Synthesis, crystal structures and DNA-cleaving activities of [Cemp]2[MCl4] (Cemp = N-carbethoxymethyl-1,10-phenanthrolinium, M = Cu(II), Zn(II), Co(II), Ni(II) and Mn(II)).

N-Carbethoxymethyl-1,10-phenanthrolinium bromide (CempBr) and its five ionic metal complexes, [Cemp]2[MCl4] where M = Cu(II) (1), Zn(II) (2), Co(II) (3), Ni(II) (4) and Mn(II) (5) were synthesized and fully characterized. Complexes 1-5 have similar structures, and consist of isolated [Cemp](+) cations and [MCl4](2-) anions in which there are no obvious interactions between the oxygen or nitrogen donor atoms in [Cemp](+) and the metal center in [MCl4](2-). Agarose gel electrophoresis studies on the cleavage of plasmid pBR322 DNA by complexes 1-5 indicated that complex 1 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanism. Kinetic assay of complex 1 afforded the maximal catalytic rate constant kmax of 0.55 h(-1) and Michaelis constant KM of 47.6 µM, respectively, which gives about 1.5×10(7)-fold rate acceleration over uncatalyzed cleavage of supercoiled DNA. Ethidium bromide displacement experiments indicated that complex 1 had a binding affinity of (1.58±1.12)×10(6) M(-1) toward calf-thymus DNA, 20-100-fold higher than those shown by CempBr and complexes 2-5. The high cleaving efficacy of complex 1 is thought to be due to the efficient catalysis of the copper(II)-coordinated center and the efficient binding of the quaternized 1,10-phenanthroline cation to DNA.

Synthesis, characterization and potent DNA-cleaving activity of copper(II)-complexed berberine carboxylate.

9-O-(4-carboxybenzyl)berberine (CBB) 1 was synthesized from the reaction of berberrubine with methyl 4-(bromomethyl)benzoate and subsequent hydrolysis. Its Cu(II) complex 2 was prepared from the reaction with Cu(NO(3))(2)·3H(2)O, and established as [Cu(CBB)(2)](NO(3))(2)·2H(2)O by means of (1)H NMR, UV, IR, elemental analysis and TGA measurements. Agarose gel electrophoresis study on the cleavage of plasmid pBR322 DNA indicated that complex 2 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanistic pathway involving the formation of singlet oxygen as the reactive species. Kinetic assay afforded the maximal first-order rate constant k(max) of 2.41 h(-1) and Michaelis constant K(M) of 2.64 mM, respectively, representing ca. 10(8)-fold acceleration in the cleavage. This catalytic efficacy is attributed to the Cu(II)-assisted formation of dimeric species, in which the two berberine subunits cooperatively bind to DNA, whereas the carboxylate-coordinated Cu(II) moiety functions as the cleavage-active center.

Spiro-[indene-1,1'-benzo[e]indolin]-2'-one.

In the title compound, C(20)H(13)NO, the indene ring is disordered over two sites with an occupancy ratio of 0.557 (2):0.443 (2). Both disordered components of indene are nearly perpendicular to the naphthalene ring system, making dihedral angles of 90.9 (2) and 85.0 (5)°. The five-membered ring of the 1H-pyrrol-2(3H)-one adopts an envelope conformation with the spiro C atom at the flap position. Inter-molecular classical N-H⋯O and weak C-H⋯O hydrogen bonding is present in the crystal structure.