ChemInform Abstract: Phosphate Anion Binding by Macrocyclic Dinucleating Ligands and Their Metal Complexes

Abstract

Abstract Four closely related dinuclear macrocyclic ligands are described: 1,13-dioxa-4,7,10,16,19,11-hexaazacyclotetracosane (OBISDIEN), 3,6,9,17,20,23-hexaazatricyclo[23.3.1.1 11,15 ]triconta-(1(29),11(30),12,14,25,27-hexaaza (BMXD), 3,6,9,16,19,22-hexaaza-27-28-dioxatricyclo-[22.2.1.1 11,14 ]-octacos-1,(26),11,13,24-tetraene (BFBD), and 3,6,9,17,20,23,29,30-octaazatri-cyclo[23.3.1.1 11,15 ]triconta-1(29),11,13,15,25,27-hexaene (BPBD). These macrocycles may be considered hexaaza ligands with two diethylenetriamine moieties bound together by bridging groups, except for BPBD, for which the bridging groups are pyridine rings, making this an octaaza ligand; however the remaining six nitrogens are analogous to those in OBISDIEN, BFBD, and BMXD. The syntheses of these ligands are outlined and compared. Each ligand forms six protonated species, which bind anions through hydrogen bonding and coulombic forces, the strength of binding increases with the number of protons, corresponding to an increase in the number of hydrogen bonds and to an increase in the coulombic attractive forces. The binding of these macrocyclic ligands to the nucleotides ATP, ADP, and AMP and their inorganic analogs, triphosphate, pyrophosphate, and phosphate, are described in detail, with equilibrium constants given for each species formed. The selectivities of the macrocyclic ligands for the nucleotides are described. With the aid of species distribution curves in competitive systems, the use of macrocycles for the separation of ATP, ADP, and AMP is suggested. It is shown that these aza macrocycles form both mono- and dinuclear metal complexes. The stabilities of the mononuclear ternary Cu(II) complexes are increased by hydrogen bonds between the coordinated phosphate and the protonated amino groups, with a maximum attained with three hydrogen bonds. For dinuclear ternary complexes protonation and deprotonation reduce the stability since the former reduces the number of amino donors coordinating the Cu(II), while the latter increases the number of hydroxide ions coordinated directly with the metal ion. The dinuclear Cu(II) complex shows a preference for the binding of ATP over ADP, especially in moderately alkaline solution.