NO Generation from Nitrite at Zinc(II): Role of Thiol Persulfidation in the Presence of Sulfane Sulfur.

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.