Factors Influencing the Configuration and Conformation of Diamine Chelate Rings in Platinum(II) Compounds:  2,4-Bis(methylamino)pentane Complexes

Abstract

Complexes of the type [PtX(2)(Me(2)DAP)] (Me(2)DAP = 2,4-bis(methylamino)pentane) have been prepared and studied by (1)H NMR spectroscopy, molecular mechanics/dynamics (MMD) calculations, and X-ray crystallography. The coordinated Me(2)DAP ligand has four asymmetric centers. Complexes with an enantiomeric form of the ligand (e.g., RR-Me(2)DAP, RR being the configurations of the two asymmetric carbons) have three possible configurations, namely, SRRR, RRRR, and SRRS at N, C, C, and N, respectively. Indeed these three isomers were obtained in respective ratios of 9:1: approximately 0 for X = I(-) and of 7:3:1 for X = Cl(-). Complexes with the meso ligand (RS-Me(2)DAP) have four possible configurations, i.e., SRSR, RRSS, RRSR, and SRSS at N, C, C, and N, respectively (the latter two constitute an enantiomeric pair). Only the two symmetrical isomers were obtained in the ratios of 9:1 for X = I(-) and 1:1 for X = Cl(-). In addition, the preferred chelate ring conformations in solution (CDCl(3)) were determined to be the following: delta-chair (SRRR), lambda-skew (RRRR), fluxional chair (SRRS), fluxional skew (SRSR), and lambda-chair (RRSS). This information was used to assess the contributions of intra- and interligand interactions to determine the conformational stability. MMD calculations employing the AMBER force field [as modified by Yao et al. (Yao, S.; Plastaras, J. P.; Marzilli, L. G. Inorg. Chem. 1994, 33, 6061) and extended to include parameters for the Cl(-) ligands] provided minimum-energy structures for all five X = Cl(-) complexes. These structures agreed well with the experimentally determined solution conformations except for SRSR, which had a lowest energy delta-chair instead of skew conformation. X-ray structural studies of the SRSR species (X = Cl(-) and X = I(-)) confirmed the delta-chair conformation. The results suggest that an equatorial N-methyl group has nonbonded clashes with the cis chloride ligand; therefore, axial N-methyl groups are favored. However, in solution, the solvent and entropy (connected with fluxionality of conformers) are factors which, to some degree, can overcome the interligand steric interaction.

Sterically hindered complexes of platinum(II) with planar heterocyclic nitrogen donors. A novel complex with 1-methyl-cytosine has a spectrum of activity different from cisplatin and is able of overcoming acquired cisplatin resistance

“…The Pt-I bond distance (2.592(1) Å ) is in agreement with previously reported values for platinum(II) complexes [13,22,24]. Also the Pt-N(AmPIC) bond distance (2.036(6) Å ) is in good agreement with previously reported values for pyridine derivatives [22,25].…”

Interaction of N-acetylmethionine with a non-C2-symmetrical platinum diamine complex

“…Exchange between chelate ring conformations has been noted for six-membered chelate rings involving a platinum atom; however, only one set of resonances were observed even at very low temperatures (ca. À50°C) [12]. Thus, interconversion of ring conformations appears to be an unlikely explanation.…”

“…The Pt(Et 2 en)I 2 compound was synthesized based on previous methods [12,13]. In a typical synthesis, 220 mg of K 2 PtCl 4 was dissolved in 10 mL H 2 O and an excess ($4 g) of KI was added.…”

New Steric Hindrance Approach Employing the Hybrid Ligand 2-Aminomethylpiperidine for Diminishing Dynamic Motion Problems of Platinum Anticancer Drug Adducts Containing Guanine Derivatives

“…G bases coordinated to platinum complexes with nonbulky amine groups, such as (NH 3 ) 2 (cisplatin) and en (ethylenediamine), exhibit fast rotation around the Pt−N7 bond on the NMR time scale. − For complexes with a six-membered chelate ring, several conformations, including chair, skew, and boat, can be adopted. This additional flexibility results in low-energy structures with axial N -methyl groups, according to molecular mechanics and dynamics calculations on Me 2 DAP Pt G 2 complexes , ( Me 2 DAP = N , N ‘-dimethyl-2,4-diaminopentane). Rapid rotation about the Pt−N7 bond is generally observed.…”