title: Synthesis, spectroscopic characterization, photochemical and photophysical properties and biological activities of ruthenium complexes with mono- and bi-dentate histamine ligand.
abstract: The monodentate cis-[Ru(phen)(2)(hist)(2)](2+)1R and the bidentate cis-[Ru(phen)(2)(hist)](2+)2A complexes were prepared and characterized using spectroscopic ((1)H, ((1)H-(1)H)COSY and ((1)H-(13)C)HSQC NMR, UV-vis, luminescence) techniques. The complexes presented absorption and emission in the visible region, as well as a tri-exponential emission decay. The complexes are soluble in aqueous and non-aqueous solution with solubility in a buffer solution of pH 7.4 of 1.14 × 10(-3) mol L(-1) for (1R + 2A) and 6.43 × 10(-4) mol L(-1) for 2A and lipophilicity measured in an aqueous-octanol solution of -1.14 and -0.96, respectively. Photolysis in the visible region in CH(3)CN converted the starting complexes into cis-[Ru(phen)(2)(CH(3)CN)(2)](2+). Histamine photorelease was also observed in pure water and in the presence of BSA (1.0 × 10(-6) mol L(-1)). The bidentate coordination of the histamine to the ruthenium center in relation to the monodentate coordination increased the photosubstitution quantum yield by a factor of 3. Pharmacological studies showed that the complexes present a moderate inhibition of AChE with an IC(50) of 21 μmol L(-1) (referred to risvagtini, IC(50) 181 μmol L(-1) and galantamine IC(50) 0.006 μmol L(-1)) with no appreciable cytotoxicity toward to the HeLa cells (50% cell viability at 925 μmol L(-1)). Cell uptake of the complexes into HeLa cells was detected by fluorescence confocal microscopy. Overall, the observation of a luminescent complex that penetrates the cell wall and has low cytotoxicity, but is reactive photochemically, releasing histamine when irradiated with visible light, are interesting features for application of these complexes as phototherapeutic agents.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos-SP, Brazil.
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Cardoso
authors.forename: Inara
authors.initials: I
authors.lastname: de Aguiar
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Camilo
authors.forename: Márcia V S
authors.initials: MV
authors.lastname: Lima
authors.forename: Amando S
authors.initials: AS
authors.lastname: Ito
authors.forename: Maurício S
authors.initials: MS
authors.lastname: Baptista
authors.forename: Christiane
authors.initials: C
authors.lastname: Pavani
authors.forename: Tiago
authors.initials: T
authors.lastname: Venâncio
authors.forename: Rose M
authors.initials: RM
authors.lastname: Carlos
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006632:Histamine / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D055668:Photochemical Processes; D011725:Pyridines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D012995:Solubility; D013057:Spectrum Analysis; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D008024:Ligands; D009942:Organometallic Compounds; D011725:Pyridines; D014867:Water; D012428:Ruthenium; D006632:Histamine; D000110:Acetylcholinesterase; C023666:pyridine