Influence of solvent and ligand-structure on the extent of intramolecular stacking interactions in mixed ligand complexes

Abstract

The importance of aromatic-ring stacking for the creation of certain structural arrangements in large bio-molecules has often been emphasized ( e.g. [1]). However, the fact that at low concentrations stacking interactions between smaller molecules like amino acids and nucleotides can be promoted by the formation of a metal ion-bridge has only recently been recognized [2]. For example, the stacking between the indole moiety of tryptophanate (Trp − and the purine system of adenosine 5′-triphosphate (ATP 4−) is facilitated in ternary M(ATP)(Trp) 3− complexes [3, 4]. Similarly, the hydrophobic interaction between the isopropyl moiety of leucinate (Leu −) and the purine residue of ATP 4− is also promoted in M(ATP)(Leu) 3− complexes [4]. Based on the stability constants of the complexes and 1H-NMR shift experiments the percentage of M(A)(B) 3− cl was estimated for both types of ternary complexes: ▪ The formation of the species M(ATP)(Trp) 3− cl was first shown [5] in 1974; its occurrence was subsequently confirmed by studies in several laboratories using different methods [6]. To learn more about the factors which govern the position of the intramolecular equilibrium (1), we have now used the following simple systems, since with them structural alterations are easily achieved: ▪ In 50% aqueous dioxane (I = 0.1, 25 °C) the stacking interaction is most pronounced for n = 1; i.e. for the ternary complex Cu(Phen)(C 6H 5CH 2COO) + about 60 percent exists in the closed form. If phenylacetate is replaced by 2-(β-naphthyl)acetate the concentration of the closed isomer increases to about 80 percent. Ligands R(CH 2) nCOO − with n = 0 or n > 1 form ternary complexes with a less pronounced intramolecular stacking interaction. Variation of the solvent composition also leads to a change in the percentage of [Cu(Phen)(C 6H 5CH 2COO +] cl: solvent H 2O 30% diox. 60% diox. 90% diox. % closed isomer: 48 56 64 48 The observation of a maximal degree of formation for the closed isomer in about 60% aqueous dioxane is very surprising, because the stability of binary adducts like (Phen)(RCOO −) decreases with increasing dioxane concentration. Hence, two opposite effects must be operating in the presence of metal ions. This puzzling result is of interest for biological systems, because in these the water activity may also be altered, e.g. at the surface or in grooves of proteins. Hydrophobic interactions are important, e.g., in adduct formation between carboxypeptidase A and the inhibitor β-phenylpropionate [7]. Presently we are repeating the experiments in several ethanol/water mixtures to provide a broader generalization.