Biophysical characterization of complexation of DNA with block copolymers of poly(2-dimethylaminoethyl) methacrylate, poly(ethylene oxide), and poly(propylene oxide)

The interactions of DNA (salmon testes) with two new cationic block copolymers made of poly(2-dimethylaminoethyl) methacrylate and poly(ethylene oxide), PEO-pDMAEMA, or poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), L92-pDMAEMA, were studied with the aim to understand their different in vitro transfection efficiencies when used as nonviral delivery vectors. PEO-pDMAEMA does not show surface activity while L92-pDMAEMA is as surface active as its parent Pluronic L92. Surface tension, titration microcalorimetry, ethidium bromide displacement, and zeta-potential measurements were carried out in phosphate buffers at pH 5 and 7. The association of L92-pDMAEMA with DNA was strongly exothermic at both pHs; the critical aggregation concentration (CAC) corresponded to a N/P ratio of 0.3, the maximum energy evolved was reached for N/P ratios of 0.82 and 1.27 at pH 5 and pH 7, respectively, and the saturation occurred for N/P ratios close to 2. The presence of L92 in the structure of this new block copolymer apparently did not modify the thermodynamic parameters of the interaction with DNA. In contrast, the interaction with PEO-pDMAEMA was significantly less exothermic, and CAC and saturation occurred for N/Ps equal to 0.43 and 1.37, respectively. The strong affinity of L92-pDMAEMA for DNA was reflected in its capacity to displace ethidium bromide and in the jump in the values of the zeta potential when N/P is near 1. Above the N/P ratio at which electroneutral polyplexes are formed, only at pH 5 an excess of L92-pDMAEMA is incorporated in the complexes, resulting in positively charged complexes. The profile of the zeta-potential values obtained for mixtures of L92-pDMAEMA with Pluronic P123 showed a shift to a lower N/P ratio, owing to an easier interaction of L92-pDMAEMA molecules with DNA in the presence of P123. Additionally, a visual inspection of the systems indicates that P123 contributes to stabilize/solubilize the DNA/cationic polymer aggregates, by avoiding the typical phase separation near the charge neutralization point. The information obtained can be particularly useful to optimize the conditions to form efficient polyplexes for gene delivery systems.     

NMR determination of enantiomeric composition of 1-substituted 3-amino-1,2-dicarba-closo-dodecaboranes using Eu(hfc)3

Experimental conditions for determination of enantiomeric composition of 1-substituted 3-aminocarboranes by ¹H and ¹³C NMR spectroscopy using chiral shift reagent Eu(hfc)₃ have been found.     

Methyl 2,3‐dideoxy‐2‐S‐methylmercurio‐2‐thio‐β‐d‐manno‐oct‐2‐ulo­pyranosonate‐(2,6)

The hexo­pyran­osyl ring of the title compound, [Hg(CH₃)(C₉H₁₅O₇S)], adopts the ⁴C₁ chair conformation, and the anomeric configuration of the thio­methyl­mercury linkage is β. The compound exists as two symmetry‐independent conformers, A and B, within the unit cell, and each shows an almost linear S—Hg—C arrangement. Most of the bond distances and angles in A and B are similar, although a marked difference exists in the side‐chain conformation. Weak secondary intramolecular (between Hg and ring O) and intermolecular (between A and B conformers) interactions are documented.     

A very large diversity space of synthetically accessible compounds for use with drug design programs

We have constructed a very large virtual diversity space containing more than 10¹³ chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range.     

Identification of acylated xanthone glycosides by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry in positive and negative modes from the lichen Umbilicaria proboscidea

The xanthoside composition of the crude extract of Umbilicaria proboscidea (L.) Schrader was characterized using LC-UV diode array detection and LC-atmospheric pressure chemical ionization (APCI) MS methods. The presence of acylated xanthone-O-glucosides was determined by both positive and negative ion LC-APCI-MS methods. Based on UV and MS spectral data and NMR spectroscopy, a total of 14 compounds (6-O-acylated umbilicaxanthosides A and B) were identified in U. proboscidea for the first time. In order to further develop the applicability of LC-MS techniques in phytochemical characterization, the effect of different ionization energy on fragmentation was studied using APCI. The optimal ionization conditions were achieved in positive ion APCI by using ammonium acetate buffer and in negative ion APCI by using formic acid (pH 4).     

Ate complexes of Ge(II) and Sn(II) with bidentate ligands [LiE(OCH2CH2NMe2)3]2 (E=Ge, Sn): synthesis and structure

The reaction of equimolar quantities of LiOCH₂CH₂NMe₂ and E¹⁴(OCH₂CH₂NMe₂)₂ (E¹⁴=Ge, Sn) in ether yielded new ate complexes [LiE¹⁴(OCH₂CH₂NMe₂)₃]₂ (E¹⁴=Ge (1), Sn (2)) with bidentate ligands. The compounds 1 and 2 are white crystalline substances which are highly soluble in THF and pyridine and very sensitive to the traces of oxygen and moisture. The structures of these compounds are studied by X-ray diffraction analysis. The ate complexes 1 and 2 are powerful nucleophiles and may be employed as ligands (neutral) in the coordination chemistry of the transition metals. The electronegative O-substituents at the divalent E¹⁴ atoms render them less oxidizable than alkyl- or aryl-substituted derivatives, and the bidentate ligands, owing to intramolecular donor-acceptor interactions, make them more thermodynamically stable compared to monodentate ligands.     

Critical Points in a Crystal and Procrystal

The critical points in the model electron density distributions of LiF, NaF, NaCl, and MgO crystals, constructed from accurate X-ray diffraction data, are determined. For LiF and MgO they are compared with those obtained from a Hartree–Fock electron density calculation. Both experiment and theory show the same type of critical points on the bond lines. The topological features in areas between structural units, where the electron density is low and near-uniform, turn out to be model dependent and cannot be established well with the data available. Topological analysis of procrystals (hypothetical systems consisting of spherical atoms or ions placed on the same sites as atoms in real crystal) show that (3, –1) critical points, usually connected with bonding interaction, are observed on interatomic lines in these nonbonded systems as well.     

Spatial structure of β-substituted alkoxyvinyl trifluoromethyl ketones

Spatial structure of six β-substituted enones, with common structure R₁O–CR₂CH–COCF₃, were R₁ = C₂H₅, R₂ = H (ETBO); R₁ = R₂ = CH₃ (TMPO); R₁ = C₂H₅, R₂ = C₆H₅ (ETPO); R₁ = C₂H₅, R₂ = 4- O₂NC₆H₄ (ETNO); R₁ = C₂H₅, R₂ = C(CH₃)₃ (ETDO) were investigated by ¹H and ¹⁹F NMR, infrared spectroscopy and AM1 calculations. NMR spectra revealed that enones (MBO), (ETBO) and (TMPO) are exclusively (3E) isomers, whereas in (ETPO), (ETNO) and especially in (ETDO) the percentage of (3Z) isomers is significant and depends on the nature of solvents. Conformational behaviour of studied enones are determined by the rotation around of CC double bond, C–C and C–O single bonds (correspondingly trifluoroacetyl and alkoxy groups), and (EZZ) conformer being the most stable in all cases. IR spectra revealed that with the exception of (ETDO) (EZZ) conformer is most populated in all cases. Bulky substituents like phenyl or tert-butyl group at β-position of enone result in the equilibrium mainly between (EZZ) and (ZZZ) forms, whereas β-hydrogen and β-methyl substituents determine the equilibrium between (EZZ) and (EEZ) or (EZE) conformers.     

Crystal structure and nontrivial magnetic properties of CuII binuclear complex based on 4-methyl-2,6-bis{[2-(4,6-dimethyl-pyrimidin-2-yl)hydrazono]methyl}phenol

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