In using homochiral systems, nature blocks our observation of certain interesting aspects of the cooperativity of helical systems, a cooperativity which can lead to large chiral amplification effects. This can act to alleviate the burden of synthesizing enantiomerically pure building blocks for these synthetic systems, and this can be seen most clearly in the simplest version of the nylons, the polyisocyanates, which are stiff helical polymers with a high degree of cooperativity along the polymer chains ().14
This cooperativity arises from infrequent helical reversals which separate long blocks of opposing helical senses, forcing many units of the chain to take the same helical sense. In this way the chiral bias on each unit of the chain is amplified, with the resulting relative proportions of right- and left-handed segments determined experimentally by measuring the chiral optical properties of the polymers.
Figure 2. Circular dichroism spectra in hexane solution at room temperature of the homopolymers and copolymers of (R)- and (S)-2,6-dimethylheptyl isocyanates plotted as molar ellipticity against wavelength. Reprinted with permission from reference (more ...)
Questions concerning helical polymers with variable sense were first addressed by Italian researchers in Pisa under the supervision of Piero Pino in the 1960s who began to synthesize stereoregular isotactic vinyl polymers with chiral, non-racemic pendant groups [i.e., from (S)- and (R)-3-methyl-1-pentene] and discovered the absence of a linear relationship between the optical activities of such polymers in solution and the configurational enantiomeric characteristics of the monomer units. This nonlinear relationship was difficult to understand except as arising from the chiral units affecting some aspect of the chain conformation. Although the measurements were made in solution rather than with the crystal, the results pointed to the presence of a helical conformation. A full understanding, however, was prevented by the absence of an accessible chromophore, therefore limiting a direct observation of the chiral optical properties by circular dichroism (CD). Moreover, the magnitudes of the cooperative effects were limited by the flexibility of the polymer since helical reversal states were relatively easily accessible. Such structural defects limited the cooperativity, which is responsible for the nonlinear effects.
To gain further insight into the chiral optical properties of isotactic vinyl polymers, Pino and coworkers in Pisa used the Ziegler-Natta catalysts to produce polymers with high stereoregularity from chiral monomers of 1-alkenes. It was well-known from previous work that increasing isotacticity leads to increased crystallinity and therefore to decreased solubility, so that samples could be fractioned based on their isotacticity by dissolution in increasingly high boiling solvents at high temperatures. All fractions of the optically active polymers produced in this way showed increased optical activity compared with the starting monomer units ().15,16
However, as isoctaticity increased, as evidenced by decreasing solubility, so did the temperature- dependence of the optical activity.
Table 1. Physical properties of poly-(S)-3-methyl-1-pentene fractions having different stereoregularity
According to the data reported in , Pino hypothesized that helical conformations can exist above the melting point and in dilute solution. Although such conformations could be experimentally evidenced in the crystals of isotactic vinyl polymers, there had been no experimental means to directly address the question in solution. This issue was taken up by Allegra and coworkers in Milan using force field calculations. They found that helical conformations were important in isolated chains,17,18
therefore strongly supporting Pino’s hypothesis.
If the isotactic polymer chain exists as a series of left-handed and right-handed segments separated by helical reversals, the data in can be understood. The bias per unit from the chiral pendant groups casting the left- and right-handed helical senses into a diastereomeric relationship must be multiplied by the number of units with the same helical sense, and the chiral optical properties arise not from the units but rather from the helical conformation. Later study performed by Pino and coworkers suggested the possibility of roughly estimating the population of the proposed helical reversals and even their possible effect on the overall polymer properties.19
At the time of initial work, direct experimental evidence was sought through observation by CD of the helical chromophore, but this could not be probed because of its inaccessible wavelength. To further seek other avenues to support their hypothesis, Pino and coworkers synthesized an isotactic copolymer of styrene with a large excess of (R)-3,7-dimethyl-1-octene.20
The result of their findings is reported in . The large increase in the CD signal of the aromatic chromophore in the copolymer compared with the model compound was suggested as arising from an extended conformation of the polymer, which could only reasonably be helical. The experiment was further extended to isotactic copolymers derived from monomeric units offering conflicting information to the helical sense of the chain. A series of copolymers of enantiomers from three structurally different 1-alkenes [(S)-5-methyl-1-heptene; (S)-4-methyl-1-hexene and (R)-3,7-dimethyl-1-octene] were then synthesized and their optical activities were measured.21
The results are reported in .
Figure 3. CD spectra at 25°C of the diethyl ether extractable fraction of the styrene-(R)-3,7-dimethyl-1-octene copolymer (A) and of (3S,9S)-3,9-dimethyl-6-phenylundecane (B) in chloroform; De is based on one unit of styrene. Reprinted (more ...)
Figure 4. Molar rotator power (), referred to one monomeric unit, in hydrocarbon solution for the unfractionated methanol-insoluble polymers obtained from samples having different optical purity (Pi) of (S)-5-methyl-1-heptene (A), (S)-4-methyl-1-hexene (more ...)
Alternative studies to confirm the helical hypothesis were also performed by the Italian researchers by synthesizing copolymers of enantiomerically pure units randomly dispersed among achiral units and by measuring the optical activity using mixtures of homopolymers as a control. A linear response of the optical activity to the proportion of the chiral units was observed only in the mixture of homopolymers. In the copolymer of the chiral and achiral units, 50% of the chiral unit was enough to yield the full optical activity.22
However, in the seminal works performed in Italy, cooperative effects were limited by the flexible nature of vinyl polymers. Clearly, these chiral, nonlinear relationships could be further amplified using helical polymers with a lower probability of helical reversals, that is, stiff polymers. This is the subject of the next section.