NMR of some benzodiazepine drugs: Structure elucidation with lanthanide-induced shifts of N-1 substituted benzodiazepinones

Two 1,4-benzodiazepinones of psychopharmacological interest, pinazepam (2) and prazepam (3), were studied in solution by ¹³C and ¹H NMR. ¹H variable-temperature experiments showed that the seven-membered ring exists in a simple pseudo-boat form at room temperature, but the energy barrier is higher in 3 (ΔG_405°c = 82.8 kJ mol^?1) than in diazepam (1). Moreover, upon addition of LSR, the boat conformation is retained in the lanthanide ion-substrate complex, as with 1 in the solid state. Using a concentration-dependent shift technique and a computer-assisted LIS method, the conformations of the N-branched side-chain were investigated. Two preferred orientations were found for the propargyl group of 2, while three unequally populated conformations of the cyclopropyl moiety of 3 are distributed preferentially in the sterically unhindered space around the complex.     

X-ray crystallographic structure of the 9,10-dihydro-11,12bis[(1,3,3-trimethylureido)methyl]-9,10ethanoanthracene dihydrate

As a part of studies on MDR reversal agents, structure of the 9,10-dihydro-11,12-bis[(1,3,3-trimethylureido)methyl]-9,10-ethanoanthracene dihydrate is reported. Crystal data: C₂₆H₃₄N₄O₂ × 2 H₂O; mol. mass 470.60; monoclinic; space group: C2/c, a = 15.7492(6) Å; b = 7.2245(3) Å; c = 24.3442(10) Å; β = 106.795(2)^∘; V = 2651.73(22) ų; z = 4; dx = 1.179 mg/m³; μ = 0.64 mm⁻¹; F(000) = 1016; final R = 0.061 for 2501 reflections [I > 4 σ (I)]. Only half of the molecule is unique. The two nonplanar rings from the independent part of 9,10-dihydro-9,10-ethanoanthracene adopt a boat conformation. Crystallographic data demonstrate the “syn-syn” conformation of urea substituents in the molecule. In the crystal, water molecules are linked to the main species by H-bonds: O3′⋅sH12w—O1—H11w⋅sO3′(1.5 − x, 0.5 − y, 1 − z).     

Geometries with dual affine planes and symplectic quadrics

Farmer and Hale [3] prove that every copolar space fully embedded in a finite projective space PG(n, q), with q>, is the copolar space arising from a symplectic polarity. We show that this result is still valid in arbitrary projective spaces; this provides a different and shorter proof of [3] in the finite case.     

Universal additive effect of temperature on the rheology of amorphous solids

Extensive measurements of macroscopic stress in a 2D Lennard-Jones glass, over a broad range of temperatures (T) and strain rates (γ), demonstrate a very significant decrease of the flowing stress with T, even much below the glass transition. A detailed analysis of the interplay between loading, thermal activation, and mechanical noise leads us to propose that over a broad (γ, T) region, the effect of temperature amounts to a mere lowering of the strains at which plastic events occur, while the athermal avalanche dynamics remains essentially unperturbed. Up to the vicinity of the glass transition, temperature is then shown to correct the athermal stress by a (negative) additive contribution which presents a universal form, thus bringing support to and extending an expression proposed by Johnson and Samwer [Phys. Rev. Lett. 95, 195501 (2005)].     

Bifurcation analysis of a generalized Gause model with prey harvesting and a generalized Holling response function of type III

In this paper we study a generalized Gause model with prey harvesting and a generalized Holling response function of type III: . The goal of our study is to give the bifurcation diagram of the model. For this we need to study saddle-node bifurcations, Hopf bifurcation of codimension 1 and 2, heteroclinic bifurcation, and nilpotent saddle bifurcation of codimension 2 and 3. The nilpotent saddle of codimension 3 is the organizing center for the bifurcation diagram. The Hopf bifurcation is studied by means of a generalized Liénard system, and for b=0 we discuss the potential integrability of the system. The nilpotent point of multiplicity 3 occurs with an invariant line and can have a codimension up to 4. But because it occurs with an invariant line, the effective highest codimension is 3. We develop normal forms (in which the invariant line is preserved) for studying of the nilpotent saddle bifurcation. For b=0, the reversibility of the nilpotent saddle is discussed. We study the type of the heteroclinic loop and its cyclicity. The phase portraits of the bifurcations diagram (partially conjectured via the results obtained) allow us to give a biological interpretation of the behavior of the two species.