Protection against Peroxynitrite-Mediated Nitration Reaction by Intramolecularly Coordinated Diorganoselenides

Abstract

A series of intramolecularly Se···X (X = N, O) coordinated diorganoselenides and -sulfides are synthesized by using the heteroatom-directed lithiation route and characterized by multinuclear (1H, 13C, 77Se) NMR, IR spectroscopy, and electrospray mass spectrometry (ES-MS). The intramolecular Se···O interactions in diorganoselenides 26−31 have been studied by multinuclear NMR studies in solution and in the solid state by single-crystal X-ray crystallography. The protection against peroxynitrite-mediated nitration reaction (PN assay) by diorganoselenides/-sulfides (with and without intramolecular coordination) has been evaluated. The PN assay data of diorganoselenides reveal that the selenides 20−22, having a basic amino group (sp3-N donor) in close proximity of selenium, are more active compared to the diorganoselenides 16−19, having an imino group (sp2-N donor), and also show much higher protective action than the unsubstituted diorganoselenides 14 and 15. The diorganoselenides 16−31 were oxidized to corresponding selenoxides 44−59. The redox properties of the selenoxides 13 and 44−59 have been investigated by cyclic voltammetry and potentiometric titration experiments. Two redox potentials for in situ-generated ferrocenyl selenoxides (50, 54−59) were observed. The reduction of selenoxides 13 and 48 to ebselen (2) and selenide 20 with benzenethiol (PhSH) was monitored by ES-MS.

A water‐soluble selenoxide reagent as a useful probe for the reactivity and folding of polythiol peptides

“…However, it would also be notable that the value of k 1 for DTT red at pH 10.0 is significantly larger than the k av values determined for polythiol peptides. This may reflect the redox potential of DTT ox (−327 mV), which is lower than that of l ‐cystine (−238 mV) [24].…”

“…The two‐electron reduction potential ( E° ) for DHS ox was determined by the potentiometric titration method described in the literature [23,24] with sodium dithionite (Na 2 S 2 O 4 ) as a reducing titrant. Measurement was performed in a two‐electrode cell system with a single compartment containing a platinum spiral wire indicator electrode and an Ag/AgCl electrode connected to a millivolt meter (Toa HM‐70V).…”

“…In contrast, selenoxides possess much higher redox potentials than the aforementioned reagents. May and coworkers [23] and Singh and coworkers [24] reported the redox potentials of various selenoxide reagents (380-490 mV) and suggested that selenoxides can be useful as a SS-forming reagent to thiols, such as benzenethiol and GSH. The redox potential of DHS ox (375 ± 15 mV at 25 • C) measured in this study was found to be comparable, supporting the high oxidizing ability of DHS ox to generate SS bonds.…”

Selenium-Based Drug Design

“…The results of stopped-flow kinetic experiments were consistent with a rapid and stoichiometric initial reaction of GSH with selenoxide to generate a kinetically detectable intermediate, followed phenylaminoalkyl selenides and represent, to our knowledge, the first evidence for the intermediacy of a thioselenurane species in the reaction of thiols with selenoxides. Previously, Kumar et al [38] had proposed the formation of a thioselenurane in the reaction between benzenethiol and a substituted phenyl benzyl selenoxide, since they observed via ESI-MS a cyclization product that could arise from such a species; however, they were unable to obtain any structural evidence for this proposed intermediate (Fig. 3).…”

“…Among the proposed selenium intermediates in the redox reactions of organoselenium compounds are species such as selenenic and seleninic acids, selenones, spirodioxaselenanonanes, and thiolseleninates. Thus, for example, evidence has been reported for the formation of a thiolseleninate intermediate in the reactions between ebselen oxide and certain thiols [38,39] and for a spirodioxaselenanonane intermediate in the reaction between di(3-hydroxypropyl) selenide and tert-butyl hydroperoxide [40]. The reactivity and instability of some tetra-coordinate selenium compounds, coupled with fast reaction rates for the reactions of organoselenium compounds with oxidants or with reducing agents such as thiols, have made it difficult for several investigators to clearly characterize thioselenurane-like intermediates (see Cowan et al [36] for further discussion of this point).…”