A Very Rare Example of a Structurally Characterized 3′-GMP Metal Complex. NMR and Synthetic Assessment of Adducts Formed by Guanine Derivatives with [Pt(L^tri)Cl]Cl Complexes with an N,N′,N″ Tridentate Ligand (L^tri) Terminated by Imidazole Rings

[Pt­(<i>N</i>(R)-1,1′-Me₂dma)­Cl]Cl complexes with tridentate ligands (bis­(1-methyl-2-methylimidazolyl)­amine, R = H; <i>N</i>-(methyl)­bis­(1-methyl-2-methylimidazolyl)­amine, R = Me) were prepared in order to investigate Pt­(<i>N</i>(R)-1,1′-Me₂dma)<b>G</b> adducts (<b>G</b> = monodentate N9-substituted guanine or hypoxanthine derivative). Solution NMR spectroscopy is the primary tool for studying metal complexes of nucleosides and nucleotides because such adducts rarely crystallize. However, [Pt­(<i>N</i>(H)-1,1′-Me₂dma)­(3′-GMPH)]­NO₃·5H₂O (<b>5</b>) was crystallized, allowing, to our knowledge, the first crystallographic molecular structure determination for a 3′-GMP platinum complex. The structure is one of only a very few structures of a 3′-GMP complex with any metal. Complex <b>5</b> has the syn rotamer conformation, with 3′-GMP bound by N7. All Pt­(<i>N</i>(R)-1,1′-Me₂dma)<b>G</b> adducts exhibit two new downfield-shifted <b>G</b> H8 signals, consistent with <b>G</b> bound to platinum by N7 and a syn/anti rotamer mixture. Anticancer-active monofunctional platinum­(II) complexes have bulky carrier ligands that cause DNA adducts to be distorted. Hence, understanding carrier-ligand steric effects is key in designing new platinum drugs. Ligand bulk can be correlated with the degree of impeded rotation of the <b>G</b> nucleobase about the Pt–N7 bond, as assessed by the observation of rotamers. The signals of syn and anti rotamers are connected by EXSY cross-peaks in 2D ROESY spectra of Pt­(<i>N</i>(H)-1,1′-Me₂dma)<b>G</b> adducts but not in spectra of Pt­(<i>N</i>(H)­dpa)<b>G</b> adducts (<i>N</i>(H)­dpa = bis­(2-picolyl)­amine), indicating that rotamer interchange is more facile and carrier-ligand bulk is lower in Pt­(<i>N</i>(H)-1,1′-Me₂dma)<b>G</b> than in Pt­(<i>N</i>(H)­dpa)<b>G</b> adducts. The lower steric hindrance is a direct consequence of the greater distance of the <b>G</b> nucleobase from the H4/4′ protons in the <i>N</i>(R)-1,1′-Me₂dma carrier ligand in comparison to that from the H6/6′ protons in the <i>N</i>(H)­dpa carrier ligand. Although in <b>5</b> the nucleotide is 3′-GMP (not the usual 5′-GMP) and the <i>N</i>(H)-1,1′-Me₂dma carrier ligand is very different from those typically present in structurally characterized Pt­(II) <b>G</b> complexes, the rocking and canting angles in <b>5</b> adhere to long-recognized trends.