Adenosine 5'-triphosphate (ATP4-): Aspects of the coordination
chemistry of a multitalented biological substrate
Department of Chemistry, Inorganic Chemistry, University
of Basel, Spitalstrasse 51, CH-4056 Basel, Switzerland
Abstract: Firstly, the self-stacking properties of ATP4-
and the effects of metal ions and protons on these properties are described.
Some examples involving macrochelate formation between phosphate-coordinated
metal ions (M²+;) and N7 of the adenine residue in MATP2-
are discussed, and this is followed by considerations on mixed ligand
complexes consisting of ATP4-, M2+, 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
(PMEA2-; Adefovir), i.e., of PMEApp4-, are compared
with those of (2'-deoxy)ATP4- with regard to their metal
ion-binding qualities, and in this way it can be explained why PMEApp2-
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.
*Plenary lecture presented at the 2nd Santa Marķa Workshop
on Chemistry Devoted to Bioinorganic Chemistry, Santa Marķa del Mar,
Havana, Cuba, 7-11 July 2003. Other presentations are published in this
issue, pp. 321-388.
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