Locked chromophores as CD and NMR probes for the helical conformation of tetraamidic macrocycles

Abstract

A series of tetraamidic homochiral macrocycles have been built convergently upon the introduction in the covalent scaffold of two 1,1'-binaphthyl-2,2'-diol derivatives, joined by aromatic spacers of differing shapes and rigidity (p-phenyl, 4,4'-biphenyl, 3,3'-biphenyl) through aromatic amide functionalities, perfectly positioned to intramolecularly hydrogen bond the naphtholic oxygen acceptors of the binaphthyl units, in order to effectively lock the central chromophores in spatial proximity. The combination of several techniques, namely NMR and CD spectroscopies, and computational modeling, allows for a clear depiction of the structure and conformation of the macrocycles in solution. In the case of the shape "unstable" 3,3'-biphenyl spacer, the preferred conformation of a "wrapped" form in a relatively polar (EtOH) solvent is clearly signalled by CD spectroscopy by analyzing the changes in the shape of the induced CD signal deriving from the central, achiral chromophore absorption band. The rigid, covalent scaffold in which the two central 3,3'-biphenyl spacers are embedded raises the energetic barrier for the rotation around the aryl-aryl bonds of the spacers to a value (8.0 kcal mol(-1)) much higher than the value calculated in the case of unlocked biphenyls.