Departamento de Física, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ 22451-900, Brazil.
Departamento de Físico-Química, Instituto de Química, Universidade Federal Fluminense, Niterói, RJ 24020-150, Brazil.
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Jan 15;189:133-138. doi: 10.1016/j.saa.2017.08.013. Epub 2017 Aug 5.
The stability of ternary copper(II) complexes of a heterocyclic ligand, L (L being 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen)) and the fluorescent antibacterial agent norfloxacin (NFX) as the second ligand was studied at pH7.4 and different ionic strengths. Fluorescence quenching upon titration of NFX with the binary complexes allowed to obtain stability constants for NFX binding, K, as a function of ionic strength. The K values vary by more than two orders of magnitude when buffer concentration varies from 0.5 to 100mM. It was observed that previously synthesized ternary complexes dissociate in buffer according with the obtained stability constants. This shows that equimolar solutions of NFX and binary complexes are equivalent to solutions of synthesized ternary complexes. The interaction of the ternary copper complexes with anionic SDS (sodium dodecyl sulfate) micelles was studied by fluorescence and electron paramagnetic resonance (EPR). Titration of NFX-loaded SDS micelles with the complexes Cu:L allowed to determine the stability constants inside the micelles. Fluorescence quenching demonstrated that SDS micelles increase the stability constants by factors around 50. EPR spectra gave details of the copper(II) local environment, and demonstrated that the structure of the ternary complexes inside SDS micelles is different from that in buffer. Mononuclear ternary complexes formed inside the micelles, while in buffer most ternary complexes are binuclear. The results show that anionic membrane interfaces increase formation of copper fluoroquinolone complexes, which can influence bioavailability, membrane diffusion, and mechanism of action of the antibiotics.
研究了在 pH7.4 和不同离子强度下，杂环配体 L（L 为 2,2'-联吡啶（bipy）或 1,10-菲咯啉（phen））与荧光抗菌剂诺氟沙星（NFX）的三元铜（II）配合物的稳定性，作为第二个配体。通过用二元配合物滴定 NFX 进行荧光猝灭，可以得到 NFX 结合的稳定常数 K，作为离子强度的函数。当缓冲浓度从 0.5 到 100mM 变化时，K 值变化超过两个数量级。观察到先前合成的三元配合物根据获得的稳定常数在缓冲液中解离。这表明 NFX 和二元配合物的等摩尔溶液相当于合成的三元配合物的溶液。通过荧光和电子顺磁共振（EPR）研究了三元铜配合物与阴离子 SDS（十二烷基硫酸钠）胶束的相互作用。用配合物 Cu：L 滴定负载 NFX 的 SDS 胶束，可以确定胶束内的稳定常数。荧光猝灭表明 SDS 胶束将稳定常数提高了约 50 倍。EPR 谱给出了铜（II）局部环境的细节，并证明了三元配合物在 SDS 胶束内的结构与在缓冲液中的结构不同。单核三元配合物在胶束内形成，而在缓冲液中大多数三元配合物是双核的。结果表明，阴离子膜界面增加了铜氟喹诺酮配合物的形成，这可能会影响抗生素的生物利用度、膜扩散和作用机制。
