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

Abstract

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.

The First Pure ΛHT Rotamer of a Complex with a cis‐[Metal(nucleotide)2] Unit: A cis‐[Pt(amine)2(nucleotide)2] ΛHT Rotamer with Unique Molecular Structural Features

“…[28] The chelate ring of 1 has the d pucker (opposite to the l pucker found in aqueous solution) and puretwist pucker (T, C 2 symmetry, q 2 0.365(1) ); [63] the value of q 2 is slightly smaller than those found for the Me 4 DACH adducts 2 and 3. [43] 5'-GMP ligands: Geometrical parameters relevant to the purine systems of 1 are in excellent agreement with values previously reported. [28,29] The presence of a proton on N1 is confirmed by the value of 125.2(5)8 for the C2-N1-C6 bond angle.…”

“…[61] We have proposed that the weakness of the latter CD features is caused by the greater "6-in" canting of the purine bases permitted by the smaller steric interaction between the guanine H8 and the cis amine (an NÀH instead of an N À Me on the same side of the platinum coordination plane). [43] In the limit of complete canting, the bases lie in the platinum coordination plane, and a negligible CD signal is expected.…”

“…[43] The very slow rate of interconversion between rotamers of these three complexes ensures that the measured CD spectra are those of the pure rotamers. As expected from earlier work, [43] the spectra of the two DHT rotamers have nearly a mirror relationship to that of the LHT rotamer because this change inverts the chirality of the coupled p!p* electronic transitions of the two purines.…”

“…[43] [PtA C H T U N G T R E N N U N G (DAP)(Me-5'-GMP) 2 ] (4, DAP= 1,3-diaminopropane, Me-5'-GMP = phosphate methyl ester of 5'-GMP), [29] and…”

“…[2,25,26] In DNA and oligonucleotide HT adducts and for all related HT forms characterized by solid-state crystallography, the chirality of the HT conformer typically found is D. All known cis-[metal(6-oxopurine nucleotide) 2 ] adducts (involving 5'-GMP, 5'-IMP, and their phosphate methyl esters) crystallize in the DHT conformation, not only for square-planar Pt with several carrier ligands, but also for examples of square-planar and octahedral complexes of Co, Cu, Zn, Cd, and Pd. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Also, the D conformation is found in all solid-state structures of Pt compounds with G nucleosides. [27-30, 32-34, 38, 41-47] Furthermore, all known structures of cis-[metal(6-oxopurine nucleotide) 2 ] adducts in the HH conformation have nucleotides that are linked by a sugar-phosphate backbone.…”