The long term goal of this research is to construct compounds capable of acting as specific catalysts in a fashion comparable to that of enzymes. Such compounds, often called enzyme mimics, should possess a cavity that is complementary in shape and size to that of the substrate molecule along with functional groups properly arranged in space to allow approximation to the reaction sites of the substrate molecule. A class of (1)n metacyclophanes which we have named """"""""calixarenes"""""""" (Gr., """"""""calix""""""""; """"""""arene"""""""", indicating the presence of aromatic rings in the macrocyclic array) have the potential for satisfying these criteria, and it is with the synthesis, characterization, and chemistry of these compounds that the present study is concerned. During the present grant period, improvements in the construction of the basic macrocycle have been made, and additional methods for introducing functional groups have been made, and additional methods for introducing functional groups have been developed. The conformational behavior of the entire series of calixarenes (containing 4,5,6,7, and 8 aryl rings) as well as three oxacalixarenes have been studied via dynamic 1H NMR, and the probable shapes of these molecules in solution have been established. The complexing characterisitics of the calixarenes have been investigated, and it has been found that some of them form rather tight complexes with alkylamines in solution. Some polyfunctional calixarenes have been constructed, and investigations of their catalytic behavior have been initiated. Several of the programs of the present grant period will be continued and extended, and increasing attention will be devoted to the testing of appropriately functionalized calixarenes as hydrolysis catalysts (chymotrypsin mimic and phosphatase mimic), aldolization catalysts (aldolase mimic), farnesol phosphate catalysts), and oxygen carriers (heme mimic). Studies of calixarene catalysis might possibly shed light on the mechanism of enzymic catalysts, will certainly establish patterns for the production of better synthetic catalysts, and will produce many new compounds with novel structures which may have interesting properties and useful pharmacological activities.
