Macromolecular stereochemistry of poly(p-biphenylmethyl-L-glutamate): linkage between biphenyl twist sense and polypeptide conformation and observation of microaggregation-driven, sudden, temperature-dependent chiral optical changes

Abstract

In the expectation that the normally equally populated left-(M) and right-handed (P) twist senses of a biphenyl moiety would, in the side chain of a polypeptide, be perturbed by the helical conformation of the main chain and therefore potentially reveal characteristics of the side-chain conformation, we have carried out the syntheses of the ortho-and para-substituted biphenylmethyl esters of poly(L-glutamic acid) and poly(L-aspartic acid). In the aspartate series the appropriate N-carboxyanhydrides yielded polymer for both the ortho-and para-substituted biphenylmethyl esters. The para isomer was not soluble in solvents appropriate to ultraviolet circular dichroism measurements while the ortho isomer indicated the absence of the a-helical conformation. In the glutamate series although we could not obtain a crystalline N-carboxyanhydride from the ortho isomer, in the para isomer we were able to obtain a high polymer, which, in a variety of solvents, both adopts the a-helical conformation and displays a strong positive circular dichroism band associated with the biphenyl chromophore. This chiral optical characteristic is almost entirely lost on dichloroacetic acid denaturation of the polypeptide. As a complete surprise, dilute solutions of poly(pbiphenylmethyl L-glutamate) in several helicogenic solvents, with the notable exception of chloroform, exhibit a sudden, large, almost concentration-independent, reversible change in their optical activity properties just below 0 O C . Intrinsic viscosity and light-scattering measurements point to aggregation associated with this change while ultraviolet, infrared, and excimer fluorescence measurements offer no evidence for significant conformational changes of the polypeptide chain or of the relationships among the biphenyl groups.

Poly‐γ‐p‐Biphenylmethyl‐Glutamate as Enantiodifferentiating Alignment Medium for NMR Spectroscopy with Temperature‐Tunable Properties

“…After successful synthesis of the homopolymers Poly‐ d ‐ 1 and Poly‐ l ‐ 1 we investigated their chiroptical properties by CD spectroscopy (Figure ). The general course and the temperature dependence of CD spectra of Poly‐ l ‐ 1 could be reproduced in accordance to the literature . With decreasing temperature in the range from 323 to 273 K, only a small increase of intensity is observed in the region of 222 nm, which is generally assigned to the homopolypeptide backbone.…”

“…More interestingly, PBPMLG exhibits a significant temperature‐dependent effect on its optical behaviour. Dilute solutions of the polymer in several solvents show a sudden change of the specific rotation below 273 K . The corresponding circular dichroism (CD) spectra confirm that the α‐helical structure remains, while a strong CD band associated with the biphenyl chromophore emerges .…”

“…Dilute solutions of the polymer in several solvents show a sudden change of the specific rotation below 273 K . The corresponding circular dichroism (CD) spectra confirm that the α‐helical structure remains, while a strong CD band associated with the biphenyl chromophore emerges . It is proposed that this transition is caused by association caused by a phase transition at lower temperatures with an ordered supramolecular structure, in which the chains of the polymer aggregate in parallel .…”

Synthesis of Side-Chain Modified Polypeptides

“…In related work, biphenyl "end-on" modified lysine, glutamate, and aspartate NCAs were prepared ( Figure 3D,E). 28,29 While the modified aspartate polymers were found to possess disordered conformations, poly(p-biphenylmethyl-Lglutamate) was found to be soluble, and α-helical in many solvents. Poly(p-phenylbenzamido-L-lysine) was soluble in DMF and found to form a layered S A2 smectic structure in the solid-state, with the polypeptide backbone in the β-sheet conformation.…”

Biphenyl twist sense linkage between side-chain and main-chain conformations in a poly(glutamate ester)

“…2 This result requires that the local mirror image twist senses about the biphenyl bond are substantially unequal in energy in spite of the 10 bonds intervening between the coupled chiral units, i.e., the biphenyl group and the LY helix. Since this coupling must depend on the side-chain conformation and since the extensive work on optically active small-molecule bridged biphenyls4 allows translation of the CD behavior of PPBLG into the twist sense preference, i.e., left-handed, and with less certainty, the approximate excess of this sense of between 12 and 24 70, the observation* offers an opportunity to use an unusually subtle parameter to compare experiment to theory in the area of force-field calculations of the polypeptide sidechain conformationO3J…”