Nitroxyl

<h2 id="generation">Generation</h2>
Nitroxyl is produced from the reagents <a href="/facts/Angeli%2527s_salt/jqb839Qe">Angeli's salt</a> (Na2N2O3) and <a href="/facts/Piloty%2527s_acid/q6sbDVzK">Piloty's acid</a> (PhSO2NHOH).<a class="footnote-ref" id="fnref:4" href="#fn:4">4</a> Other notable studies on the production of HNO exploit cycloadducts of acyl nitroso species, which are known to decompose via hydrolysis to HNO and acyl acid. Upon <a href="/facts/Photodissociation/nzRyzh8I">photolysis</a> these compounds release the acyl nitroso species which then further decompose.<a class="footnote-ref" id="fnref:5" href="#fn:5">5</a>
HNO is generated via <a href="/facts/Organic_oxidation/6DdmXG4S">organic oxidation</a> of <a href="/facts/Oxime/xRlPfB6K">cyclohexanone oxime</a> with <a href="/facts/Lead_tetraacetate/w18pPVlQ">lead tetraacetate</a> to form 1-nitrosocyclohexyl acetate:<a class="footnote-ref" id="fnref:6" href="#fn:6">6</a>

This compound can be <a href="/facts/Hydrolyzed/JTvwIHPs">hydrolyzed</a> under <a href="/facts/Base_(chemistry)/M9wA7qeM">basic</a> conditions in a <a href="/facts/Buffer_solution/zrLz9eaa">phosphate buffer</a> to HNO, <a href="/facts/Acetic_acid/uyBKA2Pd">acetic acid</a>, and <a href="/facts/Cyclohexanone/Hf3YTWjB">cyclohexanone</a>.
<a href="/facts/Dichloramine/MCxK0nTN">Dichloramine</a> reacts with the <a href="/facts/Hydroxide_ion/zW0wxpWD">hydroxide ion</a>, which is always present in water, to yield nitroxyl and the <a href="/facts/Chloride_ion/m9NUaUDR">chloride ion</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7">7</a>
Alkali metals react with <a href="/facts/Nitric_oxide/UvhdvDzp">nitric oxide</a> to give salts of the form MNO (M = metal).<a class="footnote-ref" id="fnref:8" href="#fn:8">8</a> However, generation of the (unstable) free acid from these salts is not entirely straightforward (see below).

<h2 id="reactions">Reactions</h2>
Nitroxyl is a <a href="/facts/Weak_acid/vJ4rj6Lu">weak acid</a>, with <a href="/facts/Acid_dissociation_constant/t4YyRtKC">pKa</a> of about 11, the conjugate base being the triplet state of NO−, sometimes called nitroxide. Nitroxyl itself, however, is a singlet ground state. Thus, deprotonation of nitroxyl uniquely involves the forbidden spin crossing from the singlet state starting material to triplet state product:

1HNO + B− → 3NO− + BH
Due to the <a href="/facts/Spin-forbidden_reactions/WJVIEu4w">spin-forbidden</a> nature of deprotonation, proton abstraction is many orders of magnitude slower (k = 4.9×104 M−1 s−1 for deprotonation by OH−) than what one would expect for a heteroatom proton-transfer process (processes that are so fast that they are sometimes <a href="/facts/Diffusion-controlled_reaction/FuF3WdTa">diffusion-controlled</a>).
The Ka of starting from or ending with the electronic excited states has also been determined. When process of deprotonating singlet state HNO to obtain singlet state NO− has a pKa is about 23. On the other hand, when deprotonating triplet HNO to obtain triplet NO−, the pKa is about −1.8.<a class="footnote-ref" id="fnref:9" href="#fn:9">9</a><a class="footnote-ref" id="fnref:10" href="#fn:10">10</a>
Nitroxyl rapidly decomposes by a bimolecular pathway to <a href="/facts/Nitrous_oxide/Jvys91lI">nitrous oxide</a> (k at 298 K = 8×106 M s):<a class="footnote-ref" id="fnref:11" href="#fn:11">11</a>

2 HNO → N2O + H2O
The reaction proceeds via dimerization to <a href="/facts/Hyponitrous_acid/A12bMxGX">hyponitrous acid</a>, H2N2O2, which subsequently undergoes dehydration. Therefore, HNO is generally prepared <a href="/facts/In_situ/YolKlaCC">in situ</a> as described above.
Nitroxyl is very reactive towards nucleophiles, including <a href="/facts/Thiol/VemKEDP9">thiols</a>. The initial adduct rearranges to a <a href="/facts/Sulfinamide/z9PWzyro">sulfinamide</a>:<a class="footnote-ref" id="fnref:12" href="#fn:12">12</a>

HNO + RSH → RS(O)NH2
<h2 id="detection">Detection</h2>
In biological samples, nitroxyl can be detected using <a href="/facts/Fluorescent/qsJVT2qP">fluorescent</a> sensors, many of which are based on the reduction of copper(II) to copper(I) with concomitant increase in fluorescence.<a class="footnote-ref" id="fnref:13" href="#fn:13">13</a>

<h2 id="medicinal-chemistry">Medicinal chemistry</h2>
Nitroxyl donors, known as <a href="/facts/Nitroso/Irref1C6">nitroso</a> compounds, show potential in the treatment of heart failure and ongoing research is focused on finding new molecules for this task. 

<h2 id="see-also">See also</h2>
<ul><li><a href="/facts/Nitroxyl_radical/yXccq8Iq">Nitroxyl radicals</a> (also called aminoxyl radicals) — chemical species containing the R2N−O• functional group</li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1">Doctorovich, F.; Bikiel, D.; Pellegrino, J.; Suárez, S. A.; Larsen, A.; Martí, M. A. (2011). "Nitroxyl (azanone) trapping by metalloporphyrins". Coordination Chemistry Reviews. 255 (23–24): 2764–2784. doi:10.1016/j.ccr.2011.04.012. hdl:11336/68714. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></li>
<li id="fn:2">Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. ISBN 978-0-08-037941-8. <a href="978-0-08-037941-8" target="_blank">978-0-08-037941-8</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></li>
<li id="fn:3">Wiberg, Egon; Holleman, Arnold Frederick (2001). Inorganic Chemistry. Elsevier. ISBN 978-0-12-352651-9. <a href="978-0-12-352651-9" target="_blank">978-0-12-352651-9</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></li>
<li id="fn:4">Nagasawa, H. T.; Kawle, S. P.; Elberling, J. A.; DeMaster, E. G.; Fukuto, J. M. (1995). "Prodrugs of Nitroxyl as Potential Aldehyde Dehydrogenase Inhibitors vis-a-vis Vascular Smooth Muscle Relaxants". J. Med. Chem. 38 (11): 1865–1871. doi:10.1021/jm00011a005. PMID 7783118. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></li>
<li id="fn:5">Cohen, A. D.; Zeng, B.-B.; King, S. B.; Toscano, J. P. (2003). "Direct observation of an acyl nitroso species in solution by time-resolved IR spectrocopy". J. Am. Chem. Soc. 125 (6): 1444–1445. doi:10.1021/ja028978e. PMID 12568581. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></li>
<li id="fn:6">Sha, Xin; Isbell, T. Scott; Patel, Rakesh P.; Day, Cynthia S.; King, S. Bruce (2006). "Hydrolysis of Acyloxy Nitroso Compounds Yields Nitroxyl (HNO)". J. Am. Chem. Soc. 128 (30): 9687–9692. doi:10.1021/ja062365a. PMID 16866522. <a href="/wiki/J._Am._Chem._Soc." target="_blank">/wiki/J._Am._Chem._Soc.</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></li>
<li id="fn:7">White, George Clifford (1986). The handbook of chlorination (2nd ed.). New York: Van Nostrand Reinhold. p. 169. ISBN 978-0-442-29285-0. <a href="978-0-442-29285-0" target="_blank">978-0-442-29285-0</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></li>
<li id="fn:8">Schenk, P. W. (1963). "Nitrogen: Sodium nitroxyl". In Brauer, Georg (ed.). Handbook of Preparative Inorganic Chemistry. Vol. 1. Translated by Riley, Reed F. (2nd ed.). NY, NY: Academic Press. pp. 514–515. LCCN 63-14307 – via the Internet Archive. <a href="https://archive.org/details/Handbook_of_Preparative_Inorganic_Chemistry_1_2_Brauer/page/n537" target="_blank">https://archive.org/details/Handbook_of_Preparative_Inorganic_Chemistry_1_2_Brauer/page/n537</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></li>
<li id="fn:9">Shafirovich, V.; Lymar, S. V. (2002). "Nitroxyl and its anion in aqueous solutions: Spin states, protic equilibria, and reactivities toward oxygen and nitric oxide". Proceedings of the National Academy of Sciences of the United States of America. 99, 7340 (11): 7340–7345. doi:10.1073/pnas.112202099. PMC 124232. PMID 12032284. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124232" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124232</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></li>
<li id="fn:10">Bianco, C. L.; Toscano, J. P.; Bartberger, M. D.; Fukuto, J. M. (2017). "The chemical biology of HNO signaling". Archives of Biochemistry and Biophysics. 617: 129–136. doi:10.1016/j.abb.2016.08.014. PMC 5318259. PMID 27555493. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318259" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318259</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></li>
<li id="fn:11">Shafirovich, V.; Lymar, S. V. (2002). "Nitroxyl and its anion in aqueous solutions: Spin states, protic equilibria, and reactivities toward oxygen and nitric oxide". Proceedings of the National Academy of Sciences of the United States of America. 99, 7340 (11): 7340–7345. doi:10.1073/pnas.112202099. PMC 124232. PMID 12032284. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124232" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124232</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></li>
<li id="fn:12">Bianco, C. L.; Toscano, J. P.; Bartberger, M. D.; Fukuto, J. M. (2017). "The chemical biology of HNO signaling". Archives of Biochemistry and Biophysics. 617: 129–136. doi:10.1016/j.abb.2016.08.014. PMC 5318259. PMID 27555493. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318259" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318259</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></li>
<li id="fn:13">Rivera-Fuentes, Pablo; Lippard, Stephen J. (2015). "Metal-Based Optical Probes for Live Cell Imaging of Nitroxyl (HNO)". Acc. Chem. Res. 38 (11): 2427–2434. doi:10.1021/acs.accounts.5b00388. hdl:1721.1/107934. PMID 26550842. <a href="/wiki/Acc._Chem._Res." target="_blank">/wiki/Acc._Chem._Res.</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></li>
</ol>

Nitroxyl open-in-new

Nitroxyl