A Quantum Chemical Study of Cu²⁺ Interacting with Guanine−Cytosine Base Pair. Electrostatic and Oxidative Effects on Intermolecular Proton-Transfer Processes

Abstract

The influence of metal cations (M = Cu+, Ca2+ and Cu2+) coordinated to N7 of guanine on the intermolecular proton-transfer reaction in guanine−cytosine base pair has been analyzed using the B3LYP density functional approach. Gas phase metal cation interaction stabilizes the ion pair structure derived from the N1−N3 single-proton-transfer reaction, the effects being more pronounced for the divalent cations than for the monovalent one. For Cu2+GC the reaction is largely favored due to both electrostatic and oxidative effects. Hydration of the metal cation disfavors the reaction due to the screening of electrostatic effects. However, for Cu2+ the reaction can still be easily produced, especially for certain local environments of the metal cation for which Cu2+ induces the oxidation of guanine. Therefore, the ability of Cu2+ to oxidize guanine turns out to be a key factor for this mutagenic process.

Association of Cu2+with Uracil and Its Thio Derivatives: A Theoretical Study

“…In contrast, in the uracil cation the spin density at the oxygen atoms is rather small (0.2 at O4 and 0.09 at O2), and is mostly located at C5 (0.55) and N1 (0.29). The oxidizing character of Cu 2 + was pointed out before by Noguera et al [7] in a study on its complexes with guanine-cytosine base pair. Hence, we could envisage association of Cu 2 + as a two-step process, the first of which is charge transfer from the base to the metal dication, and the second one the attachment of Cu + to the resulting molecular ion.…”

“…[1][2][3][4][5][6][7] Uracil, which forms part of these compounds, has been the subject of many studies because of its biological and pharmaceutical activities. [2,[8][9][10][11][12][13] Also, its thio derivatives have attracted similar interest, because 2-thiouracil and 4-thiouracil have been identified as minor components of t-RNA and can be used as anticancer and antithyroid drugs.…”

Unimolecular Reactivity of Uracil–Cu2+ Complexes in the Gas Phase

“…[16] The situation is rather similar in [CuA C H T U N G T R E N N U N G (uracilÀH)] + and [Cu(thiouracilÀH)] + complexes, which can also be viewed as the result of Cu + attachment to the uracilÀH and thiouracilÀH radicals formed by deprotonation of the corresponding uracil radical cations. [10] The oxidative power of Cu 2 + in interaction with other systems has also been pointed out, [17] and it seems to play a crucial role in many biological processes. [18,19] The aim of the present study is to go one step further in the study of the interactions between Cu 2 + and uracil, by exploring the experimental unimolecular reactivity of the complexes produced in the gas phase by electrospray ionization.…”

Aromaticity of H-bonded and metal complexes of guanine tautomers

“…Distortion of a proper DNA structure is also induced by stabilization of rare guanine tautomers caused by metal cations [13,14] and formation of non-Watson-Crick base pairs [15,16]. Metal ions can also weaken [17,18], and in some cases even disrupt [19], one or more hydrogen bonds in the base pairs and stabilize non-canonical structures of nucleic acids [20]. Such interactions between metal cations and nucleobases can be direct or solvent-mediated [21].…”