Extent of the Acidification by N7-Coordinated cis-Diammine-Platinum(II) on the Acidic Sites of Guanine Derivatives

Abstract

Coordination of two monoprotonated 2'-deoxyguanosine 5'-monophosphate species, H(dGMP)⁻, via N7 to cis-(NH₂)₂Pt²⁺ gives the complex cis-(NH₂)₂Pt(H·dGMP)₂ which is a four-protonic acid. The corresponding acidity constants were measured by potentiometric pH titrations (25℃; I = 0.1 M, NaNO₃). The first two protons are released from the two -P(O)₂(OH)⁻ groups (PK_a/1= 5.57; PK_a/2 = 6.29) and the next two protons are from the H(N1) sites of the guanine residues (PK_a/3 = 8.73; PK_a/4 = 9.48). The micro acidity constants of the various sites are also evaluated. Comparison of these data with those determined for the three-protonic H₂(dGMP)^± (PK_a/1 = 2.69 for the H⁺(N7) site; PK_a/2 = 6.29 for -P(O)₂(OH)⁻ ;PK_a/3 = 9.56 for H(N1)) shows that on average the N-7-coordinated Pt²⁺ acidifies the phosphate protons by Δ pK_a = 0.36 and the H(N1) sites by Δ pK_a = 0.46. These results are further compared with those obtained previously for cis-(NH₂)₂Pt(L)₂, where L = 9-ethylguanine or monoprotonated 2'-deoxycytidine 5'-monophosphate. Conclusions regarding platinated DNA are also presented.

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