Local Observation of Field Polarity Dependent Flux Pinning by Magnetic Dipoles

A scanning Hall probe microscope is used to study flux pinning in a thin superconducting Pb film covering a square array of single-domain Co dots with in-plane magnetization. We show that single flux quanta of opposite sign thread the superconducting film below T(c) at the opposite poles of these dipoles. Depending on the polarity of the applied field, flux lines are attracted to a specific pole of the dipoles, due to the direct interaction with the vortexlike structures induced by the local stray field.     

Influencing receptor-ligand binding mechanisms with multivalent ligand architecture

Multivalent ligands can function as inhibitors or effectors of biological processes. Potent inhibitory activity can arise from the high functional affinities of multivalent ligand-receptor interactions. Effector functions, however, are influenced not only by apparent affinities but also by alternate factors, including the ability of a ligand to cluster receptors. Little is known about the molecular features of a multivalent ligand that determine whether it will function as an inhibitor or effector. We envisioned that, by altering multivalent ligand architecture, ligands with preferences for different binding mechanisms would be generated. To this end, a series of 28 ligands possessing structural diversity was synthesized. This series provides the means to explore the effects of ligand architecture on the inhibition and clustering of a model protein, the lectin concanavalin A (Con A). The structural parameters that were varied include scaffold shape, size, valency, and density of binding elements. We found that ligands with certain architectures are effective inhibitors, but others mediate receptor clustering. Specifically, high molecular weight, polydisperse polyvalent ligands are effective inhibitors of Con A binding, whereas linear oligomeric ligands generated by the ring-opening metathesis polymerization have structural properties that favor clustering. The shape of a multivalent ligand also influences specific aspects of receptor clustering. These include the rate at which the receptor is clustered, the number of receptors in the clusters, and the average interreceptor distance. Our results indicate that the architecture of a multivalent ligand is a key parameter in determining its activity as an inhibitor or effector. Diversity-oriented syntheses of multivalent ligands coupled with effective assays that can be used to compare the contributions of different binding parameters may afford ligands that function by specific mechanisms.     

Synthesis and Absolute Configuration of New Trichloro Steroids with Cyclopropane-Containing Side Chains

The determination of the absolute configuration of the trichloro steroids 2a and 2c (cf. Scheme 1) by means of two X-ray crystal structure analyses is reported and applies also to the determination of the absolute configurations of several derived steroidal cyclopropanes [1]. The preparation of the chlorinated derivatives 2a-c is described and the spectroscopic properties of 1 and 2 are summarized.     

Structure of 9α, 11β-dichloro-4-pregnene-3,20-dione,C21H28O2Cl2

The crystal and molecular structure of 9, 11-dichloro-4-pregnene-3,20-dione, C₂₁H₂₈O₂C1₂, has been determined:M _r =383.4,P3₁,a=7.358(2),c=30.137(20) Å,V _c =1413(2)ų,Z=3,D _x =1.35 g cm^–3, (MoK)=0.71073Å,=3.6 cm^–1,F(000)=612,T80K,R=0.060,R _w =0.052 for 2376 unique observed reflections. The steroid skeleton exhibits a flattening of theA ring relative to the rest of the molecule caused by halogen substituents. The title compound has a very high relative binding affinity for the rabbit uterine progesterone receptor. The high binding affinity may result from the flattening of theA ring relative to the rest of the steroid skeleton.     

Thermodynamics of dissolving and solvation processes for benzoic acid and the toluic acids in aqueous solution

Experimental data are presented for the solubility in water of benzoic and toluic acids from 5° to 65°C. From the solubility the molality of the monomeric form of the acid is calculated using literature data for both ionization and dimerization of the acid. These data for the monomer combined with data from the literature for vaporization of the solid and ionization in both the gas phase and the aqueous phase yield entropy and enthalpy changes for the solvation of molecular and anionic forms of the acid. A similar procedure is also applied to literature data for the solubility of benzene in water. It is shown that the hydration entropies of the monomeric forms are a linear function of their partial molar volumes. It is concluded that hydration of the undissociated o-toluic acid may be crucial to the increased acidity of that acid compared to benzoic acid.     

pH as a trigger of peptide beta-sheet self-assembly and reversible switching between nematic and isotropic phases

The hierarchical self-assembly of rationally designed synthetic peptides into beta-sheet tapes, ribbons, fibrils, and fibers opens up potentially useful routes to soft-solidlike materials such as hydrogels, organogels, or liquid crystals. Here, it is shown how incorporation of Glu (-CH(2)CH(2)COOH) or Orn (-CH(2)CH(2)CH(2)NH(2)) into the primary structure of an 11 amino acid peptide enables self-assembly to be rapidly (seconds) and reversibly controlled by simply changing pH. Solutions of monomeric peptide, typically at concentrations in excess of 0.003 v/v, can be switched within seconds to, for example, nematic gel states comprised of interconnected orientationally ordered arrays of fibrils or vice versa. This is to be compared with the lyophilized peptide dissolution route to nematic fluids and gels which is impracticably long, taking many hours or even days. An important design principle, that stabilization of fibrillar dispersions requires of the order of one unit of net positive or negative charge per peptide molecule, is first demonstrated and then used to design an 11 amino acid peptide P(11)-3 (CH(3)CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Gln-Gln-Gln-NH(2)) whose self-assembly behavior is independent of pH (1 < pH < 10). pH control is then incorporated by appropriately positioning Glu or Orn side chains so that the peptide-peptide free energy of interaction in the tapelike substructure is strongly influenced by direct electrostatic forces between gamma-COO(-) in Glu(-) or delta-NH(3)(+) in Orn(+), respectively. This design principle is illustrated by the behavior of two peptides: P(11)-4 (CH(3)CO-Gln-Gln-Arg-Phe-Glu-Trp-Glu-Phe-Glu-Gln-Gln-NH(2)) which can be switched from its nematic to its isotropic fluid state by increasing pH and P(11)-5 (CH(3)CO-Gln-Gln-Orn-Phe-Orn-Trp-Orn-Phe-Gln-Gln-Gln-NH(2)) designed to exhibit the converse behavior. Acid-base titrations of fibrillar dispersions reveal deprotonation of the gamma-COOH of Glu or of the delta-NH(3)(+) of Orn(+) occurs over wide bands of up to 5 pH units, a feature of polyelectrolytes. The values of the energy parameters controlling self-assembly can therefore be smoothly and continuously varied by changing pH. This enables isotropic fluid-to-nematic transitions to be triggered by relatively small additions of acid or base, typically 1 part in 10(3) by volume of 1 M HCl or NaOH.     

Molecular level model for the agonist/antagonist selectivity of the 1,4-dihydropyridine calcium channel receptor

Summary Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxylate], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5-carboxylate], and Bay O 9507 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(4-nitrophenyl)-pyridine-5-carboxylate] were determined. The conformations of the 1,4-DHP rings of these activator analogues of Bay K 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate] do not suggest that their activator properties are as strongly correlated with the degree of 1,4-DHP ring flattening as was indicated for members of the corresponding antagonist series. The solid state hydrogen bonding of the N(1)-H groups of the activators is not, unlike that of their antagonist counterparts, to acceptors that are directly in line with the donor. Rather, acceptor groups are positioned within ± 60 degrees of the N(1)-H bond in the vertical plane of the 1,4-DHP ring. Previously determined structure-activity relationships have indicated the importance of this N(1)-H group to the activity of the 1,4-DHP antagonists. Based on these observations, a model is advanced to describe the 1,4-DHP binding site of the voltage-gated Ca²⁺ channel and its ability to accommodate both antagonist and activator ligands.