Are the Thiouracils Sulfur Bases in the Gas-phase?

Abstract

The gas-phase proton affinities of 2- and 4-thiouracil and 2,4-dithiouracil have been measured by means of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. High-level ab initio calculations, in the framework of the G2(MP2) theory, have been carried out to establish the nature of the protonation site. Thiouracils behave as bases of rather similar moderate strength in the gas phase, the 2,4-dithiouracil being the most basic of the three. In all cases, the protonation takes place at the heteroatom attached to position 4, hence although, in general, thiocarbonyls are stronger bases than carbonyls in the gas phase, 2-thiouracil behaves as an oxygen base. For 2-thiouracyl and 2,4-dithiouracil, the most stable protonated conformer is the enol−enethiol form that cannot be formed by either direct protonation of the corresponding neutral or a unimolecular tautomerization of the oxygen or sulfur protonated species. We have shown that alternative mechanisms involving the formation of hydrogen bonded dimers between the protonated form and the neutral form, followed by appropriate proton transfers within the dimer, can be invoked to explain the formation of the most stable conformer.

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

“…To confirm or discard this statement, we compared the difference in affinity between sulfur and oxygen by estimating binding energies of Pb 2ϩ ions on neutral molecules at a B3LYP/6-311ϩG(3df,2p)// B3LYP/6-31G(d,p) level. To this purpose, we only took into account the canonical forms, which are the most stable ones [9, 34 -38] and the only structures likely to be present in the gas phase [9,39]. We have considered monodentate coordination either on X or Y heteroatom (C(2) or C(4) carbonyl or thiocarbonyl, respectively) (see Figure 1S of the supplemental information, which can be found in the electronic version of this article).…”

“…We have considered monodentate coordination either on X or Y heteroatom (C(2) or C(4) carbonyl or thiocarbonyl, respectively) (see Figure 1S of the supplemental information, which can be found in the electronic version of this article). Dissociation energies D 0 , calculated at 0 K are gathered in the Table 2 together with experimental proton affinities [9,40]. Note that the D 0 values were estimated without considering BSSEs, which are negligible at this level of theory [23].…”

“…Comparison of the values obtained for U-X/2SU-X and U-Y/4SU-Y pairs shows that Pb 2ϩ affinity is greater for sulfur than for oxygen, probably due to the greater polarizability of the former. The second effect is called "zwitterionic effect", as introduced by Lamsabhi et al [9] during their study about the proton affinity of thiouracils. In fact, the analysis of the charge distribution of uracil and thiouracils showed that the contribution of zwitterionic resonance structures such Ib (Scheme 1) is important in this kind of interaction.…”

“…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.…”

Theoretical Investigation of Tautomerism Stability of Hydantoin in the Gas Phase and in the Solution

“…Also, understanding of the relative stabilities of heterocyclic tautomers and any subsequent conversions between tautomeric forms is very vital for both structural chemists and biologists 1,2 . Along this line, relative stabilities of various tautomeric structures of five-, six-and sevenmembered ring (dioxo, oxo/thio, oxo/seleno, dithio and diseleno combinations) were investigated using both theoretical and experimental tools [3][4][5][6][7][8][9][10][11][12] …”