Validated stability-indicating HPLC method for paricalcitol in pharmaceutical dosage form according to ICH guidelines: application to stability studies

A stability-indicating HPLC method with diode array detection for the determination of paricalcitol, a synthetic vitamin D2 analog, was developed. Analytical parameters were studied according to International Conference on Harmonization guidelines. A C18 column (250 x 4.6 mm, 5 microm particle size) maintained at 25 degrees C was used as the stationary phase, and acetonitrile-water (70 + 30, v/v) as the mobile phase. Chromatograms were recorded at 250 nm. In forced degradation studies, the effects of acid, base, oxidation, temperature, and UV light were investigated and showed no interference with the drug peak. The method was found to be linear (r = 0.9989) at concentrations ranging from 0.6 to 10.0 mg/L paricalcitol, precise (repeatability and intermediate precision estimated as RSD less than 3.5%), accurate (recoveries higher than 95%), specific, and robust. The LOD and LOQ were 0.6 and 0.2 mg/L, respectively. The validated method was used for paricalcitol determination in a formal stability study of its pharmaceutical dosage form in preloaded syringes. The stability of a diluted solution of its pharmaceutical form in Viaflo bags was also tested. The results showed that paricalcitol was stable in preloaded syringes during a period of 30 days from preparation in the different storage conditions tested (room temperature without protection from daylight and 4.4 degrees C with protection from daylight). On the contrary, paricalcitol was quickly lost when stored in Viaflo bags by adsorption onto the walls of the container.     

Divalent metal vinylphosphonate layered materials: compositional variability, structural peculiarities, dehydration behavior, and photoluminescent properties

A family of M-VP (M = Ni, Co, Cd, Mn, Zn, Fe, Cu, Pb; VP = vinylphosphonate) and M-PVP (M = Co, Cd; PVP = phenylvinylphosphonate) materials have been synthesized by hydrothermal methods and characterized by FT-IR, elemental analysis, and thermogravimetric analysis (TGA). Their structures were determined either by single crystal X-ray crystallography or from laboratory X-ray powder diffraction data. The crystal structure of some M-VP and M-PVP materials is two-dimensional (2D) layered, with the organic groups (vinyl or phenylvinyl) protruding into the interlamellar space. However, the Pb-VP and Cu-VP materials show dramatically different structural features. The porous, three-dimensional (3D) structure of Pb-VP contains the Pb center in a pentagonal pyramid. A Cu-VP variant of the common 2D layered structure shows a very peculiar structure. The structure of the material is 2D with the layers based upon three crystallographically distinct Cu atoms; an octahedrally coordinated Cu(2+) atom, a square planar Cu(2+) atom and a Cu(+) atom. The latter has an unusual co-ordination environment as it is 3-coordinated to two oxygen atoms with the third bond across the double bond of the vinyl group. Metal-coordinated water loss was studied by TGA and thermodiffractometry. The rehydration of the anhydrous phases to give the initial phase takes place rapidly for Cd-PVP but it takes several days for Co-PVP. The M-VP materials exhibit variable dehydration-rehydration behavior, with most of them losing crystallinity during the process.     

Deprotonation of C‐Alkyl Groups of Cationic Triruthenium Clusters Containing Cyclometalated C‐Alkylpyrazinium Ligands: Experimental and Computational Studies

The C‐alkyl groups of cationic triruthenium cluster complexes of the type [Ru₃(μ‐H)(μ‐κ²N¹,C² ‐L)(CO)₁₀]⁺ (HL represents a generic C‐alkyl‐N‐methylpyrazium species) have been deprotonated to give kinetic products that contain unprecedented C‐alkylidene derivatives and maintain the original edge‐bridged decacarbonyl structure. When the starting complexes contain various C‐alkyl groups, the selectivity of these deprotonation reactions is related to the atomic charges of the alkyl H atoms, as suggested by DFT/natural‐bond orbital (NBO) calculations. Three additional electronic properties of the C‐alkyl C? H bonds have also been found to correlate with the experimental regioselectivity because, in all cases, the deprotonated C? H bond has the smallest electron density at the bond critical point, the greatest Laplacian of the electron density at the bond critical point, and the greatest total energy density ratio at the bond critical point (computed by using the quantum theory of atoms in molecules, QTAIM). The kinetic decacarbonyl products evolve, under appropriate reaction conditions that depend upon the position of the C‐alkylidene group in the heterocyclic ring, toward face‐capped nonacarbonyl derivatives (thermodynamic products). The position of the C‐alkylidene group in the heterocyclic ring determines the distribution of single and double bonds within the ligand ring, which strongly affects the stability of the neutral decacarbonyl complexes and the way these ligands coordinate to the metal atoms in the nonacarbonyl products. The mechanisms of these decacarbonylation processes have been investigated by DFT methods, which have rationalized the structures observed for the final products and have shed light on the different kinetic and thermodynamic stabilities of the reaction intermediates, thus explaining the reaction conditions experimentally required by each transformation.     

Structure and electrons in mayenite electrides

One major goal in materials chemistry is to find inexpensive compounds with improved capabilities. Stable inorganic electrides, derived from nanoporous mayenite [Ca12Al14O32]O, are a new family that has very interesting properties such as electronic conductivity combined with transparency. However, an intriguing fundamental problem is to understand the structures of these cubic materials and to characterize their free-electron loadings. Here we report an accurate structural study for three members of the series [Ca12Al14O32]O(1-delta)e(2delta) (delta = 0, 0.15, and 0.45), from single-crystal low-temperature synchrotron X-ray diffraction. The complex structural disorder imposed by the presence of the oxide anions into the mayenite cages has been unravelled. Furthermore, the final electron density map for delta = 0.45 black mayenite has shown electron density localized into the center of the cages, which is the first experimental proof of their electride nature. The reported structural findings challenge theorists to improve predictive models in this new family of materials.     

Multifunctional lanthanum tetraphosphonates: flexible, ultramicroporous and proton-conducting hybrid frameworks

A new flexible ultramicroporous solid, La(H(5)DTMP)·7H(2)O (1), has been crystallized at room temperature using the tetraphosphonic acid H(8)DTMP, hexamethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid). Its crystal structure, solved by synchrotron powder X-ray diffraction, is characterised by a 3D pillared open-framework containing 1D channels filled with water. Upon dehydration, a new related crystalline phase, La(H(5)DTMP) (2) is formed. Partial rehydration of 2 led to La(H(5)DTMP)·2H(2)O (3). These new phases contain highly corrugated layers showing different degrees of conformational flexibility of the long organic chain. The combination of the structural study and the gas adsorption characterization (N(2) and CO(2)) suggests an ultramicroporous flexible framework. NO isotherms are indicative of a strong irreversible adsorption of NO within the pores. Impedance data indicates that 1 is a proton-conductor with a conductivity of 8 × 10(-3) S cm(-1) at 297 K and 98% of relative humidity, and an activation energy of 0.25 eV.     

Ruthenium-cluster-mediated activation of all bonds of a methyl group of 6,6'-dimethyl-2,2'-bipyridine and 2,9-dimethyl-1,10-phenanthroline: transformation of the latter into a 2-alkenyl-9-methyl-1,10-phenanthroline ligand

The treatment of [Ru3(CO)12] with 6,6'-dimethyl-2,2'-bipyridine (Me2bipy) or 2,9-dimethyl-1,10-phenanthroline (Me2phen) in THF at reflux temperature gives the trinuclear dihydride complexes [Ru3(mu-H)2(mu3-L1)(CO)8] (L1 = HCbipyMe 1 a, HCphenMe 1 b), which result from the activation of two C-H bonds of a methyl group. The hexa-, hepta-, and pentanuclear derivatives [Ru6(mu3-H)(mu5-L2)(mu-CO)3(CO)13] (L2 = CbipyMe 2 a, CphenMe 2 b), [Ru7(mu3-H)(mu5-L2)(mu-CO)2(CO)16] (L2 = CbipyMe 3 a, CphenMe 3 b), and [Ru5(mu-H)(mu5-C)(mu-L3)(CO)13] (L3 = bipyMe 4 a, phenMe 4 b) can also be obtained by treating 1 a and 1 b with [Ru3(CO)12]. Compounds 2 a and 2 b have a basal edge-bridged square-pyramidal metallic skeleton with a carbyne-type C atom capping the four Ru atoms of the pyramid base. The structures of 3 a and 3 b are similar to those of 2 a and 2 b, respectively, but an additional Ru atom now caps a triangular face of the square-pyramidal fragment of the metallic skeleton. The most interesting feature of 2 a, 2 b, 3 a, and 3 b is that their carbyne-type C atoms were originally bound to three hydrogen atoms in Me2bipy or Me2phen and, therefore, they arise from the unprecedented activation of all three C-H bonds of C-bound methyl groups. The pentanuclear compounds 4 a and 4 b contain a carbide ligand surrounded by five Ru atoms in a distorted trigonal-bipyramidal environment. They are the products of a series of processes that includes the activation of all bonds (three C-H and one C-C) of organic methyl groups, and are the first examples of complexes having carbide ligands that arise from C-bonded methyl groups. The alkenyl derivatives [Ru5(mu5-C)(mu-p-MeC6H4CHCHphenMe)(CO)13] (5 b), [Ru5(mu-H)(mu5-C)(mu-p-MeC6H4CHCHphenMe)(p-tolC2)(CO)12] (6 b), and [Ru5(mu-H)(mu5-C)(mu-PhCHCHphenMe)(PhC2)(CO)12] (7 b) have been obtained by treating 4 b with p-tolyl- and phenylacetylene, respectively. Their heterocyclic ligands contain an alkenyl fragment in the position that was originally occupied by a methyl group. Therefore, these complexes are the result of the formal substitution of an alkenyl group for a methyl group of 2,9-dimethyl-1,10- phenanthroline.     

Prediction and observation of isostructurality induced by solvent incorporation in multicomponent crystals

The crystal structures of two pharmaceutical molecules-carbamazepine and its 10,11-dihydro derivative-with acetic acid have been successfully predicted by computational methods. While the crystalline structure of the former was known a priori, no structural information was available for the latter. Possible crystal structures were generated in silico before any experimental work was performed. Although the crystal structures of the pure drug molecules are very different, incorporation of acetic acid in their crystal lattices results in isomorphic products.     

Pseudolattice theory of charge transport in ionic solutions: Corresponding states law for the electric conductivity

A statistical mechanical framework for charge transport in ionic liquid–solvent mixtures based on the existence of a statistical lattice structure (pseudolattice) throughout the whole range of concentration is reported. The ion distribution is treated in a mean-field Bragg–Williams-like fashion, and the ionic motion is assumed to take place through hops between cells of two different types separated by non-random-energy barriers of different heights depending on the cell type. Assuming non-correlated ion transport, the electrical conductivity is shown to have a maximum, arising from the competition between the concentration of charge carriers in the bulk medium and their mobilities in the pseudolattice. An explicit expression for the concentration at which this maximum occurs is given in terms of microscopic parameters, and the electrical conductivity normalized by its maximum value (κ/κ_max) is shown to follow rather closely a universal corresponding states law in concentration space when represented against the ionic concentration scaled by its value at the conductivity maximum (?_α/?_max). Ion–ion and ion–solvent interactions are explicitly considered combining the path probability method for charge transport in solid electrolytes and the Bragg–Williams approximation for interparticle interactions, and their impact on the deviations of experimental data from the universal behavior of non-correlated transport analyzed. The theoretical predictions are shown to satisfactorily predict experimental values of electrical conductivity of aqueous solutions of conventional electrolytes and of mixtures of room temperature molten salts with typical solvents.