Preparation and synthetic applications of 2-halotryptamines: synthesis of elacomine and isoelacomine

The preparation of 2-halotryptamines from tryptamine is described. New stereoselective intramolecular iminium ion spirocyclization methodology for the construction of spiro[pyrrolidine-3,3'-oxindoles] is outlined in synthetic studies of elacomine (1) and isoelacomine (2). [reaction: see text]     

Generalized Macroscopic Models for Fluid Flow in Deformable Porous Media I: Theories

This study developed generalized mathematical models to describe the motion of fluids in porous media, and applied these models to harmonic excitation applications. The problem of fluid flow in small channels of a periodic elastic solid matrix was studied at the pore scale, and the homogenization technique was applied to predict the macroscopic behavior of reservoirs. Based on the homogenization study, five separate characteristic macroscopic models were identified according to the relation between a length scale parameter and a property contrast number. These five models can be used to interpret the corresponding responses of a saturated porous medium. The relation to existing theories, such as Darcy's law, the Telegrapher's equation and Biot's theory, was investigated. The numerical results and applications are presented in Part II of the study.     

Inertia Effects in High-Rate Flow Through Heterogeneous Porous Media

The paper deals with the effects of large scale permeability–heterogeneity on flows at high velocities through porous media. The media is made of a large number of homogeneous blocks where the flow is assumed to be governed by the Forchheimer equation with a constant inertial coefficient. By assuming the validity of the Forchheimer equation at the large scale, an effective inertial coefficient is deduced from numerical simulations. Different media are investigated: serial-layers, parallel-layers and correlated media. The numerical results show that: (i) for the serial-layers, the effective inertial coefficient is independent of the Reynolds number and decreases when the variance and the mean permeability ratio increases; (ii) for the parallel-layers and the correlated media, the effective inertial coefficient is function of the Reynolds number and increases when the variance and the mean permeability ratio increases. Theoretical relationships are proposed for the inertial coefficient as function of the Reynolds number and the characteristics of the media.     

Gel-permeation chromatography. IX. Instrumental design and computer interfacing of a GPC molecular weight detector system

The detailed design and computer interfacing of a GPC molecular weight detector based on a real time viscometer are described. The working drawings presented will permit one to fabricate and duplicate the viscometer and the complete GPC molecular weight detector system. The uses and advantages of a laboratory automation system in analyzing GPC results are also described.     

Structure of [C4mpyr][NTf2] room-temperature ionic liquid at charged gold interfaces

The structure of 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([C(4)mpyr][NTf(2)]) room-temperature ionic liquid at an electrified gold interface was studied using neutron reflectometry, cyclic voltammetry, and differential capacitance measurements. Subtle differences were observed between the reflectivity data collected on a gold electrode at three different applied potentials. Detailed analysis of the fitted reflectivity data reveals an excess of [C(4)mpyr](+) at the interface, with the amount decreasing at increasingly positive potentials. A cation rich interface was found even at a positively charged electrode, which indicates a nonelectrostatic (specific) adsorption of [C(4)mpyr](+) onto the gold electrode.     

Evaluation of diverse α/β-backbone patterns for functional α-helix mimicry: analogues of the Bim BH3 domain

Peptidic oligomers that contain both α- and β-amino acid residues, in regular patterns throughout the backbone, are emerging as structural mimics of α-helix-forming conventional peptides (composed exclusively of α-amino acid residues). Here we describe a comprehensive evaluation of diverse α/β-peptide homologues of the Bim BH3 domain in terms of their ability to bind to the BH3-recognition sites on two partner proteins, Bcl-x(L) and Mcl-1. These proteins are members of the anti-apoptotic Bcl-2 family, and both bind tightly to the Bim BH3 domain itself. All α/β-peptide homologues retain the side-chain sequence of the Bim BH3 domain, but each homologue contains periodic α-residue → β(3)-residue substitutions. Previous work has shown that the ααβαααβ pattern, which aligns the β(3)-residues in a 'stripe' along one side of the helix, can support functional α-helix mimicry, and the results reported here strengthen this conclusion. The present study provides the first evaluation of functional mimicry by ααβ and αααβ patterns, which cause the β(3)-residues to spiral around the helix periphery. We find that the αααβ pattern can support effective mimicry of the Bim BH3 domain, as manifested by the crystal structure of an α/β-peptide bound to Bcl-x(L), affinity for a variety of Bcl-2 family proteins, and induction of apoptotic signaling in mouse embryonic fibroblast extracts. The best αααβ homologue shows substantial protection from proteolytic degradation relative to the Bim BH3 α-peptide.     

Enhancement of α-helix mimicry by an α/β-peptide foldamer via incorporation of a dense ionic side-chain array

We report a new method for preorganization of α/β-peptide helices, based on the use of a dense array of acidic and basic side chains. Previously we have used cyclically constrained β residues to promote α/β-peptide helicity; here we show that an engineered ion pair array can be comparably effective, as indicated by mimicry of the CHR domain of HIV protein gp41. The new design is effective in biochemical and cell-based infectivity assays; however, the resulting α/β-peptide is susceptible to proteolysis. This susceptibility was addressed via introduction of a few cyclic β residues near the cleavage site, to produce the most stable, effective α/β-peptide gp41 CHR analogue identified. Crystal structures of an α- and α/β-peptide (each involved in a gp41-mimetic helix bundle) that contain the dense acid/base residue array manifest disorder in the ionic side chains, but there is little side-chain disorder in analogous α- and α/β-peptide structures with a sparser ionic side-chain array. These observations suggest that dense arrays of complementary acidic and basic residues can provide conformational stabilization via Coulombic attractions that do not require entropically costly ordering of side chains.