Patra Ashis K, Bhowmick Tuhin, Roy Sovan, Ramakumar Suryanarayanarao, Chakravarty Akhil R
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India.
Inorg Chem. 2009 Apr 6;48(7):2932-43. doi: 10.1021/ic8017425.
Copper(II) complexes Cu(L-arg)(2)(2) (1) and [Cu(L-arg)(B)Cl]Cl (2-5), where B is a heterocyclic base, namely, 2,2'-bipyridine (bpy, 2), 1,10-phenanthroline (phen, 3), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 5), are prepared and their DNA binding and photoinduced DNA cleavage activity studied. Ternary complex 3, structurally characterized using X-ray crystallography, shows a square-pyramidal (4 + 1) coordination geometry in which the N,O-donor L-arginine and N,N-donor 1,10-phenanthroline form the basal plane with one chloride at the elongated axial site. The complex has a pendant cationic guanidinium moiety. The one-electron paramagnetic complexes display a metal-centered d-d band in the range of 590-690 nm in aqueous DMF. They show quasireversible cyclic voltammetric response due to the Cu(II)/Cu(I) couple in the range of -0.1 to -0.3 V versus a saturated calomel electrode in a DMF-Tris HCl buffer (pH 7.2). The DNA binding propensity of the complexes is studied using various techniques. Copper(II) bis-arginate 1 mimics the minor groove binder netropsin by showing preferential binding to the AT-rich sequence of double-strand (ds) DNA. DNA binding study using calf thymus DNA gives an order: 5 (L-arg-dppz) > or = 1 (bis-L-arg) > 4 (L-arg-dpq) > 3 (L-arg-phen) >> 2 (L-arg-bpy). Molecular docking calculations reveal that the complexes bind through extensive hydrogen bonding and electrostatic interactions with ds-DNA. The complexes cleave supercoiled pUC19 DNA in the presence of 3-mercaptopropionic acid as a reducing agent forming hydroxyl ((*)OH) radicals. The complexes show oxidative photoinduced DNA cleavage activity in UV-A light of 365 nm and red light of 647.1 nm (Ar-Kr mixed-gas-ion laser) in a metal-assisted photoexcitation process forming singlet oxygen ((1)O(2)) species in a type-II pathway. All of the complexes, barring complex 2, show efficient DNA photocleavage activity. Complexes 4 and 5 exhibit significant double-strand breaks of DNA in red light of 647.1 nm due to the presence of two photosensitizers, namely, L-arginine and dpq or dppz in the molecules.
制备了铜（II）配合物Cu（L-精氨酸）₂₂（1）和[Cu（L-精氨酸）(B)Cl]Cl（2 - 5），其中B是杂环碱，即2,2'-联吡啶（bpy，2）、1,10-菲咯啉（phen，3）、二吡啶并[3,2-d:2',3'-f]喹喔啉（dpq，4）和二吡啶并[3,2-a:2',3'-c]吩嗪（dppz，5），并研究了它们与DNA的结合及光诱导DNA切割活性。通过X射线晶体学对三元配合物3进行结构表征，其显示出四方锥（4 + 1）配位几何结构，其中N,O供体L-精氨酸和N,N供体1,10-菲咯啉形成基面，在伸长的轴向位置有一个氯离子。该配合物有一个悬垂的阳离子胍基部分。单电子顺磁性配合物在水DMF中显示出590 - 690 nm范围内以金属为中心的d-d带。由于在DMF-Tris HCl缓冲液（pH 7.2）中相对于饱和甘汞电极，Cu（II）/Cu（I）电对在-0.1至-0.3 V范围内，它们显示出准可逆的循环伏安响应。使用各种技术研究了配合物与DNA的结合倾向。双精氨酸铜（II）1通过显示对双链（ds）DNA富含AT序列的优先结合来模拟小沟结合剂纺锤菌素。使用小牛胸腺DNA进行的DNA结合研究给出的顺序为：5（L-精氨酸-dppz）≥1（双-L-精氨酸）＞4（L-精氨酸-dpq）＞3（L-精氨酸-phen）＞＞2（L-精氨酸-bpy）。分子对接计算表明，这些配合物通过与ds-DNA广泛的氢键和静电相互作用而结合。在作为还原剂的3-巯基丙酸存在下，这些配合物可切割超螺旋pUC19 DNA，形成羟基（·OH）自由基。在金属辅助光激发过程中，这些配合物在365 nm的UV-A光和647.1 nm的红光（Ar-Kr混合气体离子激光）下显示出氧化光诱导DNA切割活性，在II型途径中形成单线态氧（¹O₂）物种。除配合物2外，所有配合物均显示出有效的DNA光切割活性。由于分子中存在两种光敏剂，即L-精氨酸和dpq或dppz，配合物4和5在647.1 nm的红光下表现出显著的DNA双链断裂。
