Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

The acidity constants of the twofold protonated nucleotide analogue 1-[2-(phosphonomethoxy)ethyl]cytosine, H₂(PMEC)^±, as well as the stability constants of the M(H;PMEC)⁺ and M(PMEC) complexes with the metal ions M²⁺ = Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, and Cd²⁺ have been determined by potentiometric pH titrations in aqueous solution at I = 0.1 M (NaNO₃) and 25 °C. Comparison with previous results for the nucleobase-free compound (phosphonomethoxy)ethane, PME, and the parent nucleotides cytidine 5'-monophosphate (CMP^2-) and 2'-deoxycytidine 5'-monophosphate (dCMP^2-) shows that the metal ion-binding properties of PMEC^2- resemble closely those of PME^2-: This means, the primary binding site is the phosphonate group and with all of the metal ions studied, 5-membered chelates involving the ether oxygen of the -CH₂-O-CH₂-PO₃^2- chain are formed. The position of the isomeric equilibria between these chelates and the "open" complexes, -PO₃^2-/M²⁺ is calculated; the degree of formation of the chelates is identical within the error limits for the M(PME) and M(PMEC) systems. Hence, like in M(CMP) and M(dCMP) no interaction occurs with the cytosine residue in the M(PMEC) complexes. However, the monoprotonated M(H;PMEC)⁺ as well as the M(H;CMP)⁺ and M(dCMP)⁺ species carry the metal ion predominantly at the nucleobase, while the proton is at the phosph(on)ate group. The coordinating properties of PMEC^2- and CMP^2- or dCMP^2- differ thus only with respect to the possible formation of the 5-membered chelates involving the ether oxygen in M(PMEC) species, a possibility which does not exist in the complexes of the parent nucleotides. Possible reasons why PMEC is devoid of a significant antiviral activity are shortly discussed.

Keywords: Acidity constants; (S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine; Metal ion complexes; Phosphonate complexes; 9-[2-(Phosphonomethoxy)ethyl]adenine; Stability constants; Nucleotides; Phosphates; Phosphonates; Chelates; Acyclic nucleotide analogues.