Loss of Hoogsteen pairing ability upon N1 adenine platinum binding

Chloroform- and Freon-soluble mixed thymine, adenine complexes trans-[Pt(MeNH2)(2)(ChmT-N-3)(ChmA-N1)]NO3 (2) and trans-[Pt(MeNH2)(2)(ChmT-N3)(TBDMS-ado-N1)]BF4 (3) (ChmT = anion of 1-cyclohexylmethylthymine ChmTH, ChmA = 9-cyclohexylmethyladenine, TBDMS-ado = 2',3',5'-tri-tert-butyldimethylsilyladenosine) have been prepared and characterized to study their propensity to undergo Hoogsteen and/or reversed Hoogsteen pairing in solution with free ChmTH and free 3',5-diacetyl-2'-deoxyuridine, respectively, No Hoogsteen or reversed Hoogsteen pairing between 2 and ChmT takes place in CDCl3. In Freon, partial H bonding between N1 platinated TBIDIVIS-ado and 3',5'-diacetyl-2'-deoxyuridine as well as its [3-N-15] labeled analogue is unambiguously observed only below 150 K. Comparison of (1)J (N-15-H-1) coupling constants of 3',5'-diacetyl-2'-deoxyuridine involved in Hoogsteen pairing with free and N1 platinated adenine suggests that the interaction is inherently weaker in the case of platinated adenine. To better understand the complete absence of hydrogen bonding between the ChmA ligand in 2 and free ChmTH, ab initio calculations (gas phase, 0 K) have been carried out for Hoogsteen pairs involving adenine (A) and thymine (T), as well as simplified analogues of 2 and T, both in the presence and absence of counteranions. The data strongly suggest that reduction of the effective positive charge of the heavy metal ion Pt2+ by counterions diminishes interaction energies. With regard to mixtures of 2 and ChmTH in chloroform, this implies that ion pair formation between the cation of 2 and NO3- may be responsible for the lack of any measurable Hoogsteen pairing in this solvent.