Spray Drying as an Approach for Enhancement of Dissolution and Bioavailability of Raloxifene Hydrochloride.

The present study investigated the effect of spray drying raloxifene HCl (RHCL) with different classes of hydrophilic carriers (different grades of polyvinyl pyrrolidones) and cellulosic polymers) in order to determine the potential effect on dissolution rate and bioavailability of RHCL. Pre-formulation studies were conducted to select the appropriate carriers and drug:carrier ratio for preparing the spray dried compositions.The solid state interactions of the spray dried mixtures were evaluated by DSC & XRD. Preformulation studies revealed that amorphous compositions of RHCL could be obtained only with Plasdones (K12, K29/32 and S630). DSC studies showed that the crystalline nature of RHCL was significantly reduced on spray drying. Significant enhancement in dissolution rate was observed with the prepared spray dried compositions and out of the three grades of Plasdone, Plasdone K12 demonstrated the maximum enhancement in rate of release of RHCL. The pharmacokinetics of spray dried composition (1:1 RHCL: K12) and pure RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague Dawley rats. The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with spray dried mixture of RHCL, K12 (1:1) compared to animals treated with RHCL. Spray drying of RHCL with Plasdones, especially Plasdone K12, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability

Calcium silicates synthesised from industrial residues with the ability for CO2 sequestration

This work explored several synthesis routes to obtain calcium silicates from different calcium-rich and silica-rich industrial residues. Larnite, wollastonite and calcium silicate chloride were successfully synthesised with moderate heat treatments below standard temperatures. These procedures help to not only conserve natural resources, but also to reduce the energy requirements and CO2 emissions. In addition, these silicates have been successfully tested as carbon dioxide sequesters, to enhance the viability of CO2 mineral sequestration technologies using calcium-rich industrial by-products as sequestration agents. Two different carbon sequestration experiments were performed under ambient conditions. Static experiments revealed carbonation efficiencies close to 100% and real-time resolved experiments characterised the dynamic behaviour and ability of these samples to reduce the CO2 concentration within a mixture of gases. The CO2 concentration was reduced up to 70%, with a carbon fixation dynamic ratio of 3.2 mg CO2 per g of sequestration agent and minute. Our results confirm the suitability of the proposed synthesis routes to synthesise different calcium silicates recycling industrial residues, being therefore energetically more efficient and environmentally friendly procedures for the cement industry.Ministerio de Ciencia e Innovación CIT-440000-09-0

Phosphine-porphyrin conjugates : a thesis presented in partial fulfilment of the requirements for the degree of Masterate of Science in Chemistry at Massey University, New Zealand

The research carried out in this thesis comprises an investigation into the synthesis and characterisation of a variety of complexed phosphine-aldehydes, complexed phosphinoporphyrins, and phosphinoferrocene conjugates. The porphyrin and phosphine moieties are linked together via the vinyl group, a product of Wittig chemistry. In general, functionalisation occurs at the β-pyrrolic position of the porphyrin and at the para position of a phenyl group on the phosphine. Chapter One introduces the properties of porphyrins and the triphenylphosphine ligand, as well as a brief review on the types of functionalised triphenylphosphines. A brief review of existing phosphinoporphyrins is also discussed. The proposal for using the vinylic linking group (and hence Wittig chemistry) to connect the porphyrin and the phosphine moieties is also described. Chapter Two outlines the synthesis of the 4-(diphenylphosphino)benzaldehyde (5) ligand, which is a necessary precursor for the Wittig reaction with meso-tetraphenylporphyrin (TPP) phosphonium salt (1). It was discovered that the Wittig reaction of (1) with (5) led to the synthesis of the product of oxidation, phosphinoporphyrin oxide (7), instead of the desired phosphinoporphyrin (6). Therefore an alternative scheme was pursued - complexation before the Wittig reaction. Hence the remainder of the chapter describes both the synthesis and characterisation aspects of five transition metal complexes of (5). These include complexes of gold, ruthenium, tungsten, and platinum. Chapter Three describes the synthesis and characterisation of a variety of novel complexed phosphinoporphyrins, including two bis-phosphinoporphyrin complexes. This was achieved by utilising Wittig chemistry of TPP phosphonium salt (1) with the appropriate complexed phosphine-aldehyde. In each case, optimisation of the Wittig conditions was required in order to obtain the sterically and thermodynamically favoured trans isomer. Chapter Four extends the phosphinoporphyrin chemistry by investigating the synthesis of a novel phosphinoporphyrin trimer. In order to achieve this, a phosphine tris-aldehyde was synthesised. This chapter focuses on the synthesis and characterisation of tris(4-formylphenyl)phosphine oxide (20). The results of the Wittig reaction of (20) with TPP phosphonium salt (1) are also described. Chapter Five demonstrates the versatility of both the Wittig and phosphine chemistry. In this chapter, the synthesis of phosphinoferrocenes via Wittig chemistry is investigated. The ferrocene and phosphine moieties are linked via the vinyl group, in a similar manner as the phosphinoporphyrins. In this case, functionalisation occurs at the para position of a phenyl group of the phosphine to the cyclopentadienyl ring of the ferrocene. A phosphinoferrocene monomer, (24), was synthesised by Wittig reaction of a ferrocene phosphonium salt (22) with (5). Both the synthesis and characterisation of this compound is reported. Also described is the attempted synthesis of a phosphinotrisferrocene via Wittig reaction of (22) with (20). Chapter Six contains a brief summary of the results obtained during this study, and also mentions future research to be pursued in this field of study

The Role of Starbursts in the Formation of Galaxies & Active Galactic Nuclei

Starbursts are episodes of intense star-formation in the central regions of galaxies, and are the sites of roughly 25% of the high-mass star-formation in the local universe. In this contribution I review the role starbursts play in the formation and evolution of galaxies, the intergalactic medium, and active galactic nuclei. Four major conclusions are drawn. 1) Starburst galaxies are good analogues (in fact, the only plausible local analogues) to the known population of star-forming galaxies at high-redshift. 2) Integrated over cosmic time, supernova-driven galactic-winds (`superwinds') play an essential role in the evolution of galaxies and the inter-galactic medium. 3) Circumnuclear starbursts are an energetically-significant component of the Seyfert phenomenon. 4) The evolution of the population of the host galaxies of radio-quiet quasars is significantly different than that of powerful radio galaxies, and is at least qualitatively consistent with the standard picture of the hierarchical assembly of massive galaxies at relatively late times.Comment: 16 pages, 4 figures, Royal Society discussion meeting `The formation of galaxies

Komplexchemie perhalogenierter Cyclopentadiene und Alkine, VII

Coordination Chemistry of Perhalogenated Cyclopentadienes and Alkynes, VII1). - Synthesis of Several Tetrachlorometalloles of Cobalt, Rhodium, and Iridium; Structure of a Iridacyclopentadiene Derivative The reaction of dichloroethyne with CpCo(PPh3)2, RhCl(EPh3)3 (E = P, As, Sb), and IrCl(N2)(PPh3)2 leads to the formation of complexes containing a tetrachloro-1-metallacyclopentadiene unit. The crystal-structure determination of (Ph3P)2(Cl)- is reported

Metallkomplexe mit biologisch wichtigen Liganden, LXV

Cp*Co(CO)I2 (Cp* = 5-C5Me5), [(6-arene)RuCl2]2 (arene = p-cymene, hexamethylbenzene), and [Cp*MCl2]2 (M = Rh, Ir) react with -amino amides and various peptide esters to give the N,O-chelate complexes [Cp*(I)Co - NH2C(H)(R1)C(NHR2)-O]+ (1), [(6-arene)(Cl)Ru - NH2C(H)(R1)C(NHR2)O]+ (2), and [CP*(Cl)M - NH2CH2C(NHR)O]+ (M = Rh, Ir) (5, in solution), respectively. In the solid state the ligands are 1N-bonded in 5. By deprotonation of the peptide bond in 2 and 5 the neutral N, N-chelate complexes (6-arene)(Cl)Ru - NH2C(H)(R1)C(O)-2 (6) and Cp*(Cl)M - NH2C(H)(R1)C(O)NR2 (M = Rh, Ir) (7) have been obtained. Glycinenitrile is 1-bonded in (6-p-cymene)(Cl)2Ru(NH2CH2CN) (3) and Cp*(Cl)2Rh(NH2CH2CN) (4). Double deprotonated triglycine methyl ester is a N,N,N-tridentate ligand in (6-C6Me6)Ru(NH2CH2C(O)NCH2C(O)-NCH2CO2Me) (8). The anions of L-asparagine and of aspartame (L-aspartyl-L-phenylalanine methyl ester) give the complexes 9-12 with tridentate O,N,O- or O,N,N-chelate ligands. The crystal structures of 1d (L = glyglyOEt), 5a (L = glycinamide), 6e (L = glyglyOEt), and 7k (L = glyglyglyOEt) have been determined by X-ray structural analysis

Different coordination modes of an aryl-substituted hydrotris(pyrazolyl) borate ligand in rhodium and iridium complexes

Complexes TptolRh(C2H4)2 (1a) and TptolRh(CH2C(Me)C(Me)CH2) (1b) have been prepared by reaction of KTptol with the appropriate [RhCl(olefin)2]2 dimer (Tptol means hydrotris(3-p-tolylpyrazol-1-yl)borate). The two complexes show a dynamic behaviour that involves exchange between κ2 and κ3 coordination modes of the Tptol ligand. The iridium analogue, TptolIr(CH2C(Me)CHCH2) (2) has also been synthesized, and has been converted into the Ir(III) dinitrogen complex [(κ4-N,N',N'',C-Tptol)Ir(Ph)(N2) (3) by irradiation with UV light under a dinitrogen atmosphere. Compound 3 constitutes a rare example of Ir(III)-N2 complex structurally characterized by X-ray crystallography. Its N2 ligand can be easily substituted by acetonitrile or ethylene upon heating and denticity changes in the Tptol ligand, from κ4-N,N',N'',C (monometallated Tptol, from now on represented as Tptol′) to κ5-N,N′,N″,C,C″ (dimetallated Tp tol ligand, represented as Tptol″) have been observed. When complex 3 is heated in the presence of acetylene, dimerization of the alkyne takes place to yield the enyne complex [(κ5-N,N′,N′′,C,C′-Tp tol)Ir(CH2CHCCH), 7̧ in which the unsaturated organic moiety is bonded to iridium through the carbon-carbon double bond.Ministerio de Educación y Ciencia CTQ2007-62814Consolider-Ingenio 2010 CSD2007-00006Junta de Andalucía FQM-3151, FQM-672CONACYT 22934

Rapid asymmetric transfer hydroformylation (ATHF) of disubstituted alkenes using paraformaldehyde as a syngas surrogate

The authors thank Dr. Reddys (UK) and the Royal Society for an Industry Fellowship in the early stage of this work (2012–2014), and the EPSRC for funding (EP/M003868/1).As an alternative to conventional asymmetric hydroformylation (AHF), Asymmetric Transfer Hydroformylation (ATHF) using formaldehyde as a surrogate for syngas is reported. A catalyst derived from commercially available [Rh(acac)(CO)2] and Ph-BPE stands out in terms of both activity and enantioselectivity. Remarkably, not only are high selectivities achievable, the reactions are very simple to carry out, and can give higher enantioselectivity (up to 96% e.e.) and/or turnover frequencies than those that are achievable using the same catalyst (or other leading catalysts) using typical conditions for AHF.Publisher PDFPeer reviewe

Synthesis, properties, and some rhodium, iridium, and platinum complexes of a series of bulky m-terphenylphosphine ligands

A series of sterically demanding aryl phosphine ligands (L) bearing terphenyl substituents, PR2Ar′ (R = hydrocarbyl, Ar′ = 2,6-diarylphenyl radical) has been prepared and characterized. The stability of these ligands towards oxidation in the air has been tested, and theoretical and experimental studies aimed to provide information on their electronic and steric properties have been performed. Treatment of the metal dimers [MCl(COD)]2(M = Rh, Ir; COD = 1,5-cyclooctadiene) with ligands PMe2ArXyl2(L1) and PMe2ArDipp2(L5), in a 1:1 metal:ligand ratio, afforded the expected square-planar 16-electron complexes [MCl(COD)(PMe2ArXyl2)] and [MCl(COD)(PMe2ArDipp2)], respectively. These compounds were readily converted into the corresponding dicarbonyl derivatives, [MCl(CO)2(PMe2ArXyl2)] and [MCl(CO)2(PMe2ArDipp2)], respectively. While the expected κ1-P coordination mode of the PR2Ar′ ligands is found for these rhodium and iridium species, the mononuclear Pt(II) derivative obtained by reaction of PtCl2with PMe2ArDipp2has composition [PtCl2(PMe2ArDipp2)], and exhibits a bidentate κ1-P, η1-arene coordination mode involving one of the ipso carbon atoms of a flanking terphenyl aryl ring. The corresponding carbonyl compound [PtCl2(CO)(PMe2ArDipp2)], was generated under a CO atmosphere and exhibits κ1-P coordination mode.Ministerio de Ciencia CTQ2013-42501-P, CTQ2014-51912-REDC, CTQ-2014-52769-C3-3-RJunta de Andalucía FQM-119 P09-FQM-4832, FQM-2126European Union 26722

Facile synthetic procedure for and electrochemical properties of hexa(2-thienyl)benzenes directed toward electroactive materials

In the presence of RhCl3 center dot 3H(2)O and i-Pr2NEt, the cyclotrimerization of di(2-thienyl)acetylenes proceeded smoothly to afford hexa(2-thienyl)benzenes. CV analysis of the hexa(2-thienyl)benzenes showed that they may be useful as electroactive materials.</p