Copper catalyst efficiency for the CuAAC synthesis of a poly(N-isopropylacrylamide) conjugated hyaluronan

Issue title: Special issue: Advanced Functional Polymers in Medicine (AFPM): Liège, Belgium, May 2014; Guest-Editors: Christine Jérôme and Andreas Lendlein

Article type: Research Article

Authors: Seelbach, Ryan J.^{a; b} | D’Este, Matteo^a | Alini, Mauro^a | Mata, Alvaro^c | Eglin, David^{a; *}

Affiliations: [a] AO Research Institute Davos, Clavadelerstrasse, Davos Platz, Switzerland | [b] Universitat de Barcelona, Martí i Franquès, Barcelona, Spain | [c] Queen Mary, University of London, London, UK

Correspondence: [*] Corresponding author: David Eglin, AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland. Tel.: +41 81 414 24 80; Fax: +41 81 414 22 88; david.eglin@aofoundation.org

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.

Keywords: Hyaluronan, copper catalyzed azide-alkyne cycloaddition, poly(N-isopropylacrylamide), bromotris (triphenylphosphine) copper(I)

DOI: 10.3233/CH-151933

Journal: Clinical Hemorheology and Microcirculation, vol. 60, no. 1, pp. 25-37, 2015