Elevated-temperature metathesis syntheses of structurally novel alkali-metal tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes: toluene-coordinated discrete bimetallic complexes and supramolecular chains

Sodium and potassium tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes [M[Ln(tBu(2)pz)(4)]] have been prepared by reaction of anhydrous lanthanoid trihalides with alkali metal 3,5-di-tert-butylpyrazolates at 200-300 degrees C, and a 1,2,4,5-tetramethylbenzene flux for M=K. On extraction with toluene (or occasionally directly from the reaction tube) the following complexes were isolated: [Na(PhMe)[Ln(tBu(2)pz)(4)]] (1 Ln; 1 Ln=1 Tb, 1 Ho, 1 Er, 1 Yb), [K(PhMe)[Ln(tBu(2)pz)(4)]].2 PhMe (2 Ln; 2 Ln=2 La, 2 Sm, 2 Tb, 2 Ho, 2 Yb, 2 Lu), [Na[Ln(tBu(2)pz)(4)]](n) (3 Ln; 3 Ln=3 La, 3 Tb, 3 Ho, 3 Er, 3 Yb), [K[Ln(tBu(2)pz)(4)]](n) (4 Ln; 4 Ln=4 La, 4 Nd, 4 Sm, 4 Tb, 4 Ho, 4 Er, 4 Yb, 4 Lu), with the last two classes generally being obtained by loss of toluene from 1 Ln or 2 Ln, and [Na(tBu(2)pzH)[Ln(tBu(2)pz)(4)]].PhMe (5 Ln; 5 Ln=5 Nd, 5 Er, 5 Yb). Extraction with 1,2-dimethoxyethane (DME) after isolation of 2 Ho yielded [K(dme)[Ho(tBu(2)pz)(4)]] (6 Ho). X-ray crystal structures of 1 Ln (=1 Tb, 1 Ho; P2(1)/c), 2 Ln (=2 La, 2 Sm, 2 Tb, 2 Yb, 2 Lu; Pnma), 3,4 Ln (=3 La, 3 Er, 4 Sm; P2(1)/m), and 5 Ln (=5 Nd, 5 Er, and 5 Yb; P1) show each group to be isomorphous regardless of the size of the Ln(3+) ion. All complexes contain eight-coordinate [Ln(eta(2)-tBu(2)pz)(4)] units. These are further linked to the alkali metal by bridging through two (1,2,5 Ln) or three (3,4 Ln) tBu(2)pz groups which show striking coordination versatility. Sodium is coordinated by an eta(4)-PhMe, a micro-eta(2):eta(2)-tBu(2)pz, and a micro-eta(4)(Na):eta(2)(Ln)-tBu(2)pz ligand in 1 Ln, and by one eta(1)-tBu(2)pzH and two micro-eta(3)(Na):eta(2)(Ln) ligands in 5 Ln. By contrast, potassium has one eta(6)-PhMe and two micro-eta(5)(K):eta(2)(Ln) ligands in 2 Ln. Classes 3,4 Ln form polymeric chains with the alkali metal bonded by two micro-eta(3)(NNC-M):eta(2)(Ln)-tBu(2)pz ligands within [MLn(tBu(2)pz)(4)] units which are joined together by eta(1)(C)-tBu(2)pz-Na, K linkages.     

Sensitive and rapid analysis of protein palmitoylation with a synthetic cell-permeable mimic of SRC oncoproteins

The localization of oncogenic Src and Ras proteins to cellular plasma membranes is critical for the proliferation of specific cancers. In addition to other lipid modifications, these proteins require posttranslational palmitoylation of specific cysteine residues by the enzyme palmitoyl acyltransferase (PAT) in order to be stably anchored at plasma membranes. Hence, the identification of inhibitors of protein palmitoylation has significant potential to define a new class of antitumor agents. However, studies of protein palmitoylation have been hindered by the dynamic and reversible nature of cysteine acylation and the lack of sensitive and convenient assays of PAT activity. To facilitate the rapid identification of compounds that affect protein palmitoylation, we report the solid-phase synthesis of a fluorescent cell-permeable palmitoyl acyltransferase substrate that mimics the N-terminus of Src family proteins. Metabolic radiolabeling and epifluorescence microscopy of Jurkat lymphocytes treated with this Src-mimetic lipopeptide revealed that this compound is palmitoylated intracellularly, which confers localization at cellular plasma membranes. Addition of the palmitoylation inhibitor 2-bromopalmitic acid to substrate-treated cells blocked palmitoylation and diminished substrate-mediated plasma membrane fluorescence. Analysis of inhibition of palmitoylation by flow cytometry revealed that this fluorescent lipopeptide substrate represents a highly sensitive molecular probe of palmitoyl acyltransferase activity that enables unprecedented high-throughput assays of protein palmitoylation.     

Synthetic, structural and spectroscopic studies of (pseudo)halo(1,3-di-tert-butylimidazol-2-ylidine)gold complexes

A series of (pseudo)halo(1,3-di-tert-butylimidazol-2-ylidine)gold complexes [(But2Im)AuX](X = Cl, Br, I, CN, N3, NCO, SCN, SeCN, ONO2, OCOCH3, CH3) have been synthesized and characterised spectroscopically and structurally. 13C NMR chemical shifts for the carbene carbon vary widely with differing ancillary anion, correlating well with the sigma-donor ability of the latter and with the M-C(carbene) bond distance. These results reinforce the notion that N-heterocyclic carbene ligands are primarily sigma-donor ligands with little pi-acceptor ability.     

Synthesis and biological evaluation of nucleosides containing 8-amino-imidazo[1,2-α]pyrazine as an isosteric replacement for adenine

A number of novel C-nucleosides related to purine derivatives are described in which the purine moiety has been replaced by the isosteric heterocycle, 8-aminoimidazo[1,2-α]pyrazine. The nucleosides prepared include the ribo, 3′-deoxy, 2′,3′-dideoxy, and 2′,3′-unsaturated derivatives. These C-nucleosides represent derivatives containing acid stable glycosyl bonds and they can be considered as analogs of adenine- or 3-deazaade-nine-containing nucleosides. Preparation of the parent ribonucleoside was accomplished by reaction of the C-l functionalized sugar, (2ξ)-1-amino-3,6-anhydro-l-deoxy-4,5-O-isopropylidene-7-O-trityl-D-allo-heptitol with 2,3-dichloropyrazine, followed by ring closure to the 8-chloroimidazo[1,2-α]pyrazine nucleoside, conversion to the 8-amino derivative and deblocking. A single crystal X-ray structure of the parent 8-amino-3-(β-D-ribofuranosyl)imidazo[1,2-α]pyrazine is described and the conformation compared to that of formycin. The sugar-modified analogs were prepared by subsequent functional group manipulations on the sugar moiety. Biological evaluation against HIV in H9 T-lymphoid cell culture showed the nucleosides to be devoid of significant antiviral activity compared to DDA. The 3-deazaadenosine analog also demonstrated weak suppression of mouse splenic NK activity toward YAC cells (mouse lymphoma cell targets). The imidazo[1,2-α]pyrazine analog of 3-deazaadenosine showed antiinflammatory activity in vivo in the rat pleurisy carrageenan model in the same range with 3-deazaadenosine.     

Thiol- and disulfide-modified oligonucleotide monolayer structures on polycrystalline and single-crystal Au(111) surfaces

We provide a comprehensive study of single- (ss) and double-strand (ds) oligonucleotides with either 25 or 10 bases or base pairs (bp) immobilized on polycrystalline and single-crystal Au(111) surfaces. The study is based on X-ray photoelectron spectroscopy, cyclic and differential pulse voltammetry, interfacial capacitance data, and electrochemical scanning tunnelling microscopy (in situ STM). The sequences used were the 25-bp sequence from the BRCA1 gene (25-mer), while the 10-bp oligonucleotides contained solely linear adenine and thymine sequences. The oligonucleotides were modified by the dimethoxytrityl group (DMT) via a disulfide group [DMT-S-S-ss25-mer and DMT-S-S-ds(AT)₁₀], a pure disulfide group (A₁₀-S-S-T₁₀), or a thiol group [HS-ss25-mer and HS-ds-(AT)₁₀], all via a hexamethylene linker. The overall pattern suggests strategies for controlled adsorption of DNA-based molecules and recognition of complementary strands or other molecules.     

Investigation of the chiral surfactant N-dodecoxycarbonylvaline in electrokinetic chromatography: improvements in elution range and pH stability via mixed micelles and vesicles, and the hydrophobicity determination of basic pharmaceutical drugs

The chiral surfactant dodecoxycarbonylvaline (DDCV) has proven to be an effective pseudostationary phase for the separation of many enantiomeric pharmaceutical compounds. In this study the elution range and the prediction of octanol-water partitioning for the DDCV micellar system was examined. Through incorporation of DDCV in mixed micelles and unilamellar vesicles, enhancement of the elution range was observed. The mixed micelles contained a second anionic surfactant, sodium dodecyl sulfate (SDS), while the vesicles were composed of DDCV and the cationic surfactant cetyltrimethylammonium bromide (CTAB). Enantioselectivity, as well as other chromatographic and electrophoretic parameters, were compared between the mixed micelles, vesicles, and DDCV micelles. The hydrophobicity of the DDCV system was also evaluated as a predictor of n-octanol-water partition coefficients for 15 beta amino alcohols. The correlation between the logarithm of the retention factor (log k) and log P(ow) for seven hydrophobic beta-blockers and eight beta-agonists were r2 = 0.964 and r2 = 0.814, respectively.     

Topography of the potential energy hypersurface and criteria for fast-ion conduction in perovskite-related A2B2O5 oxides

We discuss the importance of the topography of the potential energy hypersurface for the ionic conductivity of perovskite-related A(2)B(2)O(5) oxides. A correlation between the energetic preference of the cations for different coordination geometries and the ionic conductivity is proposed based on a first principles periodic density functional theory study of selected possible structures for Ba(2)In(2)O(5), Sr(2)Fe(2)O(5), Sr(2)Mn(2)O(5), and La(2)Ni(2)O(5). There are a large number of low-energy local minima on the potential energy hypersurfaces of the two first compounds due to an energetic preference for BO(4) tetrahedra. Tetrahedral environments are energetically unfavorable for Mn(III) in Sr(2)Mn(2)O(5) and for Ni(II) in La(2)Ni(2)O(5), and the number of low-energy configurations is relatively low in these two cases. Consistent with our findings, in contrast to Sr(2)Fe(2)O(5) and Ba(2)In(2)O(5), Sr(2)Mn(2)O(5) and La(2)Ni(2)O(5) do not exhibit transitions to disordered phases on heating, and there appear to be no reports of enhanced ionic conductivity for these compounds. Thus we suggest that the possibility of many different oxygen orderings associated with a variety of low-energy connectivity schemes within tetrahedral layers such as in the brownmillerite-based structures of Sr(2)Fe(2)O(5) and Ba(2)In(2)O(5) is a prerequisite for high ionic conductivity in perovskite-related A(2)B(2)O(5) oxides.     

Cyclophosphamides from aminosugars and aminonucleosides

Condensation of bis-(2-chloroethyl)phosphoramidic dichloride with 3′-amino-3′-deoxy-N,N-dimethyladenosine afforded the 2′,3′-cyclicphosphorodiamidate (III). By an improved synthesis, methyl 3-amino-3-deoxy-β-D-ribofuranoside was obtained as a model compound for conversion to the analogous 2,3-cyclicphosphorodiamidate (XII). Existence of the latter as two diastereomers due to phosphorus asymmetry was shown by nmr analysis, using comparison with the 5-(O-p-nitrobenzoate) (XIII) as a basis for assignments.     

Preparation of a thermally phase-separating copolymer,poly(N-isopropylacrylamide-co-N-acryloxysuccinimide), with a controlled number of active esters per polymer chain

N-isopropylacrylamide and N-acryloxysuccinimide have been copolymerized in various mixtures of terrahydrofuran and toluene using azobisisobutyronitrile as initiator. Polymerization has been conducted for 24 h at 50°C under a slightly positive pressure of nitrogen. The copolymers were assayed for active ester content by measuring the UV absorbance (259 nm) of N-hydroxysuccinimide anion, generated by reacting the copolymers with N-isopropylamine in dimethylformamide and dissolving the resulting mixture in 0.1M HEPES buffer, pH 7.5. The molecular weight and its distribution have been estimated by gel permeation chromatography. The active ester content was found to be equivalent to the comonomer feed ratio, and the major factor controlling the molecular weight was the ratio of tetrahydrofuran to toluene. Thus, the number of active esters per polymer chain could be controlled by adjustment of the comonomer feed ratio and the ratio of tetrahydrofuran to toluene. Monomer reactivity ratios for copolymerization of N-isopropylacrylamide with N-acryloxysuccinimide were also estimated. These copolymers are useful for immobilizing binding ligands such as antibodies for subsequent thermally induced precipitation immunoassays and bioseparation processes.     

STRUCTURE OF DYE AGGREGATES AND THE MECHANISM(S) OF PHOTOSENSITIZATION OF AgBr*,†

Abstract— This paper reports the present conclusions of an extended investigation on photo-sensitization of silver bromide. A general molecular packing structure for dye aggregates on the AgBr (111) surface is proposed. This structure, along with the observed spectral absorption displacements of small aggregates, is used to elucidate the phenomena of antisensitization and supersensitization. Supersensitization is seen as a partitioning of large dye aggregates into small aggregates by a deliberately added second component or by gaps between the aggregates. This partitioning isolates antisensitizing dye in a small fraction of the aggregates and minimizes its effect. The smallest aggregates are least likely to contain an antisensitizer, and show the highest quantum efficiency for photoconductivity and photographic action. Photoconductivity measurements establish that supersensitization occurs before the electron appears in the AgBr phase.
The question of direct electron injection vs. energy transfer as mechanisms for AgBr photosensitization is examined in terms of radiationless transfer to surface Ag₂S on AgBr. The absorption of surface Ag₂S is shown to be adequate for acceptance of Förster transfer from the dye, and surface Ag₂S is known to be photographically active. However, this mechanism is inefficient, and inadequate to account for observed high efficiency infrared sensitization. Direct electron injection is seen as the more probable mechanism for efficient dye sensitization of AgBr.