Iron Complex Facilitated Copper Redox Cycling for Nitric Oxide Generation as Nontoxic Nitrifying Biofilm Inhibitor

Abstract

In this study, we developed poly(vinyl chloride) (PVC)-solvent casted mixed metal copper and iron complexes capable of catalytic generation of the antibiofilm nitric oxide (NO) from endogenous nitrite. In the absence of additional reducing agent, we demonstrated that the presence of iron complex facilitates a redox cycling, converting the copper(II) complex to active copper(I) species, which catalyzes the generation of NO from nitrite. Assessed by protein assay and surface coverage analyses, the presence of the mixed metal complexes in systems containing water industry-relevant nitrite-producing nitrifying biofilms was shown to result in a "nontoxic mode" of biofilm suppression, while confining the bacterial growth to the free-floating planktonic phase. Addition of an NO scavenger into the mixed metal system eliminated the antibiofilm effects, therefore validating first, the capability of the mixed metal complexes to catalytically generate NO from the endogenously produced nitrite and second, the antibiofilm effects of the generated NO. The work highlights the development of self-sustained antibiofilm materials that features potential for industrial applications. The novel NO-generating antibiofilm technology diverts from the unfavorable requirement of adding a reducing agent and importantly, the less tendency for development of bacterial resistance.

Zinc‐oxide nanoparticles act catalytically and synergistically with nitric oxide donors to enhance antimicrobial efficacy

“…While the enhanced biological effects of NO releasing materials have been studied with metal ions like iron and copper, [25][26][27] and polyurethane/metal-organic framework composite materials, 28 the catalytic effects of a much more mammalian cell friendly metal ion, ZnO-NPs, has not been studied until now. In the past, the ability of Zn 2+ to generate to generate NO from SNAP has been studied using a Zn wire and a solution for in vivo biodegradable bare stent and has been found to elevate NO release.…”

Enzyme Mimics for the Catalytic Generation of Nitric Oxide from Endogenous Prodrugs

“…Contributions from Amal's group concentrated on catalyzing endogenous nitrite to produce NO using copper complexes loaded into poly(vinyl chloride) (PVC) films. [73][74][75] An exemplary study from her group showed the immobilization of both iron and copper complexes into PVC matrices (Figure 3a). [74] Iron complexes were introduced as a reducing agent to convert Cu 2+ to Cu + .…”

“…[73][74][75] An exemplary study from her group showed the immobilization of both iron and copper complexes into PVC matrices (Figure 3a). [74] Iron complexes were introduced as a reducing agent to convert Cu 2+ to Cu + . Cu-Fe/PVC films generated a surge of up to 125 nM NO from 1 mM nitrite, which is 5 times higher than pure PVC films and Fe/PVC films and 2.5 times higher than Cu/PVC films.…”

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix

“…This complex immobilized together with [Fe(dttct)] onto the same matrix composed of a system able to generate nitric oxide (NO) from endogenous nitrite through Cu(II) conversion to active Cu(I). Besides nitrifying bacteria biofilm dispersion, the antibiofilm activity of these material was evidenced against Bacillus species [73].…”