Protein binding by dinuclear polypyridyl ruthenium(II) complexes and the effect of cucurbit[10]uril encapsulation
Protein binding by dinuclear polypyridyl ruthenium(II) complexes and the effect of cucurbit[10]uril encapsulation
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DOI：
10.1039/c3dt50551k
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Collins, J. Grant
中科院分区：
文献类型：
--
作者：
Li, Fangfei;Feterl, Marshall;Collins, J. Grant
人血清对潜在抗菌剂Delta Delta-[{Ru（phen）（2）}（2）（mu-bb（n））]（4+）{Delta Delta-Rubb（n）;其中phen = 1，10-菲咯啉，bb（n）= 1，n-双[4（4 '-甲基-2，2'-联吡啶）]-烷烃（n = 12和16）针对四种细菌菌株-革兰氏阳性金黄色葡萄球菌和耐甲氧西林S.金黄色葡萄球菌（MRSA），革兰氏阴性大肠杆菌和铜绿假单胞菌-已确定。结果表明，钌（II）配合物在血清中的体外活性显著降低。使用荧光光谱法来确认抗微生物活性的降低是由于钌络合物与血清蛋白人血清白蛋白（HSA）和转铁蛋白的强结合。一系列钌配合物显示出比脱辅基转铁蛋白更强的与HSA的结合，但与全转铁蛋白相当或更少，与所有三种蛋白质的结合亲和力以三核>双核>单核的顺序降低。双核络合物Delta Delta-Rubb（12）从HSA中取代华法林，初步表明钌络合物结合在华法林结合位点（Sudlow位点1）或其附近。通过NMR光谱检查Delta Delta-Rubb（12）和Delta Delta-Rubb（16）与大环主体分子葫芦[10]脲（Q[10]）的结合。在加入Q[10]后，观察到桥连配体中亚甲基质子的大的高场H-1 NMR化学位移变化，再加上ROESY光谱中一系列分子间ROE的观察，表明双核配合物将Q[10]与空腔内的桥连配体和位于门户外的金属中心结合。NMR和荧光光谱表明，Q[10]-封装的钌配合物直接结合HSA，并且具有与相应的游离金属配合物相似的亲和力。
The effect of human serum on the minimum inhibitory/bactericidal concentrations of the potential antimicrobial agents Delta Delta-[{Ru(phen)(2)}(2)(mu-bb(n))](4+) {Delta Delta-Rubb(n); where phen = 1,10-phenanthroline, bb(n) = 1,n-bis[4(4'-methyl-2,2'-bipyridyl)]-alkane for n = 12 and 16} against four strains of bacteria - Gram positive Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli and Pseudomonas aeruginosa - has been determined. The results demonstrated that the ruthenium(II) complexes have significantly decreased in vitro activity in serum. Fluorescence spectroscopy was used to confirm that the decrease in antimicrobial activity was due to the strong binding of the ruthenium complexes with the serum proteins human serum albumin (HSA) and transferrin. A series of ruthenium complexes showed stronger binding to HSA than apo-transferrin but comparable or less than with holotransferrin, with the binding affinity to all three proteins decreasing in the order trinuclear > dinuclear > mononuclear. The dinuclear complex Delta Delta-Rubb(12) displaced warfarin from HSA, tentatively suggesting that the ruthenium complexes bind at or near the warfarin-binding site, Sudlow's site 1. The binding of Delta Delta-Rubb(12) and Delta Delta-Rubb(16) to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. The large upfield H-1 NMR chemical shift changes observed for the methylene protons in the bridging ligands upon addition of Q[10], coupled with the observation of a range of intermolecular ROEs in ROESY spectra, indicated that the dinuclear complexes bound Q[10] with the bridging ligand within the cavity and the metal centres positioned outside the portals. NMR and fluorescence spectroscopy demonstrated that the Q[10]-encapsulated ruthenium complexes directly bound HSA, and with similar affinity to the corresponding free metal complexes.