Synthesis and acid-base properties of an imidazole-containing nucleotide analog, 1-(2'-deoxy-β-D-ribofuranosyl)imidazole 5'-monophosphate (dImMP2-)

Abstract

Deletion of the substituted pyrimidine ring in purine-2'-deoxynucleoside 5'-monophosphates leads to the artificial nucleotide analog dImMP2-. This analog can be incorporated into DNA to yield, upon addition of Ag + ions, a molecular wire. Here, we measured the acidity constants of H2(dImMP)± having one proton at N(3) and one at the PO 32- group by potentiometric pH titrations in aqueous solution. The micro acidity constants show that N(3) is somewhat more basic than PO32- and, consequently, the (H· dImMP) - tautomer with the proton at N(3) dominates to ca. 75%. The calculated micro acidity constants are confirmed by 31P- and 1H-NMR chemical shifts. The assembled data allow many quantitative comparisons, e.g., the N(3)-protonated and thus positively charged imidazole residue facilitates deprotonation of the P(O)2(OH)- group by 0.3 pK units. Information on the intrinsic site basicities also allows predictions about metal-ion binding; e.g., Mg2+ and Mn2+ will primarily coordinate to the phosphate group, whereas Ni2+ and Cu2+ will preferably bind to N(3). Macrochelate formation for these metal ions is also predicted. The micro acidity constant for N(3)H+ deprotonation in the (H · dImMP·H)± species (pka 6.46) and the Mn+-binding properties are of relevance for understanding the behavior of dImMP units present in DNA hairpins and metalated duplexes. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.