Unlocking the potential of bile acids in synthesis, supramolecular/materials chemistry and nanoscience

The Maitra group has explored a variety of chemistry with bile acids during the past 15 years and these experiments have covered a wide variety of chemistry - asymmetric synthesis, molecular recognition, ion receptors/sensors, dendrimers, low molecular mass organo and hydrogelators, gel-nanoparticle composites, etc. Some of what excites us in this field is highlighted in this perspective article.

Study of (Ba3MMWO9)-M-II-W-IV (M-II = Ca, Zn; M-IV = Ti, Zr) perovskite oxides: Competition between 3C and 6H perovskite structures

We describe an investigation of (Ba3MMWO9)-M-II-W-IV oxides for M-II = Ca, Zn, and other divalent metals and M-IV = Ti, Zr. In general, a 1:2-ordered 6H (hexagonal, P6(3)/mmc) perovskite structure is stabilized at high temperatures (1300 degrees C) for all of the (Ba3MTiWO9)-Ti-II oxides investigated. An intermediate phase possessing a partially ordered 1:1 double perovskite (3C) structure with the cation distribution, Ba-2(Zn2/3Ti1/3)(W2/3Ti1/3)O-6, is obtained at 1200 degrees C for Ba3ZnTiWO9. Sr substitution for Ba in the latter stabilizes the cubic 3C structure instead of the 6H structure. A metastable Ba3CaZrWO9 that adopts the 3C (cubic, Fm (3) over barm) structure has also been synthesized by a low-temperature metathesis route. Besides yielding several new perovskite oxides that may be useful as dielectric ceramics, the present investigation provides new insights into the complex interplay of crystal chemistry (tolerance factor) and chemical bonding (anion polarization and d(0)-induced distortion of metal-oxygen octahedra) in the stabilization of 6H versus 3C perovskite structures for the (Ba3MMWO9)-M-II-W-IV series.

Metal-ion-mediated tuning of duplex DNA binding by bis(2-(2-pyridyl)-1H-benzimidazole)

Studies of double-stranded-DNA binding have been performed with three isomeric bis)2-(n-pyridyl)-1H-benzimidazole)s (n = 2, 3, 4). Like the well-known Hoechst 33258, which is a bisbenzimidazole compound, these three isomers bind to the minor groove of duplex DNA. DNA binding by the three isomers was investigated in the presence of the divalent metal ions Mg2+, Co2+, Ni2+, Cu2+, and Zn2+. Ligand-DNA interactions were probed with fluorscence and circular dichroism spectroscopy. These studies revealed that the binding of the 2-pyridyl derivative to DNA is dramatically reduced in the presence of Co2+, Ni2+, and Cu2+ ions and is abolished completely at a ligand/metal-cation ratio of 1:1. Control experiments done with the isomeric 3- and 4-pyridyl derivatives showed that their binding to DNA is unaffected by the aforementioned transition-metal ions. The ability of 2-(2-pyridyl)benzimidazole changes of the ligand associated with ion chelation probably ledto such unusual binding results for the ortho isomer. The addition of ethylenediaminetetraacetic acid (EDTA) reversed the effects completely.

Understanding Connectivity between Groundwater Chemistry Data and Geological Stratigraphy via 3D Sub-surface Visualization and Analysis

This paper describes the 3D Water Chemistry Atlas - an open source, Web-based system that enables the three-dimensional (3D) sub-surface visualization of ground water monitoring data, overlaid on the local geological model. Following a review of existing technologies, the system adopts Cesium (an open source Web-based 3D mapping and visualization interface) together with a PostGreSQL/PostGIS database, for the technical architecture. In addition a range of the search, filtering, browse and analysis tools were developed that enable users to interactively explore the groundwater monitoring data and interpret it spatially and temporally relative to the local geological formations and aquifers via the Cesium interface. The result is an integrated 3D visualization system that enables environmental managers and regulators to assess groundwater conditions, identify inconsistencies in the data, manage impacts and risks and make more informed decisions about activities such as coal seam gas extraction, waste water extraction and re-use.

Peptide-lanthanide interactions. Crystal structure of a europium(III)-triglycine complex

Crystals of Eu-(Gly-Gly-Gly).(H2O)5.(ClO4)3 are triclinic, spacegroup P1BAR with a = 9.123 (2), b = 11.185 (5), c = 11.426 (2) angstrom; alpha = 90.79 (2), beta = 98.08 (1), gamma = 98.57 (2)-degrees; Z = 2. The europium cation is surrounded by four oxygens from three different peptide units and four oxygens from water molecules. The geometry around the metal is a distorted bi-capped trigonal prism. The peptide backbone conformation in this complex is compared with those in the free peptide and in various metal complexes. Considerable differences are observed between Eu(III) and Ca(II) complexes of triglycine. (C) Munksgaard 1994.

Study of (Ba3MMWO9)-M-II-W-IV (M-II = Ca, Zn; M-IV = Ti, Zr) perovskite oxides: Competition between 3C and 6H perovskite structures

We describe an investigation of (Ba3MMWO9)-M-II-W-IV oxides for M-II = Ca, Zn, and other divalent metals and M-IV = Ti, Zr. In general, a 1:2-ordered 6H (hexagonal, P6(3)/mmc) perovskite structure is stabilized at high temperatures (1300 degrees C) for all of the (Ba3MTiWO9)-Ti-II oxides investigated. An intermediate phase possessing a partially ordered 1:1 double perovskite (3C) structure with the cation distribution, Ba-2(Zn2/3Ti1/3)(W2/3Ti1/3)O-6, is obtained at 1200 degrees C for Ba3ZnTiWO9. Sr substitution for Ba in the latter stabilizes the cubic 3C structure instead of the 6H structure. A metastable Ba3CaZrWO9 that adopts the 3C (cubic, Fm (3) over barm) structure has also been synthesized by a low-temperature metathesis route. Besides yielding several new perovskite oxides that may be useful as dielectric ceramics, the present investigation provides new insights into the complex interplay of crystal chemistry (tolerance factor) and chemical bonding (anion polarization and d(0)-induced distortion of metal-oxygen octahedra) in the stabilization of 6H versus 3C perovskite structures for the (Ba3MMWO9)-M-II-W-IV series.

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.

Photocytotoxic Lanthanum(III) and Gadolinium(III) Complexes of Phenanthroline Bases Showing Light-Induced DNA Cleavage Activity

Lanthanide complexes of formulation [La(B)(2)(NO3)(3)] (1-3) and [Gd(B)(2)(NO3)(3)] (4-6), where B is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 4),dipyrido[3,2-d2',3'-f]quinoxaline (dpq in 2,5) and dipyrido[3,2-a2',3'-c]phenazine (dppz in 3, 6), have been prepared, characterized from physicochemical data, and their photoinduced DNA and protein cleavage activity studied The photocytotoxicity of the dppz complexes 3 and 6 has been studied using HeLa cancer cells. The complexes exhibitligand centered bands in the UV region The dppz complexes show thelowest energy band at 380 nm in N,N-dimethylformamide (DMF) The La(III)complexes are diamagnetic. The Gd(III) complexes (4-6) have magneticmoments that correspond to seven unpaired electrons The complexes are1(.)1 electrolytic in aqueous DMF The dpq and dppz complexes in DMFshow ligand-based reductions. The complexes display moderate binding propensity to calf thymus DNA giving binding constant values in the range of 5.7 x 10(4)-5.8 x 10(5) M-1 with a relative order. 3, 6 (dppz)> 2, 5 (dpq) > 1, 4 (phen) The binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes do not show any hydrolytic cleavage of plasmid supercoiled pUC19 DNA. The dpq and dppz complexes efficiently cleave SC DNA to its nicked circular form onexposure to UV-A light of 365 nm at nanomolar complex concentration. Mechanistic studies reveal the involvement of singlet oxygen (O-1(2)) and hydroxyl radical (HO center dot) as the cleavage active species.The complexes show binding propensity to bovine serum albumin (BSA)protein giving K-BSA values of similar to 10(5) M-1. The dppz complexes 3 and 6 show BSA protein cleavage activity in UV-A light of 365 nm The dppz complexes 3 and 6 exhibit significant photocytotoxicity in HeLa cells giving respective IC50 values of 341 nM and 573 nM in UV-A light of 365 nm for an exposure time of 15 min (IC50 > 100 mu M in dark for both the complexes) Control experiments show significant dark and phototoxicity of the dppz base alone (IC50 = 413 nM in light with 4 h incubation in dark and 116 mu M in dark with 24 h incubation). A significant decrease in the dark toxicity of the dppz base is observedon binding to the lanthanide ions while retaining similar phototoxicity.

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.

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

Corrected spacegroup for M0.5Ti2P3O12 compounds

The space group of the low thermal expansion phosphates, belonging to NASICON structural family, having divalent cations has been reassigned as RImage based on powder X-ray diffraction studies in the system M0.5Ti2P3O12. This implies further ordered distribution of M2+ cations and vacancies along the hexagonal ‘c’ direction of NASICON structure.