Ferrocene-based electrochemical sensors

Ferrocenes as Electrochemical sensors. The field of sensing molecules of interest in environmental pollution or biomedicine is rapidly growing. As far as electrochemical sensors are concerned their use is based on two different ways to gain information ... 

The intercalation of polycyclic aromatic compounds into duplex DNA structures was used to develop nucleic acid-based electrochemical sensors.66 For example, the bis-ferrocene-tethered naphthalene diimide (16) was used as a redox-active intercalator to probe DNA hybridization.67 The thiolated probe was assembled on a Au electrode, and the formation of the duplex DNA with the complementary analyte nucleic acid was probed by the intercalation of (16) into the double-stranded nucleic acid structure and by following the voltammetric response of the ferrocene units (Fig. 12.17a). The method enabled the analysis of the target DNA with a sensitivity that corresponded to ca. 1 x 10-20mol. 

Foulds and Lowe (1986) combined mass production of the base sensor and enzyme immobilization as follows. Using gold or platinum ink, a working and counter electrode were deposited on a ceramic substrate. After thermal treatment of the electrode material a solution containing GOD and a pyrrole derivative of ferrocene was electrochemically polymerized at the electrode. The pyrrole component forms a conducting polymer and the immobilized ferrocene acts as electron acceptor for GOD. The structured immobilization permits this technique to be used for successive enzyme fixation to multiparameter sensors. 

Ferrocenyl-based polymers are established as useful materials for the modification of electrodes, as electrochemical biosensors, and as nonlinear optical systems. The redox behavior of ferrocene can be tuned by substituent effects and novel properties can result for example, permethylation of the cyclopentadienyl rings lowers the oxidation potential, and the chaige transfer salt of decamethylfer-rocene with tetracyanocthylene, [FeCpJ]" (TCNE], is a ferromagnet below = 4.8 K, and electrode surfaces modified with a pentamethylferrocene derivative have been used as sensors for cytochrome c These diverse properties have provided an added impetus to studies on ferrocene dendrimers. 

The accessible ferrocene/ferrocenium redox couple of ferrocene has led to its frequent use in electrochemical anion sensors. The chemical and structural similarity between ferrocene and cobaltocenium has meant that receptors based on these complexes often share the same design. The most relevant difference is that the ferrocene derivatives are neutral (until oxidised to ferrocenium),have no inherent electrostatic interaction with anions and therefore their complexes with anions exhibit lower stability constants. 

An electrochemical OP sensor by the nonenzymatic route was reported based on chemical modification of the surface of a gold electrode with ferrocene derivative (Fc). For this purpose, the gold electrode was modified with dithioFc derivative to form an aminoFc-monolayer-modified electrode (Khan et al, 2007). The principle of operation of the aminoFc-modified electrode for OP sensing is that chloro-or cyano-substitued OP compounds covalently bind to aminoFc moieties, by which the redox potential of the surface-confined Fc can be altered. In fact, ca. 110 and 60 mV shifts in the redox potential were observed, suggesting a possible use of the sensors for detecting OPs from the potential shifts. 

Ferrocene units appended with secondary amides have also been used for anion recognition (113-115) (231). Being neutral, unlike cobaltocenium based systems, these receptors have no inherent electrostatic attraction making the NMR stability constants much lower in magnitude than for the analogous cobaltocenium systems. Electrostatic interactions can, however, be switched on by oxidation of ferrocene to ferrocenium and consequently these molecules show interesting electrochemical effects and have a potential as amperometric anion sensors. Of interest to this development of sensor technology were the novel results of electrochemical competition experiments. These results demonstrated... 

Electrochemical biosensors have been divided into two basic types enzyme-based sensor and electrochemical probe-based sensor. Alkaline phosphatase (ALP) and horse radish peroxidase (HRP) have been often employed for enzyme-based biosensors using p-nitrophenyl phosphate (PNP), a-naphtyl phosphate, 3-3, 5,5 -tetramethylbenzidine (TMB) and 2,2 -azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) as substrates of electrochemically active species, and ferrocene (Fc) and methylene blue as the electrochemical mediators. In general, enzymatic amplification of electrochemical signals enables highly sensitive detection of analytes. On the other hand, a direct detection of analytes by using electrochemical probes allows a more rapid time-response onto the detector surface and needs no enzymatic reaction. Based on the reason, a direct detection of analytes by using electrochemical probes has been... 

Recognition of fluoride in aqueous media is particularly difficult due to the strongly hydrated nature of the anion. Shinkai and co-workers have demonstrated that ferrocene-boronic acid 80 acts as a selective redox sensor for F, which operates in H20. The favorable interaction between boron and F (a hard acid and hard base, respectively) generates a stability constant of 700 for the fluoride-ferrocenium complex (determined electrochemically). Stability constants for both the Br and Gl complexes are <2M ... 

As described above, the introduction of ferrocenes as mediators for enzyme electrodes was subsequently developed as the versatile chemistry of these molecules was exploited both in redox mediation sensors and also through the use of ferrocene derivatives as labels in affinity sensors based upon electrochemical detection. 

Shinkai and coworkers reported that ferroceneboronic acid 17 (Fig. 3) acts as an electrochemical anion sensor.It exhibits excellent selectivity for fluoride ions in the presence of other halides and anions such as SCN , S04, and H2PO4 . A i ox value of 1000 M in MeOH/H20 was found for fluoride, compared to values of less than 2 M for chloride and bromide. The fluoride ion is a hard base and. therefore, interacts considerably with the hard boron atom. Oxidation results in the ferrocene group becoming more electron withdrawing. The electron density of the boron atom decreases therefore, the strength of the fluoride complex increases. A biden-tate Z7/ s(boronate) Lewis acid was also shown to act as a fluoride sensor. 

Studies of synthetic porphyrin-based anion receptors should form the basis for more effective sensors. Metallocene-substituted porphyrins examined by Beer and coworkers have proven successful in the solution-phase binding of ions such as chloride, bromide and nitrate." The cobaltocenium-substituted and ferrocene-substituted porphyrins (Figure 134) bind ions in solution, as shown by H NMR and electrochemical studies. The latter measurements reveal that the porphyrin and ferrocene redox... 

Challenges facing the development of in vitro amperometric biosensors (interference rejection, rapid response, reproducibility, response range) have been met in many cases, and commercially available devices based on disposable test strips that incorporate miniature two-or three-electrode electrochemical cells are available for a variety of analytes (see Sect. 10.3.7). Thin-fihn and thick-film technology [80] have been used to mass-produce reproducible sensing elements, and amperometric detection in oxidase-based devices occurs by peroxide oxidation or the oxidation of freely diffusing mediators such as ferricyanide and ferrocene derivatives. The screen-printing process for disposable sensor preparation has also been reviewed [144]. 

Fig. 9.13 Electrochemical detection of nucleic acid with the bioelectronic sensor based on a sandwich assay. A target nucleic acid is shown to anneal to a capture probe and a ferrocene-labeled signaling probe [58]. The thiol-terminated oligophenylethynyl molecules serve as molecular wires and provide a...

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