Targeted Strand Scission of DNA Substrates by a Tricopper(II) Coordination Complex

Abstract

A trinuclear copper complex, [Cu(3)(II)(L)(H(2)O)(3)(NO(3))(2)](NO(3))(4).5H(2)O (1) (L = 2,2',2' '-tris(dipicolylamino)triethylamine), with pyridyl and alkylamine coordination exhibits a remarkable ability to promote specific strand scission at junctions between single- and double-stranded DNA. Strand scission occurs on the 3' overhang at the junction of a hairpin or frayed duplex structure and is not dependent on the identity of the base at which cleavage occurs. Target recognition minimally requires a purine at the first unpaired position and a guanine at the second unpaired position on the 5' strand. Incorporation of the necessary recognition elements into an otherwise unreactive junction resulted in specific strand scission at that new target and helped to confirm the predictive nature of this complex. Selective strand scission requires both a reductant and dioxygen, suggesting activation of O(2) by the reduced form of 1. The reaction utilizing the trinuclear complex does not appear to involve a diffusible radical species as suggested by its high specificity of target oxidation and its lack of sensitivity to radical quenching agents. Comparisons between the trinuclear copper complex, mononuclear analogues of 1, and [Cu(OP)(2)](2+) (OP = 1,10-phenanthroline) indicate that recognition and reactivity described in this report are dependent on the multiple metal ions within the same complex which together support its unique activity.

A Copper‐Metalated, Hybrid Inorganic–Organic Polymer as an Oxidative Nuclease

“…[32][33][34][35] In particular, copper complexes afford facile nucleic acid oxidative cleavage in the presence of oxidizing and reducing agents, [36][37][38][39][40][41][42][43] in addition to the hydrolytic mechanism. [23,27,29] Most of these artificial phosphatases and nucleases offer homogeneous catalysis, while only limited applications of heterogeneous catalysts have been reported.…”

Crystal structure of dichloro-N,N-bis(pyridine-2-ylmethyl)cyclohexamino copper(II), C18H23Cl2CuN3

“…The N2-Cu1-N3, N3-Cu1-N1 and N1 pyridine -Cu1-N2 pyridine bite angles of 77.91(6)°, 82.31(6)°and 105.18(6)°respectively,correlates well with similar complexes of dipyridylamine ligands with Cu(II). All the bond distances and angles in the title structure fall within the range of similar complexes [14][15][16][17][18], with the exception of aclosely related blue Cu(II) complex containing ad ichloromethane solvate which crystallized in the C2/c space group [19]. (7) 0.0005 (7) 0.0008 (7) …”

Nuclease activity of copper(II) complex containing 1,10-phenanthroline-5,6-dione and L-phenylalanine ligands

“…This further confirmed that species exerting DNA cleavage were not the free diffusible hydroxyl radicals. Some copper-centered radicals, that are DNA-bound and not easily reached by the radical scavengers, should be responsible for cleavage [16][17][18]. Sodium azide viewed as singlet oxygen scavenger, shows a slight reduction in the activity (compare lanes 8 and 9 with lanes 0 and 1) which suggests that 1 …”