Poly(ethylene oxide-co-β-benzyl l-aspartate) Block Copolymers:  Influence of the Poly(ethylene oxide) Block on the Conformation of the Poly(β-benzyl l-aspartate) Segment in Organic Solvents

Abstract

The conformation of the poly(β-benzyl L-aspartate) segment in the poly(ethylene oxide-coβ-benzyl L-aspartate) (PEO/PBLA) block copolymers (Mw of PEO ) 5000 and 20 units of β-benzyl L-aspartate) was investigated by 1 H NMR, by specific optical rotation measurements, and by 2D 1 H, 1 H NOESY NMR in chloroform, dimethyl sulfoxide (DMSO), and mixtures of chloroform/DMSO. The comparison between the 1 H NMR spectra of the block copolymer in CDCl3 and the one in DMSO-d6 showed that the PBLA blocks adopt a different conformation depending upon the solvents. The specific rotation of the block copolymer at 546 nm demonstrated that the PBLA segments adopt a left-handed R-helix conformation in chloroform. PBLA homopolymer with the same molecular weight as the PBLA segment in the block copolymer showed no evidence of R-helix formation in the same conditions, indicating that the PEO segment in the block copolymer is essential to allow PBLA to take the R-helix structure. On the other hand, the specific rotation of the PEO/PBLA block copolymer in DMSO at the same wavelength showed that the PBLA segments have a random-coil conformation in this solvent. Moreover, the measurement of the specific rotation of the block copolymer in mixtures of x% CHCl3/(100 -x)% DMSO (0 e x e 100) demonstrated that the left-handed R-helix conformation adopted by the PBLA segments in chloroform is stable. Conversely, the PBLA homopolymer cannot be solubilized in mixtures of CHCl3/ DMSO, although this homopolymer is soluble in pure CHCl3 and in pure DMSO. The 2D 1 H, 1 H NOESY NMR spectrum in CDCl3 gave evidence of interactions between the methylene protons (CO2CH2C6H5) of the PBLA segments and the methylene protons of the PEO blocks on one hand and between the benzyl protons of the PBLA segments and the methylene protons of the PEO blocks on the other. Such interactions are not observed in DMSO-d6. Thus, the stability of the left-handed R-helix conformation of the PBLA blocks (having low molecular weights) in chloroform can be explained by the interactions existing between the PBLA and the PEO blocks. Moreover, these interactions also allow the solubilization of the block copolymer in mixtures of CHCl3/DMSO.

Synthesis and characterization of novel poly(γ‐benzyl‐L‐glutamate) derivatives tailored for the preparation of nanoparticles of pharmaceutical interest

“…It was shown that oligo(α‐amino acids) with units of aspartic acid, glutamic acid, phenylalanine and tyrosine could form, in acidic conditions, microspheres capable of encapsulating drugs such as insulin or heparin 5, 6. Poly[(ethylene oxide)‐ block ‐(β‐benzyl‐ L ‐aspartate)]7–10 or poly[(ethylene oxide)‐ block ‐(γ‐benzyl‐ L ‐glutamate)]11, 12 allowed macromolecular micelle formation as a result of their amphiphilic nature 13, 14. Recently, in response to the need for targeting systems, poly(γ‐benzyl‐ L ‐glutamate) and poly(ethylene glycol) diblock copolymers end capped with a galactose moiety have been proposed for site‐specific drug delivery 15…”

Helix–coil transformation of poly(γ-benzyl-L-glutamate) with polystyrene attached to the N or C terminus in trifluoroacetic acid–chloroform mixtures

“…Effect of PS attachment to PBLG on helix-coil transformation Cammas et al 9 reported for PEO/PBLA block copolymers that the helical content of the PBLA segment increased after attachment of the PEO due to hydrogen-bonding interactions between the two segments in organic solvent. Such an increase was also observed for other peptide/synthetic block copolymers because of the aggregation of polypeptide segments in micelles [10][11][12][13] and in microphase-segregated structures.…”

“…8 For peptide/synthetic block copolymers, in addition, effects of the synthetic polymer segments on the helical structure have been reported. Cammas et al 9 found that a left-handed helix of poly(b-benzyl-L-aspartate) (PBLA) was stabilized by the attachment of poly(ethylene oxide) (PEO) to form a PBLA/PEO diblock copolymer. Similar observations have been reported for block copolymers composed of a-helical polypeptide and PEO segments in water or hydrophobic solvents.…”

Polyether Core‐Shell Cylinder–Polymerization of Polyglycidol Macromonomers

“…It is commonly known that the amphiphilic compounds containing incompatible segments give rise to special properties in selective solvents. In such solvent, which is “good” for one part and “bad” or non‐solvent for the second part, micellar structures are formed 11–16. In water amphiphilic macromonomers PEO‐St aggregate to form micelles with their hydrophobic groups in the core and the hydrophilic PEO chains in the surrounding shell 8.…”