Phenyl Trimethylsilyl Sulfide-Mediated Controlled Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides

Biomacromolecules. 2016 Mar 14;17(3):891-6. doi: 10.1021/acs.biomac.5b01588. Epub 2016 Jan 29.

Abstract

We describe here the first example of trimethylsilyl sulfide (S-TMS) mediated controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs). We show that phenyl trimethylsilyl sulfide (PhS-TMS), an inexpensive and commercially available compound, mediates rapid ROP of a broad scope of NCA monomers, produces functional poly(amino acids) (PAAs) with controllable molecular weights (MWs), narrow polydispersity index (PDI), and an in situ generated phenyl thioester group at the C-terminus (PAA-SPhs). PhS-TMS offers more rapid chain initiation than previously reported hexamethyldisilazane (HMDS) initiator, ensuring a living polymerization with better control. Mechanistic studies suggest that a reactive trimethylsilyl carbamate (TMSC) was generated during the chain initiation and continued to regulate the chain propagation through a TMS transfer process. Considering the versatility of NCAs, and the potential of leveraging the C-terminal phenyl thioester for native chemical ligation (NCL), we believe this method may offer a powerful platform enabling the rapid generation of functional PAAs and their C-terminal conjugates for numerous biological applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Anhydrides / chemistry
  • Oligopeptides / chemistry
  • Organosilicon Compounds / chemistry
  • Polymerization*
  • Trimethylsilyl Compounds / chemistry*

Substances

  • Amino Acids
  • Anhydrides
  • Oligopeptides
  • Organosilicon Compounds
  • Trimethylsilyl Compounds
  • hexamethylsilazane