title: Sterically congested adamantylnaphthalene quinone methides.
abstract: Five new (2-adamantyl)naphthol derivatives (5-9, quinone methide precursors, QMP) were synthesized and their photochemical reactivity was investigated by preparative photolyses, fluorescence spectroscopy, and laser flash photolysis (LFP). Excitation of QMP 5 to S(1) leads to efficient excited state intramolecular proton transfer (ESIPT) coupled with dehydration, giving quinone methide QM5 which was characterized by LFP (in CH(3)CN-H(2)O, λ(max) = 370 nm, τ = 0.19 ms). On irradiation of QMP 5 in CH(3)OH-H(2)O (4:1), the quantum yield of methanolysis is Φ = 0.70. Excitation of naphthols QMP 6-8 to S(1) in CH(3)CN leads to photoionization and formation of naphthoxyl radicals. In a protic solvent, QMP 6-8 undergo solvent-assisted PT giving QM6 or zwitterion QM8 that react with nucleophiles delivering adducts, but with a significantly lower quantum efficiency. QMP 9 in a protic solvent undergoes two competitive processes, photosolvolysis via QM9 and solvent-assisted PT to carbon atom of the naphthalene giving zwitterion. QM9 has been characterized by LFP (in CH(3)CN-H(2)O, λ(max) > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs, two stable naphthalene QMs, QM10 and QM11 were synthesized thermally and characterized by X-ray crystallography. QM10 and QM11 do not react with H(2)O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative activity of 5-9 was investigated on three human cancer cell lines. Exposure of MCF-7 cells treated with 5 to 300 nm irradiation leads to an enhanced antiproliferative effect, in accordance with the activity being due to the formation of QM5.
authors.affiliation: Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000 Zagreb, Croatia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Veljković
authors.forename: Lidija
authors.initials: L
authors.lastname: Uzelac
authors.forename: Krešimir
authors.initials: K
authors.lastname: Molčanov
authors.forename: Kata
authors.initials: K
authors.lastname: Mlinarić-Majerski
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.forename: Peter
authors.initials: P
authors.lastname: Wan
authors.forename: Nikola
authors.initials: N
authors.lastname: Basarić
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D006801:Humans; D045563:Indolequinones / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D009284:Naphthols / Q000737:chemistry*; D010782:Photolysis; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
chemical_list: C574741:(2-adamantyl)naphthol; D000970:Antineoplastic Agents; D045563:Indolequinones; D009284:Naphthols; D011355:Prodrugs; C068040:quinone methide; D000218:Adamantane