N-Aryl Isoleucine Derivatives as Angiotensin?II AT2 Receptor Ligands

A novel series of ligands for the recombinant human AT₂ receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)₆] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with K_i values in the low micromolar range versus the recombinant human AT₂ receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs.     

Dynamics of Relative Phases: Generalised Multibreathers

For small Hamiltonian perturbation of a Hamiltonian systemof arbitrary number of degrees of freedom with anormally non-degenerate submanifold of periodic orbits we construct a nearbysubmanifold and an `effective Hamiltonian' on it such that the differencebetween the two Hamiltonian vector fields is small. The effective Hamiltonianis independent of one coordinate, the `overall phase', and hence thecorresponding action is preserved. Unlike standard averaging approaches,critical points of our effective Hamiltonian subject to given actioncorrespond to exact periodic solutions. We prove there has to be at least acertain number of these critical points given by global topological principles.The linearisation of the effective Hamiltonian about critical points is provedto give the linearised dynamics for the full system to leading order in theperturbation. Hence in the case of distinct eigenvalues which move at non-zerospeed with ,the linear stability type of the periodic orbit can be read offfrom the effective Hamiltonian. Our principal application is to networks ofoscillators or rotors where many such submanifolds of periodic orbits occurat the uncoupled limit – simply excite a number N 2 of the units inrational frequency ratio and put the others on equilibria, subject to anon-resonance condition. The resulting exact periodic solutions for weakcoupling are known as multibreathers. We call the approximate solutions givenby the effective Hamiltonian dynamics, `generalised multibreathers'. Theycorrespond to solutions which look periodic on a short time scale but therelative phases of the excited units may evolve slowly. Extensions aresketched to travelling breathers and energy exchange between degrees offreedom.     

Alcoolyse et glycolyse de derives organozinciques et organocadmiens par des composes chiraux

The reaction between organozinc or organocadmium derivatives and different chiral hydroxy compounds leads to the corresponding alcoholates and glycolates which can be used as initiators in polymerizations.The composition of such initiators is defined by the ratio i_S = R-M-O/O-M-O of the number of alkylalkoxy groups to the number of dialkoxy groups. This ratio depends on the nature of the organometallic and hydroxy compound and on the conditions of reaction used to prepare them.Toward a given hydroxy compound, the reactivity of the organometallic derivatives follows the order: ZnEt₂ > CdEt₂ > CdMe₂.Primary alcohols and 1,2-diols are more reactive than secondary alcohols in the case of organozinc compounds, while in the case of organocadmium compounds the secondary alcohols are more reactive than primary alcohols, but less reactive than 1,2-diols. The kinetics of the reaction can be followed by monitoring the variation of optical activity of the solution.Several compounds having definite stoichiometry have been isolated and identified by their NMR spectra.     

Bistable reaction-diffusion systems can have robust zero-velocity fronts

We show that for a class of bistable reaction-diffusion systems, zero-velocity fronts can be robust in the singular limit where one of the diffusion coefficients vanishes. In this case, stationary fronts can persist along variations of the system parameters. This property contrasts with the standard result that the front velocity v(&mgr;), expressed as a function of a control parameter &mgr;, is zero only at some isolated values &mgr;(0), and thus not giving robustness to zero-velocity fronts when &mgr; is varied. (c) 2000 American Institute of Physics.     

300 MHz 1H-NMR study of poly(propylene sulfide)

An ¹H 300-MHz NMR spectroscopic study of deuterated poly(propylene sulfide) shows that methylene protons are sensitive to triad effects. It was possible to distinguish i, h_i, s, and h_s triads. Experimental values found for different polymers are in good agreement with theoretical amounts obtained from statistical probability calculation. The methyl groups are also slightly stereosensitive. By using optically active deuterated monomers with different R/S ratios it was possible to confirm the assignment of peaks and the tacticity. Nondeuterated polymers give very complicated spectra, and only the highly stereoregular polymer could be analyzed through its ABCX₃ spin system.     

Synthesis and structural study of copolymers of l-lactic acid and bis(2-hydroxyethyl terephthalate)

Poly(ethylene terephthalate)-poly(lactic acid) (PET-PLLA) copolyesters were synthesized by the melt reaction of bis(2-hydroxyethyl terephthalate) (BHET) with l-lactic acid oligomers (OLLA) in the presence of SnCl₂, H₂O-p-toluene sulfonic acid, H₂O catalytic system. The ¹H and ¹³C NMR studies confirm the incorporation of lactate units in PET chains after reaction. Copolyesters containing nearly equimolar terephthalate/lactate ratio are not completely random and present some block-copolymer character, while the microstructure of PET-rich copolyesters is a random one. Due to a longer PET sequence length, the latter exhibit a melting point close to 210 °C while the other ones are amorphous. SEC/MALDI-TOF MS off-line coupling was used to obtain the absolute average molar masses of the copolyesters. The results indicate that the conventional polystyrene calibration method leads to a strong overestimation of PET-PLLA molar masses, while the determined by NMR is much closer to the SEC/MALDI value.