Pyridinones

A number of other heterocycHc diazo components such as thiazole, iadazole, thiophenes, and thiadiazole types (see Fig. 1), as well as heterocycHc couplers, ie, 6-hydroxy-2-pyridinone [626-06-2] barbituric acid [67-52-7] and tetrahydroquiaoline [25448-04-8] h.2L e been cited ia the Hterature (90,91). Reviews on disperse dyes have been pubUshed (92,93). 

One donor group that is only rarely observed in nature is hydroxypyridinone (Fig. 17). As mentioned previously, the sole example found in nature is cepabactin, a bidentate l-hydroxy-2-pyridinone siderophore (8 in Fig. 2) (46). The bidentate 1,... 

Fig. 18. 3-Hydroxy,2-pyridinone siderophore mimics based on an azamacrocycle central ring structure.

Trenhopo is a hexadentate tripodal ligand N(CH2CH2NHCOX)3 with X being 6-methyl-3-hydroxy-2-pyridinonate. 

Fig. 1. General formulae for hydroxypyranones and hydroxypyridinones 1, 3-hydroxy-2-pyranone 2, 3-hydroxy-4-pyranones 3, 3-hydroxy-2-pyridi-nones 4, 3-hydroxy-4-pyridinones 5, l-hydroxy-2-pyridinone. In each case the ring atoms are numbered anticlockwise, starting with the ring-oxygen or ring-nitrogen atom.

Alkyl-3-hydroxy-4-pyridinones can be converted into analogues containing, e.g., anilino-, phenylthio-, or 2-hydroxyethylthio-substitu-ents by silver(I) oxidation (Ag20 in ethanol) followed by Michael addition (71). In aminomethylation of 3-hydroxy-4- and -2-pyridinones under Mannich conditions the position of substitution can be tailored, by reaction conditions to position C4 or C6, or by converting the OH into OMe, which directs substitution to C5 (72). 

Structures of l-hydroxy-2-pyridinonate and 3-hydroxy-2-p5rridino-nate complexes may be compared with those of the more extensively studied 3-hydroxy-4-pyridinonates through the published crystal structures of their tris-ligand iron(III) complexes. The iron(III) tris-ligand complex of l-n-butyl-3-hydroxy-2-pyridinone has fac geometry it crystallizes as a trihydrate 135). 

BMOV, was reported in 1972 159) and in 1987 160). Its electrochemical preparation was described in 1978 92a), and EPR monitoring of its redox behavior, in chloroform, in 1987 160). However this now-important compound seems not to have been properly characterized until 1992 161). Since then complexes of several 3-hydroxy-4-pyridinones 162—164), and of l-hydroxy-2-pyridinone 165), have been synthesized and characterized, especially by EPR 164). VO(malt)2 exists as a cis trans equilibrium mixture in aqueous solution, and generally crystallizes as a mixture of the two isomers. However the crystal structure of the trans structure was eventually solved, confirming the expected square-pyramidal stereochemistry 166). The relative stabilities of the cis and trans forms of V 0L2 complexes depend on the nature of the bidentate ligand L , with the cis configuration favored by VO(malt)2 and VO(koj)2 167), but the trans by 3-hydroxy-4-pyridinonate ligands 164). 

Fig. 6. (a) (b) Replacement of a peptide-bound l-hydroxy-2-pyridinone unit by a catechol unit on a tris(ammoethyl)aniine (tren) cap. (c) A tren-capped hexadentate ligand with two 3-hydroxy-2-pyridinone (3,2-hopo) and one terephthalamide (tarn) chelating units. 

Log P4 for the 3-hydroxy-4-p5rridinonate complex (41.8) is, again as normal, greater than that for its 3-hydroxy-2-pyridinonate (38.3) and l-hydroxy-2-pyridinonate (36.0) analogues (148). 

An opportunity to use the thermodynamic cycle shown in Fig. 7 was provided by the requirement to estimate stability constants for cerium(IV) complexes of a series of hydroxypyridinones. As stability constants for their cerium(III) analogues had been measured and F °(Ce /Ce ) values established, stability constants for one bidentate and two tetradentate 3-hydroxy-2-pyridinones could be obtained. Log P4 for the former was calculated to be 40.9, log P2 for the complexes of the tetradentate ligands 40.6 and 41.9. These very high values, expected for a 4+ cation, are paralleled by high pCe values between 37 and 38 for the tetradentate ligands (147). 

Fig. 12. (a) An octadentate tetra(3-hydroxy-2-pyridinone) chelator on an ethane-1,2-diamine template and (b) a hybrid desferrioxamine-3-hydroxy-2-pyridinone chelator. 

Trispyrazolylborates are models for tris-histidine active sites in zinc enzymes, e.g., the matrix metalloproteinases involved in breakdown of extracellular matrices. Inhibition of these metalloproteinases may prove valuable in the treatment of, inter alios, cancer and arthritis, so efforts are being made to find appropriate ligands to block the zinc active site. The search has recently moved on from hydroxamates to hydroxypyridinones - l-hydroxy-2-pyridinone is a cyclic analogue of hydroxamic acid. As reported in Section II.B.2 earlier, hydroxypyridinones form stable five-coordinate complexes on reaction with hydrotris(3,5-phenylmethylpyrazolyl)borate zinc hydroxide. Modeling studies suggest that hydroxypyridinonate ligands should be able to access the active site in the enzyme with ease (110). 

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