Structural Characterisation of Complex Layered Double Hydroxides and TGA-GC-MS Study on Thermal Response and Carbonate Contamination in Nitrate- and Organic-Exchanged Hydrotalcites.

Layered double hydroxides (LDHs) are versatile materials used for intercalating bioactive molecules in the fields of pharmaceuticals, nutraceuticals and cosmetics, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability and improving their pharmacokinetic properties and formulation stability. Moreover, LDHs are used in various technological applications to improve stability and processability. The crystal chemistry of hydrotalcite-like compounds was investigated by X-ray powder diffraction (XRPD), automated electron diffraction tomography (ADT) and thermogravimetric analysis (TGA)-GC-MS to shed light on the mechanisms involved in ion exchange and absorption of contaminants, mainly carbonate anions. For the first time, ADT allowed a structural model of LDH_NO3 to be obtained from experiment, shedding light on the conformation of nitrate inside LDH and on the loss of crystallinity due to the layer morphology. The ADT analysis of a hybrid LDH sample (LDH_EUS) clearly revealed an increase in defectivity in this material. XRPD demonstrated that the presence of carbonate can influence the intercalation of organic molecules into LDH, since CO3 -contaminated samples tend to adopt d spacings that are approximate multiples of the d spacing of LDH_CO3 . TGA-GC-MS allowed intercalated and surface- adsorbed organic molecules to be distinguished and quantified, the presence and amount of carbonate to be confirmed, especially at low concentrations (<2 wt %), and the different types and strengths of adsorption to be classified with respect to the temperature of elimination.

Chemical selectivity in structure determination by the time dependent analysis of in situ XRPD data: a clear view of Xe thermal behavior inside a MFI zeolite.

X-ray diffraction methods in general provide a representation of the average structure, thus allowing only limited chemical selectivity. As recently shown [D. Chernyshov, et al., Acta Crystallogr., Sect. A: Found. Crystallogr., 2011, 67, 327], some structural information on a subset of atoms can be obtained using the modulation enhanced diffraction (MED), thus providing a new tool that is able to enhance selectivity in diffraction. MED uses a periodic stimulus supplied in situ on a crystal while diffraction data are collected continuously during one or more stimulation periods. Such large data sets can then be treated by different methods. Herein, we present and compare phase sensitive detection (PSD) and principal component analysis (PCA) for in situ X-ray powder diffraction (XRPD) data treatment. The application of PCA to MED data is described for the first time in the present paper. Simulated and experimental MED powder data were produced using an MFI zeolite as a static spectator in which Xe, acting as the active species, is adsorbed and desorbed in a periodic manner. By demodulating the simulated and experimental data, MED allowed the powder diffraction pattern of the responding scattering density to be obtained and enabled the selective extraction of crystallographic information on Xe by solving the crystal structure of the active species independently of the static zeolite framework. The "real world" experiments indicated that the PSD-MED approach has some limitations related to the degree of fulfilment of some theoretical assumptions. When applied to in situ XRPD data, PCA, despite being based on blind statistical analysis, gave results similar to those obtained by PSD (based on Fourier analysis) for simulated data. Moreover, PCA is complementary to PSD thanks to its capability of gathering information on the Xe substructure even in the presence of a non-periodic stimulus, i.e. using the most simple stimulus shape as a single temperature ramp. In particular, PC1 results are able to perfectly reproduce the corresponding 1Ω signal from a traditional PSD analysis. Moreover PCA can be applied directly to raw non periodic XRPD data, opening the possibility of using it during an "in situ" experiment. PCA can thus be envisaged as a very useful, fast and efficient tool to improve data collection and maximize data quality. To date, however, PSD remains superior for substructure solution from the analysis of 2Ω demodulated data.

Structural characterization and thermal and chemical stability of bioactive molecule-hydrotalcite (LDH) nanocomposites.

Layered double hydroxides (LDH) are versatile materials used for intercalating bioactive molecules, both in pharmaceutical and cosmetic fields, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability, and/or obtaining modified release properties. The properties of the intercalation compounds of Mg/Al_LDH and Zn/Al_LDH with different drugs and sunscreens, namely diclofenac, ketoprofen, gliclazide, retinoic acid, furosemide, para-aminobenzoic acid and 2-phenylbenzimidazolsulfonic (Eusolex) acid, have been studied by crystallographic, spectroscopic and thermogravimetric techniques and by solid state NMR, to shed light on their structure, their molecular interactions and their stability from the thermal and chemical viewpoint. The structural features were described with particular attention to the interaction between the organic and inorganic components and to the stability of the intercalation products. For the first time two synchrotron radiation powder diffraction patterns of organic-containing LDH were solved and refined by Rietveld methods to obtain an experimental crystal structure.

In vitro release kinetics and physical, chemical and mechanical characterization of a POVIAC®/CaCO3/HAP-200 composite.

Coralline calcium-hydroxyapatite and calcium carbonate from Porites Porites coral were added to a polymeric matrix based on polyvinyl acetate (POVIAC(®)), to obtain a novel bone substitute composite as well as a system for the controlled drug (cephalexin) release. Composite samples with different compositions were characterized by physical-chemical and mechanical methods. Furthermore, the in vitro release profile of cephalexin and the kinetic behavior of its release from these composites were analyzed by appropriate mathematical models. It was shown that there is no chemical interaction between the inorganic filler and the polymer matrix, each conserving the original properties of the raw materials. The compressive mechanical strength and Young modulus of the composite with 17.5% of POVIAC(®), has better mechanical properties than those of cancellous bone. The variation of POVIAC(®) content can affect the cephalexin release kinetic in the composite. The cephalexin release mechanism from the composites can be considered as the result of the joint contribution of a prevailing Fickian diffusion and of polymer chain relaxation. It was also demonstrated that cephalexin is occluded inside the composites and not on their surface.

Kinematic diffraction on a structure with periodically varying scattering function.

A theory is developed to describe the kinematic diffraction response of a crystal when it is subjected to a periodically varying external perturbation. It is shown that if a part of the local electron density varies linearly with an external stimulus, the diffracted signal is not only a function of the stimulation frequency Ω, but also of its double 2Ω. These frequency components can provide, under certain conditions, selective access to partial diffraction contributions that are normally summed up in the interference pattern. A phasing process applied to partial diffraction terms would allow recovery of the substructure actively responding to the stimulus. Two ways of frequency filtering are discussed (demodulation and correlation) with respect to extracting information from such an experiment. Also considered is the effect of the variation of different structural parameters on the diffraction intensity that have to be accounted for while planning modulation-enhanced experiments. Finally, the advantages and limitations of the proposed concept are discussed, together with possible experiments.

Turinese stereochemistry: Eligio Perucca's enantioselectivity and Primo Levi's asymmetry.

A reputation restored: Eligio Perucca (see photo) first observed the enantioselective adsorption of a racemic mixture to a chiral crystal (NaClO(3)) in Turin in 1919. However, this milestone in enantioselective chemistry and chiroptics went unnoticed. Identified previously as a coward who refused in 1941 to supervise the research of the budding stereochemist Primo Levi because of the race laws, Perucca was opposed to the fascist regime.

A combined high-resolution X-ray powder diffraction, computational, and XPS study of the local structure of extra-framework copper ions in over-exchanged Cu-MCM22 zeolite.

Local structure and site distribution of extra-framework copper ions in over-exchanged Cu-MCM22 zeolite were determined by a combination of high resolution X-ray powder diffraction and computational analysis. X-ray diffraction data suggested the presence of three Cu sites in six-membered rings and one site in a five-membered ring close to the interlamellar region, inside the MCM-22 supercage, whereas no Cu ions were found within the sinusoidal channels. First principle molecular orbital DFT calculations were employed to obtain, for the first time, an accurate structural description of the Cu(I) sites in the supercage, adding a structural and energetic interpretation to previous IR and EPR studies. The combined experimental and computational study suggested that Cu(I) sites facing 6-MRs are particularly stable. In general 5- or 4-fold coordination sites are located in 6-MRs while 2- or 3-fold coordination sites are located in 5-MRs. Three preferentially occupied sites were found in copper-exchanged MCM-22. X-ray photoelectron spectroscopy suggested the formation of dispersed Cu close to the surface of MCM-22 crystallites, easily reduced to Cu(I) under ultrahigh vacuum conditions.

Nonenzymic polycyclization of analogues of oxidosqualene with a preformed C-ring.

Some nonenzymic epoxide-initiated polyolefin cyclization are reported. The presented molecules are partially constrained analogues of (3S)-oxidosqualene, the natural substrate to many important cyclase enzymes. These model compounds feature a preformed C-ring with built-in stereochemical information. The experimental results allow for an instructive comparison with the enzymic processes, particularly those of the cyclases in steroid biosynthesis (i.e. lanosterol synthase).

A mesoporous pattern created by nature in spicules from Thetya aurantium sponge.

Siliceous or carbonate spicules provide support and defense to marine sponges. The inorganic envelope usually embodies a protein core. Our SAXS study of the siliceous spicules from the demosponge Thetya aurantium proves the very ordered structure assumed by the protein core inside the spicules. Indeed, not only the very sharp diffraction spots already found in previous studies on spicules from different sponges are confirmed, but also the 11 sharp spots in the diffraction pattern recorded after thermal treatment at 250 degrees C can only be interpreted in terms of a natural nanocomposite mesostructure with an hexagonal lattice formed by a three-dimensional periodic arrangement of silica cages in which the protein units act as structure directing agent.

Structural characterization of siliceous spicules from marine sponges.

Siliceous sponges, one of the few animal groups involved in a biosilicification process, deposit hydrated silica in discrete skeletal elements called spicules. A multidisciplinary analysis of the structural features of the protein axial filaments inside the spicules of a number of marine sponges, belonging to two different classes (Demospongiae and Hexactinellida), is presented, together with a preliminary analysis of the biosilicification process. The study was carried out by a unique combination of techniques: fiber diffraction using synchrotron radiation, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetric (DSC), Fourier transform infrared spectroscopy (FTIR), and molecular modeling. From a phylogenetic point of view, the main result is the structural difference between the dimension and packing of the protein units in the spicule filaments of the Demospongiae and the Hexactinellida species. Models of the protein organization in the spicule axial filaments, consistent with the various experimental evidences, are given. The three different species of demosponges analyzed have similar general structural features, but they differ in the degree of order. The structural information on the spicule axial filaments can help shed some light on the still unknown molecular mechanisms controlling biosilicification.

Fiber diffraction study of spicules from marine sponges.

A synchrotron radiation fiber diffraction structural study of the axial filament of siliceous spicules from two species of marine sponges (the Demosponge Geodia cydonium and the Hexactinellid Scolymastra joubini) was carried out. The sharpness of the spots in the diffraction patterns indicated that the protein units in the filament of both samples were highly organized. A possible explanation is that the arrangement of the protein units is similar to that of the pores in highly ordered siliceous mesoporous materials. Nevertheless, the diffraction patterns are quite different for the two types of spicules. The pattern of G. cydonium is consistent with a regular 2D hexagonal lattice of protein units in the direction perpendicular to the spicule axis, with a repeating distance of 5.8 nm; the units are linked to form fibers along the axis. The pattern of S. joubini indicates the presence of two different 2D lattices in which the repeating protein units are inclined by +50 degrees and -50 degrees with respect to the elongation axis; the distance between the units increases to 8.4 nm. This 2D model is consistent with hexagonal packing of spirally oriented cylindrical protein units elongated along the filament axis.

Synthesis, biological activity, and conformational analysis of CD-ring modified trans-decalin 1 alpha,25-dihydroxyvitamin D analogs.

A novel series of analogs of 1,25-dihydroxyvitamin D3, the hormonally active metabolite of vitamin D3, characterised by the presence of a trans-fused decalin CD-ring system, possesses surprising biological activities in combination with specific structural modifications in the flexible parts of the molecule, when compared with the natural hydrindane derivatives. (1) A large difference in biological activity is observed between the 20-epimeric trans-decalin analogs that follows a pattern opposite to what is usually observed for the natural ring size. (2) Several trans-decalin analogs that are modified in the seco-B-ring region, including previtamin derivatives, possess a pronounced vitamin D-like activity, whereas the corresponding hydrindane derivatives are inactive. The molecular origin of this behavior is still under study.

Synthesis and affinity studies of himbacine derived muscarinic receptor antagonists.

A series of himbacine (1)-related analogues has been prepared featuring three different isomeric configurations with respect to the B-ring (a, b and natural c) and three different interconnecting two-carbon unsaturated units [natural (E)-ene, (Z)-ene, and yne]. The study of the binding affinities of the nine resulting compounds, including synthetic (+)-himbacine (3c), towards the M(1)-M(4) muscarine receptor subtypes revealed that analogues 3a and 5c display a promising 10-fold selectivity for the M(2) receptor as compared to the M(1) receptor.

A novel short convergent entry into himbacine derivatives.

[reaction: see text]. The IMDA reaction of 9 leads with good stereoselectivity to exo-adduct 10b. The functionalized ABC-ring core in 10 is well suited for the convergent synthesis of analogues of himbacine, a naturally occurring M2 selective muscarine receptor antagonist, as illustrated with the further synthesis of the dehydro-derivative 5.

Metallohosts Derived from the Assembly of Sugars around Transition Metals: The Complexation of Alkali Metal Cations.

The diacetone glucose (DAGH, 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose) monoanion DAG binds as a terminal alkoxo ligand to a variety of transition metals. When it is used in excess, with respect to the oxidation state of the metal, homoleptic anionic complexes [M'(DAG)(6)](3)(-) are formed. Such complexes contain oxygen-rich cavities between pairs of DAG ligands appropriate for binding alkali metal cations. The anionic complexes have been obtained by using [Li(DAG)], 1, and [Na(DAG)], 2, whose syntheses and characterization are reported here. The reaction of 1 and 2 with [V(DAG)(3)] gave [V(DAG)(6)Li(3)], 3, and [V(DAG)(6)Na(3)], 4, respectively. An alternative synthesis of 3 and 4 involves the metathesis reaction of 1 and 2 with [VCl(3)(thf)(3)]. This strategy also led to the synthesis of [Cr(DAG)(6)Li(3)], 5, and [Ti(DAG)(6)Li(3)], 6. Three pairs of DAG shape a cavity appropriate for three lithium cations in the case of complexes 3, 5, and 6; a cavity is formed for three sodium cations in the case of 4, where the alkali cation is in a tetrahedral O(4) environment. In the anionic manganese derivative [Mn(Cl)(DAG)(4)](3)(-), the four DAG units arrange in such a way as to bind four Li cations, which form a cationic cage [Mn(Cl)(DAG)(4)Li(4)](+), and Cl(-) is bound inside as [Mn(Cl)(DAG)(4)Li(4)(&mgr;(4)-Cl)], 7. Crystallographic details: 4, prism, P2(1), a = 14.735(10) Å, b = 15.033(9) Å, c= 21.021(10) Å, beta = 107.34(2) degrees, V= 4445(5) Å(3), Z = 2, and R = 7.60; 5, prismatic, C2, a = 22.671(9) Å, b = 18.785(5) Å, c = 13.886(4) Å, beta = 126.39(2) degrees, V= 4761(3) Å(3), Z = 2, and R = 7.32; 6, prismatic, P2(1), a= 13.888(5) Å, b = 18.750(5) Å, c= 17.933(5) Å, beta = 91.84(2) degrees, V = 4667(2) Å(3), Z = 2, and R = 8.75; 7, prismatic, P2(1), a = 13.306(7) Å, b= 21.311(11) Å, c = 13.376(6) Å, beta = 95.01(2) degrees, V = 3779(3) Å(3), Z = 2, and R = 9.33.