On the solution structure of PHB: Preparation and NMR analysis of isotopically labeled oligo[(R)-3-hydroxybutanoic acids] (OHBs)

Peter Waser, Magnus Rueping, Dieter Seebach*, Elke Duchardt, Harald Schwalbe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

While the chain conformation of poly- and oligo[(R)-3-hydroxybutanoate] (PHB, OHB) is known to be 21-and 31-helical in stretched fibers and in the crystalline state, respectively (Fig. 2), the structure in solution is unknown. To be able to determine the NMR-solution structure, specifically labeled linear oligomers have been prepared: a 16-mer consisting of alternating pairs of fully 13C-labeled and non-labeled residues (1) and a 20-mer containing an O-13CH(13CH2D)-13CHD Si-13CO residue in position 9 (from the O-terminus) and a fully 13C-labeled residue in position 12 (2), both with (ι-Bu)Ph2Si protection at the O- and Bn protection at the C-terminus. The labeled (R)-3-hydroxybutanoic acid building blocks were prepared by Noyori hydrogenation of the ethyl ester of fully 13C-labeled acetoacetic acid, and the D-atoms were incorporated by D2/Pd-C reduction of a previously reported dibromo-1,3-dioxinone 8 (Scheme 1). The oligomers were obtained by a series of fragment couplings (Schemes 2 and 3). 600-MHz NMR COSY, HSQC, ROESY, and cross-correlated relaxation measurements (Figs. 4-6, 9, and 12, and Tables 1-3) at different temperatures and interpretations thereof led to assignments of all resonances, including those from the diastereotopic C(2)H2 protons, and to determination of the conformationally averaged dihedral angles φ2 and φ3 (Figs. 2, 7, and 8) in the chain of the oligoester. The conclusions are: all but five or six terminal residues adopt the same conformation; the 21 helix is not the predominant secondary structure; the structure of the HB chain is averaged, even at -30°. Our investigation confirms the high flexibility of the polyester chain, a property that has been deduced previously from biological studies of PHB in membranes, in ion channels, and as appendage of proteins.

Original languageEnglish (US)
Pages (from-to)1821-1845
Number of pages25
JournalHelvetica Chimica Acta
Volume84
Issue number6
DOIs
StatePublished - Aug 18 2001

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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