Institute of Molecular Biology and Genetics, NASU, 150 Zabolotnogo St., 03143 Kyiv, Ukraine.
Metallomics. 2019 Feb 20;11(2):338-348. doi: 10.1039/c8mt00278a.
An ability of inherently achiral macrobicyclic metal complexes iron(ii) clathrochelates to acquire an induced CD (ICD) output in the visible spectral range upon interaction with bovine serum albumin (BSA) was recently discovered. In the present work, the CD-reporting properties of iron(ii) clathrochelates to proteins and the thermodynamic parameters of their binding to albumins are evaluated. It is shown that iron(ii) clathrochelates functionalized by six ribbed carboxyphenylsulfide groups are able to discriminate between serum albumins of relative structure (here human and bovine albumins) by giving distinct ICD spectra. Besides, by the variation of the shape and intensity of CD bands, these cage metal complexes reflect the pH-triggered alterations of the tertiary structure of albumins. The constitutional isomerism (ortho-, meta- or para-isomers) of terminal carboxyphenylsulfide groups of iron(ii) clathrochelates strongly affects both the character of their ICD output upon binding with proteins and the parameters of the formed guest-host associates. Using isothermal titration calorimetry, it was determined that cage metal complexes bearing meta- and ortho-isomers of carboxyphenylsulfide groups possess higher association constants (Ka ∼ 2 × 104 M-1) and clathrochelate-to-BSA binding ratios (n = 2) than the para-isomer (Ka ∼ 5 × 103 M-1, n = 1). The iron(ii) clathrochelates are suggested to be potential molecular three-dimensional scaffolds for the design of CD-sensitive reporters able to recognize specific elements of protein surfaces.
最近发现，手性大环金属配合物铁(II)笼形配合物在与牛血清白蛋白（BSA）相互作用时，具有在可见光谱范围内获得诱导圆二色性（ICD）输出的能力。在本工作中，评估了铁(II)笼形配合物与蛋白质的 CD 报告特性及其与白蛋白结合的热力学参数。结果表明，用六个棱形羧基苯硫醚基团功能化的铁(II)笼形配合物能够通过给出独特的 ICD 光谱来区分相对结构的血清白蛋白（这里是人和牛白蛋白）。此外，通过 CD 带的形状和强度的变化，这些笼状金属配合物反映了白蛋白三级结构的 pH 触发变化。铁(II)笼形配合物末端羧基苯硫醚基团的结构异构（邻位、间位或对位异构体）强烈影响它们与蛋白质结合时的 ICD 输出特征以及形成的主客体配合物的参数。使用等温滴定量热法，确定了具有间位和邻位羧基苯硫醚基团的笼状金属配合物具有较高的结合常数（Ka∼2×104 M-1）和笼状配合物与 BSA 的结合比（n=2）比对位异构体（Ka∼5×103 M-1，n=1）高。这些铁(II)笼形配合物被认为是设计能够识别蛋白质表面特定元素的 CD 敏感报告器的潜在分子三维支架。
