M-phenylene Ethynylene Oligomers Research Articles

Organogels formed by substituent-free pyrene-appended oligo(m-phenylene ethynylene)s

A new class of pyrene-appended m-phenylene ethynylene oligomers, which bear no alkyl chains or heteroatoms, have been demonstrated to gelate organic solvents, and one of them forms chiral twisted gels in cyclohexane.

Foldamers: They’re Not Just for Biomedical Applications Anymore

Conformationally ordered synthetic oligomers, called foldamers, are a class of compounds that have ushered into prominence, and interest in these systems continues unabated, primarily as a result of the fact that they hold considerable promise for potential applications in biomedical sciences. These synthetic oligomers may provide excellent starting points for the elaboration of peptide mimics that could only be designed with difficulty on the basis of small-molecule scaffolds. By means of diverse synthetic tools, the “bottomup” foldamer approach is also highly useful in engineering new frameworks that can be successfully molded to mimic the structure and functions of biopolymers. The scope and feasibility of this concept is reflected in the exponential growth from its foundation in the early 21st century to the present stage. The recent launch of the heterofoldamer concept has further fuelled activity in this area, essentially because the conformational space that is available for foldamer design can be enormously augmented by developing oligomers that feature a variety of building blocks in the backbone. Despite offering considerable promise because of the enormous structural diversity, a breakthrough in applications of the foldamers in material science, in particular in molecular machines, is yet to be realized. The technique of using foldamers as dynamic receptors for rod-like guest molecules was first described by Moore and coworkers. In their interesting study, it was demonstrated that m-phenylene ethynylene oligomers fold into macromolecular receptors and adopt a helical architecture that binds to hydrophobic guests. In the helical conformation, these oligomers bind nonpolar ligands within the tubular hydrophobic cavity. Along this line, Huc and co-workers recently reported a fascinating finding that conveys clear indications that the time has come to scan the wide repertoire of foldamers for the purpose of developing molecular machines and nanodevices. This idea is valid because foldamers of any desired shape/architecture can be engineered by using delicate and flexible noncovalent interactions, among which the highly directional hydrogen-bonding interaction assumes prime importance. In their classic paper, Huc and coworkers demonstrated that double helical foldamers that are coiled around rod-shaped guest molecules can perform a screw-type motion, which is an unusual phenomenon that is not observed in other molecular machines (Figure 1a). The heterofoldamers described by Huc and co-workers, called

ChemInform Abstract: Conformational Ordering of Apolar, Chiral m-Phenylene Ethynylene Oligomers.

A series of m-phenylene ethynylene oligomers containing nonpolar, (S)-3,7-dimethyl-1-octanoxy side chains have been synthesized and studied. In apolar alkane solvents, oligomers of sufficient length (n > 10) were found to adopt a helical conformation with a large twist sense bias. In contrast, in chloroform the oligomers adopt a random coil conformation. Surprisingly, the strong twist sense bias was determined to be highly time dependent and is partially attributed to intermolecular aggregation.

Covalent Assembly of Molecular Ladders

[n]-Rung molecular ladders (n = 3−6) have been prepared by reacting discrete, complimentary m-phenylene ethynylene oligomers using imine formation/exchange. The nanostructures, which in the largest case measure approximately 1.6 × 6.2 nm, have been characterized by MALDI mass spectrometry and gel permeation chromatography. Although the ladder structure is a significant component in each case, the formation of higher molecular weight byproducts becomes more pronounced as the length increases. These structures represent an important first step toward the synthesis of larger, more sophisticated two-dimensional molecular grids.

Solution-Phase Structure of an Artificial Foldamer: X-ray Scattering Study

Foldamers provide important insights into the fundamentals of noncovalent folding, which is of primary importance for understanding biological systems and developing novel self-assembling materials. The structure of artificial foldamers in solution has been studied using a variety of indirect spectroscopic techniques and theoretical methods. X-ray scattering using a high flux synchrotron source has been recently shown to provide a powerful means of studying small organic and biological arrays that are formed because of noncovalent self-assembly in solution but has not been applied to foldamer structures. We present small angle X-ray scattering (SAXS) studies on a m-phenylene ethynylene oligomer (mPE) in acetonitrile, providing for the first time-direct structural data on a mPE foldamer in solution.

Solid-Phase Synthesis of m-Phenylene Ethynylene Heterosequence Oligomers

Both homo- and heterosequence m-phenylene ethynylene oligomers are synthesized using a conceptually simple iterative solid-phase strategy. Oligomers are attached to Merrifield's resin through a known triazene-type linkage. The phenylene ethynylene molecular backbone is constructed through a series of palladium-mediated cross-coupling reactions. The strategy employs two types of monomers that bear orthogonal reactivity, one being a monoprotected bisethynyl arene and the other being a 3-bromo-5-iodo arene. The catalyst conditions are tailored to the requirements of each monomer type. The monoprotected bisethynyl arene is coupled to the growing chain in 2 h at room temperature using a Pd(I) dimer precatalyst ((t)Bu3P(Pd(mu-Cl)(mu-2-methyl allyl)Pd)P(t)Bu3) in conjunction with ZnBr2 and diisopropylamine. In alternate steps, the resin is deprotected in situ with TBAF and coupled to the 3-bromo-5-iodo arene using the iodo selective Pd(tri-2-furylphosphine)4 catalyst in conjunction with CuI and piperidine; this reaction is also completed in 2 h at room temperature. These cross-coupling events are alternated until an oligomer of the desired length is achieved. The oligomer is then cleaved from the resin using CH(2)I(2)/I(2) at 110 degrees C and purified using preparatory GPC. Using this method, a series of homo- and heterosequence oligomers up to 12 units in length in excellent yield and purity were synthesized on the 100 mg scale. Longer oligomers were attempted; however, deletion sequences were found in oligomers longer than 12 units.

Foldamer dynamics expressed via Markov state models. II. State space decomposition

The structural landscape of poly-phenylacetylene (pPA), otherwise known as m-phenylene ethynylene oligomers, has been shown to consist of a very diverse set of conformations, including helices, turns, and knots. Defining a state space decomposition to classify these conformations into easily identifiable states is an important step in understanding the dynamics in relation to Markov state models. We define the state decomposition of pPA oligomers in terms of the sequence of discretized dihedral angles between adjacent phenyl rings along the oligomer backbone. Furthermore, we derive in mathematical detail an approach to further reduce the number of states by grouping symmetrically equivalent states into a single parent state. A more challenging problem requires a formal definition for knotted states in the structural landscape. Assuming that the oligomer chain can only cross the ideal helix path once, we propose a technique to define a knotted state derived from a helical state determined by the position along the helical nucleus where the chain crosses the ideal helix path. Several examples of helical states and knotted states from the pPA 12-mer illustrate the principles outlined in this article.

Sequence-Specific Binding of m-Phenylene Ethynylene Foldamers to a Piperazinium Dihydrochloride Salt

[reaction: see text] Binding properties of a series of isomeric m-phenylene ethynylene oligomers containing short amide sequences to a piperazinium dihydrochloride salt were investigated by using circular dichroism (CD) measurements. Although these isomeric oligomers exhibited similar helical conformations, high affinity was observed only for one oligomer. This behavior is presumably controlled by the orientation of amino groups of the amide sequence and the folded conformation of the oligomer.

A helicene-containing foldamer displaying highly solvent-dependent CD spectra.

[structure: see text] A m-phenylene ethynylene oligomer containing a helicene unit was synthesized to bias the twist sense of the folded helical conformation. The CD spectra of the helicene oligomer exhibited large Cotton effects that varied greatly with the solvent composition, including three separate conformational transitions.

Supramolecular control over donor-acceptor photoinduced charge separation.

A novel donor-bridge-acceptor system has been synthesized by covalently linking a p-phenylene vinylene oligomer (OPV) and a perylene diimid (PERY) at opposite ends of a m-phenylene ethynylene oligomer (FOLD) of twelve phenyl rings, containing nonpolar (S)-3,7-dimethyl-1-octanoxy side chains. For comparison, model compounds have been prepared in which either the donor or acceptor is absent. In chloroform, the oligomeric bridge is in a random coil conformation. Upon addition of an apolar solvent (heptane) the oligomeric bridge first folds into a helical stack and subsequently intermolecular self-assembly of the stacks into columnar architectures occurs. Photoexcitation in the random coil conformation, where the interaction between the donor and acceptor chromophores is small, results only in long-range intramolecular energy transfer in which the OPV singlet-excited state is transformed into the PERY singlet-excited state. In the folded conformation of the bridge, donor and acceptor are closer and their enhanced interaction favors the formation the OPV(*)(+)-FOLD-PERY(*)(-) charge-separated state upon photoexcitation. As a result, the extent of photoinduced charge separation depends on the degree of folding of the bridge between donor and acceptor and therefore on the apolar nature of the medium. As a consequence, and contrary to conventional photoinduced charge separation processes, the formation of the OPV(*)(+)-FOLD-PERY(*)(-) charge-separated state is more favored in apolar media.

Single-site modifications and their effect on the folding stability of m-phenylene ethynylene oligomers.

[reaction: see text] The folded structure of a m-phenylene ethynylene oligomer is tolerant to single-site modifications to both the backbone sequence and end groups. The helical structure is reinforced by multiple noncovalent interactions, allowing the oligomer sequence to be customized without a significant change in stability in most cases. The small changes that are observed are consistent with the expected behavior of pi-stacked systems and demonstrate subtle control over folding through single-site modifications.

Pyridine-containing m-phenylene ethynylene oligomers having tunable basicities.

Incorporation of a pyridine monomer into the backbone of a m-phenylene ethynylene oligomer allows functionalization of the interior binding cavity of the folded oligomer. The basicity of the inwardly directed pyridine moiety was modulated by changing the substituents on the pyridine ring and through oligomer folding, granting access to a pK(a) range of 5-14 in acetonitrile. [reaction: see text]

M-Phenylene ethynylene sequences joined by imine linkages: dynamic covalent oligomers.

Imine metathesis between m-phenylene ethynylene oligomers of various lengths was performed in acetonitrile, a solvent in which oligomers containing eight or more repeat units adopt a compact helical conformation. The equilibrium constants and corresponding free energy change for the imine metathesis reactions were estimated. The results showed that the magnitude of equilibrium shifting measured by the free energy change for the formation of imine-containing oligomers increases linearly below a critical product chain length and grows asymptotically above it. The linear region is ascribed to the constant increase in contact area between monomer units of adjacent helical turns as the product chain grows to the 12-mer. Once the ligation product is 12 units in length, full contact is made between adjacent helical turns. On the other hand, for imine metathesis between oligomers leading to products having more than 12 units, the driving force is the difference between the folding energy of products and that of reactants. The additional stabilizing energy is roughly constant, regardless of the chain length, since the contact area between adjacent helical turns is unchanged. Consistent with the notion that the imine bond only minimally destabilizes the helical conformation, the position of the imine bond in the ligation product has been observed to have no significant effect on the folding stability. The magnitudes of equilibrium shifting are similar for ligation products of the same length but having the imine at various positions along the sequence. This suggests that the imine bond is compatible with the m-phenylene ethynylene backbone, regardless of the position in the sequence. Imine metathesis of m-phenylene ethynylene oligomers could allow a quick access to an unbiased, dynamic library of oligomer sequences joined by imine linkages.

Folding-Driven Reversible Polymerization of Oligo(m-phenylene ethynylene) Imines: Solvent and Starter Sequence Studies

Bis(imino) end-functionalized oligo(m-phenylene ethynylene)s were equilibrated in a closed system under conditions that promote reversible imine metathesis. The metathesis reaction joins two oligomers and produces a small molecule byproduct. In polar solvents, equilibration gave high molecular weight polymers while equilibration in chloroform produced only low molecular weight oligomers. This polymerization is hypothesized to be driven by the free energy gained from the folding of the long polymer chains directed by the noncovalent, intramolecular aromatic stacking and solvophobic interactions. This polymerization was also conducted in a series of solvents in which m-phenylene ethynylene oligomers have previously shown varied, intermediate folding stabilities. These experiments revealed a good correlation of the product molecular weight with the stability of the m-phenylene ethynylene helix. The equilibrium state of the metathesis reaction was also demonstrated to depend on the chain length of the starter...

Hydrogen bond-stabilized helix formation of a m-phenylene ethynylene oligomer.

[reaction: see text] Incorporation of a single hydrogen bonded beta-turn mimic in the backbone of a m-phenylene ethynylene oligomer is shown to affect the thermodynamic properties of the folding reaction. Oligomers 1 and 2 both undergo solvophobic helix formation, but hydrogen bonded oligomer 1 was found to form a more stable helix with a higher tolerance to solvent denaturation than isomeric, non-hydrogen bonded oligomer 2.

Reversible polymerization driven by folding.

Bisfunctionalized m-phenylene ethynylene imine oligomers were polymerized in the polar solvent acetonitrile, resulting in high-molecular weight poly(m-phenylene ethynylene imine)s. It is hypothesized that this polymerization, which proceeds through the reversible metathesis of imine bonds, is driven by the folding of the long m-phenylene ethynylene imine chains. Upon conducting the polymerization in a series of solvents in which the m-phenylene ethynylene oligomers exhibit different folding stabilities, it was possible to correlate the molecular weight of the resulting poly(m-phenylene ethynylene imine)s with the helical stability of the corresponding oligomers. The polymerization was also demonstrated to be reversible and responsive to solvent and temperature changes.

The size-selective synthesis of folded oligomers by dynamic templation.

A dynamic pool of m-phenylene ethynylene oligomers generated by sequence ligation using the imine metathesis reaction was equilibrated under a variety of conditions, and the mixture of products was analyzed by HPLC. The equilibration was performed in the presence and absence of rodlike ligand 2b, which exhibits an affinity for the helical oligomers that is very length specific. Among the eight oligomers generated during metathesis equilibrium, the formation of 22-mer 6b was enhanced in acetonitrile in the presence of 2b. This particular oligomer has the highest binding affinity for 2b. Quantitative analysis by HPLC of the products indicated that 6b was produced in 66% yield in the presence of 2 equiv 2b while a 37% yield was produced in the absence of 2b. Judging from the binding affinities of oligomers 6 with 2b, the equilibrium shifting was driven by the selective binding of 6b with 2b.

Cooperativity in the folding of helical m-phenylene ethynylene oligomers based upon the 'sergeants-and-soldiers' principle.

The 'Sergeants-and-Soldiers' principle has been examined in a series of m-phenylene ethynylene oligomers containing both chiral and achiral side chains. Circular dichroism (CD) spectroscopy was used to examine the twist sense bias of the helical conformation in the polar solvent acetonitrile. A non-linear dependence of the CD signal on the amount of chiral side chains was observed revealing cooperative interactions among the side chains through the backbone. On the other hand, the experiments indicate that in acetonitrile a full bias of the helicity cannot be accomplished by chiral side chains alone. Nevertheless, the folded oligomers are highly ordered since the placement of a single chiral side chain at the beginning of an oligomer results in the induction of a strong twist sense bias into the ordered helical conformation.

Self-assembly of folded m-phenylene ethynylene oligomers into helical columns.

Circular dichroism spectroscopy has been used to study the self-assembly of two series of m-phenylene ethynylene oligomers in highly polar solvents. The helical conformation of shorter oligomer lengths was found to be stabilized in aqueous acetonitrile solutions, while longer oligomers began to interact intermolecularly. The intermolecular aggregation of the oligomers in aqueous solutions revealed a chain length dependent association that required the presence of a stable helical conformation. Evidence for intermolecular interactions is provided by Sergeants and Soldiers experiments in which the twist sense bias of a chiral oligomer is transferred to an achiral oligomer.

The Effect of Pressure on the Conformation of Two Sets of m-Phenylene Ethynylene Oligomers in PMMA and PtBMA

The effect of pressure has been studied on the emission characteristics of two sets of m-phenylene ethynylene oligomers in solid poly(methyl methacrylate) (PMMA) and polytertbutylmethacrylate (PtBMA). For oligomer 1, the tetramer, decamer, and hexadecamer (4-mer, 10-mer, and 16-mer) were used. For oligomer 2, the chain lengths 10, 16, 20, and 24 were examined. In liquid solution larger oligomers can exist either in a folded (helical) or unfolded state (random coil) or a mixture thereof depending upon the compatibility with the solvent. The 10-mer and 16-mer of oligomer 1 and 10-mer, 16-mer, 20-mer and 24-mer of oligomer 2 exist primarily in a folded conformation in the polymeric media at 1 atm. With increasing pressure, they unfold so that, between 30 and 60 kbar, one can establish the equilibrium constant as a function of pressure. The pressure derivative of this quantity gives the difference in partial molar volume ΔV‘ = VF − VU. In all cases ΔV‘ decreased with increasing pressure. ΔV‘ is larger for ...