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Allosteric ionophores

The project concerns the development of new allosteric systems which by suitable conformational coupling between heterotopic binding sites I and II should show exceptional degrees of co-operativity. Conformational changes are the basis of molecular switches within this project. These were studied with different, mostly newly synthesised, systems as a function of binding a variety of substrates, in particular of ions. With some of the host compounds new allosteric effects could already be demonstrated, opening new ways to control for example. ion binding or release by external 'signals'. Cyclohexanes with suitable substituents such as carboxylic groups were shown to switch between two chair conformations as a function of proton association and dissociation. Introduction of additional 'lever' substituents allow' control of the efficiency of such pH switches; the same holds for the conformational control by metal binding in cyclohexanothiacrowns. Heterotopic anti-cooperativity between poton and alkali cation binding was achieved in cyclohexanes bearing polyethyleneglycol and vicinal amino and hydroxy substituents. The conformations of various calixarenes were studied as a function of substitution and ring size. Calix[6]arenes in the form of phosphorylated derivatives were shown to occur in distinct conformations, which can be switched by different guest molecules. Some diphosphorylated and triphosphorylated calixarenes bind natural occurring ammonium derivatives much stronger than metal cations. An intriguing new possibility to switch host entities between binding and release of, say pyridinium-type guest molecules was found by the formation of dimeric sandwiches between two calixarene host molecules. Chair-boat interconversions in diazabicyclo[3.3.1]nonanes were characterized with several derivatives, which are the possible basis of implementation into allosteric systems. Acylation at the nitrogen atoms in chair-chair diazabicyclo[3.3.1]nonanes provided the hitherto most efficient entry into a new principle of molecular switches. Preliminary studies with benzene and cyclohexane derivatives bearing vicinal amide groups have also shown the feasibility of the concept.


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