Intramolecular hydrophobic and aromatic-ring stacking interactions in ternary complexes in solution

Abstract

One possibility of influencing the stability and structure of mixed ligand complexes [1] is through the formation of intramolecular ligand-ligand bonds. Covalent bond formation is well-known, e.g., coordinated pyruvate and glycinate form a Schiff base within the coordination sphere of a metal ion [2]. Ionic bonds may be formed between oppositely charged side chains: several amino acids are predestinated for such electrostatic interactions [3, 4]. Hydrogen bond formation also seems possible [5] ▪ and is known to exist in solid mixed ligand complexes [6]. Aromatic-ring stacking is another very subtle possibility for an influence and equilibrium (1) may even be shifted to its right side, i.e. for the logarithm of the corresponding equilibrium constant, Δ log K M ▪ (eqn. 2) [1], positive values are observed. For example, for the Mg 2+ of Ca 2+ /1,10-phenanthroline (Phen)/adenosine 5′-triphosphate (AT 4− system Δ log K M ⋍ 0.5 due to the intramolecular stacking between the purine moiety of ATP 4− and the aromatic-ring system of Phen (studied by potentiometric pH-titrations, UV-difference spectrophotometry and 1H-NMR shift measurements) [7]. This leads to an intramolecular equilibrium (3) between, an ‘open’ and ‘closed’ isomer of the ternary complex ▪ M(A)(B). About 90% of Ca(Phen)(ATP) 2− exist in the ‘closed’ form [4], while for M(tryptophanate)(ATP) 3− where M 2+ = Mn 2+, Cu 2+ or Zn 2+ the corresponding percentages are 55, 41 and 76 [4]. Hydrophobic interactions are observed between the isopropyl residue of leucinate (Leu) and Phen; e.g. of Zn(Phen)(Leu) + exist about 30% in the ‘closed’ form [8]. Estimation for M(phenylalaninate)(norvalinate) complexes, where M 2+ = Co 2+, Ni 2+ or Cu 2+, give 21, 5 and 11%, respectively, for the isomer with an intramolecular hydrophobic interaction [4, 8]. Research supported by the Swiss National Science Foundation.