Influence of Solvent Composition (Water—Dioxane Mixtures) on the Formation Degree of Intramolecular Aromatic-Ring Stacks in Binary Cu(L-Phenylalaninate)2, Cu(L-Tryptophanate)2, and Related Complexes
Authors: Liang Guogang , Sigel Helmut 
Published: March 2015

The stability constants of the binary Cu(AA)+ and Cu(AA)2 complexes, where AA⁻ = L-phenyl-alaninate (Phe⁻) or L-tryptophanate (Trp⁻), have been determined by potentiometric pH titrations in water, and in 30, 50, 70 and 80% (v/v) dioxane—water mixtures (I = 0.1 M, NaNO3; 25 °C); the corresponding data for the complexes with L-alaninate (Ala⁻), L-valinate (Val⁻), L-norvalinate (Nva⁻), and L-leucinate (Leu⁻) are taken from our recent work (G. Liang, R. Tribolet, and H. Sigel, inorg. Chim. Acta 155, 273 (1989)). The overall stability of Cu(AA)+ and Cu(AA), is governed for all amino acetates (AA⁻) by the polarity of the solvent, while the extent of the intramolecular stack formation between the aromatic side chains in Cu(AA)2 is influenced by the hydrophobic solvation properties of the organic solvent molecules (i.e., the ethylene units of dioxane). Based on the stability difference Δ log K*AA = log KCu(AA)
Cu(AA)
2-log KCu(AA)
Cuit is shown that Cu(Phe)2 and Cu(Trp)2 are more stable than Cu(Ala)2, and this increased stability is used for evaluating the extent of the stack formation (= closed form) in Cu(Phe)2 and Cu(Trp)2: the percentages of the closed forms vary between about 25 and 80% (based on Cu(AA),2/tot,), and those for Cu(Val)2, Cu(Leu)2 and Cu(Nva)2 between about 10 and 30%. The formation degree of the intramolecular side-chain adduct in Cu(AA)2 decreases (in most solvents), as one might expect, within the series: Cu(Trp)2 &gt; Cu(Phe)2 &gt; Cu(Val)2≳ Cu(Leu)2≳ Cu(Nva)2. The corresponding observations are made with M(AA)2 complexes of Co2+, Ni2+, and Zn2+. The influence of the organic solvent on the intramolecular hydrophobic and stacking adducts differs somewhat: (i) Stack formation in Cu(Phe)2 and Cu(Trp)2 is slightly inhibited by the presence of dioxane, but even in 50% (v/v) dioxane—water the formation degree of the aromatic-ring stacks is still more than 50%. (ii) Addition of some dioxane to an aqueous solution containing Cu(Val)2, Cu(Leu)2or Cu(Nva)2 favors the formation of the aliphatic side-chain adducts; the largest formation degree being reached close to a content of 70% dioxane. Both observations contrast with the general experience made at unbridged hydrophobic or stacking adducts: these are considerably destabilized already by the addition of relatively small amounts of an organic solvent to an aqueous solution. Such a destabilization of the closed Cu(AA)2 species occurs only at high concentrations of the organic solvent (usually more than 70%). It should be added that the organic solvent most probably influences the structure of the intramolecular ligand-ligand adducts giving rise to a whole series of “closed” species; a resolution is presently not possible and therefore the whole stability increase is attributed to a (single) so-called “closed” species to allow a quantification of the effect. The relevance of amino acid side-chain interactions regarding cooperativity, selectivity, evolutionary aspects, and low polarity regions, as in active-site cavities of proteins, are shortly indicated.