Scheme 12.5

tionality. The CD signal related to the imine backbone was shown to diminish rapidly and invert in sign when the chiral center in the alkyl tail was placed further away from the promesogenic group. More evidence for the role of non-covalent interactions on the stereoselectivity was obtained by performing polymerizations at various concentrations and in different solvents [75]. Variable temperature CD measurements revealed that polymer 19 has a stable conformation up to at least 55 ° C. When, however, a nitro group was introduced in the phenyl ring close to the stereogenic center, the polymer was found to adopt a less stable conformation, as was demonstrated by the dramatic and irrecoverable loss of optical activity at 55 ° C. This observation confirms that the formed polyisocyanide is a kinetically-determined product [76].

In a more recent publication, the influence of the length and the rigidity of the rod-like spacer located between the isocyanide and the chiral center of 23 were studied (see Scheme 12.6). The chiral induction through spacers A-G was investigated in detail and it was concluded that a semi-rigid twisted conformation must be adopted by the spacer in order to be able to effectively transfer the chiral information to a helical polymer backbone. The phenyl benzoate spacer A proved to do this most efficiently while no chiral induction is observed for flexible spacer C. A 21-A long teleinduction was observed for spacer G [77, 78].

Cornelissen et al. showed the potency of peptide substituents in the formation of stable polyisocyanide helices (Fig. 12.9) [79]. It was found that the helical conformation of a polyisocyanide can be effectively stabilized if a well-defined hydrogen bonding network is present between the peptide side chains at positions n and (n + 4), which are stacked above each other at a distance of @4.6A (Fig. 12.9B). Although polyisocyanides derived from peptides had been previously described by the authors [59, 80, 81], they did not recognize at that time the presence of the hydrogen bonds between the peptide side chains and did not utilize this properly to stiffen the helix of polyisocyanides with functional groups (vide infra). The stepwise addition of 34a to a nickel(II) catalyst revealed the kinetic

Scheme 12.6

nature of the polymerization, which involves a helical templating effect of the growing polymer on the incoming monomers. After eight monomers were added to the catalyst, a steep increase in the CD signal was observed. At the same time hydrogen bonding interactions between the amide protons started to become visible by XHNMR spectroscopy [82].

Polyisocyanide 33, derived from trialanine, contains two amide groups per side chain and is able to fold into a b-sheet-like architecture, mimicking the interactions present in naturally occurring b-helices [83]. Detailed infrared and XH NMR spectroscopic investigations showed that nearly all amide groups present in polymers 24-33 participated in hydrogen bonding, in a similar way as observed in the crystal structure of 34a (e.g. see Fig. 12.10A, B). Ordered arrays of hydrogen bonds along the polymeric backbone, however, were not observed for polyisocyanide 27, which is derived from alanine glycine [79, 84]. It is remarkable that in contrast to 27, polyisocyanide 26 derived from glycine-alanine did give a well-defined helical structure, suggesting that the steric bulk in the second amino-acid is of great importance, probably because it stabilizes and directs the hydrogen bonding network. Analogous to the denaturation of proteins, the hydrogen bonds in these polymers can be disrupted leading to unfolding of the helix.

Fig. 12.9 (A) Various polyisocyanides derived from peptides; (B) Schematic representation of a helical polyisocyanide stabilized by a hydrogen bonding network between the peptide side-chains.

This unfolding is, however, only possible with strong acids such as trifluoroacetic acid (TFA) and not with hydrogen bonding solvents (e.g. methanol, DMSO), thereby demonstrating the robust character of the hydrogen bonding arrays [79. 81]. Powder X-ray diffraction (PXRD) experiments showed that in the solid state the rigid polyisocyanopeptides are organized in a pseudo-hexagonal arrangement. The acidified samples, which were studied for comparison, in contrast. only gave broad signals pointing to a decreased level of organization in the polymer structure.

The peptide-derived polyisocyanides are stable in solution at room temperature, and as a result of their rigidity, it is possible to visualize the individual macro-

Fig. 12.10 (A) Crystal structure of 34a; (B) Schematic representation of the proposed orientation of the peptide side chains in 24a; (C) AFM-micrograph of 24a prepared with 1/30th equivalent of Ni(ClO4)26H2O; (D) AFM-micrograph of 25a prepared with 1/32th equivalent of TFA.

molecules by atomic force microscopy (AFM) (Fig. 12.10C) [79, 84, 85]. By measuring the contour lengths and by a careful analysis of the curvatures it was possible to determine the molecular weight, the polydispersity, and the persistence length of the polymers. The latter was found to amount to 76 nm, highlighting that these polymers are more rigid than double-stranded DNA [85]. An accurate value of 1.6 nm for the height of the fibers was obtained by AFM measurements under chloroform vapor [86], which corresponds well with the polymer chain as derived from molecular modeling and PXRD measurements [79].

The assignment of the helix sense of peptide-derived polyisocyanides by CD spectroscopy is hampered by the overlap of signals arising from the polymer backbone and the side chains. For an l-alanine based polyisocyanide containing a spectator group (i.e. a diazo chromophore) in the side chains, a right-handed (P) helical geometry was found [87]. Since the helix sense in polyisocyanides is kinetically controlled, this handedness was tentatively assigned to all l-alanine derived polyisocyanides. Selected properties of polyisocyanodipeptides (24-33) are presented in Table 12.1 [88]. When hydrogen bonds are present (e.g. 24, 25 and 30), a positive optical rotation and a strong positive Cotton effect around l = 315 nm indicate the presence of a right-handed (P) helix. When this is not the case (e.g. 27), the Cotton effect appears at lower wavelength and has an opposite sign and a lower intensity (Table 12.1). From IR and NMR spectroscopic studies it was concluded that, polyisocyanides 24, 25 and 33 retain their hydrogen bonded helical conformation for significant periods of time [89], even when they are dissolved in water after removal of the methyl ester functions. The thermal denatu-ration of these water-soluble polymers was also studied in water. It was demonstrated using VT-CD spectroscopy that the denaturation process proceeds in a cooperative fashion [79].

Table 12.1


[«] ("-dl/g-dm)

Was this article helpful?

0 0

Post a comment