Preparation of the First Bench‐Stable Phenyl Selenolate: an Interesting “On Water” Nucleophilic Reagent

Santi, Claudio; Santoro, Stefano; Battistelli, Benedetta; Testaferri, Lorenzo; Tiecco, Marcello

doi:10.1002/ejoc.200800869

Cited by 90 publications

(53 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 and Supplementary Table A) is a member of the Se-organic family of compounds recently synthesized by some of us [18] as an air- and moisture-stable noncrystalline powder that, despite its lipophilic character, shows an enhanced reactivity in water. To the best of our knowledge, this is a unique example of bulk activity in which the Se atom can be easily maintained at the oxidation state −1, the same as observed in the catalytic pocket of mammalian GPx enzymes at the beginning of the reaction cycle [19] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its d,l-polylactide microparticle formulation

Bartolini

Piroddi

Tidei

et al. 2015

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Catalytic properties and cellular effects of the glutathione peroxidase (GPx)-mimetic compound PhSeZnCl or its d,l-lactide polymer microencapsulation form (M-PhSeZnCl) were investigated and compared with the prototypical Se-organic compounds ebselen and diselenide (PhSe)2. PhSeZnCl was confirmed to catalyze the ping-pong reaction of GPx with higher Vmax than ebselen and (PhSe)2, but the catalytic efficiency calculated for the cosubstrates glutathione (GSH) and H2O2, and particularly the high reactivity against thiols (lowest KM for GSH in the series of test molecules), suggested poor biological applicability of PhSeZnCl as a GPx mimetic. Cytotoxicity of PhSeZnCl was demonstrated in various cancer cell lines via increased reactive oxygen species (ROS) generation, depletion of intracellular thiols, and induction of apoptosis. Experiments carried out in GSH S-transferase P (GSTP)-overexpressing K562 human erythroleukemia cells and in GSTP1-1-knockout murine embryonic fibroblasts (MEFs) demonstrated that this cytosolic enzyme represents a preferential target of the redox disturbances produced by this Se-compound with a key role in controlling H2O2 generation and the perturbation of stress/survival kinase signaling. Microencapsulation was adopted as a strategy to control the thiol reactivity and oxidative stress effects of PhSeZnCl, then assessing applications alternative to anticancer. The uptake of this “depowered” GPx-mimetic formulation, which occurred through an endocytosis-like mechanism, resulted in a marked reduction of cytotoxicity. In MCF-7 cells transfected with different allelic variants of GSTP, M-PhSeZnCl lowered the burst of cellular ROS induced by the exposure to extracellular H2O2, and the extent of this effect changed between the GSTP variants. Microencapsulation is a straightforward strategy to mitigate the toxicity of thiol-reactive Se-organic drugs that enhanced the antioxidant and cellular protective effects of PhSeZnCl. A mechanistic linkage of these effects with the expression pattern and signaling properties of GSTP. This has overcome the GPx-mimetic paradigm proposed for Se-organic drugs with a more pragmatic concept of GSTP signaling modulators.

show abstract

Section: Introductionmentioning

confidence: 99%

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its d,l-polylactide microparticle formulation

Bartolini

Piroddi

Tidei

et al. 2015

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4] In all the cases the on water conditions showed a rate acceleration when compared with the same reaction effected in THF. sterical hindrance on the reaction rate indicates that a SN2 mechanism is involved.…”

mentioning

confidence: 67%

<span>Highlight on the reactivity of PhSeZnX</span>

Monti

Sancineto

Palomba

et al. 2015

Proceedings of the 19th International Electronic Conference on Synthetic Organic Chemistry

Self Cite

View full text Add to dashboard Cite

Abstract:The first bench stable selenolates, PhSeZnHalides have been synthesized through a completely atom-economic oxidative insertion of the elemental zinc on the commercially available PhSeHalides. These reagents showed the characteristic nucleophilic reactivity which will be reviewed in this report. All of the reactions were strongly accelerated when effected in water suspension. Alkyl, aryl, vinyl and acyl substitutions, ring-opening reactions of epoxides and aziridines and Michael type addition will be described including the role of the zinc in the control of the chemoselectivity and stereoselectivity.

show abstract

“…In the case of 2,4-dinitrobromobenzene the corresponding selenide was obtained in moderate yield (50%). 1 Also in this case the reaction was effected by 'on water' conditions.…”

Section: Preparationmentioning

confidence: 92%

Phenylselenyl Zinc Halides

Tidei¹

2012

Synlett

View full text Add to dashboard Cite

show abstract

Preparation of the First Bench‐Stable Phenyl Selenolate: an Interesting “On Water” Nucleophilic Reagent

Abstract: Rally from C to N: The goal of the race concerns connecting carbon and nitrogen. While the SN2‐type mechanism constitutes a one‐way road to produce CH3NH3+ from Zn(CH3)+ and NH3, activation of the CH bond of methane in the Zn(NH2)+/CH4 system is a blind alley (see scheme).

Cited by 90 publications

References 59 publications

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its d,l-polylactide microparticle formulation

Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its d,l-polylactide microparticle formulation

<span>Highlight on the reactivity of PhSeZnX</span>

Phenylselenyl Zinc Halides

Contact Info

Product

Resources

About