Synthesis, photochemical reaction mechanisms of formation and biological activity of benzene, naphthalene and anthracene quinone methides

Škalamera, Đani (2015) Synthesis, photochemical reaction mechanisms of formation and biological activity of benzene, naphthalene and anthracene quinone methides. Doctoral thesis, Faculty of Science > Department of Chemistry.

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Abstract

The thesis comprises synthesis and investigation of photochemical reactivity of three novel series of quinone methide (QM) precursors, which are derivatives of benzene, naphthalene and anthracene. The photoreactivity of compounds has been studied in solid state at 14 K for 2-hydroxymethylphenol (1), and in solution at room temperature for Mannich derivatives of p-cresol, naphthalene and anthracene derivatives. The photodehydratation of compound 1 in solid state at 14 K gives a mixture of o-QM and benzoxete. Mechanisms of photochemical reactions for other compounds were studied by preparative irradiations, studying the dependence of photomethanolysis efficiency on the water content in methanol, by UV-vis and fluorescence spectroscopy and laser flash photolysis (LFP). The mechanism of photodeamination in Mannich derivatives od p-cresol is proposed, which to date has not been reported. The LFP results have demonstrated that the attack of nucleophiles to bifunctional QM generates new QM species. This observation is of particular importance in the biological systems since it could lead to cross-linking of DNA. Naphthalene derivatives were designed to investigate the optimal substitution pattern on the naphthalene chromophore for the most efficient photodehydratation. It was found that 6-(2-hydroxy-2-adamantyl)-2-(4-hydroxyphenyl)naphthalene (12) underwent the most efficient photodehydration. Antracene derivatives were prepared by the multistep synthetic procedure starting from 2-aminoanthraquinone. Photogeneration of QMs from anthracene derivatives is important due to potential application in biological systems, given that the chromophore absorbs at wavelengths >400 nm. Investigation of 3-(diphenylhydroxymethyl)-2-anthrol (16) with LFP has shown that the photogenerated QM undergoes protonation to give the cation that subsequently reacts with nucleophiles. Antiproliferative investigation on human cancer cell lines showed that 3-hydroxymethyl-2-anthrol (14) had significantly higher antiproliferative activity on irradiation, probably due to the generation of reactive QMs.

Item Type: Thesis (Doctoral thesis)
Keywords: quinone methides, Mannich derivatives of phenols, naphthylphenol, anthrol, photosolvolyses, photodehydration, photodeamination
Supervisor: Basarić, Nikola
Date: 2015
Number of Pages: 296
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Branka Maravic
Date Deposited: 24 Apr 2015 11:52
Last Modified: 24 Apr 2015 11:52
URI: http://digre.pmf.unizg.hr/id/eprint/3889

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