Small Angle X-Ray Scattering Data Analysis and Theoretical Modelling for the Size and Shape Characterization of Drug Delivery Systems Based on Vitamin E TPGS Micelles.

We developed a simple two-dimensional/two-components theoretical model that describes the structure and functionality of a VitE-TPGS system of micelles assuming a hydrophobic inner core and an outer hydrated hydrophilic shell. We then conceptually applied the developed methodology to a simple system of VitE-TPGS micelles unloaded and loaded with an active pharmaceutical ingredient, eltrombopag, to verify if the model could reliably monitor the size change of the micelle upon loading. The fit of laboratory Small Angle X-Ray Scattering data against such model allows us to extract absolute values of the micelles size under a spherical shape hypothesis as well as the distribution within the system between components and level of hydration. The intensity scale of the SAXS experimental data needs to be normalized to a reference standard (pure water) to get absolute scattered intensities. The mathematical model which has been developed under a general hypothesis of ellipsoidal micelles, is applied to our experimental data under the simplified spherical assumption, which suitably fits our experimental data.

New perspectives in macromolecular powder diffraction using single-photon-counting strip detectors: high-resolution structure of the pharmaceutical peptide octreotide.

Advances in instrumentation, as well as the development of powerful crystallographic software have significantly facilitated the collection of high-resolution diffraction data and have made X-ray powder diffraction (XRPD) particularly useful for the extraction of structural information; this is true even for complex molecules, especially when combined with synchrotron radiation. In this study, in-line with past instrumental profile studies, an improved data collection strategy exploiting the MYTHEN II detector system together with significant beam focusing and tailored data collection options was introduced and optimized for protein samples at the Material Science beamline at the Swiss Light Source. Polycrystalline precipitates of octreotide, a somatostatin analog of particular pharmaceutical interest, were examined with this novel approach. XRPD experiments resulted in high angular and d-spacing (1.87 Å) resolution data, from which electron-density maps of enhanced quality were extracted, revealing the molecule's structural properties. Since microcrystalline precipitates represent a viable alternative for administration of therapeutic macromolecules, XRPD has been acknowledged as the most applicable tool for examining a wide spectrum of physicochemical properties of such materials and performing studies ranging from phase identification to complete structural characterization.

Insulin polymorphism induced by two polyphenols: new crystal forms and advances in macromolecular powder diffraction.

This study focuses on the polymorphism of human insulin (HI) upon the binding of the phenolic derivatives p-coumaric acid or trans-resveratrol over a wide pH range. The determination of the structural behaviour of HI via X-ray powder diffraction (XRPD) and single-crystal X-ray diffraction (SCXRD) is reported. Four distinct polymorphs were identified, two of which have not been reported previously. The intermediate phase transitions are discussed. One of the novel monoclinic polymorphs displays the highest molecular packing among insulin polymorphs of the same space group to date; its structure was elucidated by SCXRD. XRPD data collection was performed using a variety of instrumental setups and a systematic comparison of the acquired data is presented. A laboratory diffractometer was used for screening prior to high-resolution XRPD data collection on the ID22 beamline at the European Synchrotron Radiation Facility. Additional measurements for the most representative samples were performed on the X04SA beamline at the Swiss Light Source (SLS) using the MYTHEN II detector, which allowed the detection of minor previously untraceable impurities and dramatically improved the d-spacing resolution even for poorly diffracting samples.

Extreme Flexibility in a Zeolitic Imidazolate Framework: Porous to Dense Phase Transition in Desolvated ZIF-4.

Desolvated zeolitic imidazolate framework ZIF-4(Zn) undergoes a discontinuous porous to dense phase transition on cooling through 140 K, with a 23 % contraction in unit cell volume. The structure of the non-porous, low temperature phase was determined from synchrotron X-ray powder diffraction data and its density was found to be slightly less than that of the densest ZIF phase, ZIF-zni. The mechanism of the phase transition involves a cooperative rotation of imidazolate linkers resulting in isotropic framework contraction and pore space minimization. DFT calculations established the energy of the new structure relative to those of the room temperature phase and ZIF-zni, while DSC measurements indicate the entropic stabilization of the porous room temperature phase at temperatures above 140 K.

An "off-axis" Mn-Mn bond in Mn2(CO)10 at high pressure.

At variance with what was previously reported, Mn2(CO)10 does not transform its conformation from staggered to eclipsed in the high pressure crystal form. X-ray powder diffraction, DFT calculations and Raman spectroscopy show that the staggered conformation is retained. Instead, a rotation and a translation of the Mn(CO)5 pyramidal units produce an "off-axis" and rather shorter Mn-Mn bond.

Reversible pressure-induced amorphization of a zeolitic imidazolate framework (ZIF-4).

We report the reversible pressure-induced amorphization of a zeolitic imidazolate framework (ZIF-4, [Zn(Im)(2)]). This occurs irrespective of pore occupancy and takes place via a novel high pressure phase (ZIF-4-I) when solvent molecules are present in the pores. A significant reduction in bulk modulus upon framework evacuation is also observed for both ZIF-4 and ZIF-4-I.

Thermal, spectroscopic, and ab initio structural characterization of carprofen polymorphs.

Commercial and recrystallized polycrystalline samples of carprofen, a nonsteroidal anti-inflammatory drug, were studied by thermal, spectroscopic, and structural techniques. Our investigations demonstrated that recrystallized sample, stable at room temperature (RT), is a single polymorphic form of carprofen (polymorph I) that undergoes an isostructural polymorphic transformation by heating (polymorph II). Polymorph II remains then metastable at ambient conditions. Commercial sample is instead a mixture of polymorphs I and II. The thermodynamic relationships between the two polymorphs were determined through the construction of an energy/temperature diagram. The ab initio structural determination performed on synchrotron X-Ray powder diffraction patterns recorded at RT on both polymorphs allowed us to elucidate, for the first time, their crystal structure. Both crystallize in the monoclinic space group type P2(1) /c, and the unit cell similarity index and the volumetric isostructurality index indicate that the temperature-induced polymorphic transformation I → II is isostructural. Polymorphs I and II are conformational polymorphs, sharing a very similar hydrogen bond network, but with different conformation of the propanoic skeleton, which produces two different packing. The small conformational change agrees with the low value of transition enthalpy obtained by differential scanning calorimetry measurements and the small internal energy computed with density functional methods.

The MYTHEN detector for X-ray powder diffraction experiments at the Swiss Light Source.

The MYTHEN single-photon-counting silicon microstrip detector has been developed at the Swiss Light Source for time-resolved powder diffraction experiments. An upgraded version of the detector has been installed at the SLS powder diffraction station allowing the acquisition of diffraction patterns over 120 degrees in 2theta in fractions of seconds. Thanks to the outstanding performance of the detector and to the calibration procedures developed, the quality of the data obtained is now comparable with that of traditional high-resolution point detectors in terms of FWHM resolution and peak profile shape, with the additional advantage of fast and simultaneous acquisition of the full diffraction pattern. MYTHEN is therefore optimal for time-resolved or dose-critical measurements. The characteristics of the MYTHEN detector together with the calibration procedures implemented for the optimization of the data are described in detail. The refinements of two known standard powders are discussed together with a remarkable application of MYTHEN to organic compounds in relation to the problem of radiation damage.

Architectural control of seeded-grown magnetic-semicondutor iron oxide-TiO(2) nanorod heterostructures: the role of seeds in topology selection.

A colloidal nonaqueous approach to semiconductor-magnetic hybrid nanocrystals (HNCs) with selectable heterodimer topologies and tunable geometric parameters is demonstrated. Brookite TiO(2) nanorods, distinguished by a curved shape-tapered profile with richly faceted terminations, are exploited as substrate seeds onto which a single spherical domain of inverse spinel iron oxide can be epitaxially grown at either one apex or any location along their longitudinal sidewalls in a hot surfactant environment. The topologically controlled arrangement of the component material lattices, the crystallographic relationships holding between them, and strain distribution across individual heterostructures have been studied by combining X-ray diffraction and absorption techniques with high-resolution transmission electron microscopy investigations. Supported by such structural knowledge, the synthetic achievements are interpreted within the frame of various mechanistic models offering complementary views of HNC formation. The different HNC architectures are concluded to be almost equivalent in terms of surface-interface energy balance associated with their formation. HNC topology selection is rationalized on the basis of a diffusion-limited mechanism allowing iron oxide heterogeneous nucleation and growth on the TiO(2) nanorods to switch from a thermodynamically controlled to a kinetically overdriven deposition regime, in which the anisotropic reactivity offered by the uniquely structured seeds is accentuated under high spatially inhomogeneous monomer fluxes. Finally, the multifunctional capabilities of the heterostructures are highlighted through illustration of their magnetic and photocatalytic properties, which have been found to diverge from those otherwise exhibited by their individual material components and physical mixture counterparts.

Anion dependent mesomorphism in coordination networks based on 2,2'-bipyridine silver(I) complexes.

The reaction of the promesogenic dihexadecyl-2,2'-bipyridine-4,4'-dicarboxylate (L16) with a number of AgX salts produces a series of silver(I) complexes [(L16)Ag(sac)], 1, [(L16)Ag(NO3)], 2, [(L16)Ag(OTf)], 3, and [(L16)3Ag2](ClO4)2, 4, whose stoichiometries, molecular architectures, supramolecular networks and mesomorphic behaviour are "anion dependent". In spite of the large differences in the single molecular structure, the one-dimensional coordination networks involving the triflate and perchlorate in complexes 3 and 4, are the key element for inducing significant argentophilic intermolecular interactions responsible for the induction of lamello-columnar mesomorphism in both Ag(I) derivatives. Moreover, a series of Ag(I) triflate model complexes have been synthesized and in order to get more insights about their solid state architectures, systematic structural studies have been performed.

MAD techniques applied to powder data: finding the structure given the substructure.

The joint probability distribution function method is applied to multiple-wavelength anomalous dispersion (MAD) powder data. The distributions are calculated by assuming prior knowledge of the scattering intensities at two wavelengths and of the anomalous-scatterer substructure. The method leads to formulas estimating the full structure phases and their reliability. The procedure has been applied to two structures, one unknown and one known; the second was used as a control for the phasing procedure. In spite of the unavoidable peak overlapping in the diffraction pattern, the formulas proved to be very effective. Combined with a new algorithm for phase extension, they enabled the solution of both crystal structures.

Colloidal semiconductor/magnetic heterostructures based on iron-oxide-functionalized brookite TiO2 nanorods.

A flexible colloidal seeded-growth strategy has been developed to synthesize all-oxide semiconductor/magnetic hybrid nanocrystals (HNCs) in various topological arrangements, for which the dimensions of the constituent material domains can be controlled independently over a wide range. Our approach relies on driving preferential heterogeneous nucleation and growth of spinel cubic iron oxide (IO) domains onto brookite TiO2 nanorods (b-TiO2) with tailored geometric parameters, by means of time-programmed delivery of organometallic precursors into a suitable TiO2-loaded surfactant environment. The b-TiO2 seeds exhibit size-dependent accessibility towards IO under diffusion-controlled growth regime, which allows attainment of HNCs individually made of a single b-TiO2 section functionalized with either one or multiple nearly spherical IO domains. In spite of the dissimilarity of the respective crystal-phases, the two materials share large interfacial junctions without significant lattice strain being induced across the heterostructures. The synthetic achievements have been supported by a systematic morphological, compositional and structural characterization of the as-prepared HNCs, offering a mechanistic insight into the specific role of the seeds in the control of heterostructure formation in liquid media. In addition, the impact of the formed b-TiO2/IO heterojunctions on the magnetic properties of IO has also been assessed.

Electron diffraction, X-ray powder diffraction and pair-distribution-function analyses to determine the crystal structures of Pigment Yellow 213, C23H21N5O9.

The crystal structure of the nanocrystalline alpha phase of Pigment Yellow 213 (P.Y. 213) was solved by a combination of single-crystal electron diffraction and X-ray powder diffraction, despite the poor crystallinity of the material. The molecules form an efficient dense packing, which explains the observed insolubility and weather fastness of the pigment. The pair-distribution function (PDF) of the alpha phase is consistent with the determined crystal structure. The beta phase of P.Y. 213 shows even lower crystal quality, so extracting any structural information directly from the diffraction data is not possible. PDF analysis indicates the beta phase to have a columnar structure with a similar local structure as the alpha phase and a domain size in column direction of approximately 4 nm.

Oxygen self-doping in hollandite-type vanadium oxyhydroxide nanorods.

A nonaqueous liquid-phase route involving the reaction of vanadium oxychloride with benzyl alcohol leads to the formation of single-crystalline and semiconducting VO 1.52(OH) 0.77 nanorods with an ellipsoidal morphology, up to 500 nm in length and typically about 100 nm in diameter. Composition, structure, and morphology were thoroughly analyzed by neutron and synchrotron powder X-ray diffraction as well as by different electron microscopy techniques (SEM, (HR)TEM, EDX, and SAED). The data obtained point to a hollandite-type structure which, unlike other vanadates, contains oxide ions in the channels along the c-axis, with hydrogen atoms attached to the edge-sharing oxygen atoms, forming OH groups. According to structural probes and magnetic measurements (1.94 mu B/V), the formal valence of vanadium is +3.81 (V (4+)/V (3+) atomic ratio approximately 4). The experimentally determined density of 3.53(5) g/cm (3) is in good agreement with the proposed structure and nonstoichiometry. The temperature-dependent DC electrical conductivity exhibits Arrhenius-type behavior with a band gap of 0.64 eV. The semiconducting behavior is interpreted in terms of electron hopping between vanadium cations of different valence states (small polaron model). Ab initio density-functional calculations with a local spin density approximation including orbital potential (LSDA + U with an effective U value of 4 eV) have been employed to extract the electronic structure. These calculations propose, on the one hand, that the electronic conductivity is based on electron hopping between neighboring V (3+) and V (4+) sites, and, on the other hand, that the oxide ions in the channels act as electron donors, increasing the fraction of V (3+) cations, and thus leading to self-doping. Experimental and simulated electron energy-loss spectroscopy data confirm both the presence of V (4+) and the validity of the density-of-states calculation. Temperature-dependent magnetic susceptibility measurements indicate strongly frustrated antiferromagnetic interactions between the vanadium ions. A model involving the charge order of the V (3+) sites is proposed to account for the observed formation of the magnetic moment below 25 K.

Topologically controlled growth of magnetic-metal-functionalized semiconductor oxide nanorods.

Colloidal semiconductor-magnetic hybrid nanocrystals with topologically controlled composition are fabricated by heterogeneous nucleation of spherical epsilon-Co domains onto anatase TiO2 nanorods. The latter can be selectively decorated at either their tips or at multiple locations along their longitudinal sidewalls, forming lattice-matched heterointerfaces regardless of the metal deposition sites. The possibility of switching between either heterostructure growth modes arises from the facet-dependent chemical reactivity of the oxide seeds, which is governed mainly by selective adhesion of the surfactants rather than by small differences in misfit-induced interfacial strain at the relevant junction points.

Colloidal synthesis and characterization of tetrapod-shaped magnetic nanocrystals.

Tetrapod-shaped maghemite nanocrystals are synthesized by manipulating the decomposition of iron pentacarbonyl in a ternary surfactant mixture under mild thermal conditions. Adjustment of the reaction parameters allows for the systematic tuning of both the width and the length of the tetrapod arms, which grow preferentially along the 111 easy axis direction. Such degree of control leads to modulation of the magnetic behavior of the nanocrystals, which evolves systematically as their surface magnetization phase and shape anisotropy are progressively increased.