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Biomedical subjects

Daniel Fernández

Publications and source records attributed to Daniel Fernández.

13 recordsLinked to original sources

Polymorphism on leflunomide: stability and crystal structures.

Two polymorphs of Leflunomide were found and studied (form I and II). Both of them were characterized by X-ray powder diffraction and thermal analysis. Single crystals were obtained and both structures were solved. Forms I and II crystallize in the space group P2(1)/c with two and one independent molecules per asymmetric unit, respectively. Thermodynamic stability of the two forms is assessed by differential scanning calorimetry. The cohesion in the crystal of form I (the more stable) is provided by both by H bonding as well as pi...pi interactions, while in form II it is given only by the former. The independent molecules in form I adopt different conformations thus allowing for a larger number of intermolecular interactions.

Anti-Inflammatory Agents, Non-Steroidal↗

Thermal behaviour and stability in Olanzapine.

The stability and thermal behaviour of two anhydrate phases and a new mixed water:DMSO solvate of Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1,5]benzodiazepine) are studied by different methods: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Raman scattering (RS). Single crystal structural data for the latter phase are presented, confirming the presence of the (Olanzapine)(2) dimer as the structural building unit of all known phases of the drug, either anhydrate or solvated. An apparent interconversion between both solid state forms is shown to be an artifact and explained in terms of a melting-recrystallization process.

Antipsychotic Agents↗

Effects of radiosynovectomy with p-32 colloid therapy in hemophilia and rheumatoid arthritis.

AIM: The aim of this study was to assess the effects of treatment with our locally produced P-32 colloidal suspension on knee synovitic inflammations of hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results with chemical synovectomy or corticoid intra-articular injections and evaluate the cost-benefit ratio. MATERIALS AND METHODS: Thirty-six hemophilic male patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires, Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26 patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10 patients). Parents' informed consent was obtained. The following procedures were performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus monthly methylene diphosphonate (MDP) controls. Patients were included in this study only if several knee episodes had occurred. Exclusion criteria included bone destruction and big Baker's cyst. Twelve RA patients were included, with similar selection criteria: 6 RA patients received P-32 therapy, and the other 6 patients intra-articular corticoids. Clinical, blind evaluation (state of joint involvement, pain, motility, requirements of antihemophilic factors, corticoids, or analgesics) was registered in follow-up charts. If required, joint aspiration was carried out. Intra-articular instillation of saline plus flushing was done before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the gamma camera for early and late imaging to confirm the absence of leakage. For intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA (macroaggregates) was used. Immobilization and relative rest for 72 hours followed the procedures. RESULTS: There were neither local or systemic effects, nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids procedures required frequent injections. Comparison of regions of interest (ROIs) in treated knees during soft-tissue scintigraphies in pre- and post-third MDP control showed knee improvement. The follow-up evaluation demonstrated an increase in joint motion, diminished volume, and less requirement and frequency of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21 of 26), thus lowering health costs. Five female RA patients (5 of 6) had decreased joint swelling and pains, resulting in increased joint motion. CONCLUSIONS: Radiosynovectomy in RA showed a 3-month pain palliative effect. One intra-articular knee radiosynoviorthesis in haemophilic patients provides a more than 3- month relief of symptoms after treatment with locally produced P-32 (11 patients). This turned out to be a safe, economic alternative procedure in emerging nations where the availability of AHF is difficult and expensive.

Adolescent↗

The purine transferase from Trypanosoma cruzi as a potential target for bisphosphonate-based chemotherapeutic compounds.

We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from Trypanosoma cruzi in the micromolar range.

Animals↗

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.

Journal Article↗

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.

Journal Article↗

Head-to-head dimers in the zwitterion of 1-hydroxy-1-phosphono-3-(1-piperidino)propylidene-1-phosphonate (PHPBP).

The title compound, C(8)H(19)NO(7)P(2), is a member of the bisphosphonate family of therapeutic compounds. PHPBP has inner-salt character, consisting of a negatively charged PO(3) group and a positively charged N atom. The six-membered piperidine ring adopts an almost-perfect chair conformation. The hydroxyl group and the N atom have gauche and trans conformations in relation to the O-C-C-C-N backbone, respectively. Hydrogen bonding is the main contributor to the packing in the crystal, which consists of head-to-head dimers formed through phosphonyl-phosphonyl hydrogen bonds, while O-H.O and N-H.O interactions join the dimers into a plane parallel to crystallographic b and c axes.

Journal Article↗

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.

Diphosphonates↗

Head-to-head dimers in the zwitterion of 1-hydroxy-3-(pyrrolidin-1-yl)propylidene-1,1-bisphosphonic acid (EB 1053).

The title compound, 1-hydroxy-1-phosphono-3-(1-pyrrolidinio)propylidene-1-phosphonate, C(7)H(17)NO(7)P(2), is a member of the bisphosphonate class of drugs. As a zwitterion, it possesses a negative charge on one of the PO(3) groups and a positive charge on the pyrrolidine N atom. A zwitterion makes a contact with a neighbouring ion through the hydroxyl O atom and two phosphonyl O atoms, one each from two different PO(3) groups. Hydrogen bonding involves O-H.O and N-H.O interactions; the former are involved in the formation of head-to-head dimers, while the latter join the dimers into a chain running along the crystallographic b axis.

Journal Article↗

17alpha,21-Dihydroxy-16beta-methylpregna-1,4-diene-3,11,20-trione (meprednisone).

The title compound, C(22)H(28)O(5), is a commercial therapeutic agent of the steroid class. Both independent molecules in the asymmetric unit have six-membered A rings that are planar, while the B and C rings adopt normal chair conformations. The five-membered D ring is in a 13beta,14alpha-half-chair conformation, and the B/C and C/D ring junctions are in trans positions. Cohesion in the crystal is provided by O-H.O hydrogen bonds, which generate chains of molecules that are organized in a plane that lies along the crystallographic b axis.

Crystallography, X-Ray↗

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.

Bone Resorption↗

Losartan potassium, a non-peptide agent for the treatment of arterial hypertension.

In the title compound, potassium 2-butyl-4-chloro-1-[[2'-(5-tetrazolido)biphenyl-4-yl]methyl]-1H-imidazol-5-ylmethanol, K(+) x C(22)H(22)ClN(6)O(-), the imidazole and tetrazole rings are at angles of 85.0 (2) and 51.8 (1) degrees, respectively, to the phenyl rings to which they are attached, while the dihedral angle between the latter two rings is 46.7 (1) degrees. The coordination sphere of the metal cation consists of six tetrazoyl N atoms, the methanol O atom and the pi cloud of one of the phenyl rings. These interactions determine the formation of columns of molecular anions that lie parallel to the b axis, while hydrogen bonding contributes to intercolumnar cohesion. Far from the centre of the columns, the hydrocarbon chain is immersed in a hydrophobic environment.

Antihypertensive Agents↗

Disodium pamidronate.

The title compound, disodium 3-ammonium-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, 2Na(+).C(3)H(9)NO(7)P(2)(2-).5H(2)O, is used for the diagnosis and treatment of a number of bone disorders. In the solid state, disodium pamidronate shows zwitterionic character and has four different modes of chelation to sodium. The metal is octahedrally coordinated by zwitterion and water O atoms. Both coordination to sodium and hydrogen bonding determine the packing in the crystal, which comprises columns lying parallel to the crystallographic a axis.

Bone Diseases↗