Ferrocene carboxylic acids

Ferrocene carboxylic acid [1271-42-7] M 230.1, m 210°(dec), 225-230°(dec). Yellow crystals from pet ether. Also crystd from aqueous ethanol. [Matsue et al. J Am Chem Soc 107 3411 1985.] Acid chloride m 49° crystallises from pentane, Xmax 458nm [J Org Chem 24 280 1959], Methyl ester crystallises from aq MeOH m 70-71°. Anhydride m 143-145° from pet ether [J Org Chem 24 1487 7959]. Amide m 168-170° from CHCl3-Et20 or m 167-169° from C6H6-MeOH. [J Am Chem Soc 77 6295 1955 76 4025 7954.]... 

For an analogous reaction of ferrocene carboxylic acid with polyethylene glycol) see reference [172]. 

In contrast to the mediator-modified electrodes, Degani et al. modified glucose oxidase itself by means of covalently bound ferrocene [4]. After modifying enzymes with ferrocene carboxylic acid, they observed direct electron transfer from the active site of the enzyme to a gold or platinum... 

Cyclic voltammetry has been also used for estimation of the rate constants for oxidation of water-soluble ferrocenes in the presence of HRP (131). There is a perfect match between the data obtained spectrophotometrically and electrochemically (Table IV), which proves that the cyclic voltammetry reveals information on the oxidation of ferrocenes by Compound II. It is interesting to note that an enzyme similar to HRP, viz. cytochrome c peroxidase, which catalyzes the reduction of H202 to water using two equivalents of ferrocytochrome c (133-136), is ca. 100 times more reactive than HRP (131,137). The second-order rate constant equals 1.4 x 106 M-1 s 1 for HOOCFc at pH 6.5 (131). There is no such rate difference in oxidation of [Fe(CN)e]4- by cytochrome c peroxidase and HRP (8). These comparisons should not however create an impression that the enzymatic oxidation of ferrocenes is always fast. The active-R2 subunit of Escherichia coli ribonucleotide reductase, which has dinuclear nonheme iron center in the active site, oxidizes ferrocene carboxylic acid and other water-soluble ferrocenes with a rate constant of... 

Ghosh et al. [14] hypoxanthine, respectively Hypoxanthine Fish Catla- Xanthine oxidase, Conducting polypyrrole Ferrocene carboxylic acid... 

Sodium phosphate monobasic [S 9638], sodium phosphate dibasic [S 0876], sodium chloride [S 7653], acetylcholinesterase from Elect-rophorus electricus (Type V-S) [C 2888], potassium chloride [P 3911], 1,2-diaminobenzenedihydrochloride [P 1526], paraoxon (o,o-diethyl o-4-nitrophenyl phosphate) [D 9286], ferrocene carboxylic acid [106887], aniline [A 9880] and acetylthiocholine chloride [A 5751] were purchased from the Sigma Chemical Company (Dorset, UK). Screen-printed transducers were purchased from Gwent Electronic Materials Ltd. (Gwent, Wales, UK). These electrode assemblies comprised a working electrode based on carbon ink doped with cobalt phthalocya-nine, an on board reference electrode (Ag/AgCl) and counter electrode (platinum) (see Fig. 24.1). 

It is possible to use cyclic voltammetry in the presence of ferrocene carboxylic acid to confirm the presence of micro-electrodes due to the typical sigmoidal-shaped profile produced [2] (Fig. 24.3). Twenty different sensors comprising micro-electrode arrays formed by this technique were analysed for reproducibility. This analysis can be performed by holding the sensors at a potential of +100 mV for 60s and recording the... 

Fig. 24.3. Cyclic voltammogram of ferrocene carboxylic acid at a bare carbon electrode (—), a poly(o-phenylenediamine)-coated working electrode (...) and at sonicated poly(o-phenylenediamine)-coated carbon working electrode (---).

Ferrocenylaethanol or ferrocene carboxylic acid and NADH dehydrogenase... 

Fig. 2 General scheme for the coupling of ferrocene carboxylic acid to amino acids and peptides...

A relatively novel class of derivatives is obtained by the covalent incorporation of organometallic moieties into cellulose. For example, cellulose ferro-cenyl derivatives have been prepared by esterification of cellulose with an intermediate derived from ferrocene carboxylic acid and triphenyl phosphite in the presence of pyridine [84]. An enzymatically cleavable cellulose ester has been developed [85], and prodrugs have been coupled to the hydroxyl or carboxyl functions of C-terminal aromatic amino acids of cellulose peptide derivatives for controlled release applications [86]. 

A C-substituted product was formed on treating phenothiazine with ferrocene carboxylic acid chloride even in the absence of AICI3... 

Now let me come back to primary substitutions at the ferrocene nucleus. Together with Vil chevskaya, we phosphorylated ferrocene and its derivatives to triferrocenylphosphine oxides [263, 264). An unusual reaction, discovered in collaboration with Perevalova and Yur eva, was the direct cyanation of ferrocene with hydrocyanic acid in the presence of ferric chloride [265,272). Initially, cyanide attacks the iron atom of the ferricinium cation, then the cyanide group transfers to the ring while the iron is simultaneously reduced. The reaction was termed by us as the ricochet (from the metal to the nucleus) substitution it may be applied to many substituted ferrocenes and to the ruthenocenium cation [273), and it is now the simplest route to ferrocene carboxylic acids through their nitriles. Further, ferrocene was studied in acid-medium reactions with oxo compounds. With aldehydes [274), the reaction was complicated by the transformation of ferro-cenylalkyl carbinol formed Initially via the carbonium ion, followed by transformation to a radical which, in its turn, was coupled to 1,2-bis-(ferrocenylalkyl)ethane (27.5). The reaction with acetone led to 2,2-di-ferrocenylpropane (276). 

Infrared studies have shown dependence of the carbonyl absorption value of a series of heteroannularly disubstituted ferrocene carboxylic acids and their methyl ethers on changes in the substituent in the other ring. Nes-meyariov and co-workers (31) have detected a shift to lower frequencies of yc=o values with increasing electron donation. For example, the carbonyl absorption was observed to be 1704 cm for I -sulfuralfluoroferrocene-carboxylic acid, but when the substituent was a methyl or ferf-butyl the... 

This latter aspect of the proposed mechanism provided the grounds upon which its validity could be tested by examining the relative rates at which an epimeric pair of ferrocene carboxylic acids, constrained by their stereochemistry to either exocyclic or endocyclic electrophilic attack, would undergo homoannular cyclization... 

The photoisomerizable enzyme monolayer electrode also revealed photoswitchable bioelectrocatalytic activity (Figure 7.10). In the presence of ferrocene carboxylic acid (5) as a diffusional electron transfer mediator, the nitrospiropyran-tethered GOx (4a) revealed a high bioelectrocatalytic activity, reflected by a high electrocatalytic anodic current. The protonated nitromerocyanine-GOx (4b) exhibited a two-fold lower activity, as reflected by the decreased bioelectrocatalytic current. By the reversible photoisomerization of the enzyme electrode between the 4a- and 4b-states, the current responses are cycled between high and low values (Figure 7.10, inset). 

Figure 3-30. Organization of a photoswitchable glucose oxidase electrode for the bioelectrocatalyzed oxidation of glucose (A) The synthesis of the photoisomerizable nitrospiropyran-FAD cofactor. (B) The reconstitution of apo-glucose oxidase, apo-GOx, with the photoisomerizable FAD-cofactor (20a). (C) The assembly of the reconstituted photoisomerizable GOx on an electrode surface and the photoswitching of the bioelectrocatalytic function of the enzyme electrode in the presence of ferrocene carboxylic acid (21) as mediator.

Figure 3-31. Cyclic voltammograms corresponding to the photoswitchable bioelectrocatalyzed oxidation of glucose, 50 mM, in the presence of ferrocene carboxylic acid, (21), 5x 0 M, as diffusional electron mediator (a) and (c) In the presence of the SP-GOx monolayer electrode generated by the irradiation of the electrode A, > 475 run. (b) and (d) In the presence of the MRlT-GOx monolayer electrode generated by the illumination of the electrode with filtered light 320 nm < A < 380 nm. Inset cychc photoswitchable ON and OFF amperometric responses of the functionalized enzyme monolayer upon the light-induced isomerization of the interface between the SP GOx and MRI I GOx, respectively. Reproduced with permission from ref. 88. Copyright 1997 American Chemical Society.

The bioelectrocatalyzed oxidation of glucose in this system originates from the primary oxidation of the ferrocene carboxylic acid, (21), to the respective ferrocenylium cation that mediates the oxidation of the enzyme s redox center and its activation towards the oxidation of glucose. Photoisomerization of the enzyme monolayer to the MRH-GO state switched-off the bioelectrocatalytic functions of the protein monolayer, and only the electrical response of the diffusional electron mediator was observed, Fig. 3-31, curves (b) and (d). By the cyclic photoisomerization of the enzyme-monolayer electrode between the SP-GOx and MRlT-GOx states, the reversible photoswitching of the enzyme activity between ON and OFF states was demonstrated, Fig. 3-31 (inset). 

The mechanical stability of the liquid/liquid boundary, accuracy, and reproducibility of the measurements were demonstrated in earlier SECM/ I TIES experiments. The SECM approach curve (iT vs. d) in Figure 2 was obtained with a 5-/xm-radius tip immersed in the aqueous solution (top phase) containing 5 mM FcCOCT (ferrocene carboxylic acid) and 0.1 M KC1, and nitrobenzene (NB) (bottom phase) containing no electroactive species (15). In this configuration, the NB layer acts as an electrical insulator,... 

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