
 redox biological signaling has significantly developed over the last couple of decades with small molecules such as no , co , h2s , and h2o2 being identified as competent signaling agents .
nitroxyl ( hno ) , the oneelectron reduced / protonated form of no , has been discussed as a signaling agent , but the lack of specific & selective detection methods hampers a better understanding of its biology .
significant advances in hno detection have occurred with the development of new copper and phosphinebased fluorescent probes and new electrochemical & mass spectrometric methods . with these mechanistically different ways to detect hno , questions regarding hno 's biology and endogenous formation can be approached .
the most significant result is that the azaylide intermediate generated from the reaction of these probes and hno rapidly and reliably undergo a staudinger ligation resulting in fluorescence and a stable amide byproduct .
reaction of these probes with rsno gives a similar azaylide , but in this case , the staudinger ligation does not occur or proceeds inefficiently .
flow cytometry experiments show that these reactions also occur in cells and that these probes only detects hno in cells .
one of the challenges starting this project was to not let our previous ideas about the chemistry dictate what experiments to do .
we knew that rsno reacts with phosphines to yield azaylides that should undergo ligations and yield fluorescence .
should we continue if we were going to see that our probes were not selective ?
zhengrui miao noticed that no one had ever really directly compared the response of these probes to hno and rsno .
he did this comparison and found fluorescence generation from hno treatment was greatly enhanced compared with rsno , and these findings initiated the study .
the overall lesson is to keep an open mind and do n't plan the outcome of your experiments !
 abstract 
 invited for this month 's cover picture is the group of prof . 
 s.  bruce king at the department of chemistry of wake forest university . 
 the cover picture shows a prefluorescent phosphinebased probe reacting with nitroxyl ( hno ) and 
 s 
 nitrosothiol ( rsno ) , nitrogen oxidederived biological signals . 
 both species react with the prefluorescent probe , but only the product from the hno reaction can complete a further chemical ligation pathway that results in fluorescence , indicating the presence of hno . the product of the probe with rsno does not complete this ligation and does not generate a fluorescent species . 
 these phosphinebased probes thus demonstrate a selectivity for hno over rsno based on their chemical reactivity and can be used in biological systems to differentiate these species . for more details , see the communication on 
 p.  110  ff . 
 
 read the full text of the article at 
 10.1002/open.201500200 
 