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: Jelena Veljković, Lidija Uzelac, Krešimir Molčanov, Kata Mlinarić-Majerski, Marijeta Kralj, Peter Wan, Nikola Basarić
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 77 Issue 10 Pg. 4596-610 (May 18 2012) ISSN: 1520-6904 [Electronic] United States
• PMID: 22533612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (2-adamantyl)naphthol
• Antineoplastic Agents
• Indolequinones
• Naphthols
• Prodrugs
• quinone methide
• Adamantane

Topics

• Adamantane (analogs & derivatives, chemistry)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Crystallography, X-Ray
• Humans
• Indolequinones (chemical synthesis, chemistry)
• Molecular Structure
• Naphthols (chemistry)
• Photolysis
• Prodrugs (chemical synthesis, chemistry)
• Spectrometry, Fluorescence
• Stereoisomerism