X-ray structure and circular dichroism of pure rotamers of bis[guanosine-5'-monophosphate(-1)](N,N,N',N'-tetramethylcyclohexyl-1,2-diamine)platinum(II) complexes that have R,R and S,S configurations at the asymmetric diamine.
The use of a sterically hindered diamine ligand (Me(4)DACH) has allowed for the first time, the isolation and characterization, both in the solid state (X-ray crystallography) and in solution (circular dichroism), of pure DeltaHT rotamers of [Pt(Me(4)dach)(5'-GMP)(2)] (compounds 1 and 2 for R,R and S,S configurations of the Me(4)DACH ligand, respectively). Comparison of the CD spectra obtained for each rotamer, which differ only in the chirality of the Me(4)DACH ligand (R,R or S,S) or in the chirality of the HT conformation (Delta or Lambda), allowed us to conclude that, in the 200-350 nm range, the contributions to the overall CD spectrum that stem from diamine chirality and diamine-induced chirality of platinum d--d transitions or from sugar chirality are negligible relative to the exciton chiral coupling that occurs for pi-pi* transitions of the cis guanines. Accurate molecular structures of 1.10 D(2)O and 2.14 D(2)O (conventional crystallographic agreement indexes R(1) convergent to 2.07 % and 2.18 %, respectively) revealed that the crystallized rotamers have a DeltaHT conformation that is in agreement with all previously reported X-ray structures of [Pt(diamine)(nucleos(t)ide)(2)] complexes. This conformation allows the 5'-phosphate to be located in proximity to the Me(4)DACH ligand so that (P)O...HC(N) hydrogen-bond interactions exists in both complexes. For both structures, the canting of the guanine planes on the coordination plane is right-handed (R; canting angle (Phi) of 80.9 degrees and 73.2 degrees, respectively); this indicates that the canting direction is driven by the HT conformation chirality (Delta for both compounds) and not by the chirality of the carrier ligand (different for the two compounds). Density functional theory analysis of the conformational space as a function of Phi indicated a good agreement between the computed and experimental structures. The increase in energy for Phi values below 65 degrees and 55 degrees (for 1 and 2, respectively) is mainly due to the short intramolecular contacts between C(8)H and the cis N-Me groups on the same side of the platinum coordination plane.
Benedetti
Michele
M
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università degli Studi di Lecce, Via Monteroni, 73100 Lecce, Italy.
Tamasi
Gabriella
G
Cini
Renzo
R
Natile
Giovanni
G
D000970:Antineoplastic Agents / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods; D003514:Cyclohexylamines / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry*; D006157:Guanosine Monophosphate / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D003959:Diamines; D008024:Ligands; D009944:Organoplatinum Compounds; D006157:Guanosine Monophosphate; C030435:1,2-cyclohexanediamine