Acid−Base and Metal Ion Binding Properties of Guanylyl(3‘→5‘)guanosine (GpG^-) and 2‘-Deoxyguanylyl(3‘→5‘)-2‘-deoxyguanosine [d(GpG)^-] in Aqueous Solution

Abstract

The acidity constants of guanylyl(3'-->5')guanosine (GpG(-)) and 2'-deoxyguanylyl(3'-->5')-2'-deoxyguanosine [d(GpG)(-)] for the deprotonation of their (N1)H sites were measured by potentiometric pH titrations in aqueous solution (25 degrees C; I = 0.1 M, NaNO(3)). The same method was used for the determination of the stability constants of the 1:1 complexes formed between Mg(2+), Ni(2+), or Cd(2+) (= M(2+)) and (GG-H)(2-), and in the case of Mg(2+) also of (GG-2H)(3-), where GG(-) = GpG(-) or d(GpG)(-). The stability constants of the M(GG)(+) complexes were estimated. The acidity constants of the H(dGuo)(+) and dGuo species (dGuo = 2'-deoxyguanosine) and the stability constants of the corresponding M(dGuo)(2+) and M(dGuo-H)(+) complexes were also measured. Comparison of these and related data allows the conclusion that N7 of the 5'G unit in GG(-) is somewhat more basic than the one in the 3'G moiety; the same holds for the (N1)(-) sites. On the basis of comparisons with the stability constants measured for the dGuo complexes, it is concluded that M(2+) binding of the GG dinucleoside monophosphates occurs predominantly in a mono-site fashion, meaning that macrochelate formation is not very pronounced. Indeed, it was a surprise to find that the stabilities of the complexes of dGuo or (dGuo-H)(-) and the corresponding ones derived from GG(-) are so similar. Consequently, it is suggested that in the M(GG)(+) and M(GG-H) complexes the metal ion is mainly located at N7 of the 5'G unit since this is the more basic site allowing also an outer-sphere interaction with the C6 carbonyl oxygen and because this coordination mode is also favorable for an electrostatic interaction with the negatively charged phosphodiester bridge. It is further suggested that Mg(2+) binding (which is rather weak compared to that of Ni(2+) and Cd(2+)) occurs mainly in an outer-sphere mode, and on the basis of the so-called Stability Ruler it is concluded that the binding properties of Zn(2+) to the GG species are similar to those of Ni(2+) and Cd(2+).

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

“…(ii) The acidification of Cd 2+ as observed in the Cd(GpG) + and Cd[d(GpG)] + complexes is with ∆ pK a = 1.8 ± 0.4 [38] within the error limits the same as given above in Table 4.…”

“…but not for the (N1)H units of guanosines with pK a values of about 9.4 [31,37,38]. In these latter cases a strong competition for binding at (N1) -between the proton and metal ion exists.…”

“…If one applies the indicated evaluation procedure [75] to the data of ref. [38], one notes that the log ∆ Cd/(GpG -H) and log ∆ Cd/d(GpG -H) values are zero within their error limits. This agrees with the earlier conclusion [38] that "no hint for the formation of significant amounts of intramolecular chelates involving both N7 sites" have been found, though low concentrations could still occur, of course.…”

“…[38], one notes that the log ∆ Cd/(GpG -H) and log ∆ Cd/d(GpG -H) values are zero within their error limits. This agrees with the earlier conclusion [38] that "no hint for the formation of significant amounts of intramolecular chelates involving both N7 sites" have been found, though low concentrations could still occur, of course. A possible explanation could be that the intramolecular stacking interaction in (IpI -H) 2-is smaller than in (GpG -H) 2-, and in fact, this is expected [137,247,248].…”

“…Since N7 of a 5'-purine unit is in general somewhat more basic than the one of a 3' unit [38,48] Figure 16) [38]. If one applies the indicated evaluation procedure [75] to the data of ref.…”