Synthesis and Structural Characterisation of a New Form of Bis(acyclovir)(ethylenediamine)platinum(II) − Correlation between the Puckering of the Carrier Ligand and the Canting of the Nucleobases

Abstract

A new conformer of the [Pt(en)(acv)2]2+ cation (en = ethylenediamine; acv = acyclovir = 9-[(2-hydroxyethoxy)methyl]guanine) has been prepared by slow crystallisation of the [Pt(en)(acv)2]SO4·2.5H2O salt. X-ray diffraction studies have shown that the guanine moieties have a Head-to-Head conformation (HH) with the two C(8)-H vectors pointing towards the same side with respect to the platinum coordination plane; the dihedral angles formed by the purine planes and the coordination plane are 58.3(2)° and 41.5(2)°, respectively. There is a correlation between the canting of the purine bases (right or left handed) and the puckering of the ethylenediamine chelate ring (δ or λ). Right-handed canting is associated with λ puckering of the chelate ring and left-handed canting with δ puckering of the chelate ring, so that in both cases one of the two purines forms an O(6)···H−N hydrogen bond with a “quasi equatorial” NH of the ethylenediamine. The “quasi equatorial” character of the NH appears to be a common feature for intramolecular H-bonds between guanine bases and cis-amines. The purine not involved in the H-bond has the six-membered ring portion leaning towards the cis purine rather than towards the cis amine and may give rise to a weak O(6)···Pt attractive interaction. Such an interaction is supported by density functional (DFT) molecular orbital calculations carried out on the model systems [Pt(NH3)4(CH2O)]2+ and Head-to-Tailcis-[Pt(NH3)2{N(=CH2)−C(=CH2)−C(=O)−NH2}2]2+. The exocyclic chains linked to N(9) each have two different orientations, and all four are stretched away from the metal centre as well as from the purine N(1)H and N(2)H2 protons. The acv and the en NH protons are instead involved in H-bonds with the sulfate anion.