Direct Detection of Nitroxyl in Aqueous Solution using a Tripodal Copper(II) BODIPY Complex

Abstract

Nitric oxide (NO) mediates both physiological and pathological processes.1,2 In addition to cardiovascular signaling, NO has been invoked to play a neurochemical role in learning and memory, and it is a powerful necrotic agent wielded by macrophages of the immune system. Whereas considerable effort has been invested to develop metal-based3-5 and other6,7 probes for detecting nitric oxide, there has been significantly less progress in the synthesis of platforms capable of detecting other reactive nitrogen species (RNS).8 Of the nitrogen oxides relevant to biology, nitroxyl (HNO), the one electron reduced, protonated analog of nitric oxide,9 is among the least thoroughly investigated.10 Interest in nitroxyl has grown with the accumulation of evidence that HNO, which has a pKa of 11.4 and exists primarily in the protonated form under physiological conditions,9 displays important biological roles with potential pharmacological applications distinct from those of nitric oxide.11-13 For example, HNO reacts directly with thiols,14 is resistant to scavenging by superoxide,15 and can activate voltage-dependent K+ channels in mammalian vascular systems.16,17 Moreover, biochemical studies suggest that HNO can be formed directly from nitric oxide synthase under appropriate conditions10,18 and that NO and HNO may be able to interconvert in the presence of superoxide dismutase (SOD).19 Despite accumulating evidence of the biological importance of HNO, studies have been hampered by the lack of a biologically compatible probe for the molecule. Only recently have chemical systems capable of discerning HNO from NO been reported, but the constructs are not suitable for work with biological samples.