An expeditious multigram-scale synthesis of lysine dendrigraft (DGL) polymers by aqueous N-carboxyanhydride polycondensation.
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.
Collet
Hélène
H
Institut des Biomolécules Max Mousseron, CNRS, Université Montpellier 1, Université Montpellier 2, DSBC, C.C. 1706, place Eugène Bataillon, 34095 Montpellier cedex 5, France.
Souaid
Eddy
E
Cottet
Hervé
H
Deratani
André
A
Boiteau
Laurent
L
Dessalces
Guy
G
Rossi
Jean-Christophe
JC
Commeyras
Auguste
A
Pascal
Robert
R
D000812:Anhydrides / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D008239:Lysine / Q000138:chemical synthesis* / Q000737:chemistry; D046911:Macromolecular Substances / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D011107:Polylysine / Q000138:chemical synthesis* / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D014867:Water
D000812:Anhydrides; D050091:Dendrimers; D046911:Macromolecular Substances; D011108:Polymers; D014867:Water; D011107:Polylysine; D008239:Lysine