Heteronuclear Nucleobase Complexes as Tools for the Isolation of the Minor Rotamer of the Parent Compound: Synthesis and Crystal Structure Determination of Head-Head and Head-Tail Forms of trans-[(CH₃NH₂)₂Pt(1-MeC-N3)₂]²⁺ (1-MeC = 1-methylcytosine)

Abstract

Nucleobase rotation about bonds with transition metal ions has been intensively studied for purine complexes of d s-a2Pt(II) (with a = N H 3 or amine) [1][2][3][4][5][6][7][8][9]. Results obtained from these studies are considered meaningful with regard to the second step (chelate closure) of reactions of the antitum or agent d s-a2PtCl2 with DNA. Favorable or unfa vorable interactions between the am(m)ine li gands at the platinum atom and exocyclic groups of the nucleobases in the vicinity of the metal co ordination site are crucial as far as rotational b ar riers are concerned [5,7,8]. Although this aspect has been studied in detail for /V7-platinated p u rines only, it is of even greater significance to N3-platinated pyrimidine nucleobases. Qualitatively, we have dem onstrated in many instances that binding of a second metal ion to a TVJ-platinated pyrimidine base (uracil, thymine, cytosine) has a We have now applied the very same principle to a related system, namely to fra«s-[a2Pt(l-M eC -N3)2]2+ (1-MeC = 1-methylcytosine) for the following reasons: First, the aspect of nucleobase rotation has hardly been studied in complexes of trans-a2Pt(II) [13]; second, we have recently been able to characterize a series of heteronuclear com plexes of this compound with the two (deproto nated) nucleobases arranged head-head [14][15][16]; third, we found that removal of the heterom etal by a suitable nucleophile can be sufficiently fast, and subsequent ligand rotation sufficiently slow, to permit crystallization of the minor rotam er (headhead) of rra/7s-[a2Pt(l-MeC-/V3)2]2+ from aqueous solution. To the best of our knowledge, this is the

Metal-Modified Nucleobase Sextet: Joining Four Linear Metal Fragments (trans-a2PtII) and Six Model Nucleobases to an Exceedingly Stable Entity

“…However, there have been cases where distinctly different signals due to rotamers have been observed. [24] Intermediate complexes: Complexes 1 b and 1 d were allowed to react with an excess of trans-[(CH 3 NH 2 ) 2 PtCl 2 ] to give 2 a and 2 b in 75 and 61 % yield, respectively. Crystals of 2 a suitable for X-ray structure determination were obtained by recrystallization from water and slow evaporation at room temperature.…”

“Directed” Assembly of Metallacalix[n]arenes with Pyrimidine Nucleobase Ligands of Low Symmetry: Metallacalix[n]arene Derivatives ofcis‐[a2M(cytosine‐N3)2]2+(M=PtII, PdII;n=4 and 6)

“…First, in the case of the trans complex, two rotamers (head-to-tail and head-to-head) are detected in solution, [24] very much as in the case of the corresponding 1-methylcytosine analogue, [25] but this is not the case with the cis isomers 1-3. Clearly, the steric congestion during the rotation of cytosine bases is larger in the cis isomers and consequently ligand rotation is more difficult.…”

The Challenge of Deciphering Linkage Isomers in Mixtures of Oligomeric Complexes Derived from 9‐Methyladenine and trans‐(NH3)2PtII Units

“…To this end, 10 was treated with thiourea (2 equiv) at room temperature and the reaction was monitored by 1 H NMR spectroscopy. We hoped to unambiguously detect initial formation of the head–head rotamer of 9 in solution, similar to the related complex trans ‐[Pt(MeNH 2 ) 2 (μ‐1MeC –H ‐ N3,N4 ) 2 Hg] 2+ , for which the head–head rotamer was even crystallized 50. Although, the reaction of 10 with thiourea was virtually instantaneous (apparent from the color change from colorless, to yellow‐brown, then brown; as observed for the mixed Pt,Hg‐1‐metylcytosine complex), equilibrium of the two rotamers of 9 was practically complete after acquisition of the first spectrum (5 min).…”