Synthesis, Spectroscopic Properties, and Photoinduced CO-Release Studies of Functionalized Ruthenium(II) Polypyridyl Complexes: Versatile Building Blocks for Development of CORM-Peptide Nucleic Acid Bioconjugates
Synthesis, Spectroscopic Properties, and Photoinduced CO-Release Studies of Functionalized Ruthenium(II) Polypyridyl Complexes: Versatile Building Blocks for Development of CORM-Peptide Nucleic Acid Bioconjugates
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DOI：
10.1021/ic400746n
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发表时间：
2013-08-19
影响因子：
4.6
通讯作者：
Schatzschneider, Ulrich
中科院分区：
文献类型：
--
作者：
Bischof, Caroline;Joshi, Tanmaya;Schatzschneider, Ulrich
式[RuCl2(L)(CO)(2)](L=bpy(CH3，CH3)=4，4‘-二甲基-2，2’-联吡啶，bpy(CH3，CHO)=4‘-甲基-2，2’-联吡啶-4-羧醛，bpy(CH3，COOH)=4‘-甲基-2，2’-联吡啶-4-羧酸，cppH=2-(吡啶-2-基)吡啶-4-羧酸，dppzcH=dipyrido[3，2-a:2‘，3’-c]phenazine-11-carboxylic酸)，合成了[RuCl(L)(CO)(2)](+)(L=tpy(COOH)=6-(2，2‘：6’，2‘-三吡啶-4’-氧基)己酸)。此外，还高产率地合成了一种含有2-(吡啶-2-基)嘧啶配体的肽核酸单体，并用该化合物合成了第一个连接在肽核酸单体主链上的Ru(II)二羰基配合物[RuCl2(cpp-L-pna)(CO)(2)]，(cpp-L-pna=tert-butyl-N-[2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-[6-(2-(pyridin-2-yl)pyrimidine-4-carboxamido)hexanoyl]glycinate))。这类金属络合物PNA生物偶联物在生物传感和生物医学方面的应用引起了人们的极大兴趣。用红外光谱、核磁共振光谱、质谱学、元素分析和紫外-可见光谱对所有配合物进行了表征。用肌红蛋白比色法研究了Ru(II)配合物在水/二甲基亚砜(49：1)中的CO释放性，结果表明它们在生理条件下在黑暗中至少稳定60min，大多数甚至长达15h，而在365 nm处观察到光诱导CO释放，主吸收峰的低能肩位于300 nm附近，这表明这些化合物是一类新的光CORM。2，2‘-联吡啶类化合物每摩尔释放1当量CO，而联吡啶、2-(2’-吡啶基)嘧啶和联吡啶并[3，2-a：2‘，3’-c]吩嗪类化合物释放量较小。和在RuCl2(CPP-L-PNA)CO_2中一样，将2-(2‘-吡啶)嘧啶络合物连接到PNA骨架上，与母体络合物相比，没有显著改变光谱性质或CO释放性质。因此，一类新型的基于Ru(II)的PhotoCORM已经被建立，它可以耦合到载体传递载体，如PNA，以促进细胞摄取而不损失母体化合物固有的球茎性质。
A series of ruthenium(II) dicarbonyl complexes of formula [RuCl2(L)(CO)(2)] (L = bpy(CH3,CH3) = 4,4'-dimethyl-2,2'-bipyridine, bpy(CH3,CHO) = 4'-methyl-2,2'-bipyridine-4-carboxyaldehyde, bpy(CH3,COOH) = 4'-methyl-2,2'-bipyridine-4-carboxylic acid, CppH = 2-(pyridin-2-yl)pyrimidine-4-carboxylic acid, dppzcH = dipyrido[3,2-a:2',3'-c]phenazine-11-carboxylic acid), and [RuCl(L)(CO)(2)](+) (L = tpy(COOH) = 6-(2,2':6',2 ''-terpyridine-4'-yloxy)hexanoic acid) has been synthesized. In addition, a high-yield synthesis of a peptide nucleic acid (PNA) monomer containing the 2-(pyridin-2-yl)pyrimidine ligand was also developed, and this compound was used to prepare the first Ru(II) dicarbonyl complex, [RuCl2(Cpp-L-PNA)(CO)(2)],(Cpp-L-PNA = tert-butyl-N-[2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-[6-(2-(pyridin-2-yl)pyrimidine-4-carboxamido)hexanoyl]glycinate) attached to a PNA monomer backbone. Such metal-complex PNA bioconjugates are attracting profound interest for biosensing and biomedical applications. Characterization of all complexes has been undertaken by IR and NMR spectroscopy, mass spectrometry, elemental analysis, and UV-vis spectroscopy. Investigation of the CO-release properties of the Ru(II) complexes in water/dimethyl sulfoxide (49:1) using the myoglobin assay showed that they are stable under physiological conditions in the dark for at least 60 min and most of them even for up to 15 h. In contrast, photoinduced CO release was observed upon illumination at 365 nm, the low-energy shoulder of the main absorption maximum centered around 300 nm, establishing these compounds as a new class of PhotoCORMs. While the two 2,2'-bipyridine complexes release 1 equiv of CO per mole of complex, the terpyridine, 2-(2'-pyridyl)pyrimidine, and dipyrido[3,2-a:2',3'-c]phenazine complexes are less effective CO releasers. Attachment of the 2-(2'-pyridyl)pyrimidine complex to a PNA backbone as in [RuCl2(Cpp-L-PNA)CO2] did not significantly change the spectroscopic or CO-release properties compared to the parent complex. Thus, a novel class of Ru(II)-based PhotoCORMs has been established which can be coupled to carrier delivery vectors such as PNA to facilitate cellular uptake without loss of the inherent CORM properties of the parent compound.