No abstract

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2+) rises to omega 500 nM. In neurons, this occurs during and after an action potential. Activation of SK channels hyperpolarizes the membrane, thus reducing cell excitability for several tens or hundreds of milliseconds. This phenomenon is called a afterhyperpolarization (AHP). Three subtypes of SK channels (SK1, SK2, SK3) have been cloned and exhibit a differential localization in the brain. SK channels may play a role in physiological and pathological conditions. They may be involved in the control of memory and cognition. Moreover, they are heavily expressed in the basal ganglia (in particular in the substantia nigra, pars compacta) and in the limbic system, suggesting that they may modulate motricity and emotional behaviour. Based on these facts, SK channel subtypes may be a suitable target for developing novel therapeutic agents, but more work is needed to validate these targets. Hence, there is a great need for selective ligands. Moreover, although the risk of peripheral side-effects for SK channel modulators appears to be low, some questions remain to be investigated. Currently, different molecules are known as SK channel modulators. Apamin is a very potent peptidic agent; it produces a strong blockade of these targets which is only very slowly reversible and it has limited selectivity. Dequalinium was found to be an effective blocker. Different chemical modulations on the dequalinium structure led to the discovery of highly potent bis-quinolinium derivatives such as UCL 1684. Other bis-(2-amino-benzimidazole) derivatives are in development. On the other hand, quaternary salts of bicuculline were reported to be effective in inhibiting AHPs. More recent developments on structurally-related molecules revealed that methyl-laudanosine is a new interesting tool for exploring SK channel pharmacology. Finally, a family of compounds has been shown to facilitate SK channel opening. Such compounds may be useful in treating disorders involving neuronal hyperexcitability.

Insoluble diorganotin functionalized polymers of the type (P-H) 1-t (P-(CH 2 ) n SnBuX 2 ) t , with n ) 4, 6, X ) Ph, Cl, and t being the degree of functionalization, were synthesized from Amberlite XE-305, an insoluble polystyrene (P-H) cross-linked with divinylbenzene. The synthesis conditions used gave rise to functionalization degrees varying from 25% to 30%. The tin-functionalized polystyrenes were characterized by elemental analysis, IR, and Raman as well as solid-state 117 Sn and 13 C NMR spectroscopy. Methodological and chemical features related to the determination of the functionalization degree have been investigated in detail. The catalytic activity of the Amberlite-grafted tin functionalities in transesterification reactions was studied.

Für die 18F‐Markierung von Radiopharmaka benötigt man annähernd wasserfreie [18F]Fluorid‐Lösungen, doch um [18F]F− von Anionaustauscherharzen zu waschen, werden üblicherweise wässrige K2CO3‐Lösungen verwendet. Ersetzt man K2CO3 durch starke organische Basen wie die Phosphazenbase P2Et (deren konjugierte Säure hier abgebildet ist), so lässt sich hoch reaktives [18F]F− ohne eine azeotrope Wasserverdampfung zurückgewinnen.