abstract
The inclusion compounds isolated from nonaqueous solutions of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) and the complexes [CpMoL(2)(CO)(2)](BF(4)) (L = MeCN, L(2) = 2,2'-biimidazole) were characterized in the solid state by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), (13)C {(1)H} CP/MAS NMR, and FTIR spectroscopy. Powder XRD showed that the compound with [CpMo(MeCN)(2)(CO)(2)](BF(4)) was amorphous, while that with [CpMo(H(2)biiM)(CO)(2)](BF(4)) was microcrystalline. The powder XRD pattern of the microcrystalline product could be satisfactorily indexed in the orthorhombic crystal system with space group P2(1)2(1)2(1) and final unit cell parameters of a = 28.489(3) angstrom, b = 19.198(2) angstrom, and c = 16.042(2) angstrom. A hypothetical structural model for the crystal packing was obtained through Monte Carlo optimizations using fixed DIMEB, [CpMo(H(2)biim)(CO)(2)](+), and BF(4)(-) geometries. In the final model the BF(4)(-) anions are housed inside the toroidal cavity of DIMEB and the organometallic complex cations are regularly distributed in between the DIMEB-tetrafluoroborate complexes, occupying the intermolecular void spaces. The cytotoxicity of the free complexes and the corresponding DIMEB adducts was tested against K1735-M2 mouse melanoma cells and H9c2 rat myoblast cells in aqueous solution. The MeCN complex and its corresponding DIMEB adduct showed no significant activity for use as chemotherapeutic agents. In contrast, the biimidazole complex exhibited significant cytotoxicity against K1735-M2 cells, especially for concentrations above 50 mu M, and the cytotoxicity was even higher when the DIMEB adduct was used. Epifluorescence microscopy indicated that mitochondrial alterations took place at an earlier time point than major changes in cell morphology.
keywords
MOLYBDENOCENE DICHLORIDE CP2MOCL2; CYCLODEXTRIN INCLUSION COMPLEXES; BETA-CYCLODEXTRIN; ALPHA-CYCLODEXTRIN; BREAST-CANCER; TITANOCENE DICHLORIDE; NIOBOCENE DICHLORIDE; CRYSTAL-STRUCTURES; MOLYBDOCENE DICHLORIDE; ANTICANCER COMPLEXES
subject category
Chemistry
authors
Pereira, CCL; Diogo, CV; Burgeiro, A; Oliveira, PJ; Marques, MPM; Braga, SS; Paz, FAA; Pillinger, M; Goncalves, IS
our authors
Filipe Alexandre Almeida Paz
Principal Researcher
Isabel Maria de Sousa Gonçalves
Associate Professor
Martyn Pillinger
Principal Researcher
acknowledgements
We are grateful to the FCT, POCI 2010, OE, and FEDER for funding (Project POCI/QUI/ 56109/2004). We also wish to acknowledge Prof. Joao Rocha for access to research facilities and Paula Esculcas for assistance in the NMR experiments. We are grateful to Celeste Azevedo for carrying out the TGA experiments and to Rosario Soares for collection of the powder diffraction data.