Preorganized metallomacrocycles: improved binding and selectivity of NH3 over primary amines

Three new metallohosts (2-4) were synthesized by the uranyl-templated macrocyclization of the appropriate dialdehydes 13a-c and 1,2-phenylenediamine in methanol. Cyclization of the dialdehyde 13b led to two isomers (3a, major, and 3b, minor), which only differed in the orientation of the isopropyl substituents on the outer phenolic rings of the terphenyl moiety. The binding constants in CDCl3 of ammonia and benzylamine were determined by 1H NMR spectroscopy. The binding of ammonia by these hosts follows 1 = 2 = 4 < 3b < 3a. The binding of benzylamine follows 1 = 2 = 4 = < 3b < 3a. Monte Carlo free-energy perturbation calculations reproduced the binding of ammonia and n-propylamine quite well. The much larger binding of benzylamine by host 3a was rationalized by a much deeper positioning of the guest in the cavity of the host compared to 3b.