D.B. Shpakovsky

Iron (III) porphyrin bearing 2,6-di-tert-butylphenol pendants deposited onto gold electrodes for amperometric determination of l-histidine

A sensitive amperometric sensor for determination of L-histidine was developed using gold electrode modified with Fe(III)-porphyrin bearing three 2,6-di-tert-butylphenol groups and one palmitoyl chain. Two methods of electrode modification were applied: direct chemisorption and embedment into dodecanethiol monolayer. Both types of electrodes were used for detection of L-histidine using Osteryoung square-wave voltammetry. The sensitivity of sensors presented towards L-histidine depends on the method of electrode modification. The detection limits observed for the electrodes incorporating with Fe(III)-porphyrin host by embedment and chemisorption were in 1 and 100 nM ranges, respectively. In addition, the determination of L-histidine with electrode modified by embedment technique was more precise, in comparison to that obtained by the direct chemisorption. Applicability of gold electrodes modified with Fe(III)-porphyrin for the direct electrochemical determination of L-histidine was demonstrated using the artificial matrix mimicking human serum.

Synthesis and antioxidative activity of metalloporphyrins bearing 2,6-di-tert-butylphenol pendants.

The novel metalloporphyrins (M=HH, Fe, Mn, Co, Cu, Zn) bearing 2,6-di-tert-butylphenol pendants as antioxidant substituents, and a long chain hydrocarbon palmitoyl group have been synthesized. The oxidation of compounds by PbO2 leads to the formation of the corresponding 2,6-di-tert-butylphenoxyl radicals studied by EPR. The activity of porphyrins in lipid peroxidation has been examined using (1) in vitro lipid peroxidation induced by tert-butylhydroperoxide in respiring rat liver mitochondria, (2) in vitro lipid peroxidation in liver homogenates of Wistar strain rats, and (3) a model process of peroxidation of (Z)-octadec-9-enic (oleic) acid as a structural fragment of lipids. The activity of these compounds depends dramatically on the nature of metal and might be changed from antioxidative (M=HH, Mn, Cu, Zn) to indifferent (M=Co), and to pro-oxidative one (M=Fe). The anti- or pro-oxidative action of these compounds may be derived from the concurrence between the involvement of 2,6-di-tert-butylphenol pendants acting as radical scavengers and redox active metal center promoting oxidation processes. The results of this study suggest that the polytopic compounds combining in one molecule 2,6-di-tert-butylphenol pendants, metalloporphyrin moiety, and a palmitoyl group, are membrane active compounds and might be studied in an effort to find novel pharmaceutical agents.

Synthesis and antioxidant activity of new organotin compounds containing a 2,6-di-tert-butylphenol moiety

ISSN 00125008, Doklady Chemistry, 2013, Vol. 451, Part 1, pp. 177–180.

2,6-Di-tert-butylphenols and phenoxyl radicals with metal—metal bonds

Abstractσ-Aryl trans-bistriphenylphosphine complexes based on 2,6-di-tert-butylphenol containing Pt—SnCl3, Pt—GeCl3 groups were synthesized. Oxidation of these compounds gives the corresponding phenoxyl radicals, which were studied by ESR spectroscopy. The transformation of the diamagnetic complexes to the paramagnetic state is accompanied by cleavage of the Pt—Sn, Pt—Ge bonds and by elimination of SnCl2, GeCl2.

Complexes of organotin compounds with bis- and trisphosphonate derivatives of 2,6-di-tert-butylphenol having antioxidant activity

Complexes of organotin compounds R2SnCl2 with bisand trisphosphonate derivatives of 2,6-di-tert-butyl-4-methylphenol (ionol) were synthesized. X-ray diffraction studies were carried out for some of them. The redox properties of the synthesized compounds were characterized by cyclic voltammetry. Antioxidant/prooxidant activity of the complexes was studied using a new electrochemical method based on measuring the rate of hydrogen atom transfer to the stable radical 2,2´-diphenyl-1-picrylhydrazyl (DPPH). The data obtained were compared with the results of studying activity of the compounds during lipid peroxidation (LP) in biological samples. A correlation is observed between the results on antioxidant activity obtained by electrochemical DPPH test and using biological samples. Unlike the initial organotin compounds, the synthesized complexes have antioxidant activity, whereas phosphorus-containing phenols exhibit the properties of efficient antioxidants and chelating agents.

Oleic acid peroxidation in the presence of metallo-porphyrins

The influence of free bases of meso-tetrakis(3,5-di-tert-butyl-4-hydroxy-phenyl)porphyrins and meso-tetraphenylporphyrins and their complexes of Co, Ni, Cu, Pt upon the radical chain oxidation of oleic acid as model substrates for lipid peroxidation has been studied. It was shown that the introduction of the antioxidative phenolic fragment into the porphyrin ring leads to the dual activity of phenolic porphyrins when compared with their tetraphenyl substituted analogues in substrate oxidation. Free base phenolic porphyrins and their nickel, copper, platinum complexes demonstrate acute inhibitory effect upon oleic acid peroxidation due to the key role of 2,6-di-tert-butylphenol moities, whereas cobalt porphyrin exhibits dual activity associated with the presence of both the redox active metal center and phenolic group.

Novel ferrocene-based inhibitor of proteins glycation

Antioxidant and antiglycating activities of 2,6-di-tert-butyl-4-[N-(4-pyridyl)iminomethyl]phenol (1), 2,6-di-tert-butyl-4-[N-(3-pyridylmethyl)-iminomethyl]phenol (2) and N-(3,5-di-tert-butyl-4-hydroxyphenyl)iminomethylferrocene (3) have been studied. Antioxidant activity of 2,6-di-tert-butylphenol bearing ferrocenyl moiety was shown to be sufficiently higher than that of the compounds 1 and 2. Based on the data obtained in comparison with aminoguanidine which is an effective protein glycation inhibitor it was established that the introduction of ferrocenyl moiety into 2,6-di-tert-butylphenol results in a dramatic increase in the antiglycating activity exceeding that for aminoguanidine.

Synthesis and study of new phenolic antioxidants with nitroaromatic and heterocyclic substituents

New polyfunctional aromatic, nitroaromatic, and heterocyclic compounds linked to the 2,6-di-tert-butylphenol moiety via –NH–, –C(O)NH–, –S–, or–C=N– spacers were synthesized. These structures provide intramolecular charge transfer (ICT) and exhibit antioxidant activity. The structures of the new compounds were established by X-ray diffraction. The novel compounds were evaluated for antioxidant activity using the DPPH assay. The presence of the 2,4,6-trinitrophenyl moiety in combination with the –NH– spacer leads to a considerable increase in the antioxidant activity of 2,6-di-tert-butylphenols. These compounds are also weak lipoxygenase inhibitors. The results of this study provide an opportunity to search for new types of antioxidants with ICT.

Comparative study of in vivo impact of water-soluble and lipophilic forms of dipicolylamine containing a 2,6-di-tert-butylphenol moiety on the oxidative status of rat tissues

The effect of lipophilic [N-(3,5-di-tert-butyl-4-hydroxybenzyl)-N,N-di(2-pyridylmethyl)]-amine and its water-soluble hydrochloride on the oxidative status of tissues of Wistar rats in vivo was studied. The change in the xanthine oxidase activity, the level of free radical processes in blood, and the antioxidant activities of blood serum were determined by spectrophometry. The contents of TBA-dependent products (TBA is thiobarbituric acid) in animal tissues were measured by biochemiluminescence under induced oxidative stress conditions. The effect of [N-(3,5-di-tert-butyl-4-hydroxybenzyl)-N,N-di-(2-pyridylmethyl)]amine on organism in vivo is multi-factorial and is more pronounced for the water-soluble hydrochloride.

Organometallic derivatives of 2,6-di-tert-butylphenols as specific inhibitors of methyl oleate oxidation

Abstract2,6-Di-tert-butylphenols containing the Pt—SnCl3 and Pt—GeCl3 groups in the para position exert a dual effect on the oxidation of methyl oleate by molecular oxygen. Initially, these compounds act as antioxidants producing the corresponding phenoxyl radicals whose decomposition is accompanied by elimination of SnCl2 and GeCl2, which are oxidation promoters.