Oxidative cleavage of DNA by a dipyridoquinoxaline copper(II) complex in the presence of ascorbic acid.
Complex [Cu(dpq)(2)(H(2)O)](ClO(4))(2).H(2)O (1), where dpq is dipyrido-[3,2-D:2',3'-f]-quinoxaline, has been prepared by reacting copper(II) perchlorate hexahydrate with dpq in methanol and structurally characterized. The complex crystallizes in the triclinic space group P-1 with the unit cell parameters a=8.646(2) A, b=12.290(5) A, c=14.283(4) A, alpha=94.01(2) degrees, beta=91.69(2) degrees,gamma=101.60 (3) degrees, V=1481.7(8) A(3) and Z=2. The structure, refined to R=0.0505 and R(w)=0.1441 for 5212 reflections with I>2sigma (I) using 440 parameters, shows the presence of a CuN(4)O chromophore in an axially compressed distorted trigonal-bipyramidal structure. The Cu-N distances lie in the range 1.969(3)-2.103(3) A. The Cu-OH(2) distance is 2.145(3) A. The complex is one-electron paramagnetic and exhibits a visible spectral d-d band at 718 nm in MeCN. It shows a quasi-reversible cyclic voltammetric response at 0.091 V (DeltaE(p)=229 mV) at 50 mV s(-1) in MeCN-0.1 M TBAP for the Cu(II)/Cu(I) couple. In 50 mM Tris-HCl/0.1 M KCl buffer-DMF mixture (1:4 v/v, pH 7.2), the couple appears at 0.089 V versus SCE. The complex undergoes facile reduction with sodium ascorbate in an aqueous DMF mixture (4:1 v/v) to form an unstable brown Cu(I) species (lambda(max)=440 nm, epsilon=7480 M(-1) cm(-1)) which converts to 1 on exposure to air giving a turnover frequency of ca. 400. Binding studies revealed that 1 is an efficient binder to calf thymus DNA. Complex 1 on reaction with supercoiled (SC) DNA in presence of ascorbic acid in a 50 mM Tris-HCl/50 mM NaCl buffer (pH 7.2) shows nuclease activity which is 4.5 times greater than that of the phen analogue.
Santra
Bidyut K
BK
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore-560012, India.
Reddy
Pattubala A N
PA
Neelakanta
Girish
G
Mahadevan
Subramony
S
Nethaji
Munirathinam
M
Chakravarty
Akhil R
AR
D001205:Ascorbic Acid / Q000378:metabolism*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism; D004563:Electrochemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004278:DNA, Superhelical; D009942:Organometallic Compounds; D011810:Quinoxalines; C460959:dipyridoquinoxaline copper(II) complex; D003300:Copper; D004247:DNA; D001205:Ascorbic Acid