The reaction mechanism of nitroprusside with HS? (Gmelin process). Evidence of bound NOSH, NSOH, NOS?, NOS2?, NO?, HNO and N2O22? intermediates.

JOSÉ A. OLABE; LEONARDO D. SLEP; SILVINA BIEZA; SARA E. BARI; VALENTÍN T. AMOREBIETA

Nápoles

Congreso; 4th International Conference on the Biology of Hydrogen Sulfide; 2016

DIPARTIMENTO DI FARMACIA UNIVERSITA? DI NAPOLI FEDERICO II

The reaction mechanism of nitroprusside [Fe(CN)5NO]2? with HS? (Gmelin process). Role of bound NOSH, NSOH, NOS?, NOS2?, NO?, HNO and N2O22? intermediatesOlabe JA,* Bari SE,* Bieza SA,* Slep LD,* Amorebieta VT#*INQUIMAE, Ciudad Universitaria, Universidad de Buenos Aires, C1428EHA CABA, Argentina#Departamento de Química, FCEN, U.N. de Mar del Plata, Mar del Plata B7602AYL, ArgentinaNitroprusside [Fe(CN)5(NO)]2− is an electrophilic anion reactive toward diverse types of O-, N-, and S-binding nucleophiles. HS− forms reversibly [Fe(CN)5(NOSH)]3−, an adduct that equilibrates very rapidly with its isomer [Fe(CN)5(NSOH)]3− and with the deprotonated [Fe(CN)5(NOS)]4− ion containing the nitrososulfide (thionitrite) ligand NOS− (Ired: λmax, 535 nm; ε = 6 ± 0.3 × 103 M−1 cm−1).[1,2,3] The stretching frequency νNO at 1370 cm−1 indicates a strongly reduced nitrosyl-species with formally a nitroxyl (NO−) ligand in the delocalized [S−N=O]− moiety. Ired reacts spontaneously by homolysis of the N-S bond giving sulfur radicals S·− which add to HS− forming highly reactive HS2.2− radicals favoring a catalytic generation of [Fe(CN)5(NO·)]3− and hydrodisulfide, HS2−. Ired adds sulfur through a HS2−/HS− interchange (transnitrosation reaction), giving [Fe(CN)5(NOS2)]4− (I550: λmax, 550 nm), also formed through the reaction of [Fe(CN)5(NO)]2− with HS2−. I550 contains the nitrosodisulfide (perthionitrite) ligand NOS2−, and transforms into the disulfur-bridged dimer, [(NC)5FeN(O)S-S(O)NFe(CN)5]6− (I575: λmax, 575 nm). Both I550 and I575 display an equilibrium redox network also comprising [Fe(CN)5(NO·)]3−/[Fe(CN)4(NO)·]2− and [Fe(CN)5(HNO)]3−, the one- and two-electron reduction products of [Fe(CN)5(NO)]2−, respectively. Under excess HS−, I575 forms a hyponitrite-bridged radical complex, [(NC)5FeN(OH)=(O·)NFe(CN)5]6− (I290: λmax, 290 nm) followed by disproportionation into the closed-shell bridged analog, with concomitant release of [Fe(CN)5(NO·)]3−. The hyponitrous/hyponitrite dimers can be subsequently reduced by HS− through proton-coupled electron transfers in the pH-range 7-12 leading to [Fe(CN)5(NH3)]3−, which forms [Fe(CN)5(H2O)]3−and free NH3.Early production of N2O arises at pH?s > 11 through a competitive decomposition of the hyponitrite dimer, and in a slower way through NO-release from [Fe(CN)5(NO·)]3−, rapid dinitrosyl formation and disproportionation into [Fe(CN)5(NO)]2− and N2O. The overall reduction process involves a series of ligand-based redox reactions, from bound NO+ down to NH3. Free NO was detected in very low yields, and some HNO probably generates at the μM/nM level from the very inert [Fe(CN)5(HNO)]3− intermediate. S8 is the unique product of sulfide oxidation, and [Fe(CN)5(H2O)]3− decomposes slowly into [Fe(CN)6)]4− and free Fe(II) aqua-ions.The mechanism illustrates an active ?NO/H2S? cross-talk involving three redox-states of nitrosyl (NO+, NO?, NO?/HNO) and sulfur (HS?, HS2?, So), and a discussion will be given on the biochemical significance of some of these species as potential signaling agents.[3][1] Quiroga SL, Almaraz AE, Amorebieta VT, Perissinotti LL, Olabe JA. Addition and redox reactivity of hydrogen sulfides (H2S/HS⁻) with nitroprusside: new chemistry of nitrososulfide ligands. Chemistry. 2011 Apr 4;17(15):4145-56. PubMed PMID: 21404343.[2] Filipovic MR, Eberhardt M, Prokopovic V, Mijuskovic A, Orescanin-Dusic Z, Reeh P, Ivanovic-Burmazovic I. Beyond H2S and NO interplay: hydrogen sulfide and nitroprusside react directly to give nitroxyl (HNO). A new pharmacological source of HNO. J Med Chem. 2013 Feb 28;56(4):1499-508. PubMed PMID: 23418783.[3] Cortese-Krott MM, Kuhnle GG, Dyson A, Fernandez BO, Grman M, DuMond JF, Barrow MP, McLeod G, Nakagawa H, Ondrias K, Nagy P, King SB, Saavedra JE, Keefer LK, Singer M, Kelm M, Butler AR, Feelisch M. Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl. Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):E4651-60.PubMed PMID: 26224837.