Minor Groove Site Coordination of Adenine by Platinum Group Metal Ions: Effects on Basicity, Base Pairing, and Electronic Structure

Dithioether- or diamine-tethered adenine derivatives react with PtII, PdII, and RhIII ions to give N3-coordinated
complexes of the types [MCl(SSN)]+ (M = Pt or Pd), [RhCl3(SSN)], or [RhCl3(NNN)] (where SSN = 1-(N9-adenine)-3,6-dithia-heptane or 1-(N9-adenine)-4,7-dithia-octane; NNN = ethylenediamine-N,9-ethyladenine). Single-crystal
X-ray analysis confirms the nature of the metal−nucleobase interaction and highlights a conserved intermolecular
hydrogen-bonding motif for all the complexes, irrespective of the metal-ion geometry. Coordination significantly
reduces the basicity of the adeninyl group, as indicated by a pKa value of −0.16 for [PtCl(N3-1-(N9-adenine)-3,6-dithia-heptane)]BF4, compared to a pKa value of 4.2 for 9-ethyladenine. The site of proton binding, N1 or N7, could
not be unambiguously assigned from the 1H NMR data, because of the similar effect on the chemical shifts of the
H2 and H8 protons. Density functional calculations at the BP-LACVP* level suggest N1 as the site of protonation
for this type of complex. This is in contrast to the N7-protonation reported for [Pt(dien)(N3-6,6‘,9-trimethyladenine)]2+,
as reported elsewhere (Meiser et al., Chem.Eur. J. 1997, 3, 388). However, further electronic structure calculations
in the gas phase reveal that the preferred site for protonation for N3-bound complexes is conformationally dependent.
N3 coordination was also found to reduce the extent of base pairing between adenine and thymine in dimethylsulfoxide
for the self-complementary complex [PtCl(L3)]+ (L3 = 1-(N9-adenine)-3,6-dithia-9-(N1-thymine)nonane), compared
to that for the uncomplexed ligand.