Sterically congested quinone methides in photodehydration reactions of 4-hydroxybiphenyl derivatives and investigation of their antiproliferative activity.
In aqueous media, photochemical excitation (S(1)) of hydroxyadamantyl, diphenylhydroxymethyl, and hydroxypropyl derivatives of 4-phenylphenol 5-9 leads to solvent-assisted deprotonation of the phenol OH, and protonation of the benzyl alcohol coupled with dehydration, that delivers quinone methides (QMs) 14-18. The QMs react with CH(3)OH converting them in high quantum yields to the photosolvolysis products (overall Φ∼ 0.1-0.5). QMs were characterized by laser flash photolysis in CH(3)CN-H(2)O and TFE. In TFE, the zwitterionic QM 15 has a lifetime of 250 ns, whereas para QMs 16 and 17 have lifetimes of 500 μs and 1.1 s, respectively. Introduction of the steric hindrance to the parent QM structure (with the adamantyl moiety), or additional stabilization by two phenyl rings, results in an increase of QM lifetimes and selectivity in the reactions with nucleophiles. In vitro studies of the antiproliferative activity of photochemically generated QMs 15-17 were carried out on one human cancer cell line. Irradiation of cells incubated with 7 showed enhanced antiproliferative activity compared to cells that were not irradiated, in accordance with the activity being due to the formation of QM 16.
Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia. nbasaric@irb.hr
Nikola
N
Basarić
Nikola
N
Cindro
Damir
D
Bobinac
Kata
K
Mlinarić-Majerski
Lidija
L
Uzelac
Marijeta
M
Kralj
Peter
P
Wan
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D045563:Indolequinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007834:Lasers; D000432:Methanol / Q000737:chemistry; D010782:Photolysis; D011522:Protons; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D045563:Indolequinones; D011522:Protons; C068040:quinone methide; C019046:4-phenylphenol; D000432:Methanol