Christian Weber

ONE-STEP SYNTHESIS OF DIALKYNYL-1,2-DIONES AND THEIR CONVERSION TO FUSED PYRAZINES BEARING ENEDIYNE UNITS

Abstract A convenient procedure for the preparation of symmetrically end-protected dialkynyl-1,2-diones 3 from lithium acetylides and oxalyl chloride in the presence of CuBr and LiBr is described. The condensation of 3 with various aromatic and heteroaromatic 1,2-diamines leads to pyrazine-based α-dialkynylated heterocycles. The enediyne substructure of diethynylquinoxaline can be thermally rearranged in a Bergman cyclization reaction.

Interleukin-10 Suppresses Tissue Factor Expression in Lipopolysaccharide-Stimulated Macrophages via Inhibition of Egr-1 and a Serum Response Element/MEK-ERK1/2 Pathway

Atherosclerosis is considered to be an inflammatory disease. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play an essential role in thrombus formation after atherosclerotic plaque rupture. Recent studies suggest that the antiinflammatory cytokine interleukin-10 (IL-10) has many antiatherosclerotic properties. Therefore, the effects of IL-10 on TF expression in response to inflammation were investigated. Mouse macrophages were stimulated with lipopolysaccharide (LPS) in the presence or absence of IL-10. Pretreatment with IL-10 resulted in a 50% decrease in TF mRNA expression and TF promoter activity. Binding of early growth response gene-1 (Egr-1) to the consensus DNA sequence, a key transcriptional activator of TF expression in response to inflammation, and the expression of Egr-1 mRNA were also inhibited by IL-10. This inhibition was independent of the induction of suppressor of cytokine signaling protein-3 by IL-10. Macrophages that had been transfected with luciferase reporter constructs containing the murine Egr-1 5′-flanking sequence exhibited reduced reporter gene activity in response to LPS stimulation with IL-10 pretreatment. Studies with deletion constructs of the Egr-1 promoter identified the proximal serum response element SRE3 as a potential regulatory site for the IL-10 mediated suppression of Egr-1 expression. Furthermore, activation of the upstream signal-transduction elements, such as mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase 1/2, and Elk-1 were also inhibited by IL-10 pretreatment. Taken together, these results demonstrate a pathway for the IL-10 mediated inhibition of TF expression during inflammation and may explain the antiatherosclerotic effects of IL-10.

Extracorporeal shock wave treatment raises blood pressure in borderline hypertensive rats.

The long-term sequelae on kidney function and blood pressure of renal shock wave treatment were studied in normotensive Wistar rats, contralaterally nephrectomized Wistar rats and borderline hypertensive F1-hybrids bred from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. Renal shock wave treatment raised arterial blood pressure in borderline hypertensive, but not in normotensive, rats. A concomitant impairment of ipsilateral renal function or perfusion was not seen despite macroscopic and microscopic evidence of a loss of functioning parenchyma. We conclude that extracorporeal shock wave treatment, by way of its detrimental effects on the kidney, has the potential to provoke arterial hypertension in rats, provided that a genetic predisposition exists.

2,3-Dialkynyl-1,4-diazabuta-1,3-dienes as Novel π-Systems: Synthesis, Structure, and Electronic Properties

The introduction of alkynyl groups into the 2,3-positions of the 1,4-diazabuta-1,3-diene (DAD) backbone succeeds along two complementary synthetic routes either by condensing triisopropylsilyl-terminated dialkynyl-1,2-diones with primary aromatic amines or by a palladium-mediated alkynylation of bis(imidoyl chlorides). X-ray crystallographic analyses of two dialkynyl DAD derivatives reveals their planar (E-s-trans-E) conformations in the solid state. However, the central CC bond of both DAD backbones investigated has a length of 1.491(2) A, and is therefore too long to indicate efficient delocalization across the DAD core. The UV/Vis spectra of dialkynyl DADs demonstrate that their absorptions in comparison to those of non-alkynyl DADs are bathochromically shifted by more than 40 nm, thereby demonstrating the suitability of the title compounds for developing NIR chromophores. The electron absorption properties of differentially N,N′-disubstituted dialkynyl DADs gave no indication for a push-pull effect across the DAD skeleton and suggest the ynimine moiety as the active chromophore of dialkynyl DADs. The electrochemical properties of the title compounds were determined by cyclo- and steady state voltammetry and show that introducing alkynyl groups leads to more easily reducible DAD systems. Again, the perception of dialkynyl DADs as covalently linked, but electronically decoupled ynimine units is corroborated by the redox potential of a differentially N,N′-disubstituted dialkynyl DAD. Similar conclusions were drawn from semiempirical MO (PM3) calculations of dialkynyl DADs.

Acetylenic NIR-chromophores: 2,3-dialkynyl-1,4-diazabuta-1,3-diene complexes of Ni(0) and Ni(II)

Abstract Acetylenic diazabutadienes (DADs) were used to modulate the electron absorption properties of Ni(0) and Ni(II) chelate complexes with respect to those of non-acetylenic DAD metal coordination compounds. Alkynylated bis( N -aryl) DAD ligands are shown to induce efficient metal-to-ligand charge-transfer in coordination compounds of the type (DAD) 2 Ni(0). These metal–ligand interactions manifest themselves as intense absorptions in the near infrared (NIR) around 800 nm and are significantly shifted batho- and hyperchromic compared to charge-transfer bands of non-acetylenic DAD metal complexes. Likewise, alkynyl substitution of bis(glyoximato)nickel(II) complexes results in a sizeable absorption band in the visible region of the electromagnetic spectrum.