Rebek Imides and Their Adenine Complexes: Preferences for Hoogsteen Binding in the Solid State and in Solution

Rebek imides ( 3 ), formed from Kemp's triacid, were developed in the mid‐1980's as model receptors for adenine derivatives. We report here the first account of their hydrogen‐bonding preferences upon binding 9‐ethyladenine ( 1 a ) in the solid state. Structural analysis begins with simple imides 3 a – e that form discrete dimers, while bis‐imide 4 forms ribbon‐like structures in the crystalline phase. The hydrogen‐bonding interface within each of the representative assemblies features short intermolecular N(3) imide ⋅⋅⋅ O(8*) imide* distances (ca. 2.95 Å), indicative of two‐point hydrogen bonding. Imides 3 f – h could be co‐crystallized with 1 a ; single‐crystal X‐ray analysis of the resulting complexes reveals hydrogen‐bonding geometries nearly identical to those observed in nucleobase complexes of adenine and pyrimidine derivatives. Imides 3 f and 3 g form 2:1 ternary assemblies with 1 a ; the complex of the former, ( 3 f ) 2 ⋅1 a , displays both Watson–Crick‐ and Hoogsteen‐type hydrogen bonding, whereas the complex of the latter, ( 3 g ) 2 ⋅1 a , shows the Hoogsteen motif and imide hydrogen bonding to N(3) of the purine base (N(3) adenine ⋅⋅⋅ N(3″) imide =3.07(1) Å). Imide 3 h forms a 1:1 complex with 1 a ( 3 h⋅1 a⋅ CHCl 3 ) and displays Hoogsteen binding exclusively. All of the 3⋅1 a assemblies show C adenine ⋅⋅⋅ O imide distances (3.38–3.75 Å) that are consistent with C‐H ⋅⋅⋅ O hydrogen bonding. Base‐pairing preferences for the Rebek imides are further explored in solution by 1 H NMR one‐dimensional NOE experiments and by computational means; in all cases the Hoogsteen motif is modestly favored relative to its Watson–Crick counterpart.