Reversible assembly of enantiomeric helical polymers: from fibers to gels

A novel class of stereocomplexes is described by the interaction of helically complementary poly(phenylacetylene)s (PPAs) carrying an α-methoxy-α-trifluoromethylphenylacetamide pendant group.


Introduction
Stereocomplexes are supramolecular entities formed by the interaction of complementary stereoregular polymers, generating a new material with different properties in comparison with the parent polymers. 1,2 Well known examples of homo-stereocomplexes are those formed by the association of an isotactic with a syndiotactic polymer (for instance, poly(methyl methacrylate)s (it-and st-PMMAs)), 3 those formed by the interaction between two enantiomeric polymers (e.g. poly-D-and poly-L-(lactic acid) (PLA)), 4 or those made from various polypeptides (D-and L-amino acids) 5 and polyamides (e.g. D-and L-poly(hexamethylene di-O-methyltartaramide)s). 6 The formation of stereocomplexes requires two complementary scaffolds, which are linked together through supramolecular interactions. Those made from PMMA and PLA have been amply studied during the last few decades, showing that the existence of stereoselective van der Waals forces is crucial for the stabilization of PMMA stereocomplexes, while those made from PLA seem to be stabilized by weak hydrogen bond interactions. 7 In this paper we describe a new class of homo-stereocomplexes (ber-like aggregates and gels), made by the interaction of helically complementary poly(phenylacetylene)s (PPAs) 8 stabilized by cooperative supramolecular hydrogen bonding among cis amide groups located on the polymer crest. We will show also that the formation of the stereocomplex is highly specic for the cis conformer and its cleavage can be conveniently tuned by interactions with solvents that modify the cis-trans amide equilibria at the pendant groups-and as a result, the inter-and intramolecular hydrogen bond interactions. This is, to our knowledge, the rst example of a stereocomplex that can be easily switched on/off by the use of solvents.

Results and discussion
The starting polymers [poly-(R)-1 and poly-(S)-1] are prepared by the polymerization of (R)-and (S)-4-N-a-methoxy-a-tri-uoromethylphenylacetamides (MTPAs) of 4-ethynylaniline [M-(R)-1 and M-(S)-1, respectively]. Poly-(R)-1 and poly-(S)-1 present 3/1 helical structures in non-donor solvents (e.g. CH 2 Cl 2 , CHCl 3 ) with preponderant right-handed [poly-(R)-1] and le-handed [poly-(S)-1] helical senses for the backbone frameworks stabilized by intramolecular hydrogen bonds among the trans amides of the pendant groups ( Fig. 1 and 2). 9 When a donor solvent (e.g. THF) is used to dissolve these polymers, the stereochemistry of the amide bonds changes to cis, the intramolecular associations disappear by competition with the donor solvent, and as a result the backbone shis to a more extended 2/1 helix with opposite helical sense, now determined by steric hindrance among the pendant groups ( Fig. 1 and 2). 9 The existence of intermolecular interactions between poly-(R)-1 and poly-(S)-1 was evaluated by circular dichroism (CD), dynamic light scattering (DLS) and scanning electron microscopy (SEM) by using mixtures with different ratios of the starting polymers in THF and CHCl 3 .
The CD spectra for all mixtures and in both solvents show signatures corresponding to the contribution of the individual components in the given ratio, indicating that the helical structures of poly-(R)-1 and poly-(S)-1 remain unaltered ( Fig. 3a and d).
Similar experiments were carried out with several poly-(R)-1/ poly-(S)-1 mixtures at different ratios. It was found that the presence of just 2% (v/v) of one component [e.g. 20 mL of poly-(S)-1 (0.1 mg mL À1 )/980 mL of poly-(R)-1 (0.1 mg mL À1 )] was enough to induce the formation of supramolecular entities larger than 400 nm (see ESI †). Moreover, the size of the aggregates can be controlled by the concentration of the starting solution at any poly-(R)-1/poly-(S)-1 ratio, becoming larger as the concentration increases (e.g. 50/50 (v/v) mixtures at 0.05 mg mL À1 afford particles of 635 nm diameter, while those at 0.5 mg mL À1 give particles of 1338 nm diameter; see ESI †).
In summary, these results indicate not only the high speci-city but also the effectiveness of the aggregation process that can be triggered by the presence of just 2% of the complementary polymer.
Additional information about the aggregates, the mechanism of aggregation and the requirements of the starting polymers are described below.

Reversibility of the stereocomplex formation
The structures of the starting polymers poly-(R)-1 and poly-(S)-1 in THF suggest that the helically complementary structures combine by intermolecular association involving hydrogen bonds among the amide groups. If this is so, temperature changes or the addition of solvents (e.g. MeOH) able to disturb hydrogen bond formation, without interfering with the secondary structures of the polymers (i.e. neither cis-trans isomerization nor helical inversion, see pages S28-S31, ESI †), should produce the cleavage of the stereocomplex through intermolecular hydrogen bonding disruption.
As a matter of fact, the DLS analysis of the 50/50 (v/v) mixture in THF at 60 C showed only the presence of isolated polymers, indicating that no stereocomplex is present at that temperature ( Fig. 4b). Furthermore, when the temperature is decreased to room temperature, the stereocomplex is recovered, showing the reversibility of its formation in solution (Fig. 4c). The size of the recovered stereocomplex aer heating at 60 C is not completely identical to that of the pristine stereocomplex, i.e. a change in size from 960 nm (pristine stereocomplex) to 375 nm (recovered stereocomplex) is observed. 10 The reassembly among polymer chains aer the heating/cooling cycle may not be strictly identical to the previous association since there are assembly points all over the polymer chain that allow a more compact aggregation.
Furthermore, if a hydrogen donor solvent such as methanol is added to the initial solution of one of the starting polymers in THF prior to the addition of the other component, the formation of the stereocomplex does not take place because the MeOH is capping the cis amide hydrogens through hydrogen bond interactions. On the contrary, if the methanol is added to the preformed stereocomplex, the ber-like aggregates are only partially cleaved and remain in solution as smaller sized suprastructures (Fig. 4d). Finally, if this solution is heated up to 60 C, the sterecomplexation is disrupted, and when the THF/ MeOH solution is cooled down, the stereocomplex formation does not take place (see a more detailed description of the phenomenon on pages S29 and S30, ESI, † including Fig. S31 and S32 †).
The cleavage of the stereocomplex can be performed not only by heat or hydrogen bond competition with MeOH, but also by the addition of solvents that decrease the donor ability of the  media. Thus, the addition of increasing amounts of CHCl 3 to the solution of the stereocomplex in THF results in its effective disruption due to the promotion of the cis amide bonds towards the trans conformation-the latter being involved in intramolecular hydrogen bond interactions-and thus, from a cistransoid 2/1 to a cis-cisoid 3/1 helix. Therefore, the intermolecular hydrogen bonds are disrupted (Fig. 4e). See a more detailed description of the phenomenon on page S31, ESI, † including Fig. S33. † All these data indicate that the aggregate is stabilized by hydrogen bonds among the cis amide groups located at the external parts of the polymer chains. Interestingly, the IR spectrum of the poly-(R)-1/poly-(S)-1 mixture in THF shows the characteristic band for cis amides (see ESI †), identical to the one found for the individual polymers in THF and different from the trans band found for the polymers in CHCl 3 . 9 Therefore, we conclude that the formation of the stereocomplex depends on two factors: cis amide functions at the crests of the polymer chains and complementary helices.
Thermal studies on the solid phase Differential scanning calorimetry (DSC) experiments were carried out in order to obtain further information on the thermal properties of the stereocomplex and its secondary structure. This technique has been shown to be useful for obtaining information on the thermal isomerizations taking place in these kinds of macromolecules [e.g. cis-transoidal to cis-cisoidal (c-t to c-c); cis-cisoidal to trans-transoidal (c-c to t-t)]. 11 Hence, lms were prepared from the 50/50 (v/v) poly-(R)-1/ poly-(S)-1 mixture in THF and in CHCl 3 (see ESI † for the experimental procedure), and the DSC traces obtained were compared with those from the parent polymers in the same solvents.
The results revealed identical DSC signatures for the lms from poly-(R)-1 and from the poly-(R)-1/poly-(S)-1 mixture when they were prepared in CHCl 3 (Fig. 5a). This fact conrms that no new species are being formed when mixing poly-(R)-1/poly-(S)-1 in that solvent. However, when the same lms are prepared in THF, the poly-(R)-1/poly-(S)-1 mixture shows the c-t to c-c transition at 147 C while the parent poly-(R)-1 exhibits the maximum at 135 C. This delay clearly indicates the presence of a new entity, the stereocomplex, different from the parent polymer, with higher thermal stability than the starting components (Fig. 5b).
Additionally, the rst cooling and second heating processes for the poly-(R)-1/poly-(S)-1 lm prepared in THF showed no

Rheology studies
In order to characterize the gel-like supramolecular structure (Fig. 6d), comparative rheological studies were carried out and the results are shown below.
Solutions of the individual polymers [poly-(R)-1 or poly-(S)-1] in either THF or CHCl 3 exhibit viscous behaviour even at 5 mg mL À1 , with low G 00 and negligible G 0 values (see ESI †). On the other hand, the rheological parameters of solutions of the 50/50 (v/v) poly-(R)-1/poly-(S)-1 mixture in THF revealed a strong dependence on the total concentration. At 0.5 mg mL À1 , only low G 00 values were detected in the stereocomplex solution (see ESI †). At 2.5 mg mL À1 the solution presented the typical behaviour of a Maxwell uid: G 00 was larger than G 0 at low frequencies and increased in a linear fashion with the frequency, with a slope close to 2 (see ESI †). Raising the concentration up to 5 mg mL À1 , the G 00 values became independent of the frequency and the curves of the two moduli showed an intersection at 6.28 rad s À1 ; beyond that frequency, G 0 values were greater than G 00 (Fig. 7a). These results conrm that at high concentrations the stereocomplex behaves as a so gel. Similar to what happens in dilute solutions, the on/off switching of the stereocomplex formation can be attained in the   gel state by changing the temperature and solvent (see Fig. S60 and S61, ESI †). 12 Finally, as could be expected from the previous CD, SEM and TEM results, similar solutions of the mixture [poly-(R)-1/poly-(S)-1 at a 50/50 (v/v) ratio] in CHCl 3 instead of THF behave as a low viscosity uid in the whole range of concentrations tested (Fig. 7b).

Stereocomplex formation mechanism: modeling
According to our hypothesis, the formation of the bers and gels originates with the aggregation among complementary helices through hydrogen bonds between the cis amide groups at the external crests of the polymer chains. In this sense, it was interesting to analyse the geometrical possibilities of that process among polymer chains with the same or opposite helicity, and with trans and cis amide conformation at the pendant groups.
The geometrical matching of the complementary helices of poly-(R)-1 and poly-(S)-1, with cis amide bonds on the outside (e.g. in THF), was studied by computer modeling. The results indicated that interaction between the cis amides of those helices is geometrically feasible (Fig. 8a), and that the formation of a supramolecular aggregate bound together via multiple hydrogen bonds would be reasonable. On the contrary, if the amides were placed in a trans conformation (e.g. in CHCl 3 ) no matching between the helices is possible, explaining the absence of aggregate. In fact, we tested experimentally other helical poly(phenylacetylene)s with similar geometrical requirements but containing trans amides in the external crests, and found no stereocomplex formation. 8d,e Moreover, the modeling also showed that no efficient matching could be produced among helices with the same helical sense, even if they presented well-placed cis amide bonds [e.g. right-handed helices of poly-(R)-1 in THF, Fig. 8b].

Monitoring stereocomplex formation by AFM
In order to monitor the formation of the stereocomplexes in the solid state, we decided to carefully examine the AFM images obtained during the formation of the aggregate with mixtures of poly-(R)-1/poly-(S)-1 in THF, and to compare them with those of the individual polymers.
Thus, AFM studies of poly-(R)-1 in THF (0.01 mg mL À1 ) present images of 2D crystals with single right-handed helix packing, and no evidence of large aggregates. 9 However, AFM images of a 50/50 (v/v) poly-(R)-1/poly-(S)-1 mixture in THF showed, in addition to some isolated 2D crystals corresponding to the le-handed [poly-(S)-1] and right-handed [poly-(R)-1] helices of the individual polymers, the presence of abundant ber-like aggregates. More precisely, bers with diameters around 3.6 and 5.0 nm are clearly distinguished, in addition to higher order ber aggregates with diameters around 80-100 nm.
The smaller bers seem to correspond to the initial aggregation steps, and in fact, a width of 3.6 nm ts exactly with the expected one for a dimer (one le-handed helix interacting with one right-handed helix, Fig. 9a). Due to its composition (50/50 mixture of both helices), this dimeric ber should not present specic helical sense on its surface, in full agreement with the experimentally observed AFM image (Fig. 9a).
As for the bers with a width of about 4.9-5.0 nm, two different varieties are observed depending on their surface. The rst types of these bers show no specic helical sense on their surface. This characteristic as well as their width (about 4.9-5 nm) ts well with the expected data for a trimer formed by two helices of one sense surrounding one helix with the opposite helical sense (Fig. 9b).
The second types of bers were found in the AFM images and present quite similar widths to the trimer but with a specic helical sense on their surface (Fig. 9c). These data match well with a pentameric structure in which one helix chain is surrounded by four other helices of the opposite helical sense. In this case, the ber surface should reect the combination of the crests of the four external helices (Fig. 9c) and therefore a specic helical sense. Moreover, modeling of this pentameric ber shows very good tting among the individual chains, leading to a maximum of about 10.5 nm crest length, in full agreement with the AFM image presented in Fig. 9c, where a single helix of poly-(R)-1 is surrounded by four helices of poly-(S)-1, producing as a result an external le-handed helical aggregate.
Naturally, due to the presence of cis amide bonds on the outer crests, these ber aggregates with small diameters (dimer, trimer, pentamer.) can keep growing and producing the larger ber aggregates (with diameters of about 80-100 nm) that at higher concentrations will afford a gel-like structure (Fig. 9d and e).
The effectivity of the binding mechanism: copolymers The modeling studies indicated that a good geometrical tting between complementary polymer chains requires the interaction of only a few cis amide groups (no more than 6 in a row per helix crest; Fig. 8a). Besides that, experimentally we know that the addition of just 2% (v/v) of one helix to 98% of the complementary one is enough to initiate the aggregation.

Conclusions
In this paper we present the rst example of a stereocomplex formed by the association of helical poly(phenylacetylene)s. The formation of this ber-like aggregate, that becomes a gel at high concentrations, requires the helical complementarity of the starting polymers and the presence, at the external part of their skeleton, of cis amide groups that provide hydrogen bonding to interconnect the helices. The binding and cleavage mechanism, and the structural and physical properties have been discussed. This is, to our knowledge, the rst example of a stereocomplex whose formation can be switched on and off by modulation of the cis-trans amide conformation of the pendant groups.