Guanine deprotonation

The observation of the electrocatalysis in Fig. 1 suggests that the Ru(bpy)3 and guanine couples have similar redox potentials. Based on the kinetics of oxidation by a series of substituted Ru(bpy)3 complexes, we predicted that the redox potential of guanine was 1.1 V (all potentials versus Ag/AgCl) [17]. Later, equilibrium titrations performed by Steenken using known one-electron oxidants showed that the potential was 1.07 V at pH 7 [39], which also implied that the guanine deprotonates in our reaction. The issue of guanine deprotonation will be discussed in depth below. 

It is very likely that similar variations in pA"a values as found in the 9-MeA/ Ptn system, namely, 4 log units attributable to hydrogen-bonding effects, will eventually also be seen with other nucleobases, provided such compounds can be prepared. We predict that, for example, the acidification of the guanine-N 1 position by Pt(II) coordination at N7 will exceed the typical value of ApAia 1.5 seen in many closely related Pt(II) am(m)ine complexes, if it is possible to generate complexes in which an appropriate microenvironment for a stabilization of the deprotonated N1 position is generated. It appears that the ready formation of hemiprotonated, N7-platinated guanine pairs (cf. Fig. 6) at pH values substantially lower than the pA"a for guanine deprotonation, in fact may be a consequence of this principle. 

It seems then that one-electron oxidized guanine in the solid-state deprotonates at the amino group. There is however no good evidence that this occurs in aqueous solution. A study of guanine derivatives in aqueous solution using pulse radiolytic techniques concluded that one-electron oxidized guanine deprotonated at Nl [55], Early ab initio calculations on guanine concluded that G(N1-H) is the more stable than G(N2-H) [56], However more recent DFT and molecular dynamics calculations have come to the opposite conclusion [57], Calculations have also been performed on G C base pairs. Hutter and Clark have concluded that proton transfer... 

Scheme 6 Deprotonation of a guanine radical cation with and without a complementary base...

Experiments with methyl guanine (27), in which the acidic proton of the radical cation is exchanged by a methyl group, support this explanation [22]. With this base in a mismatch situation (strand 25) the hole transfer becomes efficient again because a deprotonation cannot occur (Fig. 15). 

With aquated Pt(II) compounds, numerous studies have revealed the kinetic preference of the 6-oxopurine N7 site [15,35]. In addition to the favorable electrostatic potential mentioned above [23] also steric factors seem to favor coordination to the guanine N7 site, in particular [36]. Estimated relative steric parameters (in parenthesis) suggest that the guanine N7 (1.00) and hypoxanthine N7 (1.03) atoms are the least sterically hindered binding sites in alkylated nucleobases, followed by the adenine N7 (1.17) and deprotonated hypoxanthine N1 (1.17) sites and the deprotonated N3 atoms of the different pyrimidine bases (1.39 for U, 1.44 for T, and 1.56 for C), while the adenine N1 (1.58) and... 

Therefore, the N(9) radical should be more stable than the N(6) one. That is why both radicals coexist in the system and both N(9) and N(6) deprotonations take place. In the case of the guanine cation-radical, the presence of the carbonyl group in the pyridazine ring brings about two additional effects Deprotonation infringes on this ring exclusively, and double deprotonation leads to the formation of a distonic anion-radical. Scheme 1.25 depicts the differences mentioned. Adhikary et al. (2006) substantiated it experimentally (ESR and UV) and theoretically (B3LYP). 

The guanine radical cation is a weak acid = 3.9) [22]. Therefore deprotonation will depend on the environment. Bachler and Hildenbrand [38] have studied the guanine oxidation product in aqueous solution of 5 -dGMP. The best fit to their EPR spectra seems to be from the radical cation (Gua " ). 

Some experiments have been performed on guanine molecules that were originally protonated at N7. Subsequent electron loss by this molecule leads to deprotonation at N7 yielding Gua(N7 + H, N7—H), which is equivalent to the guanine radical cation. The experimental results from this guanine cation have p(C8) = 0.18, p(N2) = 0.17, and p(N3) = 0.28 [40]. 

It is not clear what the structure of one-electron oxidized guanine is in DNA. The amino-deprotonated product observed in 5-dGMP does not seem to fit parameters of the oxidation species observed in DNA. Recently, Reynisson and Steenken have proposed that the one-electron oxidized species found in ds DNA is the radical cation [41]. 

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