Tranchant Isabelle, Hervé Anne-Cécile, Carlisle Stephen, Lowe Phillip, Slevin Christopher J, Forssten Camilla, Dilleen John, Bhalla Rajiv, Williams David E, Tabor Alethea B, Hailes Helen C
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
Bioconjug Chem. 2006 Sep-Oct;17(5):1256-64. doi: 10.1021/bc060038m.
A series of ferrocenyl conjugates to fatty acids have been designed and synthesized to establish the key properties required for use in biomolecular binding studies. Amperometric detection of the ferrocene conjugates was sought in the region of 0.3 V (vs Ag/AgCl) for use in protein/blood solutions. Different linkers and solubilizing moieties were incorporated to produce a conjugate with optimal electrochemical properties. In electrochemical studies, the linker directly attached to the ferrocene was found to affect significantly the E(1/2) value and the stability of the ferrocenium cation. Ester-linked ferrocene conjugates had E(1/2) ranging from +400 to +410 mV, while amide-linked compounds ranged from +350 to +370 mV and the amines +260 to +270 mV. Folding of long-chain substituents around the ferrocene, also significantly affected by the choice of linker, was inferred as a secondary effect that increased E(1/2). The stability of the ferrocenium cation decreased systematically as E(1/2) increased. Disubstituted ferrocene ester and amide conjugates, with oxidation potentials of +640 and +570 mV, respectively, showed only a barely discernible reduction wave in cyclic voltammetry at 50 mV/s. Electrochemical measurements identified two lead compounds with the common structural characteristics of an amide and carbamate linker (compounds 17 and 21) with a C(11) fatty acid chain attached. It is envisaged that such molecules can be used to mimic and study the biomolecular binding interaction between fatty acids and molecules such as human serum albumin.
设计并合成了一系列与脂肪酸相连的二茂铁共轭物，以确定用于生物分子结合研究所需的关键性质。在0.3 V（相对于Ag/AgCl）区域寻求对二茂铁共轭物进行安培检测，以便用于蛋白质/血液溶液中。引入了不同的连接基团和增溶部分，以制备具有最佳电化学性质的共轭物。在电化学研究中，发现直接连接到二茂铁的连接基团会显著影响E(1/2)值和二茂铁阳离子的稳定性。酯连接的二茂铁共轭物的E(1/2)范围为 +400至 +410 mV，而酰胺连接的化合物范围为 +350至 +370 mV，胺类为 +260至 +270 mV。二茂铁周围长链取代基的折叠也受到连接基团选择的显著影响，被推断为增加E(1/2)的次要效应。随着E(1/2)增加，二茂铁阳离子的稳定性系统性降低。二取代的二茂铁酯和酰胺共轭物，氧化电位分别为 +640和 +570 mV，在50 mV/s的循环伏安法中仅显示出几乎难以察觉的还原波。电化学测量确定了两种具有酰胺和氨基甲酸酯连接基团（化合物17和21）共同结构特征且连接有C(11)脂肪酸链的先导化合物。预计此类分子可用于模拟和研究脂肪酸与诸如人血清白蛋白等分子之间的生物分子结合相互作用。
