RESUMO
Ternary Cu(II) complexes [Cu(II)(saltrp)(B)] (1,2), (saltrp=salicylidene tryptophan, B=1,10 phenathroline (1) or 2,2' bipyridine (2)) were synthesized and characterized. Complex 2 was structurally characterized by single crystal X-ray crystallography. The molecular structure shows a distorted square pyramidal coordination geometry (CuN(3)O(2)) in which the ONO donor Schiff base is bonded to the Cu(II) in the basal plane. The N,N donor heterocyclic base displays an axial-equatorial binding mode. CT-DNA binding studies revealed that the complexes show good binding propensity (Intrinsic binding constant, K(b)=3.32×10(5) M(-1) for 1 and K(b)=3.10×10(5) M(-1) for 2). The catalytic role of these complexes in the oxidative and hydrolytic cleavage of DNA was studied in detail. Complex 1 binds and cleaves DNA more efficiently as compared to 2. From the kinetic experiments, rate constants for the hydrolysis of phosphodiester bond of DNA backbone were determined as 1.94 h(-1) and 1.05 h(-1) for 1 and 2 respectively. It amounts to (2.93-5.41)×10(7) fold rate enhancement compared to uncatalyzed double stranded DNA, which is impressive as compared to related Cu(II) Schiff base complexes.
Assuntos
Complexos de Coordenação/síntese química , Clivagem do DNA , DNA/química , Ligação Competitiva , Simulação por Computador , Complexos de Coordenação/química , Cristalografia por Raios X , Desoxirribonucleases/síntese química , Desoxirribonucleases/química , Etídio/química , Substâncias Intercalantes/química , Modelos Moleculares , Conformação Molecular , Oxirredução , Espectrometria de Fluorescência , Termodinâmica , Temperatura de Transição , ViscosidadeRESUMO
The mononuclear dipeptide-based Cu(II) complexes [Cu(II) (trp-phe)(phen)(H2O)] â ClO4 (1) and [Cu(II) (trp-phe)(bpy)(H2O)] â ClO4 (2) (trp-phe=tryptophanphenylalanine, phen=1,10-phenanthroline, bpy=2,2'-bipyridine) were isolated, and their interaction with DNA was studied. They exhibit intercalative mode of interaction with DNA. The intercalative interaction was quantified by Stern-Volmer quenching constant (K(sq) =0.14 for 1 and 0.08 for 2). The Cu(II) complexes convert supercoiled plasmid DNA into its nicked circular form hydrolytically at physiological conditions at a concentration as low as 5â µM (for 1) and 10â µM (for 2). The DNA hydrolysis rates at a complex concentration of 50â µM were determined as 1.74â h(-1) (R=0.985) for 1 and 0.65â h(-1) (R=0.965) for 2. The rate enhancement in the range of 2.40-4.10×107-fold compared to non-catalyzed double-stranded DNA is significant. This was attributed to the presence of a H(2) O molecule in the axial position of the Cu complexes.
Assuntos
2,2'-Dipiridil/química , Complexos de Coordenação/síntese química , Cobre/química , DNA/metabolismo , Fenantrolinas/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Clivagem do DNA , Espectroscopia de Ressonância de Spin Eletrônica , Plasmídeos/química , Espectrofotometria InfravermelhoRESUMO
The complexes [Cu(II)(phen)(L-Pro)(H2O)]+ ClO4(-) (1; phen = 1,10-phenanthroline) and [Cu(II)(bipy)(L-Pro)(H2O)]+ ClO4(-) (2; bipy = 2,2'-bipyridine) were synthesized and characterized by IR, magnetic susceptibility, UV/VIS, EPR, ESI-MS, elemental analysis, and theoretical calculations. The metal center was found in a square-pyramidal geometry. UV/VIS, thermal-denaturation, and fluorescence-spectroscopic studies were conducted to assess the interaction of the complexes with CT-DNA. An intercalative mode of binding was found, with intrinsic binding constants (Kb) of 3.86x10(3) and 4.6x10(3) M(-1) and Stern-Volmer quenching constants (K) of 0.15 and 0.11 for 1 and 2, respectively. Interestingly, none of the Cu(II) complexes was able to cleave pUC-19 DNA, which is attributed to the absence of a Pro amide H-atom and inhibition of the formation of an OH radical from the axially coordinated H2O molecule.
