Platinum-Modified Adenines: Unprecedented Protonation Behavior Revealed by NMR Spectroscopy and Relativistic Density-Functional Theory Calculations

Two novel PtIV complexes of aromatic cytokinins
with
possible antitumor properties were prepared by reaction of selected
aminopurines with K2PtCl6. The structures of
both complexes, 9-[6-(benzylamino)­purine] pentachloroplatinate (IV)
and 9-[6-(furfurylamino)­purine] pentachloroplatinate (IV), were characterized
in detail by using two-dimensional NMR spectroscopy (1H, 13C, 15N, and 195Pt) in solution and
CP/MAS NMR techniques in the solid state. We report for the first
time the X-ray structure of a nucleobase adenine derivative coordinated
to PtIV via the N9 atom. The protonation equilibria for
the complexes in solution were characterized by using NMR spectroscopy
(isotropic chemical shifts and indirect nuclear spin–spin coupling
constants) and the structural conclusions drawn from the NMR analysis
are supported by relativistic density-functional theory (DFT) calculations.
Because of the presence of the Pt atom, hybrid GGA functionals and
scalar-relativistic and spin–orbit corrections were employed
for both the DFT calculations of the molecular structure and particularly
for the NMR chemical shifts. In particular, the populations of the
N7-protonated and neutral forms of the complexes in solution were
characterized by correlating the experimental and the DFT-calculated
NMR chemical shifts. In contrast to the chemical exchange process
involving the N7–H group, the hydrogen atom at N3 was determined
to be unexpectedly rigid, probably because of the presence of the
stabilizing intramolecular interaction N3–H···Cl.
The described methodology combining the NMR spectroscopy and relativistic
DFT calculations can be employed for characterizing the tautomeric
and protonation equilibria in a large family of transition-metal-modified
purine bases.