Simultaneous on-line vacuum single- and multi-photon ionization on an orthogonal acceleration time-of-flight mass spectrometer platform.

The development of orthogonal acceleration time-of-flight (oa-tof) technology is driven forward due to higher mass accuracy and resolving power than conventional linear/reflectron tof instruments. This is achieved with a more accurate definition of starting energies and coordinates of ions by spatial separation of ion generation and orthogonal ion extraction. Consequently, the ability to cover the whole mass spectral range without scanning is not given anymore. Therefore, continuous ion sources are favored for ensuring high duty cycles and thus high temporal resolution. For pulsed ion sources, high repetition rates are mandatory for covering large m/z ranges without losing their high temporal resolution. We have combined an oa-tof with deuterium lamp single-photon ionization (SPI) as a continuous ion source together with a pulsed 2000 Hz excimer (KrF) laser for resonance enhanced multi-photon ionization (REMPI). These two ionization techniques can be used simultaneously. To the best of our knowledge, this system is the first of its kind in combining a vacuum pulsed ionization source with an oa-tof instrument without any other ion storage hardware. The combination of a soft broadband ionization for organics (SPI) in combination with a very sensitive and selective soft ionization (REMPI) can be used for covering the whole mass range or in targeted on-line monitoring cases one or several smaller mass ranges. To demonstrate the simultaneous SPI/REMPI-oa-tof technique, two applicative areas are explored: on-line monitoring of coffee roast gas emissions and e-cigarette vapor. The complementary information from SPI and REMPI signals are combined in a way to exploit the advantages of both ionization types. In a further development step, a second data acquisition card is built into the system. This modification allows the independent storage of data from both ionization methods without mixing. For demonstration, a third example with a GC measurement is provided. The last example shows the possibility of modified sensitivities for different mass regions in REMPI data acquisition without affecting the SPI channel. The newly developed system shows high robustness in terms of measurements in real industrial environments. The simultaneous measurement technique provides a higher density of information in a single measurement, saving time and resources.

New 5-aminoacyl-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-ones with antiarrhythmic activity.

A series of new 5-substituted tricyclic 5,10-dihydro-11H-dibenzo[b,e][1,4]-diazepin-11-ones was identified as potential antiarrhythmic agents against bradyarrhythmias [1, 2]. The in vitro and in vivo interactions of the compounds with muscarinic receptors and the antiarrhythmic activity were examined. In receptor binding studies some derivatives showed a high affinity to the cardiac M2 receptor (Ki 10 nmol/l), an equal or smaller affinity to cortical M1 receptor and a lower affinity to the glandular M3 binding site. Functional experiments showed the derivatives as competitive antagonists with high affinity to the cardiac and smaller affinity to the intestinal muscarinic receptor. In vivo experiments correspond with the M2 selectivity. First the vagal or agonist-induced bradycardia was inhibited in rats and guinea pigs while the McNA-343 induced increase of blood pressure, methacholine-induced bronchi and bladder constriction as well as the salivation were inhibited only at higher doses. In conscious cats the tachycardia was examined in comparison with pupillomotoricity. The effect duration and the therapeutical range were determined in comparison to the M2 selective blocking agent AF-DX116. The antiarrhythmic activity was examined compared to quinidine sulfate in CaCl2-arrhythmia of rats, in atrial fibrillation and atrial flutter in dogs according to Scherf [2] and in electric induced atrial fibrillation under vagal stimulation in cats. In the atrial arrhythmias the derivatives are clearly longer effective than quinidine sulfate. The antiischemic activity was examined in the two-stages coronary ligature in dogs according to Harris. The long-running regularization of ectopies (about 2 h after i.v. injection) occurred without decrease of the heart rate, an effect particularly convenient to therapy of bradycardic dysrhythmias.

[New derivatives of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepine-11-ones with anticholinergic activity]. / Neue Derivate des 5,10-Dihydro-11H-dibenzo[b,e][1,4]diazepin-11-on mit anticholinerger Wirkung.

Starting from 2-aminobenzoic acid and correspondingly substituted 2-chloronitrobenzenes, 5-substituted-aminoacyl-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin -11- one derivatives with a differently high activity on ulcers were prepared. 8-Chloro-5,10-dihydro-5-[bis(2-hydroxyethyl)a-minoacetyl]-11H- dibenzo[b,e][1,4]diazepin-11-one hydrochloride (AWD 26-06) was selected for further clinical evaluation.

[Synthesis and neurologic action of new 11-substituted 5H-dibenzo[b,e][1,4]diazepines]. / Synthese und neurologische Wirkung neuer 11-substituierter 5H-Dibenzo[b,e][1,4]diazepine.

The synthesis of the title compounds is described. The compounds are characterized by having no cataleptogenic effect and no antagonistic effect against amphetamine stereotypies in experimental animals. The pharmacological results of the rota-rod, spontaneous motility, aggression-test, hexobarbital-potentiation and antagonism to physostigmine are reported.