New Au (III), Pt (II) and Pd (II) complexes with pentapeptide glycyl-glycyl-(L)-methyonyl-glycyl-glycine and their interaction with calf thymus DNA.
The three new Au (III), Pt (II) and Pd (II) complexes with pentapeptide glycyl-glycyl-(L)-methyonyl-glycyl-glycine have been synthesized, isolated, and spectroscopically and structurally elucidated in solution and in the solid-state. Solid-state linear-dichroic infrared (IR-LD) spectroscopy of oriented colloids in a nematic liquid crystal host, (1)H- and (13)C-NMR, TGA and DSC, UV-VIS spectroscopy, EPR, ESI- and FAB- mass spectrometry and HPLC tandem mass spectrometry (HPLC-MS/MS) have been used. Quantum chemical calculations and molecular modelling were carried out in order to determine the structures and spectroscopic properties of the ligand, the newly synthesised metal complexes and their interactions with calf thymus DNA. The pentapeptide coordinates in a tetradentate manner with the metal ions via an S-atom on the methyonyl-side chain, two N-amide nitrogens, (after a deprotonation of gly(1) and gly(2) residues) and the primary NH(2) nitrogen of N(termini). The MN(3)S chromophores are distorted to near square planar geometry. Their interaction with calf thymus DNA shows the competitive N7 (G) coordination position, where the pentapeptide residues is coordinated with the metal centers in a tridentate manner through the S-atom and both N-amide centers. This interaction leads to a transfer from a distorted square planar geometry (D(4h) symmetry) to a pseudo tetrahedral (T(d) symmetry) of the metal ions with the obtained dihedral angle values of the MN(3)N7(G) chromophors within 114.67 degrees to 110.92 degrees . The isolated Au (III) complex is stable for about 1.5 months, while the stability of the Au (III) complex/DNA adduct is decreased to 33 days.
Chapkanov
A
A
South-West University Neofit Rilski, Department of Chemistry, 66 I. Mihailov str., 2700 Blagoevgrad, Bulgaria. chapkanov@swu.bg
Miteva
Y
Y
Kolev
T
T
Spiteller
M
M
Koleva
B
B
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000031:analogs & derivatives; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D004355:Drug Stability; D006046:Gold / Q000737:chemistry*; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D013053:Spectrophotometry
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D009842:Oligopeptides; C550455:glycylglycyl-methionyl-glycylglycine; D010984:Platinum; D010165:Palladium; D006046:Gold; D004247:DNA; C427203:calf thymus DNA; D002945:Cisplatin