OUTER-SPHERE MACROCHELATION IN [PD(EN)(5'-GMP-N7)(2)]CENTER-DOT-9H(2)O AND[PT(EN)(5'-GMP-N7)(2)]CENTER-DOT-9H(2)O - X-RAY CRYSTALLOGRAPHY AND NMR-SPECTROSCOPY IN SOLUTION

X-ray crystallography shows that [Pd(en)(5'-GMP-N7)(2)]. 9H(2)O and [Pt(en)(5'-GMP-N7)(2)]. 9H(2)O are isostructural square-planar complexes with the bases coordinated head-to-tail in the A configuration. The sugar conformations are C3'-endo (N-type), anti (chi=-155.6 and -155.5 degrees, Pd and Pt), gauche(+). Macrochelate rings are formed via intramolecular H-bonding between the monoanionic 5'-phosphate groups and coordinated ethylenediamine NH (N ... OP 2.92 Angstrom). Electrostatically-bonded axial water molecules (Pd-O = 3.365 Angstrom, Pt-O = 3.493 Angstrom) play key roles in a network of H-bonding involving the phosphate oxygens. ethylenediamine NH, and C6O. H-1{N-15} NMR shifts together with P-31{H-1} NOE's show that macrochelation involving NH ... 5'-phosphate H-bonding is present in solution both at pH 7 where the coordinated nucleotide is dianionic and also at low pH (2-3) where it is monoanionic (as in the crystal). The Pt complex is relatively nontoxic to cells in culture (IC50 > 0.5 mM for H9 and C8166 cells), and the Pd complex, which dissociates in solution to give 5'-GMP and an N1, N7-bridged oligomer as a minor product below pH 6 but as the major product at pH > 7.6, exhibits marginal anti-HIV activity.