Theoretical Calculations of Stability and Proton Transfer

Numerous important contributions from Gassman, Almlof, and Ghosh include studies of chlorin 73 tautomerism (93JPC10964). Tlie 73a and the 73b forms of H2C have both been observed experimentally (see Section III,A,4), although it is well established that 73a is the predominant tautomer (see Sections III,A and III,A,3). Using a local density functional (LDF) at the MP2/DZP2 level, they calculated the 73a/73b difference to be 39 kJ mol  

---

Tautomeric equilibrium in aqueous cw-malonaldehyde, see reaction 1 in Figure 8-4, is a prototypical reaction extensively studied in the gas phase but still relatively unknown in solution. In fact, despite the large number of NMR experiments [52,53,54] and quantum chemical calculations [55] with the polarized continuum model (PCM), [1] the actual stability of czT-malonaldehyde is not well clarified, although the trans isomer should be the predominant form in water. Secondly, the involvement of the light proton in the reaction may in principle provide relevant quantum effects even in condensed phase. All these complications did not prevent this reaction to be used as a prototypical system for theoretical studies of intramolecular proton transfer in condensed phase by several investigators [56,57,58,59,60] including ourselves. 

Although the calculations of the transition energies of different tautomeric forms of molecules have been performed in a few cases, the discussion has been restricted to the difference in electronic absorption band positions and not to the change in relative stabilities of the tautomers caused by electronic excitation. The latter problem, however, has been the subject of a few theoretical considerations for nucleic acid base pairs. Most of these studies were motivated by the need for a potential function for double proton transfer between nucleic acid bases that would allow calculation of proton tunneling probabilities for the Lowdin model of mutagenesis (Lowdin, 1965). 

A different mechanism, in which the bridge between copper and zinc is not broken and the protons needed by the reaction are provided by thd bulk solvent, has been proposed from theoretical calculations (246, 335, 336). In this mechanism a superoxide molecule forms a complex with Cu(II) thanks to the stabilizing effect of Arg-143. This stable intermediate can oxidize a second superoxide molecule by an outer-sphere electron transfer originating an E-Cu -02 complex (E = enzyme), which is subject to proton transfer from the solvent followed by electron transfer from copper, giving rise to E-Cu -02H . The hydroperoxide anion readily dissociates from the latter complex, leaving the metal in the oxidized state (246, 335). 

In the present paper the thermodynamic and kinetic aspects of the proton transfer reactions among cytosine tautomers assisted by specific solvent molecules was theoretically investigated. For the time being, bulk solvent effects were not considered and attention was only focused on the influence of hydrogen bonding on both (i) tautomers relative stability and (ii) the catalytic process occurring between adjacent positions of cytosine. The computational results on point (i) are compared with those of PCM calculations [15]. The results on point (ii) are discussed with reference to the conclusions of other theoretical studies available in the literature [16,17]. 

---