Daniel R. Vega

Alendronate zwitterions bind to calcium cations arranged in columns.

Alendronate is used clinically in the treatment of skeletal disorders, the mode of action depending on the adsorption to calcium hydroxyapatite crystals (bone). In the title compound, calcium 4-ammonium-1-hydroxybutylidene-1,1-bisphosphonate, Ca(2+).2C(4)H(12)NO(7)P(2)(-), alendronate is a zwitterion, possessing one negative charge on each PO(3) group and a protonated N atom. The zwitterion is disposed with its negative end facing the Ca(2+) ion, while its positive end is stretched in the opposite direction. The geometry of the carbon chain is all-trans, while the hydroxy group is approximately gauche. The Ca(2+) ion lies on a twofold axis parallel to b. The coordination sphere around the metal cation is octahedral and is determined by monodentate- and bidentate-coordinated alendronate zwitterions. The O.O bite distance is 3.080 (2) A. Coordinated Ca(2+) metal cations are arranged at the centre of a column running along c.

Solid-State Forms of Zoledronic Acid: Polymorphism in Hydrates

Solid-state forms of zoledronic acid, a nitrogen-containing bisphosphonate used for treatment of bone diseases are studied using different experimental techniques (DSC, TG, and XRD). Two degrees of hydration have been obtained, containing one and three water molecules per zoledronic acid molecule. The crystal structure of the trihydrated form is reported. Two different anhydrated forms have been obtained when the hydrated ones were heated. Besides, during the dehydration process, an amount of metastable amorphous phase appears, as a function of the dehydration rate. The stability of the obtained crystalline forms is examined under high humidity and a different trihydrated form was obtained, setting clear that the same degree of hydration (trihydrated) can be obtained in two different crystalline forms, and then very different thermal behaviors have been observed.

The calcium-binding properties of pamidronate, a bone-resorption inhibitor

The title compound, calcium bis(3-ammonio-1-hydroxypropylidene-1,1-bisphosphonate) dihydrate, Ca(2+).2C(3)H(10)NO(7)P(2)(-).2H(2)O, consists of calcium octahedra arranged in columns along the c axis and coordinated by hydrogen-bonded molecular anions. The Ca(2+) cation lies on a twofold axis. Pamidronate adopts a twisted conformation of the hydroxyalkylamine backbone that enables the formation of an intramolecular N-H...O hydrogen bond. The molecular anion is chelating monodentate as well as bidentate, with an O...O bite distance of 3.0647 (15) A.

Magnetism, resistivity and magnetoresistance in Ca1−xYxMnO3

We present magnetic and transport studies on the manganite Ca 1-x Y x MnO 3 (x ≤ 0.25). A small Y concentration produces an important decrease in the electrical resistivity and increases the magnetization but full ferromagnetic order is not achieved. The samples with 0.05 ≤ x < 0.18 show magnetoresistive effects. For x ≥ 0.18 indications of charge order were observed in the magnetization and resistivity behaviors.

1-[2-(1-Hydroxy­cyclo­hexyl)-2-(4-methoxy­phenyl)­ethyl]­di­methyl­ammon­ium chloride (venlafaxine hydro­chloride)

The crystal structure of racemic Venlafaxine hydrochloride, C(17)H(28)NO(2)(+).Cl(-), consists of two types of parallel chains formed by translated Venlafaxine(+) cations, hydrogen bonded by Cl(-) anions, and characterized by the opposite chirality of their constituent molecules. These chains organize in two different types of broad layers of opposite handedness, related by a glide plane.

The Zn2+ salt of pamidronate: a role for water in the metal-cation binding properties of bisphosphonates.

Pamidronate (3-ammonium-1-hydroxypropylidene-1,1-bisphosphonate) is used clinically in the treatment of diseases affecting bone tissue. In the salt zinc pamidronate dihydrate, Zn(2+).2C(3)H(10)NO(7)P(2)(-).2H(2)O, pamidronate is a zwitterion with an overall charge of -1. The carbon chain adopts a trans conformation, separating maximally the positively charged N atom from the negative phosphonate groups. The Zn(2+) ion lies on an inversion center and is surrounded by a sixfold coordination sphere provided by two bidentate chelating zwitterions and two water molecules. The bidentate O.Zn.O bond angle is 92.70 (7) degrees, while the O.O bite distance is 3.018 (3) A.

Diaqua-bis[1-hydroxy-2-(imidazol-3-ium-1-yl)-1,1'-ethyl-idenediphophonato-κO,O']zinc(II).

In the title complex, [Zn(C5H9NO7P2)2(H2O)2], the zinc atom is coordinated by two bidentate zoledronate [zoledronate = (2-(1-imidazole)-1-hydroxy-1,1′-ethylidenediphophonate)] ligands and two water molecules. The coordination number is 6. There is one half-molecule in the asymmetric unit with the zinc atom located on a crystallographic inversion centre. The anion exists as a zwitterion with an overall charge of −1; the protonated nitrogen in the ring has a positive charge and the two phosphonates groups each have a single negative charge. There are two intramolecular O—H⋯O hydrogen bonds. The molecules are linked into a chain by intermolecular O—H⋯O hydrogen bonds. Adjacent chains are further linked by O—H⋯O hydrogen bonds involving the aqua ligands. An N—H⋯O interaction is also observed.

Bromination of sugar enones and enonolactones

Abstract Bromination of 2,4,6- tri -O- benzoyl -3- deoxy - d -erytro- hex -2- enono -1,5- lactone (1) took place diastereoselectively to afford a single product: 2,4,6- tri -O- benzoyl -2,3- dibromo -3- deoxy - d - altrono -1,5- lactone (2). The configuration of C-2 and C-3 was determined as R,R by NMR spectroscopy and taking into account considerations of the stereochemical course of the bromination. The configuration of 2 was confirmed by X-ray analysis, which also revealed that the conformation of the lactone ring consists of a 4 H 3 ( d ) distorted half-chair. The bromine addition to 2,5,6,7- tetra -O- benzoyl - d -arabino- hept -2- enono -1,4- lactone (5), readily prepared by DBU-promoted elimination from the perbenzoylated lactone derivative 4, was also diastereoselective and led to the dibromo derivative 6, whose configuration for C-2 and C-3 was assigned as S,S. Bromination of the α,β-unsaturated carbonyl system of 2-propyl 6-O- acetyl -3,4- dideoxy -α- d -glycero- hex -3- enopyranosid -2- ulose (7) afforded an unsaturated monobromo derivative: 2-propyl 6-O- acetyl -3- bromo -3,4- dideoxy -α- d -glycero- hex -3- enopyranosid -2- ulose (8), suggesting that dehydrobromination occurred after addition of bromine.

Two members of the bisphosphonate class of drugs: a zwitterion and a molecular compound

The compounds studied in this paper, viz. (1-ammonio-1-phosphonopropyl)phosphonate, C(3)H(11)NO(6)P(2), (I), and 1-(acetylamino)propylidene-1,1-bisphosphonic acid dihydrate, C(5)H(13)NO(7)P(2).2H(2)O, (II), are members of a commonly used family of therapeutic agents. Compound (I) is an inner salt with separated negative (on the ionized PO(3) group) and positive (on the tetrahedral N atom) charges, while (II) possesses neutral phosphonyl groups and one amide N atom. Both structures have a C-C-C-N backbone, which has comparable geometric parameters in (I) and (II); the main difference was found in one of the N-C-P bond angles, which is lengthened in (II) because of an intramolecular O(PO(3))-H.O(C=O) interaction. The hydrogen-bonding scheme in the crystal of (I) includes all possible donor atoms, namely all the H atoms of the ammonium group and the phosphonic acid functions. As a result of these interactions, the zwitterions are organized into a plane running along the crystallographic x axis. In (II), the intermolecular interactions include all possible donor atoms, except for the N atom; the packing differs from that of (I) in that the molecules are arranged in a chain running parallel to the x axis. In the chains, the molecules form head-to-head dimers, while the crystallization water molecules contribute to the intra- and interchain cohesion.

Synthesis of Enantiomeric Polyhydroxyalkylpyrrolidines from 1,3-Dipolar Cycloadducts. Evaluation as Inhibitors of a β-Galactofuranosidase

Enantiomeric 2,3,4-tris(hydroxyalkyl)-5-phenylpyrrolidines have been synthesized from the major cycloadducts obtained by the 1,3-dipolar cycloaddition of sugar enones with azomethine ylides derived from natural amino acids. Reduction of the ketone carbonyl group of the cycloadducts, which possess a basic structure of bicyclic 6-(menthyloxy)hexahydropyrano[4,3-c]pyrrol-7(6H)one, afforded a number of pyrrolidine-based bicyclic systems. A sequence of reactions, which involved hydrolysis of the menthyloxy substituent, reduction, N-protection, and degradative oxidation, afforded varied pyrrolidine structures having diverse configurations and patterns of substitution; in particular, polyhydroxylated derivatives have been obtained. The unprotected products were isolated as pyrrolidinium trifluoroacetates. Because of the furanose-like nature of the target trihydroxyalkyl pyrrolidines, these molecules have been evaluated as inhibitors of the β-galactofuranosidase from Penicillium fellutanum. The compounds showed practically no inhibitory activity for concentration of pyrrolidines in the range of 0.1-1.6 mM.