Abstract
BACKGROUND: Poly(N-isopropylacrylamide) conjugated
hyaluronan (HA-pN), a brush-like copolymer system which serves as a polymer vehicle for
cellular and drug delivery, has been previously synthesized via the copper catalyzed
azide-alkyne reaction (CuAAC) using a combination of copper sulfate and ascorbic acid
(CuAsc) as the catalytic system of choice. Bromotris(triphenylphosphine) copper(I)
(CuBr(PPh3)3) is an alternative catalytic compound containing a
phosphorous ligand which stabilizes copper in the +1 oxidative state in aqueous solvents
and can be employed at true catalyst concentrations.
OBJECTIVE: CuAsc and CuBr(PPh3)3 were compared for
their efficiency; 1) in the synthesis of HA-pN via CuAAC; 2) in producing thermoresponsive
compositions and 3) in being extracted from the polymeric compositions.
METHODS: The synthesis of the brush copolymer was carried out under strict
Schlenk conditions, then characterized by ATR-FTIR, 1H NMR, ICP-SFMS, and
rheological measurements.
RESULTS: CuBr(PPh3)3 catalyzed CuAAC leads to better
grafting in water, at a true catalyst concentration, compared to CuAsc. Polymeric
solutions exhibited similar traits of increasing mechanical stiffness with rising
temperature. Despite purification via chelation and/or dialysis, residual copper was
present in similar concentrations in the final polymers.
CONCLUSIONS: In the CuAAC driven copolymer synthesis of the HA-pN,
CuBr(PPh3)3 is a better catalyst than CuAsc.
