Partial Depolymerization and Solubilization of Poly[(R)-3-hydroxybutanoate] (PHB) and Its Copolymer with (R)-3-Hydroxyvalerate (BIOPOL®) by Treatment with Li-Amides/LiCl in Tetrahydrofuran at Low Temperature

Seebàch, Dieter; Beck, Albert K.; Brändli, Urs; Müller, Dieter G.; Przybylski, Michael; Schneider, Klaus

doi:10.2533/chimia.1990.112

Cited by 15 publications

(1 citation statement)

References 3 publications

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“…[51 -60] A preferred folding mode for PHB in the solid state was revealed when we treated a stirred suspension of PHB in THF at À 75 °C with LiN(SiMe 3 ) 2 (Li-HMDS): The resulting mixture contained an increasing amount of 15-mer (by size-exclusion chromatography), indicating that the polymer chain is folded in crystalline domains, that the cleavage by Li-HMDS occurs at the folding points, and that ca.15 HB units span the thickness of the crystallites. [61,62] For the 2 1 -helical PHB structure, which has a ca. 6 Å pitch, [49] the crystallite would be ca.…”

Section: Figure 5 Phb Detected In Various Kingdoms Of Lifementioning

confidence: 99%

No Life on this Planet Without PHB

Seebàch

2023

Helvetica Chimica Acta

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The history of discovery by Rosetta Reusch of oligo-and poly-β-hydroxybutyrates (OHBs and PHBs) consisting of less than ca. 150 HB units is described. These 'short-chain' biopolymers can be detected in all living organisms and have numerous physiological activities of fundamental importance for the chemistry of life. The largest are components of ion channels such as Ca 2 + -polyphosphate-PHB (Ca-PPi-PHB) in genetically competent E. coli and in mammalian mitochondria. Sequences with chain lengths < ca. 30 occur covalently attached to proteins (posttranslational PHBylation), and methyl esters of the dimer and trimer are used by certain bacteria as highly efficient antioxidants. With synthetic monodisperse OHBs (up to 128mer) our group has contributed structural investigations, and we have shown that OHBs � 16 alone make phospholipid bilayer vesicles permeable to Ca ions. An extensive biochemical analysis of the TRPM8 protein channel, responsible for the sense of heat in our skin, proved to be fully active only when PHBylated. Reasons for the difficulty of detecting OHBs and PHBs are discussed: the polyester chain is highly flexible, and there is ester cleavage by base, acid, nucleophiles, Lewis acids, and heat -in stark contrast to peptides. PHBs may be called a ubiquitous but fleeting species in the chemistry of life -worth being appreciated and studied much more intensively in the future! A speculation about PHB's possible role in prebiotic compartmentalization is presented, and recent uses of compartmentalization in organic synthesis are briefly mentioned. Portions of the figures used herein were presented in a lecture at the International Symposium on Biopolymers on September 13, 2022, in Sion (Switzerland).

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Section: Figure 5 Phb Detected In Various Kingdoms Of Lifementioning

confidence: 99%

No Life on this Planet Without PHB

Seebàch

2023

Helvetica Chimica Acta

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A Molecular-Dynamics Simulation Study of the Conformational Preferences of Oligo(3-hydroxyalkanoic acids) in Chloroform Solution

Gee

Hamprecht

Schuler

et al. 2002

HCA

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The GROMOS96 molecular-dynamics (MD) program and force field was used to calculate the conformations at 298 K in CHCl 3 solution of two hexakis(3-hydroxyalkanoic acids). One consists of (R)-3-hydroxybutanoate (HB) residues only: HÀ(OCH(Me)ÀCH 2 ÀCO) 6 ÀOH (1). The other one carries the side chains of valine, alanine, and leucine: HÀ(OCH(CHMe 2 )CH 2 ÀCOÀOÀCH(Me)ÀCH 2 ÀCOÀOÀCH(CH 2 CHMe 2 )ÀCH 2 ÀCO) 2 ÀOH (2), with homochiral 3-hydroxyalkanoate (HA) moieties. In both cases, the conformational equilibria were sampled 2500 times for 25 ns. Other than clusters of arrangements with interresidual hydrogen bonding (between the O-and C-terminal OH and COOH groups, and with chain-bound ester carbonyl O-atoms; Fig. 6), there are no preferred backbone conformations in which the molecules 1 and 2 spend more than 5% of the time. Specifically, neither the 2 1 -nor the 3 1 -helical conformation of the oligoester backbone (found in stretched fibers, in lamellar crystallites, and in single crystals of polymers PHB and of oligomers OHB) is sampled to any significant extent ( Fig. 8 and 9), in spite of the high population, in both oligomers, of the (À)-synclinal conformation around the C(2)ÀC (3) bond (angle f 2 in Fig. 2). In contrast to b-oligopeptides, for which strongly preferred secondary structures are found after a few ns, and for which the number of conformations levels off with time, the number of conformational clusters of the corresponding oligoesters found by our force-field MD calculations increases steadily over the observation time of 25 ns (Fig. 5). Thus, the conclusion from biological and physical-chemical studies, according to which the PHB chain is extremely flexible, is confirmed by our computational investigation: in CHCl 3 solution, the hexakis(3-hydroxyalkanoate) chain samples its conformational space randomly! 1. Introduction. ± Associated with the biological role of the short-chain poly[(R)-3-hydroxybutanoate] (PHB) [1], which has been shown to allow the passage of ions across phospholipid bilayer membranes under voltage-driven and concentration-driven conditions [2], or to function as a transmembrane ion-channel when associated with Ca polyphosphate [1 ± 3], is the question of its secondary structure. From the investigation of PHB or PHB derivatives in the solid state, two different folding patterns were recognized: a 2 1 helix in stretched fibers [4] and in lamellar crystallites of the polymer

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Synthesis and NMR Analysis in Solution of Oligo(3-hydroxyalkanoic acid) Derivatives with the Side Chains of Alanine, Valine, and Leucine (β-Depsides): Coming Full Circle from PHB toβ-Peptides to PHB

Albert

Seebàch

Duchardt

et al. 2002

HCA

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Oligomers of 3-hydroxyalkanoic acids that contain two, three, and six residues with and without O-terminal (tBu)Ph 2 Si and C-terminal PhCH 2 protection have been synthesized in such a way that the side chains on the oligoester backbone were those of the proteinogenic amino acids Ala (Me), Val (CHMe 2 ), and Leu (CH 2 CHMe 2 ). The enantiomerically pure 3-hydroxyalkanoates were obtained by Noyori hydrogenation of the corresponding 3-oxo-alkanoates with [Ru((R)-binap)Cl 2 ](binap 2,2'bis(diphenylphosphanyl)-1,1'-binaphthalene)/H 2 (Scheme 1), and the coupling was achieved under the conditions (pyridine/(COCl) 2 , CH 2 Cl 2 , À 788) previously employed for the synthesis of various oligo(3-hydroxybutanoic acids) (Schemes 2 and 3). The Cotton effects in the CD spectra of the new oligoesters provided no hints about chiral conformation (cf. a helix) in MeOH, MeCN, octan-1-ol, or CF 3 CH 2 OH solutions (Figs. 1 and 2). Detailed NMR investigations in CDCl 3 solution (Figs. 3 ± 6, and Tables 1 ± 5) of the hexa(3-hydroxyalkanoic acid) with the side chains of Val (HC), Ala (HB), Leu (HH), Val, Ala, Leu (from O-to C-terminus; 3) gave, on the NMR time-scale, no evidence for the presence of any significant amount of a 2 1 -or a 3 1 -helical conformation, comparable to those identified in stretched fibers of poly[(R)-3-hydroxybutanoic acid], or in lamellar crystallites and in single crystals of linear and cyclic oligo[(R)-3-hydroxybutanoic acids], or in the corresponding b-peptide(s) (the oligo(3-aminoalkanoic acid) analogs; 1 ± 3). Thus, the extremely high flexibility (averaged or −random-coil× conformation) of the polyester chain (COÀO rotational barrier ca. 13 kcal/mol; no hydrogen bonding), as compared to polyamide chains (COÀNH barrier ca. 18 kcal/mol; hydrogen bonding) has been demonstrated once again. The possible importance of this structural flexibility, which goes along with amphiphilic properties, for the role of PHB in biology, in evolution, and in prebiotic chemistry is discussed. Structural similarities of natural potassiumchanneling proteins and complexes of oligo(3-hydroxybutanoates) with Na , K , or Ba 2 are alluded to (Figs. 7 ± 9).1. Indroduction. ± The short-chain version of poly[(R)-3-hydroxybutanoic acid] (c-PHB), 1, has been detected in numerous biological systems, and we believe that it is fair to say that the biopolymer PHB is present in all living organisms 3 ). The low-molecularweight PHB has been shown to cause phospholipid membranes to become permeable for cations, such as Na, K, Rb, Ca or Ba, under voltage-driven (patch-clamp experiments [5]) and under concentration-driven (artificial vesicles [6]) conditions. Furthermore, a Ca polyphosphate-PHB complex consisting of ca. 140 HB and 70 phosphate units and containing ca. 35 Ca 2 ions has been identified as a Ca-specific ion Helvetica Chimica Acta ± Vol. 85 (2002) 633 1 ) Part of the projected Ph. D. Theses of M. A. and E. D., ETH-Z¸rich and MIT, respectively.

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Partial Depolymerization and Solubilization of Poly[(R)-3-hydroxybutanoate] (PHB) and Its Copolymer with (R)-3-Hydroxyvalerate (BIOPOL®) by Treatment with Li-Amides/LiCl in Tetrahydrofuran at Low Temperature

Cited by 15 publications

References 3 publications

No Life on this Planet Without PHB

No Life on this Planet Without PHB

A Molecular-Dynamics Simulation Study of the Conformational Preferences of Oligo(3-hydroxyalkanoic acids) in Chloroform Solution

Synthesis and NMR Analysis in Solution of Oligo(3-hydroxyalkanoic acid) Derivatives with the Side Chains of Alanine, Valine, and Leucine (β-Depsides): Coming Full Circle from PHB toβ-Peptides to PHB

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