Catechol, III

Fig. 9.72Structures of MCPA(4-chloro-2-methylphenoxyacetic acid (I)), its metabolites 4-chloro-o-cresol (II), 5-chloro-3-methyl catechol (III), 4-chloro-2-methyl muconic acid (IV), reagent pentafluorobenzyl bromide (V), and the derivatives VI-VIII from l-lll Source Reproduced with permission from the American Chemical Society [155]... 

Figure 2. Intermediates in the aerobic bacterial metabolism of benzene. (I) c/s-benzene dihydrodiol, (II) catechol, (III) 2-hydroxymuconic semialdehyde, (IV) cis, cis- muconic acid.

Enterobactin (ent), the cycHc triester of 2,3-dihydroxy-A/-benzoyl-l-serine, uses three catecholate dianions to coordinate iron. The iron(III)-enterobactin complex [62280-34-6] has extraordinary thermodynamic stabiUty. For Fe " +ent , the estimated formal stabiUty constant is 10 and the reduction potential is approximately —750 mV at pH 7 (23). Several catecholate-containing synthetic analogues of enterobactin have been investigated and found to have lesser, but still impressively large, formation constants. 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

Fig. 16.6 The 1,3-diphenyl propane skeleton of flavonoids and the numbering system for flavonoids. Three structural features optimise the radical scavenging properties of a flavonoid (i) an orto-dihydroxy structure of the B-ring (catechol) (ii) 2,3 double bond in conjugation with a 4-oxo group (iii) 3- and 5-hydroxy groups (Bors and Saran, 1987).

Figure 1 Electrochemical detection of catechol, acetaminophen, and 4-methyl catechol, demonstrating the selectivity of differential pulse detection vs. constant potential detection. (A) Catechol, (B) acetaminophen, and (C) 4-methylcatechol were separated by reversed phase liquid chromatography and detected by amperometry on a carbon fiber electrode. In the upper trace, a constant potential of +0.6 V was used. In the lower trace, a base potential of +425 mV and a pulse amplitude of +50 mV were used. An Ag/AgCl reference electrode was employed. Note that acetaminophen responds much more strongly than catechol or 4-methylcatechol under the differential pulse conditions, allowing highly selective detection. (Reproduced with permission from St. Claire, III, R. L. and Jorgenson, J. W., J. Chromatogr. Sci. 23, 186, 1985. Preston Publications, A Division of Preston Industries, Inc.)...

The effect of the amino acid spacer on iron(III) affinity was investigated using a series of enterobactin-mimic TRENCAM-based siderophores (82). While TRENCAM (17) has structural similarities to enterobactin, in that it is a tripodal tris-catechol iron-binding molecule, the addition of amino acid spacers to the TRENCAM frame (Fig. 10) increases the stability of the iron(III) complexes of the analogs in the order ofbAla (19)complex stability is attributed to the intramolecular interactions of the additional amino acid side chains that stabilize the iron-siderophore complex slightly. 

The terephthalamide moiety (Fig. 13) is similar in structure to catechol, but has a higher affinity for iron(III) at physiological conditions and consequently has been used in the synthesis of siderophore mimics. The higher pFe values are due to the... 

Fe(III) displacement of Al(III), Ga(III), or In(III) from their respective complexes with these tripodal ligands, have been determined. The M(III)-by-Fe(III) displacement processes are controlled by the ease of dissociation of Al(III), Ga(III), or In(III) Fe(III) may in turn be displaced from these complexes by edta (removal from the two non-equivalent sites gives rise to an appropriate kinetic pattern) (343). Kinetics and mechanism of a catalytic chloride ion effect on the dissociation of model siderophore-hydroxamate iron(III) complexes chloride and, to lesser extents, bromide and nitrate, catalyze ligand dissociation through transient coordination of the added anion to the iron (344). A catechol derivative of desferrioxamine has been found to remove iron from transferrin about 100 times faster than desferrioxamine itself it forms a significantly more stable product with Fe3+ (345). 

Catalytic Activity of Co(II) and Co(III) Complexes in Autoxidation of DI-ferf-P,UTYI,CATECHOL (52) ... 

The rate of the Ir(III) catalyzed reaction was found to be first-order in [Ir] and [H2DTBC], but independent of 02 concentration in chloroform (56). The mechanism proposed for the reaction (Scheme 4) postulates that the protonation of the hydroperoxo a-oxygen by the hydroxy group of the bonded catechol in Int 1 leads to the formation of H202. The o-qui-none ligand of Int 2 is replaced by the partially coordinated catechol in the next step. In order to comply with the experimental rate law, the rate-determining step needs to be the reaction of the oxygen adduct (B) with catechol. 

The cleavage of catechols with the incorporation of oxygen is clearly favored in the presence of some of the iron(III) complexes as catalysts. Que and co-workers proposed a substrate activation mechanism for these reactions, wherein the delocalization of the unpaired spin density... 

The mechanism shown in Scheme 5 postulates the formation of a Fe(II)-semi-quinone intermediate. The attack of 02 on the substrate generates a peroxy radical which is reduced by the Fe(II) center to produce the Fe(III) peroxide complex. The semi-quinone character of the [FeL(DTBC)] complexes is clearly determined by the covalency of the iron(III)-catechol bond which is enhanced by increasing the Lewis acidity of the metal center. Thus, ultimately the non-participating ligand controls the extent of the Fe(II) - semi-quinone formation and the rate of the reaction provided that the rate-determining step is the reaction of 02 with the semiquinone intermediate. In the final stage, the substrate is oxygenated simultaneously with the release of the FemL complex. An alternative model, in which 02 attacks the Fe(II) center instead of the semi-quinone, cannot be excluded either. 

According to a recent study with iron(III) complexes of tripodal ligands, systematic variation of one ligand arm strongly affects the steric shielding of the iron(III) center and the bonding of catechol substrates (61). It was shown that the dioxygenation reactions of catechols... 

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