title: Biotinylated Platinum(II) Ferrocenylterpyridine Complexes for Targeted Photoinduced Cytotoxicity.
abstract: Biotinylated platinum(II) ferrocenylterpyridine (Fc-tpy) complexes [Pt(Fc-tpy)(L(1))]Cl (1) and [Pt(Fc-tpy)(L(2))]Cl (2), where HL(1) and HL(2) are biotin-containing ligands, were prepared, and their targeted photoinduced cytotoxic effect in cancer cells over normal cells was studied. A nonbiotinylated complex, [Pt(Fc-tpy)(L(3))]Cl (3), was prepared as a control to study the role of the biotin moiety in cellular uptake properties of the complexes. Three platinum(II) phenylterpyridine (Ph-tpy) complexes, viz., [Pt(Ph-tpy)(L(1))]Cl (4), [Pt(Ph-tpy)(L(2))]Cl (5), and [Pt(Ph-tpy)(L(3))]Cl (6), were synthesized and explored to understand the role of a metal-bound Fc-tpy ligand over Ph-tpy as a photoinitiator. The Fc-tpy complexes displayed an intense absorption band near 640 nm, which was absent in their Ph-tpy analogues. The Fc-tpy complexes (1 mM in 0.1 M TBAP) showed an irreversible cyclic voltammetric anodic response of the Fc/Fc(+) couple near 0.25 V. The Fc-tpy complexes displayed photodegradation in red light of 647 nm involving the formation of a ferrocenium ion (Fc(+)) and reactive oxygen species (ROS). Photoinduced release of the biotinylated ligands was observed from spectral measurements, and this possibly led to the controlled generation of an active platinum(II) species, which binds to the calf-thymus DNA used for this study. The biotinylated photoactive Fc-tpy complexes showed significant photoinduced cytotoxicity, giving a IC50 value of ∼7 μM in visible light of 400-700 nm with selective uptake in BT474 cancer cells over HBL-100 normal cells. Furthermore, ferrocenyl complexes resulted in light-induced ROS-mediated apoptosis, as indicated by DCFDA, annexin V/FITC staining, and sub-G1 DNA content determined by fluorescent activated cell sorting analysis. The phenyl analogues 4 and 5 were photostable, served as DNA intercalators, and demonstrated selective cytotoxicity in the cancer cells, giving IC50 values of ∼4 μM.
authors.affiliation: Department of Inorganic and Physical Chemistry and ‡Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Koushambi
authors.initials: K
authors.lastname: Mitra
authors.affiliation: Department of Inorganic and Physical Chemistry and ‡Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Abhijith
authors.initials: A
authors.lastname: Shettar
authors.affiliation: Department of Inorganic and Physical Chemistry and ‡Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.affiliation: Department of Inorganic and Physical Chemistry and ‡Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Akhil R
authors.initials: AR
authors.lastname: Chakravarty
mesh_terms: D001710:Biotin / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D000075163:Metallocenes / Q000737:chemistry*; D055668:Photochemical Processes; D017671:Platinum Compounds / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D005296:Ferrous Compounds; D000075163:Metallocenes; D017671:Platinum Compounds; D011725:Pyridines; D001710:Biotin; C023666:pyridine; C004998:ferrocene