Spontaneous catalytic generation of nitric oxide from S-nitrosothiols at the surface of polymer films doped with lipophilic copperII complex.
A new approach for preparing potentially more blood-compatible nitric oxide (NO)-generating polymeric materials is described. The method involves creating polymeric films that have catalytic sites within (lipophilic copper(II) complex) that are capable of converting endogenous S-nitrosothiols present in blood (S-nitrosoglutathione (GSNO), S-nitrosocysteine (CysNO), etc.) to NO. The catalytic NO generation reaction involves the initial reduction of Cu(II) to Cu(I) within the complex by appropriate reducing agents (e.g., thiolates or ascorbate), followed by the reduction of S-nitrosothiols to NO by the Cu(I) complex at the polymer/solution interface. The NO fluxes observed when PVC or polyurethane films containing the copper(II) complex are placed in solutions containing physiological levels of nitrosothiols (muM levels) reach ca. 8 x 10-10 mol cm-2 min-1, greater than that produced by normal endothelial cells that line all healthy blood vessels. It is thus anticipated that this spontaneous catalytic generation of NO from endogenous nitrosothiols will render such polymeric materials more thromboresistant when in contact with blood in vivo.
Oh
Bong Kyun
BK
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
Meyerhoff
Mark E
ME
D002384:Catalysis; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D011143:Polyvinyl Chloride / Q000737:chemistry*; D019736:Prostheses and Implants; D026423:S-Nitroso-N-Acetylpenicillamine / Q000737:chemistry; D026403:S-Nitrosothiols / Q000737:chemistry*; D013499:Surface Properties
D020099:Coated Materials, Biocompatible; C477933:Cu(II)-dibenzo(e,k)-2,3,8,9-tetraphenyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene; D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D011140:Polyurethanes; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D003300:Copper; D026423:S-Nitroso-N-Acetylpenicillamine; D011143:Polyvinyl Chloride