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

Abstract

The structures and relative stabilities of the complexes between Cu2+ and uracil, 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil were investigated by B3LYP/6-311+G(2df,2p)//B3LYP/6-31G* DFT calculations. In those systems in which both types of basic centers, that is, a carbonyl and a thiocarbonyl group, are present, association of Cu2+ with the oxygen atom is systematically favored, in contrast to what was found for the corresponding Cu+ complexes. This can be understood by considering that association of Cu2+ is immediately followed by oxidation of the base, which accumulates the negative charge at the oxygen atoms. Similarly, for 2,4-dithiouracil the most basic site for Cu+ attachment is the sulfur atom at the 4-position, while for association of Cu2+ it is sulfur at the 2-position. In contrast, differences between uracil-Cu+ and uracil-Cu2+ complexes are very small, and in both cases the oxygen atom at the 4-position is the most basic. Cu2+ binding energies are about 4 and 1.2 times larger than Cu+ binding energies and proton affinities, respectively. Uracil- and thiouracil-Cu2+ complexes are thermodynamically unstable but kinetically stable with respect to their dissociation into uracil*+ + Cu+ or thiouracil*+ + Cu+. The Cu2+ binding energies vary with the difference between the second ionization potential of the metal and the first ionization potential of the base. regardless of the reference acid (H+, Cu+, Cu2+) the basicity trend is 2,4-dithiouracil > 4-thiouracil > 2-thiouracil > uracil.

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

“…Also, the presence of a peak at m/z 131.9 indicates that the HNCO fragment lost in the unimolecular fragmentation contains C2. The presence of a peak at m/z 132.9 leads also to an ambiguity, since it may arise from loss of 15 CO species and confirms that the loss of NCO involves C2. When the spectra of 3-15 N-uracil is analyzed, the absence of peaks at m/z 132.9 unambiguously shows that the NCO fragment lost does not involve C2 and N1 at the same time.…”

“…In this respect, we recently started a systematic study on the reactivity of uracil and its thio derivatives towards proton, [14] copper(I), [11] and copper(II). [15] Significant dissimilarities between the interactions with Cu I and Cu II are found and explained as a result of the oxidation of uracil when interacting with the metal dication, which is not observed when the interaction involves the monocation. [11] One of the most significant consequences is that [uracil-Cu] 2 + complexes can be viewed as the interaction between Cu + and uracil · + radical cation, since the spin density is located exclusively on the uracil moiety, which in turn bears a net charge of + 1.…”

“…[11] One of the most significant consequences is that [uracil-Cu] 2 + complexes can be viewed as the interaction between Cu + and uracil · + radical cation, since the spin density is located exclusively on the uracil moiety, which in turn bears a net charge of + 1. [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.…”

“…Unless otherwise noted, mass-tocharge ratios mentioned throughout this paper refer to peaks which include the most abundant copper isotope ( 63 Cu). All nucleobases but [3][4][5][6][7][8][9][10][11][12][13][14][15] N-uracil (see Acknowledgements) and copper dichloride were purchased from Aldrich and were used without further purification.…”

Gas-phase interactions between lead(II) ions and thiouracil nucleobases: A combined experimental and theoretical study

“…Consequently, a detailed knowledge of structural and reactivity changes induced by substitution of one or both oxygen atoms by the more polarizable sulfur atom is helpful to understand the underlying reasons of their different role in biological activity. Recently, the gas-phase protonation of thiouracil derivatives [9] and their association with Cu ϩ [10], Cu 2ϩ [11][12][13], Ca 2ϩ [14], and alkali metals [15] were examined. In the present study, electrospray ionization was used to generate Pb 2ϩ /thiouracil complexes.…”