The Impact of Antiaromatic Subunits in [4n+2] π-Systems: Bispentalenes with [4n+2] π-Electron Perimeters and Antiaromatic Character.

Three series of stable, neutral, π-extended bispentalene derivatives, with two pentalenes fused to a central benzene or naphthalene moiety, have been prepared through a modified double carbopalladation cascade reaction. While these chromophores feature skeletons with [4n+2] π-electron perimeters, the two 8 π-electron pentalene subunits strongly influence bonding and spectral properties. (1)H NMR spectra showed large upfield shifts of the protons in the pentalene moieties, comparable to antiaromatic monobenzopentalenes. Further investigations on magnetic ring currents through NICS-XY-scans suggest a global paratropic current and a local diatropic current at the central benzene ring in two of the series, while the third series, with a central naphthalene ring, showed more localized ring currents, with stronger paratropic ring currents on the pentalene moieties. X-ray diffraction analyses revealed planar bispentalene cores with large double- and single-bond alternation in the pentalene units, characteristic for antiaromaticity, and small alternation in the central aromatic rings. In agreement with TD-DFT calculations, both optical and electrochemical data showed much smaller HOMO-LUMO energy gaps compared to other neutral, acene-like hydrocarbons with the same number of fused rings. Both experimental and computational results suggest that the molecular properties of the presented bispentalenes are dominated by the antiaromatic pentalene-subunits despite the [4n+2] π-electron perimeter of the skeletons.

Thioglycine and L-thiovaline: biologically active H2S-donors.

Thioglycine and l-thiovaline are stable under acidic and basic conditions but in the presence of bicarbonate they liberate the gasotransmitter H(2)S. In cells both thioamino acids were proven to enhance cGMP formation and promote vasorelaxation in mouse aortic rings. Given that H(2)S is known to lower arterial hypertension, reduce oxidative stress and exhibit cardioprotective effects in preclinical models, H(2)S donors hold promise as novel treatments for cardiovascular diseases.

Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase.

Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates the second messenger cGMP and hence, leads to a number of physiological responses including vasodilation, inhibition of platelet aggregation and neurotransmission. Whilst many activating and stimulating modulators of sGC were identified and studied in recent years, only two selective inhibitors are known: ODQ and NS 2028. Furthermore, a synthetic approach to these inhibitors has not been reported yet. Herein, we describe a novel and efficient synthesis of these inhibitors, as well as the preparation of three different classes of NS 2028 analogues. Biological evaluation of this library using rat aortic smooth muscle cells revealed four new compounds with good to moderate sGC inhibitory activity. Our experiments underline the major importance of the oxadiazole ring in ODQ and NS 2028 for the efficiency of this class of inhibitors.