Unusual hydrogen bonding patterns of N7 metallated, N1 deprotonated guanine nucleobases: acidity constants of cis-[Pt(NH3)2(Hegua)2]2+ and crystal structures of cis-[Pt(NH3)2(egua)2]·4H2O and cis-[Pt(NH3)2(egua)2]· Hegua·7H2O (Hegua = 9-ethylguanine)

Abstract

Three closely related complexes of cis-Pt^II(NH₃)₂ with neutral 9-ethylguanine (Hegua) and anionic (N¹ deprotonated) 9-ethylguanine (egua), respectively, have been prepared and studied: cis-[Pt(NH₃)₂(Hegua)(egua)]CIO₄·2H₂O 1, cis-[Pt(NH₃)₂(egua)₂]·4H₂O 2 and cis-[Pt(NH₃)₂(egua)₂]·Hegua·7H₂O 3. The crystal structures of complexes 2 and 3 have been determined. Platinum co-ordination in all cases is through N⁷ of neutral (1) or anionic (1–3) guanine. The Pt^II electrophile co-ordinated at N⁷ acidifies the N¹ proton of neutral 9-ethylguanine (pK_a= 9.57 ± 0.04), giving pK_a1= 8.02 ± 0.01 and pK_a2= 8.67 ± 0.01 for the two Hegua ligands in cis-[Pt(NH₃)₂(Hegua)₂]²⁺. All three compounds display interesting hydrogen-bonding patterns either in the solid state and/or in solution. According to ¹H NMR interaction shifts of guanine NH and NH₂ resonances of complex 1 in Me₂SO solution, this compound forms three intermolecular hydrogen bonds between neutral and deprotonated guanine ligands. For complex 2, hydrogen bonding between two deprotonated guanines in the solid state is via N¹ and N²H₂. In complex 3, the neutral 9-ethylguanine is hydrogen bonded to one of the two anionic guanine ligands through three hydrogen bonds, involving N¹, N²H₂ and O⁶. This pattern represents a mismatch between two guanines, brought about by initial co-ordination of a Pt^II electrophile to N⁷ and subsequent deprotonation of the N¹ position of the metallated nucleobase. The model character of these compounds with regard to metal-induced mutagenicity is briefly discussed.