New palladium(II) and platinum(II) complexes with 9-aminoacridine: structures, luminiscence, theoretical calculations, and antitumor activity

Inorg Chem. 2008 Aug 4;47(15):6990-7001. doi: 10.1021/ic800589m. Epub 2008 Jul 1.

Abstract

The new complexes [Pd(dmba)( N10-9AA)(PPh 3)]ClO 4 ( 1), [Pt(dmba)( N9-9AA)(PPh 3)]ClO 4 ( 2), [Pd(dmba)( N10-9AA)Cl] ( 3), and [Pd(C 6F 5)( N10-9AA)(PPh 3)Cl] ( 4) (9-AA = 9-aminoacridine; dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl) have been prepared. The crystal structures have been established by X-ray diffraction. In complex 2, an anagostic C-H...Pt interaction is observed. All complexes are luminescent in the solid state at room temperature, showing important differences between the palladium and platinum complexes. Complex 2 shows two structured emission bands at high and low energies in the solid state, and the lifetimes are in agreement with excited states of triplet parentage. Density functional theory and time-dependent density functional theory calculations for complex 2 have been done. Values of IC 50 were also calculated for the new complexes 1- 4 against the tumor cell line HL-60. All of the new complexes were more active than cisplatin (up to 30-fold in some cases). The DNA adduct formation of the new complexes synthesized was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pB R322 were also obtained.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminacrine / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chelating Agents
  • Circular Dichroism
  • Electrophoresis, Agar Gel
  • Humans
  • Luminescence*
  • Microscopy, Atomic Force
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Palladium / chemistry*
  • Platinum / chemistry*
  • Quantum Theory
  • Time Factors

Substances

  • Antineoplastic Agents
  • Chelating Agents
  • Organometallic Compounds
  • Platinum
  • Palladium
  • Aminacrine