449. Hydroxamic acids. Part II. The synthesis and structure of cyclic hydroxamic acids from pyridine and quinoline

Cunningham, Kay; Newbold, G. T.; Spring, F. S.; Stark, J. C.

doi:10.1039/jr9490002091

Cited by 48 publications

(14 citation statements)

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“…Indeed, 1,2-HOPO based ligand systems have previously been referred to as 'cyclic hydroxamic acids' rather than as the tautomeric conjugated aromatic ring system, based on similarity of UV-visible spectra to simpler analogs which cannot undergo this keto-enol tautomerisation. 39 An examination of the crystal packing for H 2 1 reveals a secondary arrangement of two distinct ligands to form dimers, which are held together by the π stacking of adjacent 1,2-HOPO ring systems at a separation of ca. 3.4 Å and a complex network of intra-and intermolecular hydrogen bonds.…”

Section: Synthesis and Structurementioning

confidence: 99%

Highly Luminescent Lanthanide Complexes of 1-Hydroxy-2-pyridinones

et al. 2008

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The synthesis, X-ray structure, stability, and photophysical properties of several trivalent lanthanide complexes formed from two differing bis-bidentate ligands incorporating either alkyl or alkyl ether linkages and featuring the 1-hydroxy-2-pyridinone (1,2-HOPO) chelate group in complex with Eu(III), Sm(III) and Gd(III) are reported. The Eu(III) complexes are among some of the best examples, pairing highly efficient emission ( Eu tot Φ ~ 21.5 %,) with high stability (pEu ~ 18.6) in aqueous solution, and are excellent candidates for use in biological assays. A comparison of the observed behavior of the complexes with differing backbone linkages shows remarkable similarities, both in stability and photophysical properties. Low temperature photophysical measurements for a Gd(III) complex were also used to gain insight into the electronic structure, and were found to agree with corresponding TD-DFT calculations for a model complex. A comparison of the high resolution Eu(III) emission spectra in solution and from single crystals also revealed a more symmetric coordination geometry about the metal ion in solution due to dynamic rotation of the observed solid state structure.

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Section: Synthesis and Structurementioning

confidence: 99%

Highly Luminescent Lanthanide Complexes of 1-Hydroxy-2-pyridinones

et al. 2008

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“…The hydroxyurea analogues of Table 1 were obtained from commercial sources (acetohydroxamic acid, formamidoxime and guanazole from EGA Chemie, N-hydroxyguanidine sulfate from Eastman, and N-methylhydroxylamine hydrochloride from Fluka) or synthesized as follows : hydroxyurea [16], formohydroxamic acid [17], N-hydroxyurethane [I 81, benzohydroxamic acid and salicylohydroxamic acid [I 91, glycine hydroxamic acid [20], N-hydroxyoxamide [21] (m.p. 147 OC; anal.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Active Site of Ribonucleotide Reductase of Escherichia coli, Bacteriophage T4 and Mammalian Cells by Inhibition Studies with Hydroxyurea Analogues

Larsen¹,

Sjöoberg²,

Thelander³

1982

European Journal of Biochemistry

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Hydroxyurea specifically inhibits the enzyme ribonucleotide reductase by inactivating the essential tyrosine free radical in one of the two non-identical subunits constituting the enzyme. Studies on the reactivity of hydroxyurea analogues towards the free radical salt, potassium nitrosodisulphonate, and the radical-containing B2 subunit of Escherichia coli ribonucleotide reductase showed that, to obtain maximal enzyme inhibition, the most important parameter of an analogue was the ability to undergo a one-electron oxidation. Also, a common geometrical feature for the analogues with high inhibitory potency was the planarity of the molecules.Results of inhibition studies with analogues containing bulky substituents but having about the same ability to reduce the free radical salt suggested that the tyrosine free radical of protein B2 is located in a pocket about 0.4 nm wide and more than 0.6 nm deep.The ribonucleotide reductases of E. coli, TCinfected E. coli and mammalian cells all contain the same tyrosine free radical structure. Still the mammalian reductase showed a 75-fold higher sensitivity to inhibition by 3,4-dihydroxybenzohydroxamic acid than the E. coli reductase. In contrast, the sensitivity to hydroxyurea was the same for both enzymes. The dihydroxybenzohydroxamic acid and hydroxyurea both reacted immediately (tip < 5 s) with the free radical salt. Therefore the difference in sensitivity between the mammalian and bacterial reductase most probably reflects different topologies of their active sites with the site of the mammalian enzyme being more exposed.The T4-induced reductase showed a 10-fold increased sensitivity towards both hydroxyurea and the polyhydroxybenzohydroxamic acids compared to the E. coli enzyme, indicating a greater ability of the T4 tyrosine free radical to undergo a one-electron reduction. A closer understanding of the different topologies of the active sites of different ribonucleotide reductases could be of great value in the design of target-directed drugs.Ribonucleotide reductase is an allosteric enzyme present in all cells that make D N A and it catalyzes the formation of deoxyribonucleotides from ribonucleotides [I]. In Escherichia coli the enzyme consists of a 1 : 1 complex between two non-identical subunits, proteins B1 and B2, of molecular weights 160000 and 78000 respectively. Protein B1 contains binding sites for the ribonucleoside diphosphate substrates and for the nucleoside triphosphate effectors and it also has oxidation/reduction-active disulfides, which donate the electrons necessary for the reduction. Protein B2 contains nonheme iron and a tyrosine free radical necessary for enzyme activity [2,3]. The active site of the E. coli reductase is known to contain structural elements from both proteins B1 and B2. This was shown in studies using the substrate analogues 2'-chloro-2'-deoxycytidine diphosphate and 2'-azido-2'-deoxycytidine diphosphate, both of which function as highly specific suicidal inhibitors [4].A similar general construction of ribonucfeotide reductase h...

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“…The starting compounds, viz., aminoacetic acid N hydroxyamide (GlyHA) and DL 2 aminopropionic acid N hydroxyamide (DL AlaHA), were synthesized according to known procedures. 26 Synthesis of hydroxamic acids 3 and 4 (general method). The hydroxamic acid GlyHA or DL AlaHA (30 mmol) was added to a solution of triacetonamine (2,2,6,6 tetramethylpiperidin 4 one) (38 mmol) in anhydrous EtOH (70 mL).…”

Section: Methodsmentioning

confidence: 99%

Cyclic hydroxamic acids derived from α-amino acids 1. Regioselective synthesis, structure, NO-donor and antimetastatic activities of spirobicyclic hydroxamic acids derived from glycine and DL-alanine

et al. 2010

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The reactions of glycine hydroxamic and DL alanine hydroxamic acids with triacetonamine are chemoselective and afford 1 hydroxy 7,7,9,9 tetramethyl 1,4,8 triazaspiro[4.5]decan 2 one (3) and (±) 1 hydroxy 3,7,7,9,9 pentamethyl 1,4,8 triazaspiro[4.5]decan 2 one (4), re spectively. The X ray diffraction study showed that compound 3 crystallizes as a solvate with MeCN (1 : 1). As shown by ESR measurements, spiro hydroxamic acids 3 and 4 are NO donors in in vitro biological systems. The NO donor activity of compounds 3 and 4 was found to be substantially higher in the presence of DMSO. Homologue 4 is a stronger NO donor than 3. Compound 4 also exhibits high antimetastatic activity (81%) on the B16 melanoma model.

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449. Hydroxamic acids. Part II. The synthesis and structure of cyclic hydroxamic acids from pyridine and quinoline

Cited by 48 publications

References 0 publications

Highly Luminescent Lanthanide Complexes of 1-Hydroxy-2-pyridinones

Highly Luminescent Lanthanide Complexes of 1-Hydroxy-2-pyridinones

Characterization of the Active Site of Ribonucleotide Reductase of Escherichia coli, Bacteriophage T4 and Mammalian Cells by Inhibition Studies with Hydroxyurea Analogues

Cyclic hydroxamic acids derived from α-amino acids 1. Regioselective synthesis, structure, NO-donor and antimetastatic activities of spirobicyclic hydroxamic acids derived from glycine and DL-alanine

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