A unique geometry of the active site of angiotensin-converting enzyme consistent with structure-activity studies

Summary Previous structure-activity studies of captopril and related active angiotensin-converting enzyme (ACE) inhibitors have led to the conclusion that the basic structural requirements for inhibition of ACE involve (a) a terminal carboxyl group; (b) an amido carbonyl group; and (c) different types of effective zinc (Zn) ligand functional groups. Such structural requirements common to a set of compounds acting at the same receptor have been used to define a pharmacophoric pattern of atoms or groups of atoms mutually oriented in space that is necessary for ACE inhibition from a stereochemical point of view. A unique pharmacophore model (within the resolution of approximately 0.15 Å) was observed using a method for systematic search of the conformational hyperspace available to the 28 structurally different molecules under study. The method does not assume a common molecular framework, and, therefore, allows comparison of different compounds that is independent of their absolute orientation.Consequently, by placing the carboxyl binding group, the binding site for amido carbonyl, and the Zn atom site in positions determined by ideal binding geometry with the inhibitors' functional groups, it was possible to clearly specify a geometry for the active site of ACE.     

Shadowing and the Plasma-Sheath Transition Layer

Summary. This paper gives a rigorous derivation of the system μ ² d ² w ₀ \over dζ ² =w ² ₀ +ζ , w ₀ (ζ ₀ )=-(-ζ ₀ ) ^1/2 , dw ₀ \over dζ (ζ ₀ )= 1\over 2 (-ζ ₀ ) ^-1/2 , ζ ₀ <0 , governing the electric potential in the transition layer joining quasi-neutral plasma to space charge sheath in a weakly ionized plasma. The parameter μ represents the tolerance for ``shadowing,' i.e., it measures the ``distance' between the true solution of the full Euler-Poisson system and the solution of the reduced order limit equation for w ₀ (ζ) . Received February 22, 2001; accepted September 21, 2001 Online publication November 30, 2001     

Experimental and kinetic modeling study of oxidation of acetonitrile

Oxidation of acetonitrile has been studied in a flow reactor in the absence and presence of nitric oxide. The experiments were conducted at atmospheric pressure in the temperature range 1150–1450 K, varying the excess air ratio from slightly fuel-lean to very lean. Oxidation of CH₃CN was slow below 1300 K. Nitric oxide, hydrogen cyanide and nitrous oxide were detected as important products. A detailed chemical kinetic model for oxidation of acetonitrile was developed, based on a critical evaluation of data from literature. The rate coefficients for the reactions of CH₃CN and CH₂CN with O₂ were calculated from ab initio theory. Modeling predictions were in satisfactory agreement with experiments. Calculations were sensitive to thermal dissociation of CH₃CN and to the branching fraction for CH₃CN + OH to CH₂CN + H₂O and HOCN + CH₃, respectively. More work is desirable for these steps, as well as for reactions of CH₂CN and HCCN.     

Self-similar fluid-dynamic limits for the Broadwell system

This report discusses a new approach for the resolution of the fluid-dynamic limit for the Broadwell system of the kinetic theory of gases, appropriate in the case of Riemann, Maxwellian data. Since the formal limiting system is expected to have self-similar solutions, we are motivated to replace the Knudsen number in the Broadwell model so that the resulting model admits self-similar solutions =x/t and then let go to zero. The limiting procedure is justified and the resulting limit is a solution of the Riemann problem for the fluid-dynamic limit equations. A class of Riemann data for which this program can be carried out is exhibited. Furthermore, it is shown that for the Carleman model the complete program can be done successfully for arbitrary Riemann data.     

A Geometric Level-Set Formulation of a Plasma-Sheath Interface

In this paper, we present a new geometric level-set formulation of a plasma-sheath interface arising in plasma physics. We formally derive the explicit dynamics of the interface from the Euler-Poisson equations and study the local-time evolution of the interface and sheath in some special cases.     

Synthesis of the Phenylpyridal Scaffold as a Helical Peptide Mimetic

Phenylpyridal‐ and phenyldipyridal‐based scaffolds have been designed and synthesized as novel helical peptide mimetics. The synthesis required optimisation and selective alkylation in producing 2,6‐functionalized 3‐hydroxypyridine derivatives for a convergent scheme. The pyridine analogues were coupled by a series of Suzuki/Stille types cross‐coupling reactions. A series of biaryl and ter‐aryl substituted heterocycles were produced. The synthetic approach was concise and high yielding allowing large variability at the wanted side‐chain attachment points. A number of compounds were synthesised to show the versatility of the strategy.