Revealing Unexpected Mechanisms for Nucleophilic Attack on SS and SeSe Bridges

Heverly‐Coulson, Gavin S.; Boyd, Russell J.; Mó, Otília; Yáñez, Manuel

doi:10.1002/chem.201203328

Cited by 14 publications

(16 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43,52 In more general terms, it should also be stressed that recent investigations of nucleophilic attacks on S-S bridges continue to reveal unexpected reaction mechanisms. 53 It is evident that putative reaction scenarios become even more intricate when mechanochemical activation comes into play. Indeed, external forces can activate new reactions channels, among which C-S or S-S bond rupture without the direct intervention of OH − are apparently the most plausible options.…”

mentioning

confidence: 99%

Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution

et al. 2016

View full text Add to dashboard Cite

The reduction of disulfides has a broad importance in chemistry, biochemistry and materials science, particularly those methods that use mechanochemical activation. Here we show, using isotensional simulations, that strikingly different mechanisms govern disulfide cleavage depending on the external force. Desolvation and resolvation processes are found to be crucial, as they have a direct impact on activation free energies. The preferred pathway at moderate forces, a bimolecular S2 attack of OH at sulfur, competes with unimolecular C-S bond rupture at about 2 nN, and the latter even becomes barrierless at greater applied forces. Moreover, our study unveils a surprisingly rich reactivity scenario that also includes the transformation of concerted S2 reactions into pure bond-breaking processes at specific forces. Given that these forces are easily reached in experiments, these insights will fundamentally change our understanding of mechanochemical activation in general, which is now expected to be considerably more intricate than previously thought.

show abstract

mentioning

confidence: 99%

Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Another consideration is that the strength of the nucleophile is as much important as the leaving group ability. This topic has been rigorously investigated by Bachrach and co-workers [208] who investigated the mechanism of a series of nucleophilic substitution reactions involving different species as nucleophiles and leaving groups in methylsulfenyl derivatives (level of theory: B3LYP/augcc-pVDZ) and found in all cases an addition-elimination mechanism.…”

Section: Nucleophilic Attack Of a Thiol/thiolate Anion At Diselenidesmentioning

confidence: 99%

“…Finally, it is worth to mention also some analyses focused on the chalcogen-chalcogen bond nature, carried out on symmetric and asymmetric disulfides and diselenides of general formula R 1 XXR 2 (X = S, Se; R 1 , R 2 = CH 3 , OH, F, NH 2 ) [208]. Yanez, Boyd and co-workers investigated the nucleophilic attacks of Fand CNat the dichalcogenide substrates (level of theory: B3PW91/6-311+G(2df,p)).…”

Section: Nucleophilic Attack Of a Thiol/thiolate Anion At Diselenidesmentioning

confidence: 99%

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

Tiezza¹,

Ribaudo

Orian³

2019

COC

View full text Add to dashboard Cite

Organodiselenides are an important class of compounds characterized by the presence of two adjacent covalently bonded selenium nuclei. Among them, diaryldiselenides and their parent compound diphenyl diselenide attract continuing interest in chemistry as well as in close disciplines like medicinal chemistry, pharmacology and biochemistry. A search in SCOPUS database has revealed that in the last three years 105 papers have been published on the archetypal diphenyl diselenide and its use in organic catalysis and drug tests. The reactivity of the Se-Se bond and the redox properties of selenium make diselenides efficient catalysts for numerous organic reactions, such as Bayer- Villiger oxidations of aldehydes/ketones, epoxidations of alkenes, oxidations of alcohols and nitrogen containing compounds. In addition, organodiselenides might find application as mimics of glutathione peroxidase (GPx), a family of enzymes, which, besides performing other functions, regulate the peroxide tone in the cells and control the oxidative stress level. In this review, the essential synthetic and reactivity aspects of organoselenides are collected and rationalized using the results of accurate computational studies, which have been carried out mainly in the last two decades. The results obtained in silico provide a clear explanation of the anti-oxidant activity of organodiselenides and more in general of their ability to reduce hydroperoxides. At the same time, they are useful to gain insight into some aspects of the enzymatic activity of the GPx, inspiring novel elements for rational catalyst and drug design.

show abstract

“…This theoretical model has proven to be very reliable for the treatment of organoselenium compounds and recently was shown to be well suited for the description of disulfide and diselenide bridges, [42] using the coupled cluster CCSD(T) ab initio method as a reference. This theoretical model has proven to be very reliable for the treatment of organoselenium compounds and recently was shown to be well suited for the description of disulfide and diselenide bridges, [42] using the coupled cluster CCSD(T) ab initio method as a reference.…”

Section: Computational Detailsmentioning

confidence: 99%

“…[25][26][27][28] Consequently, the most powerful techniques in protein sequencing are based on the cleavage of SAS or SeASe bridges within the protein, but the mechanisms at the molecular level are far from being well understood. [42] Nucleophilic attacks or oxidation processes on disulfides and diselenides give rise to mixed SASe bridges [43][44][45] which are important in some biochemical processes. [31][32][33][34][35][36][37] In all cases, it was found that the SAS or the SeASe bond fission is the dominant process, although in the systems investigated the substituents attached to S or Se were either identical or ones of similar electronegativity.…”

Section: Introductionmentioning

confidence: 99%

Dramatic substituent effects on the mechanisms of nucleophilic attack on Se-S bridges

et al. 2013

Self Cite

View full text Add to dashboard Cite

The reactions of XSeSX, XSeSY, and YSeSX (X, Y = CH3, NH2, OH, F) with F(-) and CN(-) nucleophiles have been investigated by means of B3PW91/6-311+G(2df,p) and G4 calculations. In systems where the two substituents are not identical (XSeSY), the more stable of the two possible isomers corresponds to those in which the most electronegative substituent is attached to Se. Nucleophilic attack takes place at Se, independent of the nature of the nucleophile, with the only exception being XSeSF (X = CH3 , NH2 , OH), in which case the attack occurs at S. In agreement with recent results for disulfide and diselenide linkages, the mechanisms leading to Se-S bond cleavage are not always the more favorable ones because for highly electronegative substituents the most favorable process is fission of the chalcogen-substituent bond. These dissimilarities in the observed reactivity pattern as a function of the electronegativity of the substituents are due to the fact that the σ-type Se-S antibonding orbital, which for low-electronegative substituents is the lowest unnoccupied molecular orbital (LUMO), becomes strongly destabilized when the electronegativity of the substituent increases, and is replaced by an antibonding π-type Se-X (or S-X) orbital. In contrast, however, with what has been found for disulfide and diselenide derivatives, the observed reactivity does not change with the nature of the nucleophile. The activation strain model provides interesting insight into these processes, showing that in most cases the activation barriers are the consequence of subtle differences in the strain or in the interaction energies.

show abstract

Revealing Unexpected Mechanisms for Nucleophilic Attack on SS and SeSe Bridges

Cited by 14 publications

References 82 publications

Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution

Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

Dramatic substituent effects on the mechanisms of nucleophilic attack on Se-S bridges

Contact Info

Product

Resources

About