Comparison of Copper(II)-Ligand Complexes as Mediators for Preparing Electrochemically Modulated Nitric Oxide-Releasing Catheters

Further studies aimed at examining the activity of different Cu(II)-ligand complexes to serve as electron-transfer mediators to prepare novel antimicrobial/thromboresistant nitric oxide (NO)-releasing intravenous catheters are reported. In these devices, the NO release can be modulated by applying different potentials or currents to reduce the Cu(II)-complexes to Cu(I) species which then reduce nitrite ions into NO(g) within a lumen of the catheter. Four different ligands are compared with respect to NO generation efficiency and stability over time using both single- and dual-lumen silicone rubber catheters: N-propanoate-N,N-bis(2-pyridylethyl)amine (BEPA-Pr), N-propanoate-N,N-bis(2-pyridylmethyl)amine (BMPA-Pr), 1,4,7-trimethyl-1,4,7-triazacyclononane (Me(3)TACN), and tris(2-pyridylmethyl)amine (TPMA). Of these, the Cu(II)BEPA-Pr and Cu(II)Me(3)TACN complexes provide biomedically useful NO fluxes from the surface of the catheters, >2 x 10(-10) mol.min(-1).cm(-2), under conditions mimicking the bloodstream environment. Cu(II)Me(3)TACN exhibits the best stability over time with a steady and continuous NO release observed for 8 d under a nitrogen atmosphere. Antimicrobial experiments conducted over 5 d with NO-releasing catheters turned on electrochemically for only 3 or 6 h each day revealed >2 logarithmic units in reduction of bacterial biofilm attached to the catheter surfaces. The use of optimal Cu(II)-ligand complexes within a lumen reservoir along with high levels of nitrite ions can potentially provide an effective method of preventing/decreasing the rate of infections caused by intravascular catheters.