Cross‐Talks Between Sulfane Sulfur and Thiol at a Zinc(II) Site

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 H2S. 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 [(Bn3Tren)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.

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

“…Thus, these findings support our hypothesis that the [Zn II ]–nitrite moiety in 1 reacts more promptly with the relatively more nucleophilic persulfide anions as compared to the analogous reaction of thiol/thiolate due to the α-effect. Encouraged by our recent report on [Zn II ]-promoted thiol persulfidation through thiol and sulfane sulfur cross-talk, we aim to utilize the in situ generated persulfide species for facilitating NO generation from [( Bn 3 Tren )Zn II –nitrite] + ( 1 ). Notably, the insertion of the S 3 moiety into the [Zn II ]–SAr bond, resulting in the [Zn II ]–S 4 Ar complex, has been reported previously. , A comparative reactivity study on the structurally characterized [Zn II ]–SAr and [Zn II ]–S 4 Ar complexes toward alkylation and disulfide addition reactions demonstrates that [Zn II ]–S 4 Ar is less nucleophilic as compared to [Zn II ]–SAr .…”

“…Mechanistically, we hypothesize an association between [Zn II ]–nitrite ( 1 ) and sulfane sulfur leading to {[( Bn 3 Tren )Zn II –nitrite](S n )} + ( Int-a ) (Figure , step A). While such an adduct complex could not be identified presently, perhaps due to the weak association, ESI-MS spectrometric characterization of analogous adducts {[( Bn 3 Tren )Zn II –Cl](S n )} + ( n = 4, 5, 6, 7, 8) has been recently demonstrated for the reaction of the [( Bn 3 Tren )Zn II –Cl] + complex with S 8 . Such an interaction between sulfane sulfur and the [Zn II ] site (in Int-a ) is proposed to result in a weak polarization of the S–S bond, thereby facilitating the intermolecular nucleophilic attack by thiol RSH, leading to a perthiolate species RS n S – (Figure , step B).…”

“…The reactivity of the [Zn II ]–nitrite complex ( 1 ) with thiol toward NO generation has found to be sluggish due to the poor Lewis acidity of the [Zn II ] site in 1 . However, the presence of sulfane sulfur (S 0 ) species (e.g., elemental sulfur (S 8 ) and polysulfides (RS n R, n > 2) during the reactions of [Zn II ]–nitrite ( 1 ) and thiol leads to a significantly higher yield of NO due to the more facile nucleophilic attack of the in-situ-generated reactive persulfide (RSS – ) species …”

Nitrate and Nitrite Reductions at Copper(II) Sites: Role of Noncovalent Interactions from Second-Coordination-Sphere

“…UV–vis monitoring of a reaction of [( Bz 3 Tren )­Cu II (OH 2 )]­(ClO 4 ) 2 ( 3-Cu ) with NaNO 3 in DMF/MeOH (or TBANO 3 in acetonitrile) exhibits no detectable change in the absorption pattern (Figure S15), thereby suggesting no interaction between nitrate and the copper­(II) site. Isolation of the nitrate complex from the reactions of NaNO 3 and [( Bz 3 Tren )­M II (OH 2 )]­(ClO 4 ) 2 ( 3-M , M = Cu/Zn) , in relatively less polar solvent methanol was also attempted. However, FTIR analyses of the resultants obtained from the reaction of complex 3-M and NaNO 3 show the presence of free NO 3 – (Figure S16).…”

Sulfane Decreases the Nucleophilic Reactivity of Zinc Thiolates: Implications for Biological Reactive Sulfur Species

“…Due to the ubiquity of zinc in biological contexts, much synthetic effort has gone into modeling zinc thiolate active sites, with particular attention to the impact of zinc on thiolate nucleophilicity in the context of thiolate alkylation or phosphoester cleavage. − Synthetic zinc complexes have also been shown to participate in both sulfane and disulfide activation. − Importantly, well-defined zinc polysulfanido (L n ZnS x R, x = 2, 4, R = alkyl or aryl) are isolable and have been structurally characterized, , making them useful potential precursors for studies of sulfane effects on thiolate nucleophilicity.…”