Crystal structure hydroxamic acids

Zn -PDF, 37 pM versus E. coli Fe -PDF), it was successfully used to provide co-crystals bound in the active site of both Co - and Zn -E. coli PDF [58], These structures reveal that the H-phosphonate binds to the metal in a monodentate fashion, adopting a tetrahedral coordination state similar to that of the native resting state of the enzyme. This is in contrast to later co-crystal structures obtained with more potent hydroxamic acid or reverse hydroxamate inhibitors, which bind to the metal in a bidentate fashion vide infra). Presumably these bidentate inhibitors mimic the true transition state of the enzyme, in which the metal centre slips to a penta-coordinate geometry in order to activate the Wformyl carbonyl of the substrate [56, 67]. 

R., Gallinari, P. et al. (2004) Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDACS, complexed with a hydroxamic acid inhibitor. Proceedings of the National Academy of Sciences of the United States of America, 101 (42), 15064-15069. 

In the crystal structures, the inhibitors coordinate to the active site zinc and make a series of hydrogen bonds via their hydroxamic acid moiety. The hydroxamic acids are linked by a flexible spacer with bulky cap groups. The aromatic or aliphatic spacer participates in van der Waals interactions throughout the long charmel, whereas the terminal part of the inhibitor interacts with residues at the rim of HDAC. In general, the binding mode of the cocrystallized inhibitors TSA and SAHA is conserved among the different species and subtypes [35]. 

In this chapter, we have looked at some of the intrinsic features of hydroxylamine, oxime and hydroxamic acid molecules. The insights obtained, particularly concerning the electrostatic potentials on their molecular surfaces, should provide a useful basis for proceeding to their gas phase and crystal structures and properties. 

As in the gas phase, the —C(=0)—NO portions of hydroxamic acids in the crystal phase tend to be near-planar. We have observed this in a series of eight compounds found in the Cambridge Structural Database, and Dietrich and coworkers have reported the same for five out of six others , and in the sixth the deviation is rather minor. 

Hydroxamic acids have been the subject of six papers 43 90 94 Earlier the operation of the a-effect in the reaction of p-nitrophcnyl acetate with benzohydroxamates in aqueous MeCN was discussed.43 The conformational behaviour of series of mono- (105) and di-hydroxamic acids (106) in MeOH, DMSO, and chloroform and in the solid state has been examined witii IR and NMR spectroscopy.90 X-ray crystal structure determinations of (105 X = Me, R = Me) and die monohydrate of glutarodihydroxamic acid (106 n = 3, R = H) together widi ab initio MO calculations for several hydrated and non-hydrated acids have been performed. The cis-Z conformation of the hydroxamate groups is preferentially stabilized by H-bonding witii water. 

Reaction of Os(NO)2(PPh3)2 with trifluoroacetic acid gives Os(NO)(ON= C(0)CF3)(0C0CF3)(PPh3) (Scheme 7), in which both coordinated trifluoroacetate and 0,0-tri-fluoroacetato-hydroxamate ligands are present (see p. 548 for X-ray structure).224-229 There are also two metal-metal-bonded species for which X-ray crystal structures have been determined (p. 548) ... 

The enzyme 2-C-methyl-D-erythritol-4-phosphate synthetase appears to catalyse a Bilik reaction (Figure 6.10) the substrate l-deoxyxylulose-5-phosphate is converted to the title compound via an intermediate aldehyde, whose carbonyl derives from C3 of the substrate. The first step is thus a Bilik reaction and the aldehyde is subsequently reduced by the enzyme using NADPH as reductant, The X-ray crystal structure of the Escherichia coli enzyme in complex with the promising antimalarial Fosmidomycin (a hydroxamic acid) reveals a bound Mn " coordinated to oxygens equivalent to the substrate carbonyl and 03. The stereochemistry and regiochemistry follow the normal Bilik course, although the crystallographers favour an alkyl shift rather than a reverse aldol-aldol mechanism. The intermediate aldehyde has been shown to be a catalytically competent intermediate. 

Thus the structures of tetrakis(N-isopropyl-3,3-dimethylbutano-and -2,2-dimethylpropano)hydroxamatothorium(IV) have been determined by single crystal X-ray diffraction (77). Keeping the pH as low as possible, these compounds precipitate upon the addition of an aqueous solution of thorium tetrachloride to an aqueous solution of the sodium salt of the hydroxamic acid. The analogous uranium(IV) complexes were prepared similarly under an inert atmosphere using deaerated solvents. In addition to their hydrocarbon solubility, the bulky alkyl substituents impart other interesting properties to these complexes. They melt at 127-8 and 116-7°C and, under a vacuum of 10 3 torr, sublime at 95 and 100°C, respectively ... 

Molybdenum(VI) complexes citric acid, 476 IR spectra, 469 guanidine, 283 hydroxamic adds, 506 maleic add, 475 conformation, 467 crystal structure, 476 tartaric add, 479 NMR, 468... 

A number of substances of the ferrichrome family, containing three hydroxamic acid groups coordinated to a central ferric ion, have been isolated, mainly from microbial sources. These compounds contain a cyclic hexapeptide. Crystal structures for ferrichrome A, cyc/o[LSer-LSer-Gly-Tri ((5-N-methylglutaconyl-5-N-hydroxy-Orn)] (Figs. 11 and 12) (Zalkin et al, 1966), the isomorphous alumichrome A (van der Helm et ai, 1980), and more recently ferrichrysin [LSer-LSer-Gly-tri(5-JV-acetyl- -N-hydroxy-Orn)] (Norrestam et al, 1975) and ferrichrome (Loghry and van der Helm, 1978) have been determined and show that the molecules are essentially isostruc-tural. In these molecules, the ferric ion has approximate octahedral coordination to the six oxygen atoms of the three 5-N-acetyl-5-N-hydroxy or the... 

Figure 2. Crystal and solution structure of the ferrichrome siderophores as determined by x-ray diffraction (11) and high resolution NMR (12). The ferrichrome peptides differ in the nature of the acyl substituent at the metal hydroxamate (R) and in the side chains of the three small, neutral, spacer amino acids (R1, R2, and R3). Ferrichrome M = Fe R = CHa R R2 = R3 = H (see also Figure 6 and Refs.

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