformational changes at the pendant groups when annealed in solvents with different donor abilities. This phenomenon is accompanied by an inversion of the circular polarized luminescence of the PDPA (CPL switch).

Photostability and Dynamic Helical Behavior in Chiral Poly(phenylacetylene)s with a Preferred Screw-Sense.

Helical polymers such as poly(phenylacetylene)s (PPAs) are interesting materials due to the possibility of tuning their helical scaffold (sense and elongation) once they have been prepared and by the presence of external stimuli. The main limitation in the application of PPAs is their poor photostability. These polymers degrade under visible light exposure through a photochemical electrocyclization process. In this work, it was demonstrated, through a selected example, how the photochemical degradation in PPAs is directly related to their dynamic helical behavior. Thus, while PPAs with dynamic helical structures show poor photostability under UV/Vis light exposure, poly-(R)-1, bearing an enantiopure sulfoxide group as pendant group and designed to have a quasi-static helical behavior, shows a large photostability due to the restricted conformational composition at the polyene backbone, needed to orient the conjugated double bonds prior to the photochemical electrocyclization process and the subsequent degradation of the material.

Full Control of the Chiral Overpass Effect in Helical Polymers: P/M Screw Sense Induction by Remote Chiral Centers After Bypassing the First Chiral Residue.

In helical polymers, helical sense induction is usually commanded by teleinduction mechanism, where the largest substituent of the chiral residue directly attached to the main chain is the one that commands the helical sense. In this work, different helical structures with different helical senses are induced in a helical polymer [poly-(phenylacetylene)] when the conformational composition of two different dihedral angles of a pendant group with more than two chiral residues is tamed. Thus, while the dihedral angle at chiral residue 1 [(R)- or (S)-alanine], attached to the backbone, produces an extended or bent conformation in the pendant resulting in two scaffolds with different stretching degree, the second dihedral angle at chiral residue 2 [(R)- or (S)-methoxyphenylacetamide] places the substituents of this chiral center in a different spatial orientation, originating opposite helical senses at the polymer that are induced through a total control of the "chiral overpass effect".

Merging Supramolecular and Covalent Helical Polymers: Four Helices Within a Single Scaffold.

Supramolecular and covalent polymers share multiple structural effects such as chiral amplification, helical inversion, sergeants and soldiers, or majority rules, among others. These features are related to the axial helical structure found in both types of materials, which are responsible for their properties. Herein a novel material combining information and characteristics from both fields of helical polymers, supramolecular (oligo(p-phenyleneethynylene) (OPE)) and covalent (poly(acetylene) (PA)), is presented. To achieve this goal, the poly(acetylene) must adopt a dihedral angle between conjugated double bonds (ω1) higher than 165°. In such cases, the tilting degree (Θ) between the OPE units used as pendant groups is close to 11°, like that observed in supramolecular helical arrays of these molecules. Polymerization of oligo[(p-phenyleneethynylene)n]phenylacetylene monomers (n = 1, 2) bearing L-decyl alaninate as the pendant group yielded the desired scaffolds. These polymers adopt a stretched and almost planar polyene helix, where the OPE units are arranged describing a helical structure. As a result, a novel multihelix material was prepared, the ECD spectra of which are dominated by the OPE axial array.

From Oligo(Phenyleneethynylene) Monomers to Supramolecular Helices: The Role of Intermolecular Interactions in Aggregation.

Supramolecular helices that arise from the self-assembly of small organic molecules via non-covalent interactions play an important role in the structure and properties of the corresponding materials. Here we study the supramolecular helical aggregation of oligo(phenyleneethynylene) monomers from a theoretical point of view, always guiding the studies with experimentally available data. In this way, by systematically increasing the number of monomer units, optimized n-mer geometries are obtained along with the corresponding absorption and circular dichroism spectra. For the geometry optimizations we use density functional theory together with the B3LYP-D3 functional and the 6-31G** basis set. For obtaining the spectra we resort to time-dependent density functional theory using the CAM-B3LYP functional and the 3-21G basis set. These combinations of density functional and basis set were selected after systematic convergence studies. The theoretical results are analyzed and compared to the experimentally available spectra, observing a good agreement.

The Competitive Aggregation Pathway of an Asymmetric Chiral Oligo(p-phenyleneethynylene) Towards the Formation of Individual P and M Supramolecular Helical Polymers.

A complex aggregation pathway towards two diastereomeric P and M supramolecular helices arises from the aggregation of a short, chiral, and rigid oligo(phenyleneethynylene) [OPE, (S)-1]. Thus, while AggI aggregate is obtained when a DCM solution of (S)-1 is diluted with MCH at room temperature, AggII aggregate is generated only after a slow heating (353 K)/cooling (273 K) process. Interestingly, during AggI formation (mechanism 1), short P chain oligomers are produced, which have a great tendency to aggregate in plane, yielding brick-like nanostructures that halt the aggregation process. On the other hand, after a heating/cooling cycle, long M type columnar helical aggregates (AggII ) are obtained, formed by individual supramolecular polymer chains (mechanism 2) easily visualized by AFM. The two different P/M orientations obtained for AggI and AggII reveal the dynamic character of the system and its ability to create diastereomeric helical structures under the right conditions. Different experimental protocols were explored to prepare long M type columnar helical aggregates, which are not obtained by using the previous MCH/DCM 99/1 (v/v) solvent mixture. The generation of the desired M oriented supramolecular polymer is achieved when toluene is added to the solvent mixture in a 97/2/1 MCH/Tol/DCM (v/v/v) ratio.

Photochemical Electrocyclization of Poly(phenylacetylene)s: Unwinding Helices to Elucidate their 3D Structure in Solution.

Photochemical electrocyclization of poly(phenylacetylene)s (PPAs) is used for the structural elucidation of a polyene backbone. This method not only allows classification of PPAs in cis-cisoidal (ω1 <90°) or cis-transoidal structures (ω1 >90°), but also approximating ω1 . A PPA solution is illuminated with visible light and monitoring the photochemical electrocyclization of the PPA helix by measuring the ECD spectra at different times. PPAs with a cis-cisoidal structure show a reduction of the ECD signal of at least 50 % before 30 min of irradiation, while cis-transoidal helices need much longer time because the transoidal bond must be isomerized. The different cis-cisoidal and cis-transoidal helices require different times to decrease their ECD signal by 50 % (t1/2 ), depending on the degree of compression or stretching of the helix, establishing a relationship between the secondary structure adopted by PPA (ω1 ) and the time required to lose the ECD vinylic signal by light irradiation.

From Sergeants and Soldiers to Chiral Conflict Effects in Helical Polymers by Acting on the Conformational Composition of the Comonomers.

Different communication mechanisms can be switched within a copolymer by acting on the conformational composition of the components and their chirality. Thus, a sergeant and soldiers effect is produced in two diastereomeric copolymer series, poly[(S)-1r -co-(S)-2(1-r) ] and poly[(R)-1r -co-(S)-2(1-r) ], owing to the presence in chloroform of a preferred conformation in (S)-2, and a conformational equilibrium in 1, where a P helix is induced independently of the absolute configuration of the soldier. In THF, the presence of a conformational equilibrium at the pendants of the two components produces a reciprocal chiral enhancement effect by copolymerization of the two monomers, while in DMF, a third chiral to chiral communication switch is produced due to the presence of a single conformer at the pendant group of the two components. In such a case, a chiral conflict or chiral accord effect is produced depending if the two components induce the same or the opposite helical sense.

A Stimuli-Responsive Macromolecular Gear: Interlocking Dynamic Helical Polymers with Foldamers.

Herein, macromolecular gears composed of helical poly(phenylacetylenes) (PPAs) bearing short oligopeptides as pendant groups are described, in which the two structural motifs (framework and substituents) are combined. These gears are obtained by polymerization of the acetylene groups introduced at the C-terminus of short oligopeptides formed by achiral (Aib)n units (n=1-3) derivatized at the N-terminus by a single enantiomer (R or S) of α-methoxy-α-trifluoromethylphenylacetic acid (MTPA, Mosher's reagent). The chiral information of the MTPA is transmitted to the achiral Aib fragments and, through either chiral tele-induction and/or chiral harvesting mechanisms, is further transferred to the polyene backbones, which adopt preferentially P or M helical senses. Moreover, these materials also show dynamic behavior and respond to the action of external stimuli by either inverting the P/M sense and/or modifying the elongation in fully reversible processes.

Chiral Overpass Induction in Dynamic Helical Polymers Bearing Pendant Groups with Two Chiral Centers.

The dynamic behavior of helical polymers bearing pendant groups with two chiral centers was studied. Controlled conformational changes at the chiral units placed either closer to or further away from the main chain promote different helical structures. Although the first residue is usually responsible for determining a specific helicity (P or M), we now found that the second chiral center is also able to induce a preferred helical sense when it is located closer in space to the main chain, thereby cancelling the order from the first chiral moiety. This result was achieved through proper coordination with a metal cation. As proof of concept, poly(phenylacetylene)s (PPAs) that bear one and two chiral amino acid units of different sizes and configuration combinations (l/d-alanine and l/d-phenylalanine) as pendants were evaluated. In total, ten polymers were studied. This constitutes the first report of axial control from a remote stereocenter in polymers bearing complex chiral pendants.

Raman Optical Activity (ROA) as a New Tool to Elucidate the Helical Structure of Poly(phenylacetylene)s.

Poly(phenylacetylene)s are a family of helical polymers constituted by conjugated double bonds. Raman spectra of these polymers show a structural fingerprint of the polyene backbone which, in combination with its helical orientation, makes them good candidates to be studied by Raman optical activity (ROA). Four different well-known poly(phenylacetylene)s adopting different scaffolds and ten different helical senses have been prepared. Raman and ROA spectra were recorded and allowed to establish ROA-spectrum/helical-sense relationships: a left/right-handed orientation of the polyene backbone (Mhelix /Phelix ) produces a triplet of positive/negative ROA bands. Raman and ROA spectra of each polymer exhibited the same profile, and the sign of the ROA spectrum was opposite to the lowest-energy electronic circular dichroism (ECD) band, indicating a resonance effect. Resonance ROA appears then as an indicator of the helical sense of poly(phenylacetylene)s, especially for those with an extra Cotton band in the ECD spectrum, where a wrong helical sense is assigned based on ECD, while ROA alerts of this misassignment.