ABSTRACT
(Per)thionitrite (SNO- /SSNO- ) intermediates play vital roles in modulating nitric oxide (NO) and hydrogen sulfide (H2 S) dependent bio-signalling processes. Whilst the previous preparations of such intermediates involved reactive H2 S/HS- or sulfane sulfur (S0 ) species, the present report reveals that relatively stable thiocarbonyl compounds (such as carbon disulfide (CS2 ), thiocarbamate, thioacetic acid, and thioacetate) react with nitrite anion to yield SNO- /SSNO- . For instance, the reaction of CS2 and nitrite anion (NO2 - ) under ambient condition affords CO2 and SNO- /SSNO- . A detailed investigation involving UV/Vis, FTIR, HRMS, and multinuclear NMR studies confirm the formation of SNO- /SSNO- , which are proposed to form through an initial nucleophilic attack by nitrite anion followed by a transnitrosation step. Notably, reactions of CS2 and nitrite in the presence of thiol RSH show the formation of organic polysulfides R-Sn -R, thereby illustrating that the thiocarbonyls are capable of influencing the pool of bioavailable sulfane sulfurs. Furthermore, the availability of both NO2 - and thiocarbonyl motifs in the biological context hints at their synergistic metal-free activations leading to the generation of NO gas and various reactive sulfur species via SNO- /SSNO- .
ABSTRACT
Nitrite-to-NO transformation is of prime importance due to its relevance in mammalian physiology. Although such a one-electron reductive transformation at various redox-active metal sites (e.g., Cu and Fe) has been illustrated previously, the reaction at the [ZnII] site in the presence of a sacrificial reductant like thiol has been reported to be sluggish and poorly understood. Reactivity of [(Bn3Tren)ZnII-ONO](ClO4) (1), a nitrite-bound model of the tripodal active site of carbonic anhydrase (CA), toward various organic probes, such as 4-tert-butylbenzylthiol (tBuBnSH), 2,4-di-tert-butylphenol (2,4-DTBP), and 1-fluoro-2,4-dinitrobenzene (F-DNB), reveals that the ONO-moiety in the [ZnII]-nitrite coordination motif of complex 1 acts as a mild electrophile. tBuBnSH reacts mildly with nitrite at a [ZnII] site to provide S-nitrosothiol tBuBnSNO prior to the release of NO in 10% yield, whereas the phenolic substrate 2,4-DTBP does not yield the analogous O-nitrite compound (ArONO). The presence of sulfane sulfur (S0) species such as elemental sulfur (S8) and organic polysulfides (tBuBnSnBntBu) during the reaction of tBuBnSH and [ZnII]-nitrite (1) assists the nitrite-to-NO conversion to provide NO yields of 65% (for S8) and 76% (for tBuBnSnBntBu). High-resolution mass spectrometry (HRMS) analyses on the reaction of [ZnII]-nitrite (1), tBuBnSH, and S8 depict the formation of zinc(II)-persulfide species [(Bn3Tren)ZnII-Sn-BntBu]+ (where n = 2, 3, 4, 5, and 6). Trapping of the persulfide species (tBuBnSS-) with 1-fluoro-2,4-dinitrobenzene (F-DNB) confirms its intermediacy. The significantly higher nucleophilicity of persulfide species (relative to thiol/thiolate) is proposed to facilitate the reaction with the mildly electrophilic [ZnII]-nitrite (1) complex. Complementary analyses, including multinuclear NMR, electrospray ionization-MS, UV-vis, and trapping of reactive S-species, provide mechanistic insights into the sulfane sulfur-assisted reactions between thiol and nitrite at the tripodal [ZnII]-site. These findings suggest the critical influential roles of various reactive sulfur species, such as sulfane sulfur and persulfides, in the nitrite-to-NO conversion.
ABSTRACT
Transformations of sulfane sulfur compounds (e. g. organic polysulfides (R-Sn -R, n>2) and elemental sulfur (S8 )) play pivotal roles in the biochemical landscape of sulfur, and thus supports signaling activities of H2 S. Although a number of previous reports illustrate amine mediated reactions of S8 and thiol (RSH) yielding R-Sn -R, this report illustrates that a tripodal [ZnII ] complex [(Bn3 Tren)ZnII -OH2 ](ClO4 )2 (1) facilitates the reactions of sulfane sulfur and thiol (RSH), thereby offering an amine-free biologically relevant complementary route. UV-vis monitoring of the reactions and a set of control experiments underline the definitive role of [ZnII ] coordination motif in the reactions of sulfane sulfur (e. g. S8 and R-Sn -R) with RSH. Detailed investigations (UV-vis, NMR, ESI-MS, intermediate trapping, and TEMPO radical interference experiments) disclose the key differences in the [ZnII ] versus previously known amine mediated routes. Moreover, the persulfide (RSS- ) trapping experiments using 1-fluoro-2,4-dinitrobenzene (F-DNB) reveal the intermediacy of RSS- species in the [ZnII ] mediated reactions of sulfane sulfur and thiol, thereby demonstrating [ZnII ] assisted persulfidation of thiol in the presence of sulfane sulfur species. Of broader impact, this study underscores the feasible influence of biologically relevant [ZnII ] coordination motifs (e. g. carbonic anhydrase) on the sulfane sulfur chemistry in biology.
Subject(s)
Sulfhydryl Compounds , Zinc , Sulfur/chemistry , Sulfur CompoundsABSTRACT
Transformations of nitrogen-oxyanions (NOx- ) to ammonia impart pivotal roles in sustainable biogeochemical processes. While metal-mediated reductions of NOx- are relatively well known, this report illustrates proton-assisted transformations of NOx- anions in the presence of electron-rich aromatics such as 1,3,5-trimethoxybenzene (TMB-H, 1 a) leading to the formation of diaryl oxoammonium salt [(TMB)2 N+ =O][NO3- ] (2 a) via the intermediacy of nitrosonium cation (NO+ ). Detailed characterizations including UV/Vis, multinuclear NMR, FT-IR, HRMS, X-ray analyses on a set of closely related metastable diaryl oxoammonium [Ar2 N+ =O] species disclose unambiguous structural and spectroscopic signatures. Oxoammonium salt 2 a exhibits 2 e- oxidative reactivity in the presence of oxidizable substrates such as benzylamine, thiol, and ferrocene. Intriguingly, reaction of 2 a with water affords ammonia. Perhaps of broader significance, this work reveals a new metal-free route germane to the conversion of NOx â toâ NH3 .
