RESUMO
Eight rhenium(I) tricarbonyl aqua complexes with the general formula fac-[Re(CO)3(N,N'-bid)(H2O)][NO3] (1-8), where N,N'-bid is (2,6-dimethoxypyridyl)imidazo[4,5-f]1,10-phenanthroline (L1), (indole)imidazo[4,5-f]1,10-phenanthroline (L2), (5-methoxyindole)-imidazo[4,5-f]1,10-phenanthroline (L3), (biphenyl)imidazo[4,5-f]1,10-phenanthroline (L4), (fluorene)imidazo[4,5-f]1,10-phenanthroline (L5), (benzo[b]thiophene)imidazo[4,5-f]1,10-phenanthroline (L6), (5-bromothiazole)imidazo[4,5-f]1,10-phenanthroline (L7), and (4,5-dimethylthiophene)imidazo[4,5-f]1,10-phenanthroline (L8), were synthesized and characterized using 1H and 13C{1H} NMR, FT-IR, UV/Vis absorption spectroscopy, and ESI-mass spectrometry, and their purity was confirmed by elemental analysis. The stability of the complexes in aqueous buffer solution (pH 7.4) was confirmed by UV/Vis spectroscopy. The cytotoxicity of the complexes (1-8) was then evaluated on prostate cancer cells (PC3), showing a low nanomolar to low micromolar in vitro cytotoxicity. Worthy of note, three of the Re(I) tricarbonyl complexes showed very low (IC50 = 30-50 nM) cytotoxic activity against PC3 cells and up to 26-fold selectivity over normal human retinal pigment epithelial-1 (RPE-1) cells. The cytotoxicity of both complexes 3 and 6 was lowered under hypoxic conditions in PC3 cells. However, the compounds were still 10 times more active than cisplatin in these conditions. Additional biological experiments were then performed on the most selective complexes (complexes 3 and 6). Cell fractioning experiments followed by ICP-MS studies revealed that 3 and 6 accumulate mostly in the mitochondria and nucleus, respectively. Despite the respective mitochondrial and nuclear localization of 3 and 6, 3 did not trigger the apoptosis pathways for cell killing, whereas 6 can trigger apoptosis but not as a major pathway. Complex 3 induced a paraptosis pathway for cell killing while 6 did not induce any of our other tested pathways, namely, necrosis, paraptosis, and autophagy. Both complexes 3 and 6 were found to be involved in mitochondrial dysfunction and downregulated the ATP production of PC3 cells. To the best of our knowledge, this report presents some of the most cytotoxic Re(I) carbonyl complexes with exceptionally low nanomolar cytotoxic activity toward prostate cancer cells, demonstrating further the future viability of utilizing rhenium in the fight against cancer.
Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias da Próstata , Rênio , Humanos , Masculino , Complexos de Coordenação/química , Rênio/farmacologia , Rênio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
The aquation reactions of four rhenium(I) dicarbonyl complexes, [Re(CO)2(NN)(PR3)(Cl)], where NN = 1,10-phenanthroline (Phen) and 2,9-dimethyl-1,10-phenanthroline (DMPhen) and PR3 = 1,3,5-triaza-7-phosphaadamantane (PTA) and 1,4-diacetyl-1,3,7-triaza-5-phosphabicylco[3.3.1]nonane (DAPTA). Additionally, the anation reactions of the corresponding aqua complexes with Cl- were investigated. Single crystals of [Re(CO)2(DMPhen)(PTA)(Cl)]·DMF and [Re(CO)2(DMPhen)(DAPTA)(Cl)] were obtained, and their structures were determined using X-ray diffraction. The Re-Cl interatomic distances are 2.4991(13) and 2.4922(6) Å, respectively, indicating a mild trans influence effect of the phosphine ligands. The rate constants, kaq, for the aquation reactions of these complexes spanned a range of (3.7 ± 0.3) × 10-4 to (15.7 ± 0.3) × 10-4 s-1 with the two Phen complexes having rate constants that are 2.5 times greater than those of the DMPhen complexes at 298 K. Similarly, the second-order anation rate constants (kCl) of the resulting aqua complexes, [Re(CO)2(NN)(PR3)(H2O)]+, with Cl- ions at 298 K varied between (2.99 ± 0.05) × 10-3 and (6.79 ± 0.09) × 10-3 M-1 s-1. Likewise, these rate constants for the Phen complexes were almost 2 times faster than those of the DMPhen complexes. The pKa values of the four aqua complexes were determined to be greater than 9.0 for all of the complexes with [Re(CO)2(Phen)(PTA)(H2O)]+ having the highest pKa value of 9.28 ± 0.03. From the pKa values and the ratios of the aquation and anation rate contants, which give thermodynamic Cl- binding constants, the speciation of the rhenium(I) complexes in blood plasma, the cytoplasm, and the cell nucleus were estimated. The data suggest that the aqua complexes would be the dominant species in all three environments. This result may have important implications on the potential biological activity of these complexes.
Assuntos
Complexos de Coordenação/farmacologia , Complexos de Coordenação/farmacocinética , Rênio/farmacologia , Rênio/farmacocinética , Disponibilidade Biológica , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Cinética , Modelos Moleculares , Estrutura Molecular , Rênio/químicaRESUMO
A range of N,O-donor atom salicylidene complexes of the type fac-[M(O,N-Bid)(CO)3(L)](n) (O,N-Bid = anionic N,O-bidentate ligands; L = neutral coordinated ligand) have been studied. The unique feature of the complexes which crystallize in a monoclinic isostructural space group for complexes containing methanol in the sixth position (L = MeOH) is highlighted. The reactivity and stability of the complexes were evaluated by rapid stopped-flow techniques, and the methanol substitution by a range of pyridine type ligands indicates significant activation by the N,O-salicylidene type of bidentate ligands as observed from the variation in the second-order rate constants. In particular, following the introduction of the sterically demanding and electron rich cyclohexyl salicylidene moiety on the bidentate ligand, novel limiting kinetic behavior is displayed by all entering ligands, thus enabling a systematic probe and manipulation of the limiting kinetic constants. Clear evidence of an interchange type of intimate mechanism for the methanol substitution is produced. The equilibrium and rate constants (25 °C) for the two steps in the dissociative interchange mechanism for methanol substitution in fac-[Re(Sal-Cy)(CO)3(MeOH)] (5) by the pyridine type ligands 3-chloropyridine, pyridine, 4-picoline, and DMAP are k3 (s(-1)), 40 ± 4, 13 ± 2, 10.4 ± 0.7, and 2.11 ± 0.09, and K2 (M(-1)), 0.13 ± 0.01, 0.21 ± 0.03, 0.26 ± 0.02, and 1.8 ± 0.1, respectively.
Assuntos
Compostos Organometálicos/química , Cristalografia por Raios X , Cinética , Modelos Moleculares , Estrutura Molecular , Análise Espectral/métodosRESUMO
A series of fac-[Re(N,O'-Bid)(CO)3(L)] (N,O'-Bid = monoanionic bidentate Schiff-base ligands with N,O donor atoms; L = neutral monodentate ligand) has been synthesized, and the methanol substitution reactions have been investigated. The complexes were characterized by NMR, IR, and UV-vis spectroscopy. X-ray crystal structures of the compounds fac-[Re(Sal-mTol)(CO)3(HOCH3)], fac-[Re(Sal-pTol)(CO)3(HOCH3)], fac-[Re(Sal-Ph)(CO)3(HOCH3)], and fac-[Re(Sal-Ph)(CO)3(Py)] (Sal-mTol = 2-(m-tolyliminomethyl)phenolato; Sal-pTol = 2-(p-tolyliminomethyl)phenolato; Sal-Ph = 2-(phenyliminomethyl)phenolato; Py = pyridine) are reported. Significant activation for the methanol substitution is induced by the use of the N,O bidentate ligand as manifested by the second order rate constants, with limiting kinetics being observed for the first time. Rate constants (25 °C) (k1 or k3) and activation parameters (ΔHk, kJ mol(-1); ΔSk, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Re(Sal-mTol)(CO)3(HOCH3)] 3-chloropyridine: (k1) 2.33 ± 0.01 M(-1) s(-1); 85.1 ± 0.6, 48 ± 2; fac-[Re(Sal-mTol)(CO)3(HOCH3)] pyridine: (k1) 1.29 ± 0.02 M(-1) s(-1); 92 ± 2, 66 ± 7; fac-[Re(Sal-mTol)(CO)3(HOCH3)] 4-picoline: (k1) 1.27 ± 0.05 M(-1) s(-1); 88 ± 2, 53 ± 6; (k3) 3.9 ± 0.03 s(-1); 78 ± 8, 30 ± 27; (kf) 1.7 ± 0.02 M(-1) s(-1); 86 ± 2, 49 ± 6; fac-[Re(Sal-mTol)(CO)3(HOCH3)] DMAP (k3) 1.15 ± 0.02 s(-1); 88 ± 2, 52 ± 7. An interchange dissociative mechanism is proposed.
Assuntos
Compostos Organometálicos/química , Rutênio/química , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/síntese química , Bases de Schiff/química , Análise EspectralRESUMO
A steric parameter (θN-sub) is introduced to describe the steric bulk at the nitrogen atom on a range of PNP ligands used in ethylene tri- and tetramerization. This parameter was calculated for the free ligands and different metal complexes thereof and compared to catalytic data. A specific tendency is observed for the value of θN-sub and 1-hexene selectivity, and a slight increase in 1-octene selectivity is found with increased bulkiness of the substituents on the nitrogen atom.
Assuntos
Aminas/química , Etilenos/química , Teoria Quântica , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Estrutura MolecularRESUMO
The Re(I) centres of two Re(I)-tricarbonyl complexes, viz. tricarbonyl(pyridine-κN){5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olato-κ(2)N(1),O}rhenium(I), [Re(C23H21N4O)(CO)3], (I), and {5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olato-κ(2)N(1),O}tricarbonyl(pyridine-κN)rhenium(I), [Re(C28H23N6O)(CO)3], (II), are facially surrounded by three carbonyl ligands, a pyridine ligand and either a 5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olate [in (I)] or a 5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olate [in (II)] ligand, in a slightly distorted octahedral environment. The crystal structure of (I) is stabilized by two intermolecular C-H···O interactions and that of (II) is stabilized by three intermolecular C-H···O hydrogen-bonding interactions.
Assuntos
Complexos de Coordenação/química , Piridinas/química , Quinolinas/química , Rênio/química , Cristalografia por Raios X , Ligantes , Estrutura MolecularRESUMO
Water-soluble fac-[Re(CO)(3)(L,L'-Bid)(X)] (L,L'-Bid = tropolonato, X = H(2)O, methanol) complexes have been synthesized, and the aqua and methanol substitution reactions were investigated in water (pH range 6.3-10.0) and methanol, respectively, and compared. Thiocyanate ions were used as monodentate entering ligand. The complexes were characterized by UV-vis, IR, and NMR spectroscopy. The crystal structures of the complexes [NEt(4)] fac-[Re(Trop)(CO)(3)(H(2)O)].NO(3).H(2)O (reactant) and fac-[Re(CO)(3)(Trop)(Py)], a substitution product, are reported. Overall it was found that the aqua substitution of fac-[Re(CO)(3)(Trop)(H(2)O)] is about 10 times faster than the methanol substitution reaction for fac-[Re(CO)(3)(Trop)(MeOH)], with forward and reverse rate and stability constants [k(1) (M(-1) s(-1)), k(-1) (s(-1)), K(1), (M(-1))] for thiocyanate as monodentate entering ligand as follows: fac-[Re(CO)(3)(Trop)(H(2)O)] = 2.54 ± 0.03, 0.0077 ± 0.0005, 330 ± 22/207 ± 14 and fac-[Re(CO)(3)(Trop)(MeOH)] = 0.268 ± 0.002, 0.0044 ± 0.0002, (61 ± 3)/(52 ± 4). The activation parameters [ΔH()(k1) (kJ mol(-1)), ΔS()(k1) (J K(-1) mol(-1))] for the aqua and methanol complex respectively are 56.1 ± 0.7, -49 ± 2 and 64 ± 1, -43 ± 5.
Assuntos
Complexos de Coordenação/química , Metanol/química , Rênio/química , Água/química , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Cinética , Ligantes , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectrofotometria UltravioletaRESUMO
In the title compound, [Zr(C(11)H(10)NO)(4)]·2C(3)H(7)NO, the Zr(IV) ion is coordinated by four bidentate 5,7-dimethylquinolin-8-olate ligands in a slightly distorted square-anti-prismatic coordination environment. The asymmetric unit also contains two N,N'-dimethyl-formamide (DMF) solvent mol-ecules. In the crystal, a weak C-Hâ¯O hydrogen bond links the complex mol-ecule to a solvent mol-ecule and weak π-π stacking inter-actions [centroid-centroid distance = 3.671â (3)â Å] also occur. One of the DMF solvent mol-ecules was refined as disordered over three sets of sites, with refined occupancies in the ratio of 0.391â (9):0.342â (10):0.267â (7).
RESUMO
In the title compound, [Nb(CH(3)O)(2)(C(5)H(7)O(2))Cl(2)], a slightly distorted octa-hedral coordination geometry is observed around the Nb(V) atom with Nb-O distances in the range of 1.8254â (16)-2.0892â (16)â Å and Nb-Cl distances of 2.3997â (14) and 2.4023â (12)â Å. The O-Nb-O angles vary between 81.36â (7) and 172.65â (7) °, while the trans Cl-Nb-Cl angle is 167.34â (2)°. There are no hydrogen bonds observed.
RESUMO
The title compound, C(14)H(12)FNO, crystallizes as the trans phenol-imine tautomer. The two benzene rings are essentially coplanar, being inclined to one another by 9.28â (7)°. This is at least in part due to the intra-molecular O-Hâ¯N hydrogen bond between the hy-droxy O atom and the imine N atom. The crystal structure is stabilized by an array of weak C-Hâ¯O and C-Hâ¯F inter-actions, which link the mol-ecules into a stable three-dimensional network.
RESUMO
The title compound, [Pt(C29H29NP2)2](CF3SO3)2, consists of a Pt(II) atom, situated on an inversion centre, coordinated by two diphosphinoamine bidentate ligands and charge-balanced by two trifluoro-methane-sulfonate anions. The Pt(II) atom has a distorted square-planar geometry defined by the four P atoms. The distortion is illustrated by the P-Pt-P bite angle of 70.31â (4)°. The geometry around the N atom deviates from a trigonal-planar geometry, evidenced by the P-N-P bite angle of 102.3â (2) °. The N atom is displaced by 0.114â (4)â Å from the C/P/P plane. In order to coordinate, the orientation of the phenyl rings alters from a C(s) conformation to a C(2v) conformation. The cyclo-pentane ring is slightly twisted: the puckering parameters are q(2) = 0.420â (5)â Å and Ï = 26.5â (8) °. The trifluoro-methane-sulfonate anion displays a 0.511â (11):0.489â (11) positional disorder. Weak inter- and intra-molecular C-Hâ¯O hydrogen bonds influence the crystal packing.
RESUMO
In the title compound, [Ir(C(18)H(15)P)(2)(CO)(3)]PF(6)·CH(3)OH, the Ir(I) atom is coordinated by two triphenyl-phosphine ligands in axial sites and three carbonyl ligands in the equatorial plane of a fairly regular trigonal bipyramid: the equatorial C-Ir-C angles range from 115.45â (9) to 126.42â (10)°. The small deviations from the ideal tetra-hedral geometry around the P atoms are illustrated by C-P-C angles ranging from 104.08â (9) to 106.46â (9)°. In the crystal, the mol-ecules are linked by weak C-Hâ¯F, C-Hâ¯O and C-Hâ¯π inter-actions.
RESUMO
The title compound, fac-[Re(C(12)H(12)N(3))(CO)(3)]Br·0.5H(2)O, crystallizes with a cationic rhenium(I) unit, a bromide ion and half a water mol-ecule, situated on a twofold rotation axis, in the asymmetric unit. The Re(I) atom is facially surrounded by three carbonyl ligands and a tridentate bis-(pyridin-2-ylmeth-yl)amine ligand in a distorted octahedral environment. N-Hâ¯Br, O-Hâ¯Br, C-Hâ¯O and C-Hâ¯Br hydrogen bonds are present in the crystal structure and π-π stacking is also observed [centroid-centroid distances = 3.669â (1)â Å and 4.054â (1)â Å], giving rise to a three-dimentional network. The mol-ecules pack in a head-to-head fashion along the ac plane.
RESUMO
In the title salt, C(15)H(13)N(4)O(+)·NO(3) (-), an extensive network of N-Hâ¯N, N-Hâ¯O and C-Hâ¯O hydrogen-bond inter-actions are observed throughout the structure. Further stabilization is obtained by π-π stacking inter-actions between inversion-related quinoline systems and inversion-related pyridine rings, with respective centroid-centroid distances of 3.5866â (6) and 3.3980â (6)â Å.
RESUMO
In the title compound, C(20)H(18)N(4)O(2), the dihedral angles between the central benzene ring and the pyridine rings are 57.55â (6) and 22.05â (8)°. The mol-ecular conformation is stabilized by intra-molecular N-Hâ¯N inter-actions and in the crystal structure an inter-molecular asymmetric cyclic hydrogen-bonding association involving both amide N-H donors and a common amide O-atom acceptor gives a chain extending along the c axis.
RESUMO
A range of fac-[Re(CO)(3)(L,L'-Bid)(H(2)O)](n) (L,L'-Bid = neutral or monoanionic bidentate ligands with varied L,L' donor atoms, N,N', N,O, or O,O': 1,10-phenanthroline, 2,2'-bipydine, 2-picolinate, 2-quinolinate, 2,4-dipicolinate, 2,4-diquinolinate, tribromotropolonate, and hydroxyflavonate; n = 0, +1) has been synthesized and the aqua/methanol substitution has been investigated. The complexes were characterized by UV-vis, IR and NMR spectroscopy and X-ray crystallographic studies of the compounds fac-[Re(CO)(3)(Phen)(H(2)O)]NO(3)·0.5Phen, fac-[Re(CO)(3)(2,4-dQuinH)(H(2)O)]·H(2)O, fac-[Re(CO)(3)(2,4-dQuinH)Py]Py, and fac-[Re(CO)(3)(Flav)(CH(3)OH)]·CH(3)OH are reported. A four order-of-magnitude of activation for the methanol substitution is induced as manifested by the second order rate constants with (N,N'-Bid) < (N,O-Bid) < (O,O'-Bid). Forward and reverse rate and stability constants from slow and stopped-flow UV/vis measurements (k(1), M(-1) s(-1); k(-1), s(-1); K(1), M(-1)) for bromide anions as entering nucleophile are as follows: fac-[Re(CO)(3)(Phen)(MeOH)](+) (50 ± 3) × 10(-3), (5.9 ± 0.3) × 10(-4), 84 ± 7; fac-[Re(CO)(3)(2,4-dPicoH)(MeOH)] (15.7 ± 0.2) × 10(-3), (6.3 ± 0.8) × 10(-4), 25 ± 3; fac-[Re(CO)(3)(TropBr(3))(MeOH)] (7.06 ± 0.04) × 10(-2), (4 ± 1) × 10(-3), 18 ± 4; fac-[Re(CO)(3)(Flav)(MeOH)] 7.2 ± 0.3, 3.17 ± 0.09, 2.5 ± 2. Activation parameters (ΔH(k1)(++), kJmol(-1); ΔS(k1)(), J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Re(CO)(3)(Phen)(MeOH)](+) iodide 70 ± 1, -35 ± 3; fac-[Re(CO)(3)(2,4-dPico)(MeOH)] bromide 80.8 ± 6, -8 ± 2; fac-[Re(CO)(3)(Flav)(MeOH)] bromide 52 ± 5, -52 ± 15. A dissociative interchange mechanism is proposed.
Assuntos
Compostos Organometálicos/síntese química , Compostos Radiofarmacêuticos/síntese química , Rênio/química , 2,2'-Dipiridil/química , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/química , Cristalografia por Raios X , Cinética , Ligantes , Espectroscopia de Ressonância Magnética , Metanol/química , Modelos Moleculares , Estrutura Molecular , Fenantrolinas/química , Ácidos Picolínicos/química , Espalhamento a Baixo Ângulo , Termodinâmica , Água/química , Difração de Raios XRESUMO
In the title compound, [RhCl(3)(CH(3)CN)(C(18)H(21)P)(2)]·2CH(3)CN, the complex mol-ecule lies on a twofold rotation axis that passes through the Rh(III) atom, one Cl atom, and the C and N atoms of the coordinated acetonitrile mol-ecule. The Rh(III) atom is coordinated by two P atoms in trans positions, three Cl atoms and an acetonitrile mol-ecule in a distorted octa-hedral geometry. Intra-molecular C-Hâ¯Cl inter-actions are observed. The uncoordinated acetonitrile mol-ecule is disordered over two sites with occupancies of 0.588â (4) and 0.412â (4).
RESUMO
The binuclear molecule of the title compound, [Hf(2)(C(10)H(6)F(3)O(2))(6)(OH)(2)]·2C(3)H(7)NO, lies across an inversion centre and contains a Hf(IV) atom which is eight-coordinated and surrounded by three chelating ß-diketonato tris-(4,4,4-trifluoro-1-phenyl-acetyl-acetonate (tfba(-)) ligands and two bridging OH(-) groups in a distorted square-anti-prismatic geometry. The Hf-O bond lengths vary from 2.073â (2) to 2.244â (2)â Å and the O-Hf-O bite angles vary from 73.49â (9) to 75.60â (9)°. Weak O-Hâ¯O hydrogen-bonding inter-actions are observed between the bridging hy-droxy groups and the dimethylformamide solvent mol-ecules. The unit cell contains solvent-accessible voids of 131â Å(3), but the residual electron density in the difference Fourier map suggests no solvent mol-ecule occupies this void.
RESUMO
In the title compound, [Hf(C(11)H(10)NO)(4)]·2C(3)H(7)NO, the Hf(IV) atom is coordinated by four N,O-donating bidentate 5,7-dimethyl-8-quinolino-late (Ox(-)) ligands arranged to give a distorted square-anti-prismatic coordination polyhedron. The average Hf-O and Hf-N distances are 2.098 and 2.298â Å, respectively, and the average O-Hf-N bite angle is 70.2°. The crystal packing is controlled by π-π inter-actions between Ox(-) ligands of neighbouring mol-ecules, giving rise to a three-dimensional supra-molecular grid network. The inter-planar distances vary from 3.441â (1) to 3.509â (1)â Å, while the centroid-centroid distances vary from 3.688â (2) to 3.759â (12)â Å. A non-classical C-Hâ¯O hydrogen bond is observed between the complex and one of the solvate mol-ecules.
RESUMO
In the title compound, C(28)H(27)NP(2), the N atom adopts an almost planar geometry with the two P atoms and the C atom attached to it, with a distance of 0.066â (2)â Å between the N atom and the C/P/P plane. The distorted trigonal-pyramidal geometry of the N atom is further illustrated by bond angles ranging between 115.22â (11) and 123.53â (8)°. Bond angles varying from 99.99â (9) to 108.07â (9) ° are indicative of the distorted pyramidal environment around the P atoms. An intra-molecular C-Hâ¯P hydrogen bond occurs. In the crystal, inter-molecular C-Hâ¯π inter-actions link the mol-ecules into a supra-molecular network.