Dendrophanes: Novel Steroid-Recognizing Dendritic Receptors. Preliminary Communication

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 Å 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 (Table 2). 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.