Influence of Cu<sup>+</sup> on the RS−NO Bond Dissociation Energy of S-Nitrosothiols

Baciu, Cristina; Cho, Kyung‐Bin; Gauld, James W.

doi:10.1021/jp0443759

Cited by 35 publications

(45 citation statements)

References 19 publications

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“…Importantly, the latter two structures are antagonistic , as they imply opposite bonding patterns and formal charge distributions in the −SNO group. D versus I antagonism rationalizes the unusual properties of the S—N bond that exhibits some double bond traits despite being unusually long and weak, and accounts for the dramatic effect of Lewis acid coordination on the stability of the S—N bond . Moreover, the two antagonistic structures correlate with the dual reactivity of RSNOs toward nucleophiles that can attack the —SNO group either at S or at N atoms.…”

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confidence: 81%

“…D versus I antagonism rationalizes the unusual properties of the SAN bond that exhibits some double bond traits [10] despite being unusually long and weak, [11] and accounts for the dramatic effect of Lewis acid coordination on the stability of the SAN bond. [12,13] Moreover, the two antagonistic structures correlate with the dual reactivity of RSNOs toward nucleophiles that can attack the ASNO group either at S or at N atoms. The first mode of reactivity is promoted by structure D, and the second by structure I.…”

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confidence: 99%

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Computational design of S‐nitrosothiol “click” reactions

et al. 2013

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To address a long-standing problem of finding efficient reactions for chemical labeling of protein-based S-nitrosothiols (RSNOs), we computationally explored hitherto unknown (3+2) cycloaddition RSNO reactions with alkynes and alkenes. Nonactivated RSNO cycloaddition reactions have high activation enthalpy (>20 kcal/mol at the CBS-QB3 level) and compete with alternative S-N bond insertion pathway. However, the (3+2) cycloaddition reaction barriers can be dramatically lowered by coordination of a Lewis acid to the N atom of the -SNO group. To exploit this effect, we propose to use reagents with Lewis acid and a strain-activated carbon-carbon multiple bond linked by a rigid scaffold, which can react with RSNOs with small activation enthalpies (∼5 kcal/mol) and high reaction exothermicities (∼40 kcal/mol). The proposed efficient RSNO cycloaddition reactions can be used for future development of practical RSNO labeling reactions.

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confidence: 81%

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confidence: 99%

Computational design of S‐nitrosothiol “click” reactions

et al. 2013

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“…Accordingly, bond dissociation energies of RSNO are reported to vary from Ϸ22 to 32 kcal⅐mol Ϫ1 (6, 26), and the dissociation constants of FeNO can vary by a factor of Ͼ10 6 (13, 23, 24), translating to intrinsic FeNO/SNO lifetimes ranging from seconds to years. Environmental factors that have been reported to influence SNO stability and reactivity, directly or through elicited conformational changes in proteins, include pH (low and high) (5,6,20,26), metal ions (Ca, Mg, Cu, and Fe) (6,14,20,27,28), nucleophiles (ascorbate, thiolate, and amine) (6, 13), local hydrophobicity (denaturants) (29), oxidants and reductants (6, 19), proteolytic enzymes (30), alkylators (31), O 2 tension (5, 32), and various intramolecular interactions (H-bonding, S-, N-, O-coordination, and aromatic residue interactions) (6,16,20,22,(33)(34)(35)(36). Many of these factors also affect FeNO stability (17,23,24).…”

Section: Red Blood Cell Vasodilation ͉ S-nitrosohemoglobin ͉ S-nitrosmentioning

confidence: 99%

Assessment of nitric oxide signals by triiodide chemiluminescence

Hausladen

Rafikov

Angelo

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

101

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Nitric oxide (NO) bioactivity is mainly conveyed through reactions with iron and thiols, furnishing iron nitrosyls and S-nitrosothiols with wide-ranging stabilities and reactivities. Triiodide chemiluminescence methodology has been popularized as uniquely capable of quantifying these species together with NO byproducts, such as nitrite and nitrosamines. Studies with triiodide, however, have challenged basic ideas of NO biochemistry. The assay, which involves addition of multiple reagents whose chemistry is not fully understood, thus requires extensive validation: Few protein standards have in fact been characterized; NO mass balance in biological mixtures has not been verified; and recovery of species that span the range of NO-group reactivities has not been assessed. Here we report on the performance of the triiodide assay vs. photolysis chemiluminescence in side-by-side assays of multiple nitrosylated standards of varied reactivities and in assays of endogenous Fe-and S-nitrosylated hemoglobin. Although the photolysis method consistently gives quantitative recoveries, the yields by triiodide are variable and generally low (approaching zero with some standards and endogenous samples). Moreover, in triiodide, added chemical reagents, changes in sample pH, and altered ionic composition result in decreased recoveries and misidentification of NO species. We further show that triiodide, rather than directly and exclusively producing NO, also produces the highly potent nitrosating agent, nitrosyliodide. Overall, we find that the triiodide assay is strongly influenced by sample composition and reactivity and does not reliably identify, quantify, or differentiate NO species in complex biological mixtures. red blood cell vasodilation ͉ S-nitrosohemoglobin ͉ S-nitrosylationT he biological effects of nitric oxide (NO) are mediated in large part through binding to transition metals and cysteine thiols at active or allosteric sites within regulatory proteins (1), which elicits changes in protein activity, protein-protein interactions, and protein location (1). Within tissues, many dozens of S-nitrosylated proteins have been identified, and signatures of NO bound to nonheme and heme iron have been detected (1, 2). Additionally, NO can be transported in endocrine or paracrine fashion by reacting with heme iron and cysteine thiols in proteins [hemoglobin (Hb) and albumin] and peptides (glutathione and cysteinlyglycine) to form NO adducts with longer biological lifetimes (3-5); release of NO bioactivity from stable adducts is effected by allosteric and redox-based mechanisms that alter FeNO or S-nitrosothiol (SNO) reactivity (5, 6). An updated discussion of the factors influencing reactivity of S-nitrosohemoglobin, S-nitrosoalbumin, and low-molecular-weight SNO in the context of vasoregulation (5-15) can be found in supporting information (SI) Text.The dynamic distribution of protein and low-molecular-weight NO compounds that subserve NO transport and signaling instantiate the variation in both FeNO and SNO reactivities (4,6,13...

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“…65–67 The varying rates of nitrosothiol decompositions reported by different research groups can be traced possibly to adventitious metal ion catalysis from the water used in preparing reagent solutions. Even in our case, with the maximum metal ion concentrations of 0.43 ppb in Pb 2+ , small differences can be observed in EDTA-laced reaction solutions and those that are not (see traces a and b in Fig.…”

Section: Mechanismmentioning

confidence: 99%

“…[R16] has been justified through density functional theory studies that report that Cu(I) binds more strongly to the S center than to the N center of the nitrosothiol. 65 This preferential binding weakens and lengthens the S–N bond, thus facilitating its cleavage. It is difficult to extrapolate this proposed mechanism into the physiological environment, but some experimental results have shown that protein-bound Cu 2+ catalyzed nitric oxide generation from nitrosothiols, but not with the same efficiency as the free hydrated ion.…”

Section: Mechanismmentioning

confidence: 99%

Detailed mechanistic investigation into the S-nitrosation of cysteamine

et al. 2012

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The nitrosation of cysteamine (H2NCH2CH2SH) to produce cysteamine-S-nitrosothiol (CANO) was studied in slightly acidic medium by using nitrous acid prepared in situ. The stoichiometry of the reaction was H2NCH2CH2SH + HNO2 → H2NCH2CH2SNO + H2O. On prolonged standing, the nitrosothiol decomposed quantitatively to yield the disulfide, cystamine: 2H2NCH2CH2SNO → H2NCH2CH2S–SCH2CH2NH2 + 2NO. NO2 and N2O3 are not the primary nitrosating agents, since their precursor (NO) was not detected during the nitrosation process. The reaction is first order in nitrous acid, thus implicating it as the major nitrosating agent in mildly acidic pH conditions. Acid catalyzes nitrosation after nitrous acid has saturated, implicating the protonated nitrous acid species, the nitrosonium cation (NO+) as a contributing nitrosating species in highly acidic environments. The acid catalysis at constant nitrous acid concentrations suggests that the nitrosonium cation nitrosates at a much higher rate than nitrous acid. Bimolecular rate constants for the nitrosation of cysteamine by nitrous acid and by the nitrosonium cation were deduced to be 17.9 ± 1.5 (mol/L)−1 s−1 and 6.7 × 104 (mol/L)−1 s−1, respectively. Both Cu(I) and Cu(II) ions were effective catalysts for the formation and decomposition of the cysteamine nitrosothiol. Cu(II) ions could catalyze the nitrosation of cysteamine in neutral conditions, whereas Cu(I) could only catalyze in acidic conditions. Transnitrosation kinetics of CANO with glutathione showed the formation of cystamine and the mixed disulfide with no formation of oxidized glutathione (GSSG). The nitrosation reaction was satisfactorily simulated by a simple reaction scheme involving eight reactions.

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Influence of Cu⁺ on the RS−NO Bond Dissociation Energy of S-Nitrosothiols

Cited by 35 publications

References 19 publications

Computational design of S‐nitrosothiol “click” reactions

Computational design of S‐nitrosothiol “click” reactions

Assessment of nitric oxide signals by triiodide chemiluminescence

Detailed mechanistic investigation into the S-nitrosation of cysteamine

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Influence of Cu+ on the RS−NO Bond Dissociation Energy of S-Nitrosothiols

Cited by 35 publications

References 19 publications

Computational design of S‐nitrosothiol “click” reactions

Computational design of S‐nitrosothiol “click” reactions

Assessment of nitric oxide signals by triiodide chemiluminescence

Detailed mechanistic investigation into the S-nitrosation of cysteamine

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Product

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Influence of Cu⁺ on the RS−NO Bond Dissociation Energy of S-Nitrosothiols