Mass spectrometry and n-in-one analytics in early drug discovery: Combinatorial chemistry libraries, lipophilicity and absorption screening

This thesis describes current and past n-in-one methods and presents three early experimental studies using mass spectrometry and the triple quadrupole instrument on the application of n-in-one in drug discovery. N-in-one strategy pools and mix samples in drug discovery prior to measurement or analysis. This allows the most promising compounds to be rapidly identified and then analysed. Nowadays properties of drugs are characterised earlier and in parallel with pharmacological efficacy. Studies presented here use in vitro methods as caco-2 cells and immobilized artificial membrane chromatography for drug absorption and lipophilicity measurements. The high sensitivity and selectivity of liquid chromatography mass spectrometry are especially important for new analytical methods using n-in-one. In the first study, the fragmentation patterns of ten nitrophenoxy benzoate compounds, serial homology, were characterised and the presence of the compounds was determined in a combinatorial library. The influence of one or two nitro substituents and the alkyl chain length of methyl to pentyl on collision-induced fragmentation was studied, and interesting structurefragmentation relationships were detected. Two nitro group compounds increased fragmentation compared to one nitro group, whereas less fragmentation was noted in molecules with a longer alkyl chain. The most abundant product ions were nitrophenoxy ions, which were also tested in the precursor ion screening of the combinatorial library. In the second study, the immobilized artificial membrane chromatographic method was transferred from ultraviolet detection to mass spectrometric analysis and a new method was developed. Mass spectra were scanned and the chromatographic retention of compounds was analysed using extract ion chromatograms. When changing detectors and buffers and including n-in-one in the method, the results showed good correlation. Finally, the results demonstrated that mass spectrometric detection with gradient elution can provide a rapid and convenient n-in-one method for ranking the lipophilic properties of several structurally diverse compounds simultaneously. In the final study, a new method was developed for caco-2 samples. Compounds were separated by liquid chromatography and quantified by selected reaction monitoring using mass spectrometry. This method was used for caco-2 samples, where absorption of ten chemically and physiologically different compounds was screened using both single and nin- one approaches. These three studies used mass spectrometry for compound identification, method transfer and quantitation in the area of mixture analysis. Different mass spectrometric scanning modes for the triple quadrupole instrument were used in each method. Early drug discovery with n-in-one is area where mass spectrometric analysis, its possibilities and proper use, is especially important.

Microbially Induced Mineral Beneficiation

The divergent role of microbes in the field of mineral processing starting from mining and beneficiation to efficient waste disposal has been well recognized now. The roles of various microorganisms and bioreagents in the beneficiation of minerals are illustrated in this paper. Various types of microorganisms useful in bringing about selective flotation and flocculation of various oxide and sulfide minerals are illustrated. Interfacial phenomena governing microbe-mineral interactions are discussed with reference to bacterial cell wall architecture, cell surface hydrophobicity, electrokinetic data, and adsorption behavior on various minerals. Applications of microbially induced mineral beneficiation are demonstrated with respect to beneficiation of iron ores, bauxite, limestone, and complex multimetal sulfides.

Future chemistry teachers use of knowledge dimensions and high-order cognitive skills in pre-laboratory concept maps

This poster describes a pilot case study, which aim is to study how future chemistry teachers use knowledge dimensions and high-order cognitive skills (HOCS) in their pre-laboratory concept maps to support chemistry laboratory work. The research data consisted of 168 pre-laboratory concept maps that 29 students constructed as a part of their chemistry laboratory studies. Concept maps were analyzed by using a theory based content analysis through Anderson & Krathwohls' learning taxonomy (2001). This study implicates that novice concept mapper students use all knowledge dimensions and applying, analyzing and evaluating HOCS to support the pre-laboratory work.

An acid method for the volumetric estimation of water-soluble dithiocarbamates

Dithiocarbamates have been estimated previously by reaction with a strong acid, the carbon disulfide evolved being converted into a xanthate and the latter estimated iodimetrically. In the present method, a water-soluble dithiocarbamate is reacted with a decinormal mineral acid and the excess acid is determined to compute the amount of dithiocarbamate present. This method is applicable for the determination of a dithiocarbamate in a mixture containing thiuram disulfide.

Click chemistry inspired synthesis of ferrocene amino acids and other derivatives

This work reports the synthesis of a wide range of ferrocenyl-amino acids and other derivatives in excellent yield. Diverse amino acid containing azides were synthesized and ligated to ferrocene employing click reaction to access ferrocenyl amino acids. Chiral alcohols, esters, diols, amines containing azido group were tagged to ferrocene via click reaction to generate ferrocene derived chiral derivatives. A novel strategy for direct incorporation of ferrocene into a peptide and a new route to 1, 1′disubstituted ferrocene amino acid derivative are reported.

Emerging trends at the interface of chemistry and biology: Applications to the design of human therapeutics

This article describes recent developments in the design and implementation of various strategies towards the development of novel therapeutics using first principles from biology and chemistry. Strategies for multi-target therapeutics and network analysis with a focus on cancer and HIV are discussed. Methods for gene and siRNA delivery are presented along with challenges and opportunities for siRNA therapeutics. Advances in protein design methodology and screening are described, with a focus on their application to the design of antibody based therapeutics. Future advances in this area relevant to vaccine design are also mentioned.

Oxygen chemistry in copper oxides: evidence for O− species

Core-level spectroscopic studies suggest that cuprates nominally supposed to contain Cu3+ions are likely to have the excess positive charge on oxygen instead, giving rise to O-type species (oxygen holes)

Am unexpected entry into the silver(I) chemistry of diphosphazane ligands: Crystal and molecular structures of [Ag{Ph2PN(Pr-i)PPh2}(CF3SO3)](2), [Ag{Ph2PN(Pr-i)PPh(OC6H3Me2-2,6)}(2)]PF6, and [Ag-3(mu-Cl)(2){Ph2PN(R)PPh2}(3)]PF6 (R = H, Pr-i)

Mononuclear, binuclear and trinuclear silver(l) complexes were obtained unexpectedly while probing the reactivity of diphosphazane ligands of the type X2PN(Pr-i)PXY towards the ruthenium-based precursor Ru(bipy)(2)Cl-2 center dot 2H(2)O, in the presence of a silver salt as a chloride scavenger. Subsequently, the reactions of AgX [X = Cl, NO3 or CF3SO3] with Ph2PN(R)PPh(Y) [R = H, Y = Ph; R = Pr-i, Y = Ph or OC6H3Me2-2,6] in a 1: 1 or 1:2 molar ratio have been investigated. Mononuclear or binuclear Ag(I) complexes containing either chelating or bridging diphosphazane ligands are obtained. Trinuclear silver(l) complexes are accessible by the treatment of diphosphazane ligands, Ph2PN(R)PPh2 [R = H, Pr-i] with AgCl using piperidine as the solvent. In the presence of a suitable chloride donor species, the mononuclear and binuclear complexes of Ph2PN(Pr-i)PPh2 are transformed slowly to the trinuclear complex [Ag-3(mu-Cl)(2){Ph2PN(Pr-i)PPh2}(3)]X, over a period 20 h. The structures of representative complexes have been confirmed by X-ray crystallography and the salient structural features are discussed

Acidification of lakes in Finland : regional estimates of lake chemistry and critical loads

Yhteenveto: Järvien happamoituminen Suomessa: Alueellinen vedenlaatu ja kriittinen kuormitus

Crystal chemistry of a new solid solution in the BaO-Bi2O3-Nb2O5 system: Ba-5x/2-Bi(1-x)5/3Nb5O15

A solid solution of the type Ba5x/2Bi(1-x)5/3Nb5O15 has been identified in the BaO-Bi2O3-Nb2O5 system for the first time. The limits of the solid solution are within the range 0.52 <= x <= 0.80. The compositions x = 0.52, 0.60, 0.72, 0.77, 0.78, and 0.80 were synthesized by the solid-state technique from the starting materials in stoichiometric quantities. The powder X-ray patterns of all the phases in the domain indicate a structural similarity to tetragonal tungsten bronzes (TTBs). The compositions below x = 0.52 and those above x = 0.80 exhibit barium niobate and bismuth niobate impurities, respectively. Single crystals of the composition x = 0.77 were obtained by the melt cooling technique. The crystal structure of Ba3.85/2Bi1.15/3Nb5O15 (x = 0.77) was solved in the tetragonal space group P4bm (No. 100) with a = 12.4938 (14) angstrom, c = 3.9519 (2) A, V = 616.87 (10) angstrom(3), and Z = 2 and was refined to an R index of 0.034. Dielectric measurements on all the phases indicate a typical relaxor behavior with a broad phase transition at T-m approximate to 300 K.

Chemistry of the incomplete decomposition of ammonium perchlorate (AP)

Results are presented to show that as the thermal decomposition of orthorhombic ammonium perchlorate proceeds there is an accumulation, in the solid, of hydrochloric and nitric acids, the concentrations of which increase up to 15% decomposition after which they decrease until they reach the original values.

Solid-state chemistry of high-temperature oxide superconductors:The experimental situation

High-temperature superconductivity in oxides of the type(La, Ln)2?xBax(Sr)xCuO4, Y(Ln)Ba2Cu3O7??, La3?xBa3+xCu6O14, and related systems is discussed with emphasis on aspects related to experimental solid-state chemistry. All of these oxides possess perovskite-related structures. Oxygen-excess and La-deficient La2CuO4 also exhibit superconductivity in the 20�40 K just as La2?xBax(Srx)CuO4; these oxides are orthorhombic in the superconductivity phase. The crucial role of oxygen stoichiometry in the superconductivity ofYBa2Cu3O7?? (Tc = 95 ± 5K) is examined; this oxide remains orthorhombic up to ? ? 0.6 and becomes tetragonal and nonsuperconducting beyond this value of ?. Oxygen stoichiometry in this and related oxides has to be understood in terms of structure and disorder. The structure of La3?xBa3+xCu6O14 is related to that of YBa2Cu3O7, the orthorhombic structure manifesting itself when the population of O1 oxygens (along the Cusingle bondOsingle bondCu chains) is preponderant compared to that of O5 oxygens (along thea-axis); nearly equal populations of O1 and O5 sites give rise to the tetragonal structure. A transition from a high-Tc (95 K) superconductivity regime to a low-Tc (not, vert, similar60 K) regime occurs in YBa2Cu3O7?? accompanying a change in ?. There is no evidence for Cu3+ in these nominally mixed valent copper oxides. Instead, holes are present on oxygens giving rise to O? or O2?2 species, the concentration of these species increasing with the lowering of temperature. Certain interesting aspects of the superconducting oxides such as domain or twin boundaries, Raman spectra, microwave absorption, and anomalous high-temperature resistivity drops are presented along with the important material parameters. Preparative aspects of the superconducting oxides are briefly discussed. Phase transitions seem to occur atTc as well as at not, vert, similar240 K in YBa2Cu3O7.