344592-22-9

Upstream product

• 92763-46-7 cis-[Pt(Me₂N(CH₂)3PPh₂-P)2Cl₂] 
• 961-04-6 (γ-N,N-dimethylaminopropyl)diphenylphosphine 
• 29679-67-2 N,N-dimethyl-2-diphenylphosphinoethylamine 

Relevant academic research and scientific papers

Structure and dynamics of a platinum(II) aminophosphine complex and its nucleobase adducts

The anti-cancer aminophosphine complex, cis-[Pt(Me2N(CH2)2PPh2-N,P)Cl(Me 2N(CH2)2PPh2-P)]Cl, 1, is shown, by 1H and 31P NMR studies, to Undergo reversible chelate ring-closing and -opening in aqueous solution. The rate for this process (21 ± 2 s-1 at pH* 8.5, 295 K), which is slow on the NMR timescale, varies significantly with pH values, chloride ion concentration and temperature. The chelate-ring-opened form is favoured at acidic pH values. The activation parameters which govern this process, have been determined via 31P-2-D EXSY NMR spectroscopy, and the mechanism of chelate ring-opening is discussed. The X-ray crystal structure of the ring-opened complex, cis-[Pt(Me2N(CH2)2PPh2-N,P)Cl(Me 2NH(CH2)2PPh2-P)](NO3) 2·1.5H2O, 1a, shows that the Pt-N bond is relatively long (2.147 A). The nucleotide 5′-guanosine monophosphate (5′-GMP) binds via N7 and displaces the Cl ligand. Unusually for a platinum(II) amine complex, GMP binding is rapid and reversible. Two isomeric GMP adducts are formed in a 3: 1 ratio below pH* 6 (pH meter reading in D2O). Above pH* 8.2, the predominant species are non N7-bound adducts. The on-rate for 5′-GMP binding to the ring-closed form cis-[Pt(Me2N(CH2)2PPh2-N,P)2 ]2+, complex 2, to give the major adduct (pH* 8.5, 298 K) is 0.20 s-1 and the off-rate is 0.018 s-1. The 5′-GMP adducts were modelled by molecular mechanics calculations. These revealed possible hydrogen bonding between the dangling arm amino group and the 5′-phosphate. Supporting evidence for this came from solution studies with other GMP derivatives (3′, 5′-cyclic GMP, 3′-GMP and 9-ethylguanine). Our findings are discussed in terms of potential new methods for drug delivery and new approaches to drug design.

Control of aminophosphine chelate ring-opening in Pt(II) and Pd(II) complexes: Potential dual-mode anticancer agents

We show that bis(aminophosphine) complexes of the type [M(R1R2N(CH2)nPPh2)2 ]2+, M = Pt(II) or Pd(II), can exist in chelate ring-closed and ring-opened forms both in the solid state and in aqueous solution. The equilibrium between them in solution can be controlled by the nature of the groups R1 and R2 (H, Me, Bz, cyclohexyl), by the bridge length n, and by the pH and Cl- concentration. X-Ray crystal structures are reported for the ring-closed complexes cis-[Pt(H2N(CH2)2PPh2-P,N)2 ]Cl2, cis-[Pt(H2N(CH2)3PPh2-P,N)2 ]Cl2, and cis-[Pt(Me(H)N(CH2)2PPh2-P,N)2][HCl 2]2, the mono-ring-opened complex cis-[Pd(Me2N(CH2)2PPh2-N,P)Cl(Me 2NH(CH2)2PPh2-P)](NO3) 2, the di-ring-opened complex cis-[Pt(Me2N(CH2)3PPh2-P)2 CL2], and, for comparison, the monochelate cis-[Pd(Me2N(CH2)3PPh2-N,P)CL2 ]. These square-planar complexes exhibit varying degrees of distortion and variable M-N bond lengths dependent not only on the trans influence of P but also on steric effects within the complex, pH-induced chelate ring-opening of cis-[Pt(Me2N(CH2)2PPh2-P,N)2 ]CL2 had an associated pK value of 6.9. In contrast, complexes with R1 and R2 = H, n = 2 or 3 or R1 = H and R2 = Me, n = 2, are more difficult to ring-open. Thus the complexes cis-[Pt(Me(H)N(CH2)2-PPh2-P,N)2]CL 2 and cis-[Pt(H2N(CH2)3PPh2-P,N)2 ]CL2, had associated pK values of 2.1 and 2.9, respectively. These aminophosphine complexes may exhibit anticancer activity by two mechanisms: by disrupting mitochondrial membrane potentials as bis-chelated (ring-closed) lipophilic cations, or by direct binding to DNA bases as ring-opened complexes.