Thermally stable helical poly(4-carboxyphenyl isocyanide) with a helicity memory assisted by metal coordination

Introduction

Helical polymers with a controlled handedness have the potential for developing novel helical polymer-based asymmetric catalysts and chiral materials for sensing and separating chiral molecules. Hence, a large number of helical polymers with optical activity have been prepared to develop such chiral materials, which have become of practical use during the past decades.^{1, 2} Among the helical polymers prepared to date, helical poly(phenylacetylene)s and poly(phenyl isocyanide)s bearing achiral functional pendant groups are unique^{1, 2} because helices can be induced in the as-prepared optically inactive polymers through noncovalent interactions between the functional pendants and chiral molecules. Furthermore, the induced helices can be memorized after replacing the chiral molecules with achiral ones³ or after simply removing the chiral molecules.⁴ The induced helices of the poly(phenylacetylene)s are dynamic; therefore, the use of achiral molecules is essential for the memory of the induced helical conformation, except for a polyacetylene bearing 2,2′-biphenol-derived pendants.⁵ In sharp contrast, achiral molecules are not required to memorize the induced helicity in polyisocyanides. Typically, a helix is induced in the sodium salt of poly(4-carboxyphenyl isocyanide) (poly-1-Na) upon complexation with chiral amines, such as (R)-phenylglycinol ((R)-2), which is accompanied by the syn-anti configurational isomerization around the C=N backbone. Therefore, the induced helical structure of the polyisocyanide (h-poly-1-Na) is automatically memorized during the helicity induction process, thereby retaining its preferred-handed helicity, even after (R)-2 is completely removed (Figure 1a).^{4, 6} The polyisocyanide (h-poly-1-Na) with the helicity memory, however, is thermally unstable and loses its helical memory at high temperature due to the syn-anti isomerization of the main-chain.^{4, 6, 7} To overcome this problem, h-poly-1-Na was cross-linked by diamines in water to produce a chemically cross-linked hydrogel, which maintained its optical activity derived from the helicity memory, even at 90 °C.⁸

Figure 1

Schematic illustrations of (a) a preferred-handed helicity induction with (R)-2 in poly-1-Na in water and the memory of the helicity (h-poly-1-Na) after complete removal of (R)-2, and (b) intramolecular and (c) intermolecular physical cross-linking of h-poly-1-Na with divalent (M²⁺) and trivalent (M³⁺) metal ions in water. A full color version of this figure is available at Polymer Journal online.

We envisioned that the thermal stability of h-poly-1-Na would also be improved in the presence of divalent (M²⁺) and trivalent (M³⁺) metal ions that can coordinate to the pendant carboxylate residues in h-poly-1-Na, thereby forming a noncovalently cross-linked network through intra- and/or intermolecular coordination (Figure 1b and c). Noncovalent cross-linking with metal ions may be superior to covalent cross-linking because the former metal-coordinated cross-linked helical polymers^{9, 10, 11} are recyclable and applicable to the development of metal-catalyzed asymmetric catalysis.¹² To this end, h-poly-1-Na was noncovalently cross-linked with a series of divalent (M²⁺) and trivalent (M³⁺) metal ions in dilute and concentrated aqueous solutions, and the thermal stabilities of the resulting h-poly-1-Na complexed with metal ions in solution and in a hydrogel were investigated using circular dichroism (CD) spectroscopy.

Experimental procedures

Optically inactive poly-1-Na was prepared by the polymerization of sodium 4-isocyanobenzoate with NiCl₂·6H₂O in water according to the reported method.^{4, 6} The number–average molecular weight (M_n) and molecular weight distribution (M_w/M_n) of poly-1-Na were estimated using its methyl esters by size-exclusion chromatography with polystyrene standards (Tosoh, Tokyo, Japan). Poly-1-Na (M_n=2.7 × 10⁴ and M_w/M_n=2.7 or M_n=3.2 × 10⁴ and M_w/M_n=2.5) was then annealed with (R)-2 in water at 50 °C for 45 days to induce a preferred-handed helicity. The resulting optically active poly-1-Na was isolated in a similar manner as previously reported,^{4, 6} producing h-poly-1-Na containing no (R)-2, but showing an optical activity due to its helicity memory (Figure 1a) (see the Supplementary Information for more detailed experimental procedures).

Results and discussion

h-Poly-1-Na (M_n=2.7 × 10⁴, M_w/M_n=2.7) with a macromolecular helicity memory prepared by the previously reported method^{4, 6} showed an induced circular dichroism in the iminomethylene backbone (ca. 300–460 nm) and in the aromatic pendant regions (200–ca. 300 nm), which are solely due to the preferred-handed helical structure (Figure 2a and b, red lines).^{4, 6} However, the helical structure of h-poly-1-Na is not thermally stable and readily unfolds into the corresponding optically inactive, as-prepared poly-1-Na in water at high temperature through the configurational isomerization of the C=N double bonds.⁶

Figure 2

(a, b) Circular dichroism (CD) and absorption spectra of h-poly-1-Na (0.050 mg ml⁻¹) in water in the absence (red lines) and presence of (a) Co²⁺ (0.4 equiv.) and (b) Tb³⁺ (0.2 equiv.) ions before (blue lines) and after (dashed blue lines) heating at 90 °C for 20 min. (c, d) Relative CD intensities (%) of h-poly-1-Na in the presence of a series of (c) divalent (0.2 (black bars) and 0.4 equiv. (white bars)) and (d) trivalent (0.2 equiv.) (black bars) ions before and after heating at 90 °C for 20 min. The relative CD intensities (%) were estimated using the first Cotton effect (CD_1st) intensities of h-poly-1-Na with metal ions before heating as the base values. A full color version of this figure is available at Polymer Journal online.

The thermal stability of h-poly-1-Na in a dilute aqueous solution in the presence of a series of divalent and trivalent metal ions (Figure 2c and d) was then evaluated by measuring the CD of the solution after heating at 90 °C for 20 min, which showed that the optical activity of h-poly-1-Na completely disappeared in water in the absence of metals, as already mentioned. Figure 2a and b show the typical CD and absorption spectra of h-poly-1-Na in the presence of 0.4 equiv. of divalent Co²⁺ and 0.2 equiv. of trivalent Tb³⁺ ions before (blue lines) and after (dashed blue lines) heating at 90 °C for 20 min, respectively. Upon complexation with the Co²⁺ and Tb³⁺ ions, the CD spectral patterns of h-poly-1-Na significantly changed—in particular, those in the pendant aromatic regions (200 to ca. 300 nm)—accompanied by a remarkable increase of the CD intensities along with a change in their absorption spectra with a redshift, indicating a variation in the chiral arrangement of the aromatic groups along the helical polymer backbone through metal coordination.

Interestingly, the macromolecular helicity memory of the h-poly-1-Na, namely, its preferred-handed helical structure, was almost retained upon heating at 90 °C for 20 min once complexed with the Co²⁺ and Tb³⁺ ions. The estimated relative CD intensities of the h-poly-1-Na complexed with the Co²⁺ and Tb³⁺ ions before and after heating, which were based on the first Cotton effect (CD_1st) intensities of the h-poly-1-Na-metal complexes before heating, as the base values were 91% and 88%, respectively (Figure 2c and d), indicating that the thermal stability of the helical structure of h-poly-1-Na was significantly improved, which was mostly due to an intramolecular physical cross-linking by metal coordination (Figure 1b).

In a similar way, the effects of the metal species on the stability of the helical structure of h-poly-1-Na were then investigated by measuring the CD spectra of h-poly-1-Na in the presence of a variety of divalent (M²⁺) (0.2 and 0.4 equiv.) and trivalent (M³⁺) (0.2 equiv.) metal ions before and after heating at 90 °C for 20 min, and the relative CD intensities (CD_1st) are summarized in Figure 2c and d, respectively. The CD intensities of h-poly-1-Na with 0.2 equiv. of divalent metal ions, except for the Cu²⁺ ion, drastically decreased at 90 °C, showing relative CD intensities of 6–21% (Figure 2c, black bars), while the Cu²⁺ ion, which is known to have a higher binding affinity toward carboxylate anions than the other divalent metal ions used in the present study,^{13, 14} effectively stabilized the h-poly-1-Na helix with a relative CD intensity of 53% (Figure 2c). In the presence of 0.4 equiv. of divalent metal ions, however, the thermal stability of h-poly-1-Na was significantly improved in the following order based on the relative CD intensity: Cu²⁺ and Co²⁺ (91%)>Ni²⁺ (87%)>Zn²⁺ (85%)>Ca²⁺ (79%)>Mg²⁺ (64%). This order is consistent with the binding affinity of these divalent metal ions toward carboxylate anions.^{13, 14} It should be noted that the h-poly-1-Na helix with an excess handedness was almost completely retained upon complexation with 0.4 equiv. of Cu²⁺ and Co²⁺ ions. The CD titration experiments of Cu²⁺ (Supplementary Figure S1) and Co²⁺ (Supplementary Figure S2) ions with h-poly-1-Na and subsequent annealing at 90 °C for 20 min revealed that 0.3 equiv. of Cu²⁺ ions is sufficient to stabilize the helical structure of h-poly-1-Na.

As anticipated, 0.2 equiv. of the trivalent metal ions enhanced the thermal stability of the h-poly-1-Na helix compared to 0.2 equiv. of the divalent metal ions (Figure 2c and d). Importantly, the macromolecular helicity memory of h-poly-1-Na was almost retained upon complexation with 0.2 equiv. of lanthanide ions after heating at 90 °C for 20 min irrespective of the kind of lanthanide used, showing relative CD intensities of 83–91% (Figure 2d), and the h-poly-1-Na complexed with Yb³⁺ ions retained its helicity memory with a relative CD intensity of 50% upon further heating at 90 °C for 16 h in water. The observed high stability of the h-poly-1-Na helix assisted by trivalent lanthanide coordination is attributed to their large effective ionic radii¹⁵ as well as their preference for high coordination numbers and high binding affinities toward carboxylate anions.^{16, 17, 18}

Interestingly, when the h-poly-1-Na concentration in water was higher than 30 mg ml⁻¹, the solution of the h-poly-1-Na became viscous and gelled within 1.5 h after the addition of a small amount of Tb³⁺ ions (0.025–0.050 equiv.), thus producing an optically active hydrogel (gel_Tb–h-poly-1-Na) through noncovalent intermolecular cross-linking with the Tb³⁺ ions (Figure 1c). The hydrogel (gel_Tb–h-poly-1-Na) composed of h-poly-1-Na (50 mg ml⁻¹) and 0.050 equiv. of Tb³⁺ ions exhibited an induced circular dichroism (Figure 3a, blue line) with a CD spectral pattern similar to that of h-poly-1-Na complexed with 0.2 equiv. of Tb³⁺ ions in dilute solution (Figure 2b, blue line). More interestingly, the helical structure of the h-poly-1-Na chains with the helicity memory in the hydrogel (gel_Tb–h-poly-1-Na) cross-linked via metal coordination with 0.050 equiv. of Tb³⁺ ions was unexpectedly stable and preserved its excess handedness, showing a relative CD intensity at 354 nm of ca. 90%, even at 90 °C, as revealed by temperature jump experiments monitored by CD (Figure 3b, filled circles), whereas h-poly-1-Na completely lost its helicity memory at 80 °C in water (Figure 3b, black line), as previously reported.⁴

Figure 3

(a) Circular dichroism (CD) and absorption spectra of h-poly-1-Na (1.0 mg ml⁻¹) in water (red lines) and gel_Tb–h-poly-1-Na ((h-poly-1-Na)=50 mg ml⁻¹, [Tb³⁺]/(monomer units of h-poly-1-Na)=0.050) (blue lines) at room temperature. The CD intensity of gel_Tb–h-poly-1-Na was normalized using the molar absorptivity at 354 nm (ɛ₃₅₄=1509). The contribution of the linear dichroism caused by macroscopic anisotropy derived from the gels was negligible. The inset shows a photograph of gel_Tb–h-poly-1-Na. (b) Temperature-dependent CD intensity changes at 354 nm of h-poly-1-Na in water (black line) and gel_Tb–h-poly-1-Na (filled circles) investigated by a temperature jump method. The gel was allowed to stand at fixed temperature, and its CD was then measured at room temperature. h-Poly-1-Na (M_n=3.2 × 10⁴ and Δɛ₃₆₀=−10.2) was used. A full color version of this figure is available at Polymer Journal online.

Conclusions

We have developed a highly versatile method for stabilizing an excess-handed helical polyisocyanide induced and memorized in the polymer backbone using divalent and trivalent metal ions as noncovalent cross-linkers through intra- and/or intermolecular metal coordination. Among the metal ions investigated, the lanthanide ions were proved to be the most efficient and remarkably improved the thermal stability of the helical polyisocyanide in solution as well as in a gel. The present lanthanide-coordinated helical polyisocyanides with heat resistance will be applicable to developing novel helical polymer-based asymmetric catalysts and chiral/chirality sensing reagents since lanthanide ions complexed with chiral ligands have been reported to catalyze a wide range of enantioselective transformations with an excellent enantioselectivity,¹⁹ and to sense the chirality of a variety of chiral molecules with high sensitivity by CD, nuclear magnetic resonance and circularly polarized luminescence.²⁰