Nuclease activity and protein-binding properties of a novel tetranuclear thiosemicarbazide Pt(II) complex.
A novel tetranuclear [Pt4(Am4M)4]·16.25H2O (1), where H2Am4M is the thiosemicarbazone ligand (Z)-2-(amino(pyridin-2-yl)methylene)-N-methylhydrazinecarbothioamide, has been synthesized and characterized by using various physico-chemical techniques. X-ray analysis revealed that the Pt(II) complex consists of a neutral tetranuclear [Pt4(Am4M)4] unit and abundant water molecules. The tetranuclear unit is stabilized by strong intramolecular π-π stacking and thus presents a ship-like eight-membered ring [Pt4S4] with four tridentate ligands peripherally coordinated to four Pt(II) ions, constituting a novel type of "well" structure. DNA and protein binding properties of complex 1 have been studied by UV and fluorescence spectroscopic methods. The binding constant (Kb = 3.05 × 10(6) M(-1)) and the apparent binding constant (Kapp = 7.732 × 10(6) M(-1)) to calf thymus DNA (CT-DNA) were accurately fitted by two respective non-linear equations, suggesting an efficient DNA intercalative binding mode which was confirmed by viscometric experiments. Furthermore, following agarose gel electrophoresis experiments, we observed that the plasmid DNA pUC19 could be completely digested by complex 1, depending on incubation time and concentration, indicating that complex 1 may possess an effective nuclease activity on DNA. Singlet oxygen ((1)O2) inhibitors showed an inhibitory effect on the cleavage. Fluorescence spectrometry also detected a medium affinity of complex 1 to bovine serum albumin (BSA) at different temperatures, which was tentatively assigned to a static binding mode. All these results suggested that this poly-Pt(II) complex might exhibit biological action as a potential chemotherapy agent.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.
Jia
J
Shao
Wei-Guo
WG
Bao
He
H
Tian
Bing
B
Li
Xiao-Fei
XF
Zhao
Xin
X
Qiao
Jing-Yuan
JY
Xu
D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism*; D010984:Platinum / Q000737:chemistry*; D011485:Protein Binding; D012663:Semicarbazides / Q000737:chemistry / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
D012663:Semicarbazides; D012710:Serum Albumin, Bovine; D010984:Platinum; C005151:thiosemicarbazide; D004247:DNA; C427203:calf thymus DNA; D004720:Endonucleases