A proposal for the molecular basis of μ and δ opiate receptor differentiation based on modeling of two types of cyclic enkephalins and a narcotic alkaloid

Summary The molecular basis underlying the divergent receptor selectivity of two cyclic opioid peptides Tyr-c[N -d-Orn²-Gly-Phe-Leu-] (c-ORN) and [d-Pen², l-Cys⁵]-enkephalinamide (c-PEN) was investigated using a molecular modeling approach. Ring closure and conformational searching procedures were used to determine low-energy cyclic backbone conformers. Following reinsertion of amino acid side chains, the narcotic alkaloid 7-[(1R)-1-methyl-1-hydroxy-3-phenylpropyl]-6,14-endoethenotetrahydro oripavine (PEO) was used as a flexible template for bimolecular superpositions with each of the determined peptide ring conformers using the coplanarity and cocentricity of the phenolic rings as the minimum constraint. A vector space of PEO, accounting for all possible orientations for the C₂₁-aromatic ring of PEO served as a geometrical locus for the aromatic ring of the Phe⁴ residue in the opioid peptides. Although a vast number of polypeptide conformations satisfied the criteria of the opiate pharmacophore, they could be grouped into three classes differing in magnitude and sign of the torsional angle values of the tyrosyl side chain. Only class III conformers for both c-ORN and c-PEN, having tyramine dihedral angles ₁ =–150° ± 30° and ₂=–155° ± 20°, had significant structural and conformational properties that were mutually compatible while respecting the PEO vector space. Comparison of these properties in the context of the divergent receptor selectivity of the studied opioid peptides suggests that the increased distortion of the peptide backbone in the closure region of c-PEN together with the pendant ,-dimethyl group, combine to generate a steric volume which is absent in c-ORN and that may be incompatible with a restrictive topography of the receptor. The nature and stereo-chemistry of substituents adjacent to the closure region of the peptides could also modulate receptor selection by interacting with a charged () or neutral () subsite.     

Enhancement of the solubilities of polycyclic aromatic hydrocarbons by weak hydrogen bonds with water

Summary The thermodynamics of mobile order is applied to predict the aqueous solubility of liquid and solid aliphatic and polycyclic aromatic hydrocarbons. The solubility values are mainly determined by the magnitude of the hydrophobic effect. However, contrary to the solubilities of the alkanes, the solubilities of polycyclic aromatic hydrocarbons in water predicted in absence of solute-solvent hydrogen (H) bonds are systematically too low. This shows the contribution of weak specific interactions between the OH groups and the electrons of the aromatic substances. According to the theory, these interactions are characterized by a stability bility constant K_o which can be derived from solubility data. At 25°C, this constant amounts to 80 cm³/mol, the order of magnitude of which can be explained by the competition of these intermolecular bonds with the rather weak self-association bonds in the secondary chains of water.     

Facets for the cut cone I

We study facets of the cut coneC _n , i.e., the cone of dimension 1/2n(n – 1) generated by the cuts of the complete graph onn vertices. Actually, the study of the facets of the cut cone is equivalent in some sense to the study of the facets of the cut polytope. We present several operations on facets and, in particular, a lifting procedure for constructing facets ofC _n+1 from given facets of the lower dimensional coneC _n . After reviewing hypermetric valid inequalities, we describe the new class of cycle inequalities and prove the facet property for several subclasses. The new class of parachute facets is developed and other known facets and valid inequalities are presented.     

Cotype of operators fromC(K)

Summary Forq>2, an operator fromC(K) toX is of cotypeq if and only if it factors through the Lorentz space . Forq=2, ifX is a rearrangement invariant space on [0, 1], the injectionC([0, 1])X is of cotype 2 if and only if it factors through the Lorentz space ; but there is a cotype 2 operator C(K) that does not factor through . If a Banach latticeX satisfies the Orlicz property, any bounded lattice operatorT:C(K)X is of cotype 2. We however construct a Banach lattice with the Orlicz property, but that fails to be of cotype 2.Oblatum 4-VII-1990 & 18-IV-1991Work partially supported by an NSF grant     

On vector-valued random Fourier series

Consider a (complex) Banach spaceX, such thatX C_O, and vectors(X _i ) _i ofX. Consider an independent standard normal sequence(g _i ) _i . Then if anX-valued random Fourier series _{|k| n} e ^ikt g _k x _k satisfies

Capture by stabilized continuum: Classical and quantum aspects

We review here the results of our investigations concerning chaotic atomic scattering in the presence of a laser field. Particular emphasis is put on the existence of classical stable resonance structures, induced by the intense laser field, which are embedded in the field-free continuum. We show that phase space structures in the vicinity of a resonance island play an important role in the chaotic scattering behavior and form the basis for a mechanism to enhance the lifetimes of the collisional partners. Quantum calculations, based on a wave packet propagation method, show that quantum solutions are strongly influenced by the classical phase space structures. More specifically, a wave packet is found to spread differently in the regular and chaotic regions; in the latter case it spreads exponentially with time until saturation occurs, defining the saturation time. We also investigate the dependence of the spreading rates in both the regular and chaotic regimes. Calculations with an ensemble of classical trajectories are also presented to further illustrate the smoothing effects of varying.     

Galactose oxidase models: solution chemistry, and phenoxyl radical generation mediated by the copper status

Galactose oxidase (GO) is an enzyme that catalyzes two-electron oxidations. Its active site contains a copper atom coordinated to a tyrosyl radical, the biogenesis of which requires copper and dioxygen. We have recently studied the properties of electrochemically generated mononuclear Cu(II)-phenoxyl radical systems as model compounds of GO. We present here the solution chemistry of these ligands under various copper and dioxygen statuses: N(3)O ligands first chelate Cu(II), leading, in the presence of base, to [Cu(II)(ligand)(CH(3)CN)](+) complexes (ortho-tert-butylated ligands) or [(Cu(II))(2)(ligand)(2)](2+) complexes (ortho-methoxylated ligands). Excess copper(II) then oxidizes the complex to the corresponding mononuclear Cu(II)-phenoxyl radical species. N(2)O(2) tripodal ligands, in the presence of copper(II), afford directly a copper(II)-phenoxyl radical species. Addition of more than two molar equivalents of copper(II) affords a Cu(II)-bis(phenoxyl) diradical species. The donor set of the ligand directs the reaction towards comproportionation for ligands possessing an N(3)O donor set, while disproportionation is observed for ligands possessing an N(2)O(2) donor set. These results are discussed in the light of recent results concerning the self-processing of GO. A path involving copper(II) disproportionation is proposed for oxidation of the cross-linked tyrosinate of GO, supporting the fact that both copper(I) and copper(II) activate the enzyme.     

Activation of bismuth(III) derivatives in ionic liquids: novel and recyclable catalytic systems for Friedel-Crafts acylation of aromatic compounds

The activity of four bismuth(III) derivatives when employed as Friedel-Crafts catalysts for the acylation of aromatics was found to increase dramatically when dissolved in ionic liquids. Solutions of bismuth oxide or triflate in [emim][NTf(2)] and [bmim][NTf(2)] are the most efficient catalytic systems, with catalyst loading as low as 1% leading to clean, high-yielding acylation of a variety of benzene derivatives. These improved Friedel-Crafts catalytic systems can also be efficiently recycled as opposed to traditional systems. [reaction: see text]     

Photochemistry of 3-Substituted 1-Iminopyridinium Ylides. Regiospecific versus non-regiospecific photoisomerization patterns [1]

3-Substituted 1-iminopyridinium ylides 1 undergo photo-induced ring enlargement to 1H-1,2-diazepines. With strongly electron-withdrawing substituents the ring expansion process is regiospecific and leads exclusively to 4-substituted 1 H-1, 2-diazepines. Weak electron-donating substituents, like a methyl group and halogen atoms, do not have any directing effect since both 4- and 6-substituted 1 H -1,2-diazepines are obtained. With strong electron-donating substituents no diazepines are formed; instead one observes photo-induced isomerization to the 2-aminopyridine derivatives, the process being non-regiospecific. Regiospecific photo-induced ring expansion processes are explained in terms of a simple HMO model.