Dendrophanes: Novel steroid-recognizing dendritic receptors. Preliminary communication

Article abstract of DOI:10.1002/hlca.19960790320

The H₂O-soluble dendritic cyclophanes (dendrophanes) 3-5 of first to third generation with molecular weights up to nearly 20 kD were synthesized, purified, and characterized. Cyclophane 2, which served as the initiator core (generation zero), was prepared from tetrabromocyclophane 10 in a four-step sequence which involved as the first transformation a high-yielding, four-fold Pd(0)-catalyzed Suzuki cross-coupling reaction with 4-(benzyloxy)phenyl-boronic acid to give 18. The X-ray crystal-structure analysis of tetrabromocyclophane 10 displayed an open, nearly rectangular box with opposite aromatic walls being 8.3 and 11.4 A apart and of suitable size for the incorporation of steroidal substrates. ¹H-NMR Binding titrations in borate-buffered D₂O/CD₃OD 1:1 showed that cyclophane-tetracarboxylate 2 forms 1:1 inclusion complexes with steroids. Complexation was found to be enthalpically driven with higher binding affinities measured for the more apolar substrates. ¹H-NMR Titrations in the same solvent also provided clear evidence for core-selective complexation of testosterone (21) by the dendrophanes 3 (1st), 4 (2nd), and 5 (3rd generation) carrying up to 108 carboxylate surface groups. The stability of the corresponding 1:1 complexes was hardly affected by the size of the dendritic shell, although some generation-dependent conformational changes in the receptor cavity seemed to take place. Remarkably, host-guest exchange kinetics in all recognition processes were fast on the ¹H-NMR time scale.