Quantitative measures of similarity between pharmacologically active compounds

A theoretical measure of molecular similarity based on ab initio computations of electron density derived from molecular orbital wave functions is first applied to a model series (CH₃CH₂CH₃, CH₃OCH₃, and CH₃SCH₃) and then to the rings in a series of prostaglandins and to some histamine H2 antagonists. Comparison in terms of valence electron density seems to be a good basis for structure-activity studies.     

Nanoscale skeletal nickel catalysts prepared via ‘bottom up’ method

NiAl nanoparticles are of considerable importance because of interest in examining the effects of size, surface area, and composition on their physical and catalytic properties. Recently, a new method for the ‘bottom up’ wet chemical preparation of nickel aluminides has been reported. The ability to leach the aluminum from this system provides an entrance to the preparation of skeletal‐type metal catalysts similar to those produced in Raney‐type systems. Furthermore, it is believed that these nanoparticulate catalysts should provide high surface areas and high activities, while the presence of aluminum within the bulk of these catalysts provides additional stability. Here, we present the results of studies conducted on this system which compare their properties and behavior with traditional bulk Raney nickel systems. Additionally, we show that we are able to alter the properties of these nanoparticles by changing the stoichiometric ratio of nickel and aluminum. The properties of all systems have been analyzed through the use of nitrogen adsorption, X‐ray diffraction, and elemental analysis. Finally, the catalysts generated have been compared for their activity in the hydrogenation of butyronitrile. Copyright © 2002 John Wiley & Sons, Ltd.     

Outer-sphere effects on reduction potentials of copper sites in proteins: the curious case of high potential type 2 C112D/M121E Pseudomonas aeruginosa azurin

Redox and spectroscopic (electronic absorption, multifrequency electron paramagnetic resonance (EPR), and X-ray absorption) properties together with X-ray crystal structures are reported for the type 2 Cu(II) C112D/M121E variant of Pseudomonas aeruginosa azurin. The results suggest that Cu(II) is constrained from interaction with the proximal glutamate; this structural frustration implies a "rack" mechanism for the 290 mV (vs NHE) reduction potential measured at neutral pH. At high pH (～9), hydrogen bonding in the outer coordination sphere is perturbed to allow axial glutamate ligation to Cu(II), with a decrease in potential to 119 mV. These results highlight the role played by outer-sphere interactions, and the structural constraints they impose, in determining the redox behavior of transition metal protein cofactors.     

Hyperfine interactions,including Bhf[FrFe], studied in the decay chain of225Ra by alpha and gamma anisotropy measurements

A low temperature nuclear orientation experiment has been performed on the 14.8d²²⁵Ra activity. Gamma anistotropy [²²¹Fr (4.8m) and²¹³Bi (45.6m)] and alpha anisotropy [²²⁵Ac (10.0d),²²¹Fr,²¹⁷At (32.3ms) and²⁰⁹Po (4.2μs)] measurements has been carried out and values for the hyperfine field of²²⁵Ac and²²¹Fr in iron and the magnetic moment of²¹³Bi are reported.     

Solid phase synthesis of 5-aminopyrazoles and derivatives

The development of a novel solid phase synthesis of some 5-aminopyrazoles and derivatives is described. Reaction of hydrazines with solid supported β-keto-nitrile (1) affords 5-aminopyrazoles (2) the amino group of which is readily acylated or sulphonylated. Generation of the solid supported β-keto-nitrile (1) is non trivial and represents a key step in the overall synthesis.     

Sensitivity to envelope coherence

Measurements are reported on the ability of observers to discriminate whether the envelope of two amplitude-modulated sinusoids are in phase or out of phase. Spacing between the two carriers was either 2/3 or 4/3 octave, and the depth of modulation was varied to determine threshold. Discrimination performance improved as the level of the carriers increases up to about 60 dB SPL. The frequency locus of the two carriers (geometric mean of the two frequencies), which varied from 500 to 8000 Hz in different experiments, had little effect on discrimination accuracy. Discrimination performance was relatively constant for modulation rates below 100 Hz and deteriorates for higher modulation rates. These results are compared with data obtained from comodulation masking release experiments.