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89Zr−immunoPET is a hot topic as 89Zr cumulates the advantages of 64Cu and 124I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1‐hydroxy‐2‐piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3‐C of the (PIPO)H component and at the Zr4+ cation. The 44 lowest energy structures out of more than 1000 configurations/conformations returned by calculations based on density functional theory were examined. Comparison of the ROESY data and the calculated interatomic H⋅⋅⋅H distances allowed us to select the most probable configuration and conformations of the major complex. [ABSTRACT FROM AUTHOR]

Many siderophores incorporate as bidentate chelating subunits linear and more seldomly cyclic hydroxamate groups. In this work, a comparative study of the uranyl binding properties in aqueous solution of two monohydroxamic acids, the prototypical linear N-methylacetohydroxamic acid (NMAH) and the cyclic analog 1-hydroxypiperidine-2-one (PIPOH), has been carried out. The complex [UO2(PIPO)2(H2O)] crystallized from slightly acidic water solutions (pH ＜ 5), and its molecular structure was determined by X-ray diffraction. The uranyl speciation in the presence of both ligands has been thoroughly investigated in a 0.1 M KNO3 medium at 298.2 K by the combined use of four complementary techniques, i.e., potentiometry, spectrophotometry, Raman spectroscopy, and affinity capillary electrophoresis. Preorganization of the hydroxamate ligand for chelation by incorporation into a cyclic structure, as in PIPO−, results in an increase of nearly one order of magnitude in the formation constants of the uranyl complexes of 1 : 1 and 1 : 2 metal/ligand stoichiometries. [ABSTRACT FROM AUTHOR]

Many siderophores incorporate as bidentate chelating subunits linear and more seldomly cyclic hydroxamate groups. In this work, a comparative study of the uranyl binding properties in aqueous solution of two monohydroxamic acids, the prototypical linear N-methylacetohydroxamic acid (NMAH) and the cyclic analog 1-hydroxypiperidine-2-one (PIPOH), has been carried out. The complex [UO2(PIPO)2(H2O)] crystallized from slightly acidic water solutions (pH ＜ 5), and its molecular structure was determined by X-ray diffraction. The uranyl speciation in the presence of both ligands has been thoroughly investigated in a 0.1 M KNO3 medium at 298.2 K by the combined use of four complementary techniques, i.e., potentiometry, spectrophotometry, Raman spectroscopy, and affinity capillary electrophoresis. Preorganization of the hydroxamate ligand for chelation by incorporation into a cyclic structure, as in PIPO−, results in an increase of nearly one order of magnitude in the formation constants of the uranyl complexes of 1 : 1 and 1 : 2 metal/ligand stoichiometries. [ABSTRACT FROM AUTHOR]

An efficient semisynthesis of silylated l-amino acids by reaction of silylated benzaldehydes with a phosphonium l-amino acid used as a Wittig reagent is described. The efficiency of the silylated l-amino acids in peptide synthesis was investigated by coupling both the carboxylic acid and the amino moiety with l-alanine and phenylalanine derivatives, respectively. The silylated derivatives were treated with KF or tetrabutylammonium fluoride to give the corresponding fluorosilyl derivatives without racemization. The hydrolysis of the fluorosilylated derivatives in phosphate buffer at pH 7.2 was checked. Finally, the 18F-labelling of di- tert-butylsilylated saturated and unsaturated dipeptides was achieved in hot DMSO with a mixture of K[18F]/cryptand (K2.2.2) and acetic acid. The 18F-labelled dipeptides were obtained with radiochemical yields and molar activities of up to 31 % and 410 GBq/µmol, respectively. Consequently, this semisynthesis involving a Wittig reaction offers a new and efficient route for the design and 18F-labelling of Si-based amino acids and peptide derivatives, which may find applications in PET imaging. [ABSTRACT FROM AUTHOR]

Six- and seven-membered cyclic hydroxamic acids, such as 1-hydroxypiperidine-2-one ( 1H, 1,2-PIPOH) and 1-hydroxyazepan-2-one ( 2H), have recently been identified in some mixed siderophores as one of their three chelating subunits. Compared to their ubiquitous noncyclic counterparts, cyclic hydroxamates are preorganized for metal binding. Surprisingly, the coordination chemistry of these bidentate, monoanionic ligands remains virtually unknown, even in the case of iron(III). We report herein the first structural study of the complexes of 1- and of 6-, an unsaturated seven-membered ring analog of 2-, with tetravalent cations of transition metals (zirconium and hafnium), lanthanide (cerium), and actinides (thorium and uranium). Structural characterization by means of X-ray crystallography of the corresponding ML4 complexes evidenced distorted square antiprismatic coordination geometries with the exception of U4+, which favors a dodecahedral arrangement. [ABSTRACT FROM AUTHOR]