Design and Synthesis Of Ferrocene Probe Molecules for Detection by Electrochemical Methods

Abstract

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.

Amphiphilic block copolymers with aldehyde and ferrocene-functionalized hydrophobic block and their redox-responsive micelles

“…Electrochemical detection of biomolecules is of special interest due to their low cost, miniaturization, rapidity, and sensitivity. [33][34][35][36][37] Moreover, the self-assembly of the block copolymer-biomolecule conjugates may induce redox-responsive micelles, which may change their physical parameters such as shape or size in response to redox reactions. Therefore, as well as the synthesis, the conjugation of a model drug O-benzylhydroxylamine was also demonstrated as an example of how the new block copolymer can be utilized to conjugate bioactive molecules by aldehyde groups and subsequently quantify the degree of the conjugation by ferrocene moieties.…”

Applications of Tailored Ferrocenyl Molecules as Electrochemical Probes of Biochemical Interactions

“…Melting points are uncorrected. 1 H NMR and 13 C NMR spectra were recorded in CDCl 3 at the field indicated unless otherwise indicated. 1-Bromo-14-(tetrahydropyran-2-yloxy)tetradecane was prepared as previously described (18).…”

“…After evaporation in vacuo, the product was purified by flash silica chromatography (hexane/EtOAc, 1:1) to give 2-(14-hydroxytetradecyl)-isoindole-1,3-dione (37 mg, 67%) (17). 1 H NMR (300 MHz; CDCl 3 ) 1.29 (m, 18H), 1.60 (m, 6H), 3.60 (m, 4H), 7.68 (m, 2H, ArH), 7.78 (m, 2H, ArH); 13 To 2-(14-hydroxytetradecyl)-isoindole-1,3-dione (37 mg, 0.10 mmol) in acetone (1 mL) was added Jones reagent (0.085 mL; for 1 mL of Jones reagent-0.23 mL H 2 SO 4 , 270 mg CrO 3 , 0.77 mL H 2 O). The reaction was stirred at rt for 1 h, 2-propanol (5 mL) was added and the mixture diluted with water (5 mL), then the acetone removed in vacuo.…”

“…We have previously demonstrated the design and synthesis of a range of molecules consisting of a functional group that confers some specific biochemical activity, linked to an electrochemical label, to enable the reporting of activity (13). The two groups were linked by a spacer group, which was chosen to influence the solubility and enhance the electrochemical properties of the molecule, and may also improve the biochemical functionality through structural or specific chemical interactions.…”

Detecting the electron density of benzene using ferrocene as an indicator

“…Synthesis and applications of ferrocenyl-substituted benzene have been pursued for several years [9,10]; we found that some phenomena can be elucidated through electrochemical properties of ferrocene [11][12][13]. Therefore, ferrocene could be used as an electrochemically sensitive probe to detect the electron density of the benzene ring [14,15]. Though tricarbonylchromium complex before, the influence of the tricarbonylchromium unit on the electrochemical properties of ferrocene was not studied [8].…”