Dmitrii V. Belykh

Opening of the extra ring in pheophorbide a methyl ester by the action of amines as a one-step method for introduction of additional fragments at the periphery of chlorin macroring

Opening of the extra ring in pheophorbide a methyl ester by the action of amines differing in the number, size, and structure of substituents on the nitrogen atom was studied with a view to synthesize chlorine e6 13-carboxamides. Main factors restricting one-step preparation of 13-carboxamides with a desired substituent were revealed. The obtained experimental data can be used as a basis for predicting the possibility for onestep preparative synthesis of particular chlorin e6 13-carboxamide via reaction with one or another amine.

Synthesis of amide derivatives of chlorin e 6

A number of secondary and tertiary chlorin e6-13-amides were synthesized in high yield by the action of primary and secondary amines on methylpheophorbide a under mild conditions. Unlike the secondary amides, tertiary 13-amides were shown to exist as two stereoisomers differing by orientation of the amide group plane with respect to the macroring. The reaction of methylpheophorbide a with 2-aminoethanol gave chlorin e6 derivatives containing one, two, and three hydroxy groups.

Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery

A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC50dark/IC50light ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.

Transformations of the extra ring in pheophorbide a methyl ester in the reaction with N,N,N′,N′-tetramethylmethanediamine

The reaction of N,N,N′,N′-tetramethylmethanediamine with pheophorbide a methyl ester gave the corresponding 13″-dimethylaminomethyl derivative and 13-N,N-dimethylamide derivative of chlorin e6 having a methyl acrylate moiety in the 15-position. Conditions were found for the synthesis of the latter both directly from pheophorbide a methyl ester and from its aminomethylation product. Probable mechanisms of the examined reactions were proposed.

Antiradical Activity of Porphyrins with a Diisobornylphenol Fragment at the Macrocycle Periphery

This article focuses on the antiradical activity of a number of 2,6-diisobornylphenol-porphyrin conjugates with various spacers between the porphyrin and phenolic fragments in the model reaction of ethylbenzene oxidation initiated by azoisobutyric acid dinitrile. The study has shown that the electronic effects of the groups directly related to the 2,6-diisobornylphenol fragment exert the predominant influence both on the reactivity of the phenolic hydroxyl group in interaction with free radicals and on the antiradical activity of the molecule as a whole. The antiradical activity of the molecule is generally less affected by the nature of the substituents in the porphyrin macrocycle, mainly due to a change in the stoichiometric inhibition coefficient in the presence of relatively easily oxidizable groups. It was found that the length of the spacer between the porphyrin and phenolic fragments does not affect the antiradical activity of the conjugate.

Inhibition activity of the chlorophyll a derivatives and their zink and cobalt complexes in the ethylbenzene oxidation

The inhibition activity of chlorophyll a derivatives with different substituents on the macrocycle and their Zn(II) and Co(II) chelates has been studied in the model reaction of ethylbenzene oxidation. It has been found that the values of the induction time (τ) and of the initial oxidation rate in the presence of the additives depend on the substituent on the macrocycle and the central metal atom. The inhibition parameter fτk7 (fτ is the stoichiometric inhibition factor and k7 is the rate constant of antioxidants with peroxy radicals) has been measured; its value is increased by more than an order of magnitude by introducing the metal atom into the macrocycle. The values of fτ = 1.3–2.5 calculated from the induction time and fc ≈ 1 calculated from the rate of the consumption of the Zn(II) and Co(II) complexes show that the conversion products of the complexes possess inhibition activity. The values of fτ and fτk7 for the Co(II) complexes with the amide group in the ligand environment depend on their initial concentration, a behavior that may be due to the reaction of the complexes with the hydroperoxide.