Cyclooctyne End-Functionalized Poly(morpholine-2,5-dione)s.

Abstract

The cyclooctyne-functionalized alcohol (1R,8S,9S)-bicyclo-[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) is applied as initiator for the organo-catalyzed ring-opening polymerization (ROP) of morpholine-2,5-diones based on the l-amino acids valine, isoleucine, and phenylalanine. The ROP is catalyzed by a binary system of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) applying a feed ratio of [M]/[I]/[DBU]/[TU] of 100/1/1/10. Kinetic studies reveal that BCN-OH is capable to initiate the polymerization of morpholine-2,5-diones, which proceed in a controlled manner until monomer conversions of 80%. Characterization by means of ¹H NMR spectroscopy, size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry confirm the covalent attachment of the cyclooctyne moiety as α-end group of the poly(morpholine-2,5-dione)s with maximum dispersities of 1.25. As a proof of concept, a vitamin A end-functionalized poly(2-ethyl-2-oxazoline) is coupled to a poly(ester amide) by strain-promoted azide-alkyne cycloaddition. Characterization of the block copolymer by SEC and DOSY NMR spectroscopy confirm the successful attachment of the two building blocks. The versatile cyclooctyne moiety shall facilitate a metal-free attachment of other polymer blocks, targeting ligands or dyes at the α-end group of well-defined poly(morpholine-2,5-dione)s. In consequence, the approach provides access to a new generation of functionalized poly(ester amide)s, which can be customized for specific needs.