Metal−Ligand Charge-Transfer-Promoted Photoelectronic Bergman Cyclization of Copper Metalloenediynes:  Photochemical DNA Cleavage via C-4‘ H-Atom Abstraction

• Published in: Journal of the American Chemical Society 2003-05, Vol.125 (21), p.6434-6446
• Main Authors: Benites, Pedro J, Holmberg, Rebecca C, Rawat, Diwan S, Kraft, Brian J, Klein, Lee J, Peters, Dennis G, Thorp, H. Holden, Zaleski, Jeffrey M
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Alkynes - chemistry; Analytical chemistry; Chemistry; Copper - chemistry; Cyclization; DNA - chemistry; Electrochemistry; Exact sciences and technology; Ligands; Miscellaneous; Oligonucleotides - chemistry; Organometallic Compounds - chemistry; Phosphorus Radioisotopes; Photochemistry; Plasmids - chemistry; Quantum Theory; Zinc - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja020939f

Metal-to-ligand charge-transfer (MLCT) photolyses (λ ≥ 395 nm) of copper complexes of cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne (bpod, 1), [Cu(bpod)2]PF6 (2), and [Cu(bpod)2](NO3)2 (3) yield Bergman cyclization of the bound ligands. In contrast, the uncomplexed ligand 1 and Zn(bpod)2(CH3COO)2 compound (4) are photochemically inert under the same conditions. In the case of 4, sensitized photochemical generation of the lowest energy 3π−π* state, which is localized on the enediyne unit, leads to production of the trans-bpod ligand bound to the Zn(II) cation by photoisomerization. Electrochemical studies show that 1, both the uncomplexed and complexed, exhibits two irreversible waves between E p values of −1.75 and −1.93 V (vs SCE), corresponding to reductions of the alkyne units. Irreversible, ligand-based one-electron oxidation waves are also observed at +1.94 and +2.15 V (vs SCE) for 1 and 3. Copper-centered oxidation of 2 and reduction of 3 occur at E 1/2 = +0.15 and +0.38 V, respectively. Combined with the observed Cu(I)-to-pyridine(π*) MLCT and pyridine(π*)-to-Cu(II) ligand-to-metal charge transfer (LMCT) absorption centered near ∼315 nm, the results suggest a mechanism for photo-Bergman cyclization that is derived from energy transfer to the enediyne unit upon charge-transfer excitation. The intermediates produced upon photolysis degrade both pUC19 bacterial plasmid DNA, as well as a 25-base-pair, double-stranded oligonucleotide. Detailed analyses of the cleavage reactions reveal 5‘-phosphate and 3‘-phosphoglycolate termini that are derived from H-atom abstraction from the 4‘-position of the deoxyribose ring rather than redox-induced base oxidation.