title: Copper catalyst efficiency for the CuAAC synthesis of a poly(N-isopropylacrylamide) conjugated hyaluronan.
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.
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse, Davos Platz, Switzerland.|Universitat de Barcelona, Martí i Franquès, Barcelona, Spain.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Seelbach
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse, Davos Platz, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Este
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse, Davos Platz, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: Queen Mary, University of London, London, UK.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mata
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse, Davos Platz, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Eglin
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry*; D000480:Alkynes; D001205:Ascorbic Acid / Q000737:chemistry; D001386:Azides; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D019327:Copper Sulfate / Q000737:chemistry; D061565:Cycloaddition Reaction; D006820:Hyaluronic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D000480:Alkynes; D001386:Azides; D009943:Organophosphorus Compounds; D011108:Polymers; C052970:poly-N-isopropylacrylamide; C061896:triphenylphosphine; D003300:Copper; D006820:Hyaluronic Acid; D019327:Copper Sulfate; D001205:Ascorbic Acid
keywords: Hyaluronan; bromotris (triphenylphosphine) copper(I); copper catalyzed azide-alkyne cycloaddition; poly(N-isopropylacrylamide)