Sun Biyun, Southam Hannah M, Butler Jonathan A, Poole Robert K, Burgun Alexandre, Tarzia Andrew, Keene F Richard, Collins J Grant
School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT 2600, Australia.
Dalton Trans. 2018 Feb 13;47(7):2422-2434. doi: 10.1039/c7dt04595f.
A series of mononuclear ruthenium(ii) complexes containing the tetradentate ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. In the synthesis of the [Ru(phen')(bb)] complexes (where phen' = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyl- and 3,4,7,8-tetramethyl- derivatives), both the symmetric cis-α and non-symmetric cis-β isomers were formed. However, upon standing for a number of days (or more quickly under harsh conditions) the cis-β isomer converted to the more thermodynamically stable cis-α isomer. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(ii) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the [Ru(5-NOphen)(bb)] complex had little or no activity against any of the bacterial strains. By contrast, for the other cis-α-[Ru(phen')(bb)] complexes, the antimicrobial activity increased with the degree of methylation. In particular, the cis-α-[Ru(Mephen)(bb)] complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis-α-[Ru(Mephen)(bb)] complex varied considerably across the bacteria and even within S. aureus and E. coli strains. In order to gain an understanding of the relative antimicrobial activities, the DNA-binding affinity, cellular accumulation and water-octanol partition coefficients (log P) of the ruthenium complexes were determined. Interestingly, all the [Ru(phen')(bb)] complexes exhibited stronger DNA binding affinity (K ≈ 1 × 10 M) than the well-known DNA-intercalating complex [Ru(phen)(dppz)] (where dppz = dipyrido[3,2-a:2',3'-c]phenazine).
已合成了一系列含有四齿配体双[4(4'-甲基-2,2'-联吡啶)]-1,7-庚烷的单核钌(ii)配合物，并对其生物学性质进行了研究。在[Ru(phen')(bb)]配合物（其中phen' = 1,10-菲咯啉及其5-硝基-、4,7-二甲基-和3,4,7,8-四甲基-衍生物）的合成中，形成了对称的顺-α和非对称的顺-β异构体。然而，放置数天（或在苛刻条件下更快地）后，顺-β异构体转化为热力学上更稳定的顺-α异构体。测定了钌(ii)配合物对六种细菌菌株的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）：革兰氏阳性金黄色葡萄球菌（S. aureus）和耐甲氧西林金黄色葡萄球菌（MRSA）；以及革兰氏阴性大肠杆菌（E. coli）菌株MG1655、APEC、UPEC和铜绿假单胞菌（P. aeruginosa）。结果表明，[Ru(5-NOphen)(bb)]配合物对任何细菌菌株几乎没有或没有活性。相比之下，对于其他顺-α-[Ru(phen')(bb)]配合物，抗菌活性随甲基化程度增加。特别是，顺-α-[Ru(Mephen)(bb)]配合物对所有细菌均表现出优异且一致的MIC活性。相比之下，顺-α-[Ru(Mephen)(bb)]配合物的MBC值在不同细菌之间甚至在金黄色葡萄球菌和大肠杆菌菌株内差异很大。为了了解相对抗菌活性，测定了钌配合物的DNA结合亲和力、细胞积累和水-辛醇分配系数（log P）。有趣的是，所有[Ru(phen')(bb)]配合物均表现出比著名的DNA插入配合物[Ru(phen)(dppz)]（其中dppz = 二吡啶并[3,2-a:2',3'-c]吩嗪）更强的DNA结合亲和力（K ≈ 1 × 10 M）。
