HNO/NO Conversion Mechanisms of Cu-Based HNO Probes with Implications for Cu,Zn-SOD

Abstract

High Resolution Image Download MS PowerPoint Slide HNO has broad biological effects and pharmacological activities. Direct HNO probes for in vivo applications were recently reported, which are Cu II -based complexes having fluorescence reporters with reaction to HNO resulting in Cu I systems and the release of NO. Their coordination environments are similar to that in Cu,Zn-superoxide dismutase (SOD), which plays a significant role in cellular HNO/NO conversion. However, none of these conversion mechanisms are known. A quantum chemical investigation was performed here to provide structural, energetic, and electronic profiles of HNO/NO conversion pathways via the first Cu II -based direct HNO probe. Results not only are consistent with experimental observations but also provide numerous structural and mechanistic details unknown before. Results also suggest the first HNO/NO conversion mechanism for Cu,Zn-SOD, as well as useful guidelines for future design of metal-based HNO probes. These results shall facilitate development of direct HNO probes and studies of HNO/NO conversions via metal complexes and metalloproteins.