LC–MS Determination and Pharmacokinetic Study of a Novel Sulfonylurea: Potential Hypoglycemic Agent in Rat Plasma

To support preclinical pharmacokinetic investigation of 1-[4-[2-(4-bromobenzene-sulfonaminoethyl)phenylsufonyl]-3-(trans-4-methylcyclohexyl)urea (G004), a rapid, sensitive and specific high-performance liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) method was developed and validated. Glibenclamide was employed as internal standard. After liquid–liquid extraction the analyte was analyzed on a Kromasil C₁₈ column (150 × 2.0 mm i.d.) with a mobile phase consisted of acetonitrile–water (0.05% acetic acid), 30:70 (v/v). The flow rate was 0.2 mL min⁻¹. Detection was performed on a quadrupole mass spectrometer using an electrospray ionization interface and the selected-ion monitoring (SIM) mode. The retention time was about 3.5 and 4.2 min for Glibenclamide and G004, respectively. The assay was linear over the concentration range of 2.0–500.0 ng mL⁻¹. Extraction Recovery of G004 in rat plasma was more than 87%. The intra- and inter-assay precision was lower than 11.5% (CV). This validated method was successfully applied to the pharmacokinetics of G004 in rats.     

Large deviations for martingales with some applications

Let(X _i ) be a martingale difference sequence. LetY be a standard normal random variable. We investigate the rate of uniform convergence

Eigenresonance states in the Kronig-Penney model

We investigate a sandwich of three layer systems with Dirac -functions in the Kronig-Penney model. The inner system ofN=5 atomic layers is enclosed by the two outer systems with different potential strength. The numberM of the atomic layers in the outer system is varied betweenM=9 and infinity, whereas the numberN of the inner layers is held fixed. We obtain the transmission coefficient for the finite system in the region of scattering energies (E>0). An alternating set of transmission gaps, transmission bands and bands of eigenresonance states is obtained. The normalizable eigenresonances occur (forM going to infinity), if a transmission band of the inner system overlaps a transmission gap of the outer systems. The reason for obtaining solutions of standing waves in the band of eigenresonances is the rapid change of the wave phase of a traveling wave, which occurs in a transmission band of the inner system.     

Zero cycles on conic fibrations and a conjecture of Bloch

Let X be a smooth projective surface over a number field k. Let (CH₀(X)) denote the Chow group of zero-cyles modulo rational equivalence on X. Let CH₀(X) be the subgroup of CH ₀(X) consisting of classes which vanish when going over to an arbitrary completion of k. Bloch put forward a conjecture asserting that this group is isomorphic to the Tate-Shafarevich group of a certain Galois module atttached to X. In this paper, we disprove this general conjecture. We produce a conic bundle X over an elliptic curve, for which the group (CH₀(X) is not zero, but the Galois-theoretic Tate-Shafarevich group vanishes.     

Effect of ‘Transannular Transmission’ in Dibenzo-18-Crown-6

The effect of the nature of the substituent in the monosubstituted derivatives of dibenzo-18-crown-6 on the reactivity and direction of the electrophilic substitution reaction of the unsubstituted benzene ring has been determined. This transfer is carried out via the macrocycle and therefore is called transannular transmission. The possible mechanism of this transmission is discussed.     

Existence and uniqueness of semimartingale reflecting Brownian motions in an orthant

Summary This work is concerned with the existence and uniqueness of a class of semimartingale reflecting Brownian motions which live in the non-negative orthant of ^d . Loosely speaking, such a process has a semimartingale decomposition such that in the interior of the orthant the process behaves like a Brownian motion with a constant drift and covariance matrix, and at each of the (d-1)-dimensional faces that form the boundary of the orthant, the bounded variation part of the process increases in a given direction (constant for any particular face) so as to confine the process to the orthant. For historical reasons, this pushing at the boundary is called instantaneous reflection. In 1988, Reiman and Williams proved that a necessary condition for the existence of such a semimartingale reflecting Brownian motion (SRBM) is that the reflection matrix formed by the directions of reflection be completely-L. In this work we prove that condition is sufficient for the existence of an SRBM and that the SRBM is unique in law. It follows from the uniqueness that an SRBM defines a strong Markov process. Our results have potential application to the study of diffusions arising as approximations tomulti-class queueing networks.Research supported in part by NSF Grants DMS 8657483, 8722351 and 9023335, and a grant from AT&T Bell Labs. In addition, R.J. Williams was supported in part during the period of this research by an Alfred P. Sloan Research Fellowship     

Synthesis and structural characterization of novel bridged platinum(II) biscarbene complexes

Novel bridged platinum(II) biscarbene complexes are reported: 1,1′-dimethyl-3,3′-methylene-4-diimidazolin-2,2′-diylidene platinum(II) (3) and 1,1′-dimethyl-3,3′-ethylene-4-diimidazolin-2,2′-diylidene platinum(II) complexes 4 are directly accessible in high yields starting from platinum halides. The one-pot synthesis obviates the need for multi-step reactions via metal precursors or free carbenes. An X-ray crystal structure of 1,1′-dimethyl-3,3′-methylene-4-diimidazolin-2,2′-diylidene platinum(II) dibromide (3b) confirmed the structural similarity to the known corresponding palladium complexes. Since free 1,1′-di-R-3,3′-methylene-4-diimidazolin-2,2′-diylidenes are only available in low yields this synthetic route provides an easy access to the corresponding carbene complexes.     

Chemistry of λ-2H-azaphosphirene metal complexes

In this review, important aspects of λ³-2H-azaphosphirene metal complexes are discussed in relation to synthesis, physical properties and synthetic applications; ab-initio calculations on relative energies of CH₂NP isomers and of λ³-2H-azaphosphirene metal complexes (Cr, Mo, W) are also presented. Currently, there are three routes to this unsaturated three-membered ring system, which are discussed in detail: two of them use a rearrangement of metal carbene complexes, whereas the other relies on [2+1] cycloaddition reactions of electrophilic terminal phosphanediyl complexes and carbonitriles. The structural data show characteristics of a very strained heterocyclic ring system, which partially helps to understand the reactivity of this heterocycle complex in solution. The synthetic potential of λ³-2H-azaphosphirene metal complexes is illustrated by selected examples, which demonstrate their ability to serve, under very mild conditions as precursor for various new building blocks, i.e. nitrilium phosphanylide complexes, electrophilic terminal phosphanediyl complexes and phosphavinyl-nitrene complexes.     

Triphenylphosphan-Nickel(0)-Komplexe mit Isocyanid-Liganden — [(RNC)nNi(PPh3)4–n] (n = 1–3)

Triphenylphosphane Nickel(0) Complexes with Isocyanide Ligands — [(RNC)_nNi(PPh₃)_4–n] (n = 1–3) Synthesis and properties of the isocyanide triphenylphosphane nickel(0) complexes [(RNC)Ni(PPh₃)₃], [(RNC)₂Ni(PPh₃)₂] and [(RNC)₃Ni(PPh₃)] (R = ^tBu, Cy, PhCH₂, p-TosCH₂) are described. I.r. and ³¹P n.m.r. spectra were recorded and the X-ray crystal structure of [(PhCH₂NC)₂Ni(PPh₃)₂] was determined.