Nucleobase pA values

ALTERATIONS OF NUCLEOBASE pA VALUES UPON METAL COORDINATION 391... 

ALTERATIONS OF NUCLEOBASE pA"a VALUES UPON METAL COORDINATION 401... 

Fmther increase of the PA of the nncleobases was found in anions of DNTs [77]. As it was expected, appearance of negative charge due to deprotonation of the phosphate group results in an increase of the PA values by 2.7-29 eV. However, similar to results for isolated bases, the base in the TMP anion has the lowest PA. Besides that, the PA value for CMP also becomes slightly lower than that for AMP and GMP (APA 0.3 eV). In the discnssed here investigations, P-0 group of phosphate is not considered as a protonation sites. The PA of P-0 is always much higher than PA of any nucleobase atom. 

Figure 1. (Top) Lewis formulas of nucleobases A, G, C, U (T) in different protonation states. Only single mesomeric and preferred tautomeric forms are given. Additionally, protonated forms of A, G, U (T) and twofold deprotonated form of G are not shown. (Bottom) Distribution of protonation states of nucleobases with pH. The pA a values of A -nucIcotides are used as boundaries for the neutral form.

The determination of the pAa of a nucleobase by potentiometry relies on differences in NaOH consumptions between titrations of HN03 carried out in the absence and presence of the compound whose p/fa is to be obtained (208). Curve-fit procedures using Newton-Gauss nonlinear least-squares programs are applied to calculate the pA"a value. 

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. 

The phenomenon of shifted pA"a values is now well established in nucleic acid chemistry. By in large, it refers to pA"a shifts of protonated nucleobases to higher values in nucleic acid structures, hence there is an apparent loss in acidity... 

Figure 1 The chemical units of nucleic acids, (a) The purine and pyrimidine nucleobases. (b) Nucleosides, nucleotides, and an oligonucleotide. Approximate pA a values taken from Bloomfield et al ...

It should be noted some experimental problems in study of protonation of nucleotides. At the first stage the protonation of phosphate (PU) always happens. This is explained by the significant difference in the values of PA of nucleobases protonation sites and PU. Therefore, the experimental data reflect the process of protonation of neutral forms of deoxyribonucleotides. But it is well known, that in vivo, nucleotides have a negative charge, which is balanced by the metal cations (Na+or K+). Thus, the issue of nucleobases protonation in monoanionic DNTs remains unanswered in experimental investigations. 

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