Refined ab initio 6-31G split-valence basis set optimization of the molecular structures of biphenyl in twisted,planar, and perpendicular conformations

Improved full ab initio optimizations of the molecular structure of biphenyl in twisted minimum energy, coplanar, and perpendicular conformations by use of Poles's GAUSSIAN 82 program have been performed in the 6-31G basis set. These lead to geometries and energies of much higher reliability than our earlier STO-3G results. The torsional angle Φ_min obtained now is 45.41° in close agreement with the recent experimental value of 44.4° ± 1.2°. Calculated CC distances may be converted to experimental ED r_g-values by means of independently determined linear regression correlations with very high statistical confidence, although they agree better with experimental x ray data for coplanar biphenyl without this correction. Calculated intramolecular angles are very similar for both STO-3G and 6-31G basis sets. The calculated torsional energy barrier towards Φ = 90° (ΔE⁹⁰) is 6.76 kJ/mol in close agreement with the experimental-31G value of 6.5 ± 2.0 kJ/mol. For coplanar biphenyl with D_2h-symmetry the calculated torsional energy barrier ΔE⁰ is 13.26 kJ/mol which is surprisingly much higher than the experimental value of 6.0 ± 2.1 kJ/mol. This discrepancy could not be resolved by optimizations assumed for two kinds of distortions of planarity of orthohydrogens from the molecular plane of the coplanar carbon atoms. But for the twisted minimum energy conformation asymmetric bending of ortho-H atoms lead to a torsional angle Φ_min = 44.74° together with a dihedral angle towards ortho-H of 1.22°, and consequently even to an increase of torsional energy barriers to ΔE⁰ = 13.51 and ΔE⁹⁰ = 6.91 kJ/mol.     

Synthesis and evaluation of new potential HIV-1 non-nucleoside reverse transcriptase inhibitors. New analogues of MKC-442 containing Michael acceptors in the C-6 position

Analogues of MKC-442 capable of undergoing Michael addition reactions were synthesised in order to investigate the activity against the HIV-1 mutant (Y181C). An improved activity was postulated on the basis of a possible covalent binding to the mercapto group of Cys181. Lithiation of the C-6 position of 1-ethoxymethyl-5-ethyl-1H-pyrimidine-2,4-dione (5) was followed by reaction with alpha,beta-unsaturated aldehydes and oxidation of the alcohols formed to give the alkenoyl analogues 1a-3a. Analogues 1b-3b containing an allyloxymethyl group in the N-1 position instead of the ethoxymethyl group could not be synthesised due to isomerisation of the allylic group during the metallation reaction. The NMR data for compounds 1a-3a showed a hindered rotation, which was more pronounced for the 6-cyclohexenylcarbonyl derivative 3a than for the propenyl derivatives 1a and 2a. Moderate activity against wild type HIV-1 was observed for the alcohol 8 and the ketones 2a-3a. However, no activity was observed against the Y181C mutant.     

Bridging fluorides and hard/soft mismatch in d6 and d8 complexes: the case of [Tl(mu-F)3Ru(PPh3)3

[RuCl2(PPh3)3] reacts with thallium(I) fluoride to give either [Tl(mu-F)3Ru(PPh3)3] (1) or [Tl(mu3-F)(mu2-Cl)2Ru2(mu2-Cl)(mu2-F)(PPh3)4] (2) depending on the excess of TlF used. Both 1 and 2 were fully characterized, including X-ray structure determinations. Complex 1 reacts with dihydrogen to form the known ruthenium hydride complex [Ru(H)2(H2)(PPh3)3] upon hydrogenolysis of the Ru-F bond. The reaction of 1 with activated alkyl bromides (R-Br) gives the corresponding alkyl fluorides and the trinuclear complex [Tl(mu3-F)(mu2-F)(mu2-X)Ru2(mu2-Br)(mu2-F)(PPh3)4] (X=Br, F) (3), whose structure closely resembles that of 2. However, 1 is not active as catalyst for the nucleophilic fluorination of R-Br in the presence of thallium fluoride. The effect of the bridging coordination mode of fluoride on the Ru-F bond is discussed in terms of the HSAB principle, which suggests a more general model for predicting the stability of d6 and d8 complexes containing hard ligands (such as fluoro, oxo, and amido).     

An average-of-configuration method for using Kohn-Sham density functional theory in modeling ligand-field theory

The Amsterdam Density Functional (ADF) package has been used to constrain Kohn-Sham DFT in such a fashion that a transition from KS-DFT to ligand-field theory in the form of the parametrical d(q)() model is completely well-defined. A relationship is established between the strong-field approximation of the parametrical d(2) model for the tetrahedral complexes VCl(4)(-) and VBr(4)(-) and certain fixed-orbital ADF-computed energies. In this way values for all the parameters of the d(2)() model may be computed, thus allowing the ADF results to be expressed in terms of a KS-DFT energy matrix that can be diagonalized. This means that the KS-DFT deficiency with regard to computation of nondiagonal elements has been overcome and the KS-DFT eigenenergies have become available through the KS-DFT mimicking of the ligand-field plus repulsion model. By using mutually orthogonal strong-field energy matrices, the mimicking has been further elucidated. The computed values for the empirical parameters of VCl(4)(-) and VBr(4)(-) are in good agreement with experimental data. The spectrochemical and the nephelauxetic series have been computed by including the remaining halide complexes and the quantitatively special position of F(-)() among the halides corroborated for both series.     

Anti-HIV Active Naphthyl Analogues of HEPT and DABO

Summary.  5-Isopropyl-6-naphthyl uracil and 5-isopropyl-6-naphthyl-2-thiouracil were alkylated to give N-1-(ethoxymethyl and methylthiomethyl) uracil and S²-cyclohexyl-thiouracil, respectively. 5-Ethyl-6-naphthyl uracil and 5-ethyl-6-naphthyl-2-thiouracil afforded N-1-(ethoxymethyl, methoxy-methyl, methylthiomethyl, acetoxyethoxy methyl and hydroxyethoxy methyl) uracil and S²-((2,2- diethoxyethyl), methoxycarbonylmethyl, ethoxycarbonylpropyl, methylthiomethyl, ethoxymethyl, methyl and cyclohexyl)-thiouracil upon alkylation. Received September 25, 2001. Accepted (revised) December 3, 2001     

Shear-induced sponge-to-lamellar phase transition studied by rheo-birefringence

We report on the shear induced transition from the L₃- to the L-phase studied by means of flow birefringence using the system pentaethyleneglycol monododecylether (C₁₂E₅), decane, water. The dependence of the critical shear rate, at which the transition from the isotropic state to the anisotropic takes place, on membrane volume fraction was studied in temperature ramp experiments at different constant shear rates and in isothermal shear ramp experiments. These results are compared with relaxation experiments from the shear aligned state back to the isotropic. For all these experiments power law exponents in the membrane volume fraction between 1.6 and 2.8 were found, which are rather low compared to values of current theories. The values found for the inverse critical shear rate and the decay times from the relaxation experiments differ by four orders of magnitude.     

Development of a multiplex microarray microsystem

A hybrid multiplex microarray microsystem has been developed that consists of 32 individually addressable array reaction chambers, supporting the use of multichannel pipettes for addition of up to 8 samples simultaneously. Discrimination between Campylobacter jejuni and Campylobacter coli bacteria was observed in DNA samples containing Campylobacter spp., with the same specificity and sensitivity as when compared to a full-size microarray. The spinloaded multiplex microarray microsystem described provides a novel and convenient test format for simultaneous low-density microarray analysis and is universally adaptable to other DNA, protein or small molecule microarray based applications.