Intramolecular ionic interactions in ternary amino acid complexes [1

Abstract

The so-called ‘noncovalent’ interactions [4] between biomolecules are not only crucial for the structural organization of high molecular weight biological systems, but also determine to a large extent the structure of amino acid and nucleotide containing low molecular weight metal ion complexes in solution. For example, the intramolecular equilibria between different isomers of mixed ligand complexes are well established for aromatic-ring stacking and hydrophobic interactions [3, 5, 6]. Ionic interactions between oppositely charged side-chains of two amino acids coordinated to the same metal ion are also known [7], but the extent of this interaction has so far hardly been characterized [6]. Therefore, the ionized forms of the following two amino acids were selected for such a study: ▪ In the (CH 3) 3 N + -residue the positive charge is somewhat shielded, but the advantage of this residue is that no hydrogen bonds can be formed with −O 3S−, as would have been the case with the more common H 3 N + - group. In addition, the latter group and the use of a carboxylate group (instead of the sulfonate residue in HC) would have led to additional proton equilibria, thus complicating the systems significantly. For comparison DL-alanine (Ala) with its non-reactive side chain was also employed. As a representative metal ion Cu 2+ was used, because it forms rather stable complexes with the glycinate-like structural unit. That ionic interactions between the (CH 3) 3 N + - and −O 3S-residues are possible was proven by 1H-NMR shift experiments with benzenesulfonate and the tetramethylammonium ion; the binary adduct has a stability constant of 0.7 M −1 in aqueous solution at 34 °C (I = 0.1, NaNO 3). The results for the binary amino acid parent systems are given in Table I [8]. There are indications that the sulfonate group of HC interacts with an apical position of the Cu 2+ coordination sphere and that decreasing ionic strength and the addition of dioxane favor this interaction. Such apical interactions are also known for related ligands [10]. The percentage of the ‘closed’ isomer of the ternary Cu(TMO)(HC) complex, i.e. of the isomer with an intramolecular ionic ligand-ligand interaction, was calculated [5, 6, 11] using the results obtained for the Ala −/Cu 2+/HC 2− system as a basis. From Table II it is evident that the ‘intensity’ of the ionic interaction increases with decreasing ionic strength and also with the decreasing polarity of the solvent; in other words, with the decreasing water activity. This result is exactly the behavior expected for ionic interactions, and it also holds if the optically pure ligand systems are used. The described ionic interactions are relatively weak (ΔG° ⋍ −3 kJ/mol), but they are strong enough to allow ‘flexible structural organizations’ in biological systems. t001 Negative Logarithms of the Acidity Constants for the Protonated Ligands and Logarithms of the Stability Constants for the Binary Amino Acid Cu 2+ Complexes (25 °C). Solvent Ligand (A) pK H H 2A pK H HA log K Cu CuA log K CuA CuA 2 H 2O/I = 0.1 Ala − 2.39 9.81 8.23 6.82 TMO 1.94 8.81 7.41 6.29 HC 2− 2.22 9.04 8.03 6.47 H 2O/I = 0.01 Ala 2− 2.36 9.86 8.42 6.95 TMO 1.88 a 8.71 7.25 6.16 HC 2− 2.33 9.19 8.36 6.47 60% dioxane (40% H 2O; v/v) I = 0.01 Ala 2− 3.49 10.31 10.84 8.81 TMO 2.58 8.84 9.20 7.69 HC 2− 3.65 10.06 11.30 8.18 a This value was measured for experimental reasons at I = 0.02, NaCl 4. t002 Logarithms of the Stability Constants for the Ternary Amino Acid Cu 2+ Complexes and Percentage of the Isomer with an Intramolecular Ionic Ligand-Ligand Interaction (25 °C). Solvent Ligands A/B log β Cu CuAB Δlog K Cu a2 %[CuAB] cl H 2O/I = 0.1 HC 2−/Ala 2− 15.22 ± 0.01 −1.04 HC 2−/TMO 14.57 ± 0.01 −0.87 32 H 2O/I = 0.01 HC 2−/Ala − 15.57 ± 0.01 −1.21 HC 2−/TMO 14.77 ± 0.01 −0.84 57 60% dioxane (40% H 2O; v/v) I = 0.01 HC 2−/Ala − 20.03 ± 0.02 −2.11 HC 2−/TMO 18.99 ± 0.02 −1.51 75 a2 Δ K Cu = log β Cu CuAB − (log K Cu CuA + log K Cu CuB) = log K CuA CuAB − log K Cu CuB (see [2, 3, 5, 6, 11]).