Bulky ligand substituent effect on the reaction of 5'-GMP with platinum-1,3-diamine. Rotation of 5'-GMP about the platinum-nitrogen bond and kinetic effects

Synthesis, Crystal Structure, Antitumor Activity, and DNA-Binding Properties of the New Active Platinum Compound (Bis(N-methylimidazol-2-yl)carbinol)dichloroplatinum(II), Lacking a NH Moiety, and of the Inactive Analog Dichloro(N1,N1‘-dimethyl-2,2‘-biimidazole)platinum(II)

“…A possible explanation for this phenomenon is restricted rotation around the Pt−N7 bond. This restricted rotation has been observed before for Pt compounds with 5‘-GMP coordinated and can be due to steric hindrance or the presence of H bonds . Since, in our case, the effect is pH dependent, it is likely that H bonds, present at low pH, cause the inequivalence of the two GMP's by retarding the rotation around Pt−N7.…”

Kinetic control of reactions of a sterically hindered platinum picoline anticancer complex with guanosine 5′-monophosphate and glutathione

“…Usually fast rotation of bound GMP about the Pt-N7 bond in cis-[PtA 2 (GMP) 2 ] (where A 2 are two unidentate or one bidentate amine ligand) is expected if the substituents on the two cis amine ligands are not very bulky. 30,32 In our NMR experiments only four H8 signals in two sets of two singlets were observed for complex 1, together with two methyl signals. This suggests that rotation of 5Ј-GMP about the Pt-N7 bond is fast on the NMR timescale but slow about the Pt-N bond for 2-picoline.…”

“…27-29 Each H8 is non-equivalent for both HT stereoisomers, 28,30,31 giving a total of four H8 signals for the HT stereoisomers. 32 For the 2-picoline complex 1, the 2-methyl group can be on the upper side or the lower side of the platinum plane for each HT stereoisomer, so theoretically eight H8 signals should be observed for the two HT isomers together with four methyl signals (Scheme 2) when there is slow rotation (on the NMR timescale) about both the Pt-N7 (GMP) and Pt-N (picoline) bonds. Usually fast rotation of bound GMP about the Pt-N7 bond in cis-[PtA 2 (GMP) 2 ] (where A 2 are two unidentate or one bidentate amine ligand) is expected if the substituents on the two cis amine ligands are not very bulky.…”

Conformational preferences, rotational barriers and energetics of purine nucleobase rotation and dissociation in square planar platinum(II) antitumour complexes: Structure–activity correlation

“…30À44 The geometrical parameters of the coordinated guanine base molecule were taken from the X-ray crystal structures of square planar platinum(II) complexes involving one guanine ligand coordinated through the N7 donor atom to the central metal atom. 1,13,45,46 Finally, the equilibrium PtÀN7 bond length, R e , and equilibrium bond dissociation energy, D e , were derived from the computed Morse-type potential energy curves of the dissociation of the PtÀN7 to free guanine and platinum(II) amine fragments in their unrelaxed ground state geometries. However, such a ``rigid '' model represents adequately the real model describing the GÀPt interactions, as the plethora of the experimental structural data indicate that there are no noticeable changes in the structures of the isolated guanine and platinum(II) amine fragments upon adduct formation.…”

“…Thus, for the biologically inactive platinum(II) complexes involving bulky carrier amine ligands, rotation was found to be slow on the NMR timescale. 12,13 In contrast, for platinum(II) complexes involving less bulky carrier amine ligands rotation was found to be fast on the NMR timescale 11,14 and the parent compounds exhibit signi®cant cytostatic activity.…”