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

Abstract

Metal-to-ligand charge-transfer (MLCT) photolyses (lambda > or = 395 nm) of copper complexes of cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne (bpod, 1), [Cu(bpod)(2)]PF(6) (2), and [Cu(bpod)(2)](NO(3))(2) (3) yield Bergman cyclization of the bound ligands. In contrast, the uncomplexed ligand 1 and Zn(bpod)(2)(CH(3)COO)(2) compound (4) are photochemically inert under the same conditions. In the case of 4, sensitized photochemical generation of the lowest energy (3)pi-pi 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(pi) MLCT and pyridine(pi)-to-Cu(II) ligand-to-metal charge transfer (LMCT) absorption centered near approximately 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.

DNA damage-site recognition by lysine conjugates

“…Any further cleavage on the opposite strand at the damage site leads to ds cleavage, which is hard to repair (11). The ds cleavage requires either a bifunctional reagent (12)(13)(14)(15)(16)(17)(18)(19)(20) or detection and targeting of the damaged site. The only literature example of the latter is a complex natural antibiotic, bleomycin (21).…”

Microwave assisted synthesis of symmetrically and asymmetrically substituted acyclic enediynes

“…This reaction further confirms the utility of microwave irradiation in the enediyne synthesis. Microwave irradiation of (13,14) in presence of 100 equivalent of cyclohexadiene in benzene at 850 W for 30 minutes, results no cyclization of the enediynes. This clearly indicates that these compounds are stable under experimental conditions.…”

“…12 In order to improve the biological activity of the enediynes, efforts are being made to synthesize analogous compounds with better efficacy. [13][14][15][16][17][18][19] Sonogashira coupling has been one of the reactions extensively used in the synthesis of enediyne framework. [20][21][22] Lot of work has been done recently in the development of Sonogashira coupling and one of the development was the use of microwaves in order to promote the C-C bond formation.…”

Unique Metal‐Diyne, ‐Enyne, and ‐Enediyne Complexes: Part of the Remarkably Diverse World of Metal‐Alkyne Chemistry

“…34). Bergman cyclization (576) of simple metalloenediynes have been reported (577,578). The first of these involves direct copper-pyridine charge-transfer photoexcitation (cf.…”