Dataset Information

Trapping para-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates.

ABSTRACT: The reaction of para-hydroxybenzyl alcohols with ferrocene in the presence of a catalytic amount of InCl? provided ferrocenyl phenol derivatives, an interesting class of organometallic compounds with potential applications in medicinal chemistry. This transformation exhibited a reasonable substrate scope delivering the desired products in synthetically useful yields. Evidence of involvement of a para-quinone methide intermediate in this coupling process was also provided. Preliminary biological evaluation demonstrated that some of the ferrocene derivatives available by this methodology exhibit significant cytotoxicity against several cancer cell lines with IC₅₀ values within the range of 1.07?4.89 ?M.

SUBMITTER: Gonzalez-Pelayo S

PROVIDER: S-EPMC6099632 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trapping para-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates.

González-Pelayo Silvia S López Enol E Borge Javier J de-Los-Santos-Álvarez Noemí N López Luis A LA

Molecules (Basel, Switzerland) 20180601 6

The reaction of para-hydroxybenzyl alcohols with ferrocene in the presence of a catalytic amount of InCl₃ provided ferrocenyl phenol derivatives, an interesting class of organometallic compounds with potential applications in medicinal chemistry. This transformation exhibited a reasonable substrate scope delivering the desired products in synthetically useful yields. Evidence of involvement of a para-quinone methide intermediate in this coupling process was also provided. Prelimina ...[more]

PMID: 29865205

Similar Datasets

Project description:Hydrogen atom transfer (HAT) is the mechanism by which the vast majority of radical-trapping antioxidants (RTAs), such as hindered phenols, inhibit autoxidation. As such, at least one weak O-H bond is the key structural feature which underlies the reactivity of phenolic RTAs. We recently observed that quinone methide dimers (QMDs) synthesized from hindered phenols are significantly more reactive RTAs than the phenols themselves despite lacking O-H bonds. Herein we describe our efforts to elucidate the mechanism by which they inhibit autoxidation. Four possible reaction paths were considered: (1) HAT from the C-H bonds on the carbon atoms which link the quinone methide moieties; (2) tautomerization or hydration of the quinone methide(s) in situ followed by HAT from the resultant phenolic O-H; (3) direct addition of peroxyl radicals to the quinone methide(s), and (4) homolysis of the weak central C-C bond in the QMD followed by combination of the resultant persistent phenoxyl radicals with peroxyl radicals. The insensitivity of the reactivity of the QMDs to substituent effects, solvent effects and a lack of kinetic isotope effects rule out the HAT reactions (mechanisms 1 and 2). Simple (monomeric) quinone methides, to which peroxyl radicals add, were found to be ca. 100-fold less reactive than the QMDs, ruling out mechanism 3. These facts, combined with the poor RTA activity we observe for a QMD with a stronger central C-C bond, support mechanism 4. The lack of solvent effects on the RTA activity of QMDs suggests that they may find application as additives to materials which contain H-bonding accepting moieties that can dramatically suppress the reactivity of conventional RTAs, such as phenols. This reactivity does not extend to biological membranes owing to the increased microviscosity of the phospholipid bilayer, which suppresses QMD dissociation in favour of recombination. Interestingly, the simple QMs were found to be very good RTAs in phospholipid bilayers - besting even the most potent form of vitamin E.

Dataset Information

Trapping para-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates.

Publications

Trapping <i>para</i>-Quinone Methide Intermediates with Ferrocene: Synthesis and Preliminary Biological Evaluation of New Phenol-Ferrocene Conjugates.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets