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 dImMP(2-). This analog can be incorporated into DNA to yield, upon addition of Ag+ ions, a molecular wire. Here, we measured the acidity constants of H-2(dImMP)(+/-) having one proton at N(3) and one at the PO32-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 center dot dImMP)(-) tautomer with the proton at N(3) dominates to ca. 75%. The calculated micro acidity constants are confirmed by P-31-and H-1-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 center dot dImMP center dot H)(+/-) species (pk(a) 6.46) and the Mn+-binding properties are of relevance for understanding the behavior of dImMP units present in DNA hairpins and metalated duplexes.

DNA as Sensors and Imaging Agents for Metal Ions

“…In addition to metal-ion-dependent DNAzymes that were selected from random DNA libraries through combinatorial techniques, at least two types of DNA structures were also discovered to be efficient binding motifs for a series of metal ions. One of them is DNA mismatches that can bind specific metal ions to form stable “base pairs”. − Examples include natural nucleobases such as T–T and C–C mismatches that can form stable T–Hg 2+ –T , and C–Ag + –C structures in DNA duplexes with high specificity to Hg 2+ and Ag + , respectively (Figure ), as well as artificial bases that form stabilized pairs with Ag + and Cu 2+ , ,,,− although the latter has not been widely applied in sensors because of the lack of commercial availability of the artificial bases required . The other is the DNA G-quadruplex that is stabilized or destabilized by specific metal ions, ,,,, such as K + , ,, Pb 2+ , ,, Ag + , and Cu 2+ , (Figure ).…”

Growing prospects of DNA nanomaterials in novel biomedical applications

“…39 There are also articial bases reported to form stabilized pairs with Cu 2+ . [40][41][42] In order to solve the ionic strength dependent problem of DNA-based sensors, Liu 43 et al used 2-aminopurine with high robust uorescent signalling to label DNA homopolymers for Hg 2+ and Ag + detections. To date, K + , [44][45][46][47] Mg 2+ , [48][49][50] Zn 2+ , [51][52][53] Co 2+ , 54 Mn 2+ , 48,55 and Cd 2+ metal-ion dependent DNA biosensors have been obtained through combinatorial selection and rational design of DNA structures, and these biosensors have been applied further in real-time environmental monitoring and for on-site medical diagnostics.…”