Comparison of the π-stacking properties of purine versus pyrimidine residues. Some generalizations regarding selectivity

摘要

Aromatic-ring stacking is pronounced among the noncovalent interactions occurring in biosystems and therefore some pertinent features regarding nucleobase residues are summarized. Self-stacking decreases in the series adenine > guanine > hypoxanthine > cytosine ~ uracil. This contrasts with the stability of binary (phen)(N) adducts formed by 1,10-phenanthroline (phen) and a nucleobase residue (N), which is largely independent of the type of purine residue involved, including (N1)Hdeprotonated guanine. Furthermore, the association constant for (phen)(A)~(0/4-) is rather independent of the type and charge of the adenine derivative (A) considered, be it adenosine or one of its nucleotides, including adenosine 5′-triphosphate (ATP~(4-)). The same holds for the corresponding adducts of 2,2′-bipyridine (bpy), although owing to the smaller size of the aromatic-ring system of bpy, the (bpy)(A)~(0/4-) adducts are less stable; the same applies correspondingly to the adducts formed with pyrimidines. In accord herewith, [M(bpy)](adenosine)~(2+) adducts (M~(2+) is Co~(2+), Ni~(2+), or Cu~(2+)) show the same stability as the (bpy)(A)~(0/4-) ones. The formation of an ionic bridge between –NH_3~+ and –PO_3~(2-), as provided by tryptophan [H(Trp)~±] and adenosine 5′-monophosphate (AMP~(2-)), facilitates recognition and stabilizes the indole–purine stack in [H(Trp)](AMP)~(2-). Such indole–purine stacks also occur in nature. Similarly, the formation of a metal ion bridge as occurs, e.g., between Cu~(2+) coordinated to phen and the phosphonate group of 9-[2-(phosphonomethoxy) ethyl]adenine (PMEA~(2-)) dramatically favors the intramolecular stack in Cu(phen)(PMEA). The consequences of such interactions for biosystems are discussed, especially emphasizing that the energies involved in such isomeric equilibria are small, allowing Nature to shift such equilibria easily.