Two Stage Solid Phase Extraction with Subsequent HPLC Isolation for Structure Elucidation of Major Metabolites of (+)-(R)-2-{3-(benzo[1,4]dioxan-2-yl-methylamino)-1-propyl}-3(2H)-pyridazinone (GYKI-16084)

GYKI-16084 – (+)-(R)-2-{3-(benzo[1,4]dioxan-2-yl-methylamino)-1-propyl}-3(2H)-pyridazinone hydrochloride – is a new drug candidate for the treatment of benign prostatic hyperplasia. In our study the major metabolites formed in the rat and dog were isolated from dog and rat urine, then their structures were elucidated by means of MS and NMR. A two stage solid phase extraction (SPE) procedure and a semi-preparative HPLC method were developed utilizing various mechanisms of separation. The major metabolites proved to be isomeric glucuronides of the benzodioxane moiety hydroxylated at positions 6 or 7 and {2-(2-carboxyethyl)-3(2H)-pyridazinone}.     

Stereoselectivity in the intermolecular Pauson-Khand reaction of electron-deficient terminal alkynes

A family of terminal alkyne dicobalthexacarbonyl complexes bearing groups with a range of electron-withdrawing abilities has been synthesized. After submitting these complexes to the intermolecular Pauson-Khand reaction with norbornadiene, electron-deficient substrates afforded up to 26% of the unexpected endo-cyclopentenone.     

Thermodynamic Limit and Proof of Condensation for Trapped Bosons

We study condensation of trapped bosons in the limit when the number of particles tends to infinity. For the noninteracting gas we prove that there is no phase transition in any dimension, but in any dimension, at any temperature the system is 100% condensated into the one-particle ground state. In the case of an interacting gas we show that for a family of suitably scaled pair interactions, the Gross–Pitaevskii scaling included, a less-than-100% condensation into a single-particle eigenstate, which may depend on the interaction strength, persists at all temperatures.     

Pointwise gradient estimates of solutions to onedimensional nonlinear parabolic equations

We present here an improved version of the method introduced by the first author to derive pointwise gradient estimates for the solutions of one-dimensional parabolic problems. After considering a general qualinear equation in divergence form we apply the method to the case of a nonlinear diffusion-convection equation. The conclusions are stated first for classical solutions and then for generalized and mild solutions. In the case of unbounded initial datum we obtain several regularizing effects for t > 0. Some unilateral pointwise gradient estimates are also obtained. The case of the Dirichlet problem is also considered. Finally, we collect, in the last section, several comments showing the connections among these estimates and the study of the free boundaries associated to the solutions of the diffusion-convection equation.     

Stable boundary layers in a diffusion problem with nonlinear reaction at the boundary

We prove the existence of nonconstant stable stationary solutions of an evolution problem with a nonlinear reaction acting on the boundary. These solutions present layers at certain points of the boundary. We also study the behavior of these solutions as the small parameter appearing in the equation approaches zero and show some stability properties of the profiles given by these equilibrium solutions.     

Simultaneous Determination of Carbamate and Organophosphorus Pesticides in Honeybees by Liquid Chromatography-Mass Spectrometry

Summary The potential of liquid chromatography-mass spectrometry (LC-MS) has been studied for the simultaneous determination of sixteen carbamate and organophosphorus pesticides in honeybees using a traditional sample preparation protocol based on acetone extraction and dichloromethane partitioning. The performances of both atmospheric pressure chemical ionization (APCI) and electrospray (ES) interfaces were compared. APCI offered better sensitivity and specificity for a higher range of pesticides. Limits of quantification were from 0.01 to 0.17 mg kg^–1, at which recoveries obtained were between 64 and 93%, except for pirimicarb that was at 13%, with relative standard deviations ranging from 7 to 20%. Fenitrothion, fenoxycarb, methiocarb and phoxim were found in bees from Valencian Community beehives at concentrations between 0.03 and 3.75 mg kg^–1.     

Geometric formulas for Smale invariants of codimension two immersions

We give three formulas expressing the Smale invariant of an immersion f of a (4k−1)-sphere into (4k+1)-space. The terms of the formulas are geometric characteristics of any generic smooth map g of any oriented 4k-dimensional manifold, where g restricted to the boundary is an immersion regularly homotopic to f in (6k−1)-space.The formulas imply that if f and g are two non-regularly homotopic immersions of a (4k−1)-sphere into (4k+1)-space then they are also non-regularly homotopic as immersions into (6k−1)-space. Moreover, any generic homotopy in (6k−1)-space connecting f to g must have at least a_k(2k−1)! cusps, where a_k=2 if k is odd and a_k=1 if k is even.