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

摘要

Nitric oxide (NO) mediates both physiological and pathologicalprocesses.1,2 In addition to cardiovascular signaling, NO has beeninvoked to play a neurochemical role in learning and memory, andit is a powerful necrotic agent wielded by macrophages of theimmune system. Whereas considerable effort has been invested todevelop metal-based3-5 and other6,7 probes for detecting nitricoxide, there has been significantly less progress in the synthesis ofplatforms 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 nitricoxide,9 is among the least thoroughly investigated.10 Interest innitroxyl has grown with the accumulation of evidence that HNO,which has a pKa of 11.4 and exists primarily in the protonatedform under physiological conditions,9 displays importantbiological roles with potential pharmacological applicationsdistinct from those of nitric oxide.11-13 For example, HNO reactsdirectly with thiols,14 is resistant to scavenging by superoxide,15and can activate voltage-dependent K+ channels in mammalianvascular systems.16,17 Moreover, biochemical studies suggest thatHNO can be formed directly from nitric oxide synthase underappropriate conditions10,18 and that NO and HNO may be able tointerconvert in the presence of superoxide dismutase (SOD).19Despite accumulating evidence of the biological importance ofHNO, studies have been hampered by the lack of a biologicallycompatible probe for the molecule. Only recently have chemicalsystems capable of discerning HNO from NO been reported, butthe constructs are not suitable for work with biologicalsamples.