Félix Freire

Chiral Amplification and Helical‐Sense Tuning by Mono‐ and Divalent Metals on Dynamic Helical Polymers

Herein we report the synthesis and evaluation of a newand highly dynamic poly(phenylacetylene) (PPA) derivativethat bears chiral pendants. This polymer incorporates the twoaforementioned features (selective helix induction and chiralamplification) to give a material that acts as a sensor for thevalence of metal cations. In the amplification of chiralityreported herein, the external stimulus—the trigger—is pro-vided by the selective coordination of the pendants withmono-or divalentmetalcations (achiralagents)in suchawaythat the valence of the metal determines the right- or left-handed helical sense of the polymer and its chiropticalresponse.

Nanospheres with tunable size and chirality from helical polymer-metal complexes.

A new family of nanospheres is made by complexation of divalent metals (i.e., Ca(2+), Ba(2+)) and poly(phenylacetylene) polymers bearing α-methoxyphenylacetic acid (MPA) pendants with high content of the cis isomer responsible for their helical structures. The resulting helical polymer-metal complex (HPMC) nanospheres present two interesting properties: (a) their diameter can be tuned to different sizes, to growth or to shrink, by changing the metal ion or the polymer/metal ion ratio, and (b) the helicity on the surface and the interior of the particle can be tuned to any of the two helical senses (M or P) by selection of the metal ion. The role of the solvent, the metal ion, and the helicity of the polymer in the aggregation are discussed. The ability of these nanospheres to encapsulate is demonstrated with examples.

Nanospheres, Nanotubes, Toroids, and Gels with Controlled Macroscopic Chirality†

The interaction of a highly dynamic poly(aryl acetylene) (poly-1) with Li(+), Na(+), and Ag(+) leads to macroscopically chiral supramolecular nanospheres, nanotubes, toroids, and gels. With Ag(+), nanospheres with M helicity and tunable sizes are generated, which complement those obtained from the same polymer with divalent cations. With Li(+) or Na(+), poly-1 yields chiral nanotubes, gels, or toroids with encapsulating properties and M helicity. Right-handed supramolecular structures can be obtained by using the enantiomeric polymer. The interaction of poly-1 with Na(+) produces nanostructures whose helicity is highly dependent on the solvation state of the cation. Therefore, structures with either of the two helicities can be prepared from the same polymer by manipulation of the cosolvent. Such chiral nanotubes, toroids, and gels have previously not been obtained from helical polymer-metal complexes. Chiral nanospheres made of poly(aryl acetylene) that were previously assembled with metal(II) species can now be obtained with metal(I) species.

The ON/OFF switching by metal ions of the “Sergeants and Soldiers” chiral amplification effect on helical poly(phenylacetylene)s

Here we report copolymers where the “Sergeants and Soldiers effect” can be switched ON and OFF by the presence of a metal ion. These copolymers have been prepared by a combination of achiral and chiral monomer units, where the chiral ones are unable to drive the chiral amplification unless a small amount of mono- or divalent metal ions is added. In this way, the ions act as promoters upgrading some of the chiral pendants, initially unable to induce a preferential helical sense, to a higher rank forcing the arrangement of the rest of the chain in a specific helical sense. In these copolymers, the classical “Sergeant” and “Soldier” roles are modified in such a way that the chiral units become “Sergeants” only by the effect of an achiral external stimulus, namely the metal ion. The structure of the metal complex determines its interaction in the helix with the surrounding chiral and achiral “Soldiers” and therefore also determines both the intensity of the amplification and the response of a copolymer to a certain metal. For instance, poly(1r-co-7(1−r)) shows chiral amplification (“Sergeants and Soldiers effect”) towards the right-handed helix only with divalent ions, while poly(1r-co-8(1−r)) amplifies the helix to the left-handed sense with mono- and to the right-handed sense with divalent ions. This behaviour allows, using a single copolymer, to selectively induce any of the two helical senses. The aggregation and encapsulation properties of these copolymers are also described.

Chiral 1,2-diols: the assignment of their absolute configuration by NMR made easy.

The absolute configuration of a 1,2-primary/secondary diol can be easily determined by preparation of its bis-(R)- and bis-(S)-9-AMA ester derivatives, followed by comparison of the NMR chemical shifts of the diastereotopic methylene protons in the two derivatives. Alternatively, the assignment can be carried out using only one derivative if the evolution with temperature of the signals corresponding to the CalphaH protons is analyzed.

Architecture of Chiral Poly(phenylacetylene)s: From Compressed/Highly Dynamic to Stretched/Quasi-Static Helices.

The remarkable consequences in elongation, dynamic character, response to external stimuli (e.g., solvent effects, metal cations), and aggregation observed in helical poly(phenylacetylene)s (PPAs) when either the type of linkage with the pendant groups (i.e., anilide, benzamide) or the aromatic substitution pattern (i.e., ortho, meta, para) of the parent phenylacetylene monomer undergo modification are analyzed in depth. Two series of PPAs substituted at the phenyl ring in ortho, meta, and para with either (S)-α-methoxy-α-phenylacetic acid (MPA) or (S)-phenylglycine methyl ester (PGME) linked through anilide or benzamide bonds were prepared (i.e., o-, m-, p-poly-1 and poly-2 series) and characterized both in solution and in the solid state (CD, UV-vis, Raman, NMR, DSC, TGA, X-ray, AFM, SEM). Para-substituted polymers (p-poly-1 and p-poly-2) present the most compressed and dynamic helices, which respond easily to external stimuli. Meta-substituted PPAs (m-poly-1 and m-poly-2) exist as a mixture in equilibrium of two different helices (compressed and stretched), both less dynamic than the para counterparts and with a weak response to external stimuli. Moreover, in the solid state, m-poly-1 and m-poly-2 show separate fields for the compressed and for the stretched helices. For its part, the ortho-substituted PPA (o-poly-1) presents a highly stretched, almost planar and practically rigid helical structure, inert to external stimuli and prone to aggregate. These structural changes (elongation/dynamic behavior) are rationalized on the basis of the increasing difficulties imposed by the meta- and ortho-substitution on the accommodation of the pendants within the helical structure.

Controlled modulation of the helical sense and the elongation of poly(phenylacetylene)s by polar and donor effects

The elasticity (stretched/compressed) and helical sense (clockwise/anticlockwise) of a dynamic helical poly(phenylacetylene) (PPA), bearing (R)-α-methoxytrifluorophenyl acetic acid (MTPA) pendants [poly-(R)-1], can be selectively controlled by the donor and the polar character of the solvent. The basis for this effect lies on the presence in the pendants of two independently tuneable bonds: (O)C–C(–O) and (H–)N–C(O). An increase in polarity shifts the conformational equilibrium of the (O)C–C(–O) bond in favour of the most polar synperiplanar (sp) conformer, that is more sterically demanding, thus forcing the polymer to invert its helix. A donor solvent associates with the (H–)N–C(O) bond favouring the shift to the cis form of the amide and inducing both the elongation of the polymer chain and the inversion of the helical sense (visualized as UV-Vis bathochromic shift and CD inversion respectively). This ability of poly-(R)-1 to respond to donor/polar properties occurs in solution as well as in film state. Poly-(R)-1 presents in CHCl3 identical helical sense for both the internal (polyene backbone) and for the external (described by the pendants) helices (3/1 clockwise), while in THF their senses are opposite (internal anticlockwise; external 2/1 clockwise), as proven by DSC.

Diacid Linkers That Promote Parallel β-Sheet Secondary Structure in Water

We report the development of diacid units that promote formation of a two-stranded parallel beta-sheet secondary structure between peptide segments attached via their N-termini. These linker units are formed by attaching glycine to one carboxyl group of cis-1,2-cyclohexanedicarboxylic acid (CHDA). Parallel sheet formation in water is observed when l-residue strands are attached to the CHDA-Gly unit with either of the two absolute configurations.

The leading role of cation–π interactions in polymer chemistry: the control of the helical sense in solution

Cation–π interactions determine the helical sense adopted by a polyphenylacetylene bearing (R)-α-methoxy-α-phenylacetamide as a pendant group (poly-1). These interactions take place when small amounts of Li+, Na+ and Ag+ salts dissolved in donor cosolvents are added to the polymer dissolved in a non-donor solvent and the corresponding helical polymer–metal complexes (HPMCs) are formed. Extensive spectroscopic studies (i.e., 7Li, 23Na, 1H NMR and IR among others) indicate that the pendants act as dipodal receptors for metal cations, where cation–π interactions play a major role in controlling the M or P helicity of the polymer. Although all the cations tested generate cation–π binding, each metal presents its own particular and distinctive behaviour, based on polymer/cosolvent ratios and the type of cosolvent. Manipulation of these variables allows the selective disruption or activation of the cation–π interactions (i.e., a controlled switch on/off mechanism) and the selection of the helical sense on an a la carte basis. The 3/1 helical structure of poly-1 can cause a novel “triple cascade effect” of cooperative cation–(π)n–π interactions, which further induce the high chiral amplification response found in these HPMCs. These non-covalent interactions are not found when divalent cations are used instead.

Challenging the absence of observable hydrogens in the assignment of absolute configurations by NMR: application to chiral primary alcohols

The absolute configuration of beta-chiral primary alcohols devoid of observable hydrogens on one of the beta-substituents at the asymmetric carbon (L(1)/L(2)) can be determined by comparison of the (1)H NMR of their (R)- and (S)-9-AMA ester derivatives and analysis of the Deltadelta(RS) for the L substituent and the Cbeta-H.