Functionalization of the phenolic rim of p-tert-butylcalix [8]arene with phenanthroline to create a cavity leads to formation of two regioisomers. Substitution of positions 1 and 5 produces the known C 2v -symmetric regioisomer 1,5-(2,9-dimethyl-1,10phenanthroyl)-p-tert-butylcalix[8]arene (L 1,5 ), while substitution of positions 1 and 4 produces the C s -symmetric regioisomer 1,4-(2,9-dimethyl-1,10-phenanthroyl)-p-tert-butylcalix[8]arene (L 1,4 ) described herein. [Cu(L 1,4 )I] was synthesized from L 1,4 and CuI in good yield and characterized spectroscopically. To evaluate the effect of its cavity on catalysis, Ullmann-type CÀ S coupling was chosen as proof-of-concept. Selected aryl halides were used, and the results compared with the previously reported Cu(I)/L 1,5 system. Only highly activated aryl halides generate the CÀ S coupling product in moderate yields with the Cu(I)/L 1,4 system. To shed light on these observations, detailed computational investigations were carried out, revealing the influence of the calix[8]arene macrocyclic morphology on the accessible conformations. The L 1,4 regioisomer undergoes a deformation that does not occur with L 1,5 , resulting in an exposed catalytic center, presumably the cause of the low activity of the former system. The 1,4-connectivity was confirmed in the solid-state structure of the byproduct [Cu(L 1,4 À H)(CH 3 CN) 2 ] that features Cu(I) coordinated inside a cleft defined by the macrocyclic framework.