NO Generation from Nitrite at Zinc(II): Role of Thiol Persulfidation in the Presence of Sulfane Sulfur
Tuhin Sahana, Adwaith K. Valappil, Anaswar S. P. R. Amma, Subrata Kundu
Abstract
High Resolution Image Download MS PowerPoint Slide 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 [Zn II ] site in the presence of a sacrificial reductant like thiol has been reported to be sluggish and poorly understood. Reactivity of [( Bn 3 Tren )Zn II –ONO](ClO 4 ) ( 1 ), a nitrite-bound model of the tripodal active site of carbonic anhydrase (CA), toward various organic probes, such as 4- tert -butylbenzylthiol ( t BuBnSH), 2,4-di- tert -butylphenol (2,4-DTBP), and 1-fluoro-2,4-dinitrobenzene (F-DNB), reveals that the ONO-moiety in the [Zn II ]–nitrite coordination motif of complex 1 acts as a mild electrophile. t BuBnSH reacts mildly with nitrite at a [Zn II ] site to provide S -nitrosothiol t BuBnSNO 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 (S 0 ) species such as elemental sulfur (S 8 ) and organic polysulfides ( t BuBnS n Bn t Bu) during the reaction of t BuBnSH and [Zn II ]–nitrite ( 1 ) assists the nitrite-to-NO conversion to provide NO yields of 65% (for S 8 ) and 76% (for t BuBnS n Bn t Bu). High-resolution mass spectrometry (HRMS) analyses on the reaction of [Zn II ]–nitrite ( 1 ), t BuBnSH, and S 8 depict the formation of zinc(II)-persulfide species [( Bn 3 Tren )Zn II –S n –Bn t Bu] + (where n = 2, 3, 4, 5, and 6). Trapping of the persulfide species ( t BuBnSS – ) 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 [Zn II ]–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 [Zn II ]-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.