The impact of prehydration on the clearance and toxicity of high-dose methotrexate for pediatric patients.

Abstract High-dose methotrexate (HD-MTX) is an important chemotherapy for various pediatric malignancies. However, in contrast to precise recommendations on supportive care following the start of HD-MTX infusion, studies on the hydration regimen prior to HD-MTX infusion are lacking, and the local standard differs between pediatric oncology centers. Therefore, we prospectively evaluated the relevance of two common prehydration regimens on the clearance and toxicity of MTX in a randomized crossover study.

Synthesis, characterization and reactivity of carbohydrate platinum(IV) complexes with thioglycoside ligands.

Reactions of fac-[PtMe3(4,4'-R2bpy)(Me2CO)][BF4] (R = H, 1a; tBu, 1b) and fac-[PtMe3(OAc-kappa2O,O')(Me2CO)] (2), respectively, with thioglycosides containing thioethyl (ch-SEt) and thioimidate (ch-STaz, Taz = thiazoline-2-yl) anomeric groups led to the formation of the carbohydrate platinum(IV) complexes fac-[PtMe3(4,4-R2bpy)(ch*)][BF4] (ch* = ch-SEt, 8-14; ch-STaz, 15-23) and fac-[PtMe3(OAc-kappa2O,O')(ch*)] (ch* = ch-SEt, 24-28; ch-STaz = 29-35), respectively. NMR (1H, 13C, 195Pt) spectroscopic investigations and a single-crystal X-ray diffraction analysis of 19 (ch-STaz = 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-beta-D-galactopyranose) revealed the S coordination of the ch-SEt glycosides and the N coordination of the ch-STaz glycosides. Furthermore, X-ray structure analyses of the two decomposition products fac-[PtMe3(bpy)(STazH-kappaS)][BF4] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-beta-D-glucopyranose (23a), where a cleavage of the anomeric C-S bond had occurred in both cases, gave rise to the assumption that this decomposition was mediated due to coordination of the thioglycosides to the high electrophilic platinum(IV) atom, in non-strictly dried solutions.

(OC-6-33)-(2,2'-Bipyridine-κN,N')trimeth-yl(2-methyl-sulfanyl-2-thia-zoline-κN)platinum(IV) tetra-fluoridoborate.

The asymmetric unit of the title complex, [Pt(CH(3))(3)(C(10)H(8)N(2))(C(4)H(7)NS(2))]BF(4), contains two crystallographically independent mol-ecules. The Pt(IV) atom in each complex cation exhibits a distorted octa-hedral coordination geometry, built up by three methyl ligands in a facial binding fashion, a bipyridine ligand and a monodentately N-bound 2-methyl-sulfanyl-2-thia-zoline ligand (configuration index: OC-6-33). In the crystal structure, weak inter-molecular C-H⋯F hydrogen bonds are found between the complex cations and BF(4) (-) anions.

(Acetato-κO)(2,2'-bipyridine-κN,N')trimethyl-platinum(IV) monohydrate.

In the title hydrate, [Pt(CH(3))(3)(CH(3)COO)(C(10)H(8)N(2))]·H(2)O, the Pt(IV) atom exhibits a distorted octa-hedral coordination geometry built up by three methyl ligands in a facial arrangement, a bipyridine ligand and a monodentately bound acetate ligand. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds are observed between the water mol-ecule and the platinum complex, which link the mol-ecules into chains along the c axis.

Coordination chemistry approach to the long-standing challenge of stereocontrolled chemical glycosylation.

This study clearly demonstrates that a multi-dentate metal coordination to the leaving group, along with O-5 and/or a protecting group at O-6, has a strong effect on the stereoselectivity of chemical glycosylation.