N-α,N-ε-Di(9-Fluorenylmethoxycarbonyl)-4-oxa-L-lysine

A new type of metallopolymer-polypeptide block copolymer poly(ferrocenyldimethylsilane)-b-poly (epsilon-benzyloxycarbonyl-L-lysine) was synthesized by ring-opening polymerization of epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride initiated by using a primary amino-terminated poly(ferrocenyldimethylsilane). Studies on the self-organization behavior of this polypeptide block copolymer in both the bulk state and in solution were performed. In the bulk state, a cylindrical-in-lamellar structure was observed in a compositionally asymmetric sample. Rod-like micelles with a polyferrocenylsilane core formed in a polypeptide-selective solvent alone or in the presence of a common solvent. Significantly, an additional small quantity of the common solvent assisted the formation of longer micelles and micelles with better shape-regularity. This is attributed to a decrease in the number of nucleation events and PFS core reorganization effects.

As part of the search of novel degradable polymers, amphiphilic and cationic poly(epsilon-caprolactone)-g-poly(l-lysine) (PCL-g-PlL) copolymers have been synthesized following a grafting "onto" or a grafting "from" method both applied to a macropolycarbanionic PCL derivative. The first approach led to PCL-g-PZlL containing 36% of epsilon-caprolactone and 64% of N-epsilon-Z-l-lysine units, by reaction of activated poly(N-epsilon-Z-l-lysine) on the macropolycarbanion derived from PCL. The second route was based on the anionic ring opening polymerization of N-carboxyanhydride of N-epsilon-benzyloxycarbonyl-l-lysine initiated by the macropolycarbanion derived from PCL and led to a similar copolymer containing 45% of of epsilon-caprolactone and 55% of N-epsilon-Z-l-lysine units. After deprotection of the lysine units, PCL-g-PlL copolymers were obtained. These copolymers are water-soluble and form nanometric micelle-like objects with mean diameters between 60 and 500 nm in distilled water depending on the synthesis route.

The synthesis and characterisation of new arborescent architectures of poly(L-lysine), called lysine dendrigraft (DGL) polymers, are described. DGL polymers were prepared through a multiple-generation scheme (up to generation 5) in a weakly acidic aqueous medium by polycondensing N(epsilon)-trifluoroacetyl-L-lysine-N-carboxyanhydride (Lys(Tfa)-NCA) onto the previous generation G(n-1) of DGL, which was used as a macroinitiator. The first generation employed spontaneous NCA polycondensation in water without a macroinitiator; this afforded low-molecular-weight, linear poly(L-lysine) G1 with a polymerisation degree of 8 and a polydispersity index of 1.2. The spontaneous precipitation of the growing N(epsilon)-Tfa-protected polymer (GnP) ensures moderate control of the molecular weight (with unimodal distribution) and easy work-up. The subsequent alkaline removal of Tfa protecting groups afforded generation Gn of DGL as a free form (with 35-60% overall yield from NCA precursor, depending on the DGL generation) that was either used directly in the synthesis of the next generation (G(n+1)) or collected for other uses. Unprotected forms of DGL G1-G5 were characterised by size-exclusion chromatography, capillary electrophoresis and (1)H NMR spectroscopy. The latter technique allowed us to assess the branching density of DGL, the degree of which (ca. 25%) turned out to be intermediate between previously described dendritic graft poly(L-lysines) and lysine dendrimers. An optimised monomer (NCA) versus macroinitiator (DGL G(n-1)) ratio allowed us to obtain unimodal molecular weight distributions with polydispersity indexes ranging from 1.3 to 1.5. Together with the possibility of reaching high molecular weights (with a polymerisation degree of ca. 1000 for G5) within a few synthetic steps, this synthetic route to DGL provides an easy, cost-efficient, multigram-scale access to dendritic polylysines with various potential applications in biology and in other domains.