Adenosine 5'-triphosphate (ATP4-): Aspects of the coordination chemistry of a multitalented biological substrate

Abstract

Firstly, the self-stacking properties of ATP 4-and the effects of metal ions and protons on these properties are described. Some examples involving macrochelate formation between phosphate-coordinated metal ions (M 2+ ) and N7 of the adenine residue in M(ATP) 2-are discussed, and this is followed by considerations on mixed ligand complexes consisting of ATP 4-, M 2+ , and amino acid anions with side chains that allow either aromatic-ring stacking or hydrophobic interactions with the adenine moiety; this gives rise to selectivity. Next, the properties of diphosphorylated 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA 2-; Adefovir), i.e., of PMEApp 4-, are compared with those of (2′-deoxy)ATP 4-with regard to their metal ion-binding qualities, and in this way it can be explained why PMEApp 2-is initially an excellent substrate for nucleic acid polymerases. Of course, after incorporation of the PMEA residue into the growing nucleic acid chain, this is terminated and this is how PMEA exerts its antiviral properties [its bis(pivaloyloxymethyl)ester, Adefovir dipivoxil, was recently approved for use in hepatitis B therapy]. Finally, the change in free energy connected with (macro)chelate formation or intramolecular stacking interactions and the effect of a reduced dielectric constant of the solvent on the stability of complexes and their structures in solution is considered.

Effect of the ribose versus 2′-deoxyribose residue on the metal ion-binding properties of purine nucleotides

“…16,27 ) species is well established. 2,3,18,19 As expected, any kind of chelation 28 must be reflected in an enhanced complex stability and this also holds for the mentioned cases. 16,17,26 Of course, macrochelates as indicated in equilibrium (1) will hardly form to 100%.…”

“…3 Therefore, all potentiometric pH titrations in this study (25 ºC; I = 0.1 M, NaNO 3 ) were carried out at ligand concentrations between 0.13 and 0.6 mM (see Section 4). Under these conditions self-stacking of the adenine nucleotides is negligible 17 and in the present study the properties of the monomeric species were studied, indeed.…”

“…1 can accept only two protons. The adenine and the guanine nucleotides can be protonated at their N1 or N7 sites, respectively, and in each case the terminal PO 3 2− group can bind a further proton. Hence, the following two deprotonation equilibria (2a) and (3a), the acidity constants of which were determined recently, 7 need to be considered:…”

“…These averages can now be used for the evaluation of the M(ATP) 2-systems 16,27 (see Table 2; entry 4, columns 4-6) and other systems like M(ITP) 2-or M(GTP) 2-. 27 Because the acidity constant of H(dATP) 3 Table 2.…”

Ternary complex formation and competition quench fluorescence of ZnAF family zinc sensors

“…The assumed 1:1:1 stoichiometry of interaction between ATP, Zn 2+ and the sensor, which found support in the low standard deviation of the calculated K tern values, is also justified by the multidentate character of the triphosphate moiety of ATP in other known ternary complexes [34][35][36] (the ATP's N7 donor atom is unlikely to participate in the Zn(II) binding in the ternary complex. 34 ). The 5 dissociation constants for the process of release of the ATP molecule from the ternary complex, K ATP , can be calculated from K tern constants (Table 1).…”