ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[OsIVCl4(Hazole)2]

View Author Information
University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria
Cite this: Inorg. Chem. 2011, 50, 16, 7690–7697
Publication Date (Web):July 8, 2011
https://doi.org/10.1021/ic200728b

Copyright © 2011 American Chemical Society. This publication is licensed under these Terms of Use.

  • Open Access

Article Views

1706

Altmetric

-

Citations

LEARN ABOUT THESE METRICS
PDF (1 MB)
Supporting Info (2)»

Abstract

By controlled Anderson type rearrangement reactions complexes of the general formula trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-indazole tautomer stabilization in trans-[OsIVCl4(2H-indazole)2] is unprecedented in coordination chemistry of indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H2ind)[RuIIICl4(Hind)2], where Hind = 1H-indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[OsIVCl4(Hpz)2] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV–vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported.

Synopsis

The synthesis of complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1 H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole, potential precursors for the synthesis of osmium(III) analogues of KP1019, is described. In addition, the isolation of an adduct of trans-[Os IVCl4(Hpz)2] with cucurbit[7]uril is reported. The compounds were characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV−vis, NMR), cyclic voltammetry and X-ray crystallography, and studied for cytotoxicity in three human cancer cell lines (CH1, A549 and SW480).

Introduction

ARTICLE SECTIONS
Jump To

In the past six years several research groups reported on the synthesis and screening for antiproliferative activity in vitro of osmium coordination compounds and osmium(II)-arene species, (1-3) as well as on studies of their reactivity with DNA model compounds. (4) These investigations showed that osmium is another metal that deserves attention for the development of effective inorganic antitumor drugs. Osmium analogues that are equipotent to their ruthenium congeners have the advantage of being more inert under conditions relevant for drug formulation. (2c) Of particular academic interest are also the observed or established differences between ruthenium and osmium compounds in stabilization of higher oxidation states, magnitude of spin–orbit coupling, metal–ligand exchange reactions, and so forth. (5-8)
In pursuing the goal of establishing structure-cytotoxicity relationships for osmium-azole-chlorido series and creating active metal-based antitumor drugs, we already reported the synthesis of trans-[OsIIICl2(Hazole)4]Cl, cis-[OsIIICl2(Him)4]Cl, and mer-[OsIIICl3(Hazole)3]. (3b, 9, 10) Compounds of the last type were insoluble in water, rendering tests for antiproliferative activity in vitro impossible, while trans-[OsIIICl2(Hazole)4]Cl showed noteworthy antiproliferative effects in the cell lines A549 (nonsmall cell lung cancer), CH1 (ovarian carcinoma), and SW480 (colon carcinoma), with IC50 values in the 10–6 to 10–5 M concentration range. (3b)trans-[OsIIICl2(Hpz)4]Cl was found to be more active than the ruthenium counterpart, whereas the osmium(III) imidazole complex was less cytotoxic than the ruthenium analogue in all three cell lines.
Quite recently, Anderson type rearrangement reactions (11) of (H2azole)2[OsIVCl6] in alcohols in the presence of tetrabutylammonium chloride enabled the synthesis of the next family of compounds, namely, (n-Bu4N)[OsIVCl5(Hazole)], where Hazole = 1H-pyrazole, 1H-indazole, 1H-imidazole, 1H-benzimidazole, or 1H,2,4-triazole. (5) The (n-Bu4N)+ was also substituted by biologically relevant or nontoxic cations such as Na+ and (H2azole)+. Comparison of these osmium complexes with related ruthenium analogues, such as (H2azole)2[RuIIICl5(Hazole)] (12-15) and (H2azole)[Ru IIICl4(Hazole)2] (14) showed a clear preference for higher oxidation states of the heavier congener. The efficacy of the observed transformation is dependent on the electron-donating potency of the azole heterocycle and the solvent used. A deeper substitution at osmium(IV) was first observed in the case of imidazole and benzimidazole ligands with highest basicity and further investigated for other azole heterocycles.
In this paper, we report on the synthesis, X-ray diffraction studies, and spectroscopic characterization of osmium(IV) complexes, namely, trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole. Of these compounds the osmium indazole complex is the first example in which the ortho-quinoid tautomer is stabilized upon coordination to the transition metal ion. The cytotoxic activity of all complexes has been assessed in three human cancer cell lines originating from different solid malignancies, namely, CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma). In addition, attempts to encapsulate the complexes prepared into the macrocyclic host molecule cucurbit[7]uril are also described (Chart 1).

Chart 1

Chart 1. Compounds Reported in This Worka

Chart aAll complexes have been characterized by X-ray crystallography; atom labeling was introduced for assignments of resonances in NMR spectra.

Experimental Section

ARTICLE SECTIONS
Jump To

Materials

The starting compounds [(DMSO)2H]2[OsCl6] and (H2azole)2[OsCl6] (Hazole = Hpz, Him, Hind, Hbzim) were synthesized as previously reported in the literature. (3b, 16, 17) OsO4 (99.8%) and N2H4·2HCl were purchased from Johnson Matthey and Fluka, respectively. 1H-Pyrazole, 1H-indazole, 1H-imidazole, 1H-benzimidazole, and 1-hexanol were from Aldrich and Fluka. All these chemicals were used without further purification. trans-[OsCl4(Hazole)2] (Hazole = Hpz, Him, Hbzim) complexes were prepared under argon atmosphere using standard Schlenk techniques. The synthesis of trans-[OsCl4(2H-ind)2] was performed in the solid state in an evacuated glass oven. Cucurbit[7]uril was generously offered by Marcel Wieland, Institute of Organic Chemistry, University of Vienna.

trans-[OsCl4(Hpz)2] (1)

A suspension of (H2pz)2[OsCl6] (100 mg, 0.18 mmol) in 1-hexanol (2 mL) was stirred at 160 °C for 2 h. The red precipitate formed was filtered off, washed with ethanol and dried in vacuo. Yield: 40 mg, 47%. Anal. Calcd for C6H8Cl4N4Os·0.1C2H5OH (Mr = 472.80 g/mol): C, 15.75; H, 1.83; N, 11.85. Found: C, 15.99; H, 1.59; N, 11.53. ESI-MS in MeOH (negative): m/z 332 [OsCl4], 467 [OsCl4(Hpz)2–H], ESI-MS in MeOH (positive): m/z 491 [OsCl4(Hpz)2+Na]+, 513 [OsCl4(Hpz)2+2Na–H]+. EI-MS (positive): m/z 192 [Os]+, 329 [OsCl2(Hpz)]+, 364 [OsCl3(Hpz)]+, 432 [OsCl3(Hpz)2]+, 467 [OsCl4(Hpz)2]+•. MIR, cm–1: 570, 593, 529, 662, 775, 904, 1052, 1072, 1113, 1165, 1263, 1345, 1398, 1482, 1507, 2014, 2166, 2363, and 3331. FIR, cm–1: 159, 178, 265, 287, 325, 345, 571. UV–vis (MeOH), λmax, nm (ε, M–1 cm–1): 215 (11884), 245 (5 898), 277 sh (2578), 350 sh (4796), 382 (7981). UV–vis (DMSO), λmax, nm (ε, M–1 cm–1): 350 sh (5576), 385 (8404). 1H NMR (DMSO-d6, 500.32 MHz): δ −5.59 (d, 1H, J = 2.40 Hz, H3), −2.97 (s, 1H, H5), 6.48 (brs, 1H, H4), 19.21 (s, 1H, H1) ppm. 13C{1H} NMR (DMSO-d6, 125.81 MHz): δ 73.52 (C4), 181.14 (C5), 218.41 (C3) ppm. 15N NMR (DMSO-d6, 50.69 MHz): δ 115.5 (N1) ppm. Suitable crystals for X-ray diffraction study were grown from a solution of 1 in acetone.

trans-[OsCl4N1-2H-ind)2] (2)

(H2ind)2[OsCl6] (166 mg, 0.25 mmol) was heated in the solid state at 150 °C in a glass oven for 45 h. The black product was extracted with methanol in a Soxhlet extractor for 24 h. The dark blue residue collected as a solid from the extraction thimble was recrystallized from dimethylformamide (DMF). Yield: 28 mg, 19%. Anal. Calcd for C14H12Cl4N4Os (Mr = 568.31 g/mol): C, 29.59; H, 2.13; N, 9.86. Found: C, 29.52; H, 2.14; N, 9.52. ESI-MS in MeOH (negative): m/z 567 [OsCl4(Hind)2–H]. MIR, cm–1: 591, 626, 734, 752, 838, 863, 895, 980, 1084, 1131, 1174, 1234, 1314, 1362, 1387, 1440, 1485, 1511, 1620, 1665, 3108, and 3346. FIR, cm–1: 157, 181, 194, 217, 249, 262, 310, 324, 334, 429, 459, 550, 595, and 627. UV–vis (DMF), λmax, nm (ε, M–1 cm–1): 283 (9539), 362 (9194), 459 sh (2342), 491 (2767), 628 (12055). UV–vis (DMSO), λmax, nm (ε, M–1 cm–1): 265 (9658), 289 (9025), 369 (7785), 619 (12978). 1H NMR (DMSO-d6, 500.32 MHz): δ −4.44 (s, 1H), −3.28 (s, 1H), 0.58 (d, 1H, J = 8.51 Hz), 5.18 (s, 1H), 13.68 (s, 1H) ppm. Suitable crystals for X-ray diffraction study were grown from a solution of 2 in DMF.

trans-[OsCl4(Him)2] (3)

A suspension of (H2im)2[OsCl6] (100 mg, 0.18 mmol) in 1-hexanol (2 mL) was stirred at 160 °C for 6 h. The brown precipitate formed was filtered off, washed with methanol and diethyl ether, and dried in vacuo. Yield: 37 mg, 44%. Anal. Calcd for C6H8Cl4N4Os (Mr = 468.20 g/mol): C, 15.39; H, 1.72; N, 11.97. Found: C, 15.70; H, 1.56; N, 11.65. ESI-MS in MeOH (negative): m/z 468 [OsCl4(Him)2–H], 934 [{OsCl4(Him)}2–H], ESI-MS in MeOH (positive): m/z 490 [OsCl4(Him)2+Na]+, 956 [{OsCl4(Him)2}2+Na]+. MIR, cm–1: 584, 604, 641, 682, 738, 830, 1065, 1119, 1503, 2041, 2351, and 3359. FIR, cm–1: 147, 178, 271, 281, 316, 343, 605, 643. UV–vis (MeOH), λmax, nm (ε, M–1 cm–1): 251 sh (2696), 280 (1967), 343 (5838), 374 (6458), 452 (1011). UV–vis (DMSO), λmax, nm (ε, M–1 cm–1): 344 (7209), 374 (7045), 450 sh (1422). 1H NMR (DMSO-d6, 500.32 MHz): δ −0.51 (s, 1H), 7.29 (s, 1H), 7.86 (s, 1H), 12.29 (s, 1H1) ppm. 13C{1H} NMR (DMSO-d6, 125.81 MHz): δ 119.52 {7.29}, 114.45 {7.86}, 188.36 {−0.51} ppm. 15N NMR (DMSO-d6, 50.69 MHz): δ 157.08 (N1) ppm. Suitable crystals of 3·2DMSO for X-ray diffraction study were grown from a solution of 3 in dimethylsulfoxide (DMSO).

trans-[OsCl4(Hbzim)2] (4)

A suspension of (H2bzim)2[OsCl6] (200 mg, 0.31 mmol) in 1-hexanol (3 mL) was stirred at 160 °C for 8 h. The blue precipitate formed was filtered off, washed with methanol and diethyl ether, and dried in vacuo. Yield: 146 mg, 82%. Anal. Calcd for C14H12Cl4N4Os (Mr = 568.31 g/mol): C, 29.59; H, 2.13; N, 9.86. Found: C, 29.64; H, 1.90; N, 9.68. ESI-MS in MeOH (negative): m/z 331 [OsCl4], 448 [OsCl4(Hbzim)–H], 567 [OsCl4(Hbzim)2–H]. MIR, cm–1: 591, 658, 689, 733, 775, 988, 1117, 1246, 1422, 1490, 1945, 2018, 2150, 2189, 2235, 2364, and 3338. FIR, cm–1: 161, 320, 349, 643. UV–vis (DMSO), λmax, nm (ε, M–1 cm–1): 354 sh (6318), 373 (6176), 454 (3362), 513 (4075). 1H NMR (DMSO-d6, 500.32 MHz): δ −5.58 (s, 1H, H2), 4.58 (d, 1H, J = 8.17 Hz, H4 or 7), 5.55 (t, 1H, J = 7.27 Hz, H5 or 6), 6.71 (d, 1H, J = 8.18 Hz, H4 or 7), 6.74 (t, 1H, J = 7.26 Hz, H5 or 6), 9.00 (s, 1H, H1) ppm. 13C{1H} NMR (DMSO-d6, 125.81 MHz): δ 114.64 (C8 or 9), 122.64 {6.71} (C4 or 7), 127.45 {6.74} (C5 or 6), 133.73 {4.58} (C4 or 7), 135.48 {5.55} (C5 or 6), 159.43 (C8 or 9), 200.46 (C2) ppm. Suitable crystals for X-ray diffraction study were grown from a solution of 4 in DMSO.

trans-[OsCl4(Hpz)2]·cucurbit[7]uril·11.25H2O (5·11.25H2O)

A suspension of 1 (4 mg, 0.009 mmol) and cucurbit[7]uril (10 mg, 0.009 mmol) in water (3 mL) was heated at 100 °C for 2.5 h in a closed Schlenk vial. The hot solution was filtered. Suitable crystals of 5·11.25H2O for X-ray diffraction study were grown from the filtrate at room temperature over 24 h.

Physical Measurements

Elemental analyses were performed by the Microanalytical Laboratory of the Faculty of Chemistry of the University of Vienna. MIR spectra were obtained by using an ATR unit with a Perkin-Elmer 370 FTIR 2000 instrument (4000–400 cm–1). FIR spectra were recorded on the same instrument in transmission mode using CsI pellets. UV–vis spectra were recorded on a Perkin-Elmer Lambda 20 UV–vis spectrophotometer using samples dissolved in DMSO, DMF, methanol, or water containing 1% DMSO. Electrospray ionization mass spectrometry was carried out with a Bruker Esquire 3000 instrument (Bruker Daltonics, Bremen, Germany) by using methanol as solvent. Electron impact mass spectrometry was carried out on a Finnigan MAT95 mass spectrometer. Expected and measured isotope distributions were compared. Cyclic voltammogramms were measured in a three-electrode cell using a 2 mm diameter glassy carbon disk working electrode, a platinum auxiliary electrode, and an Ag|Ag+ reference electrode containing 0.1 M AgNO3. Measurements were performed at room temperature using a EG&G PARC potentiostat/galvanostat model 273A. Deareation of solutions was accomplished by passing a stream of argon through the solution for 5 min prior to the measurement and then maintaining a blanket atmosphere of argon over the solution during the measurement. The potentials were measured in 0.2 M (n-Bu4N)[BF4]/DMSO using [Fe(η5-C5H5)2] (E1/2ox = +0.68 V vs NHE) (18) as internal standard and are quoted relative to NHE. Thermogravimetry was performed under nitrogen atmosphere on a Mettler Toledo TGA/SDTA851 instrument. The 1H, 13C and 15N NMR spectra were recorded at 500.32, 125.81, and 50.69 MHz on a Bruker DPX500 (Ultrashield Magnet) in DMSO-d6. 2D 13C,1H HSQC, 15N,1H HSQC, 13C,1H HMBC and 1H,1H COSY experiments were performed for 1, 3, and 4, while a homonuclear decoupling experiment only for 1.

Crystallographic Structure Determination

X-ray diffraction measurements were performed on a Bruker X8 APEXII CCD diffractometer. Single crystals were positioned at 35, 35, 40, 40, and 50 mm from the detector, and 1150, 1200, 3557, 1758, and 1569 frames were measured, each for 30, 80, 20, 30, and 60 s over 1° scan width for 1, 2, 3·2DMSO, 4, and 5·11.25H2O, correspondingly. The data were processed using the SAINT software. (19) The structures were solved by direct methods and refined by full-matrix least-squares techniques. Non-H atoms were refined with anisotropic displacement parameters. H atoms were inserted in calculated positions and refined with a riding model. The following software programs and computer were used: structure solution, SHELXS-97; (20) refinement, SHELXL-97; (21) molecular diagrams, ORTEP-3; (22) computer, Intel CoreDuo. Crystal data, data collection parameters, and structure refinement details for 1, 2, 3·2DMSO, 4, and 5·11.25H2O are given in Table 1.

Cell Lines and Culture Conditions

CH1 (ovarian carcinoma, human) cells were a gift from Lloyd R. Kelland (CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, U.K.). A549 (nonsmall cell lung cancer, human) and SW480 (colon carcinoma, human) cells were kindly provided by Brigitte Marian (Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Austria). Cells were grown in 75 cm2 culture flasks (Iwaki/Asahi Technoglass) as adherent monolayer cultures in Minimal Essential Medium (MEM) supplemented with 10% heat-inactivated fetal bovine serum, 1 mM sodium pyruvate, and 2 mM l-glutamine (all purchased from Sigma-Aldrich) without antibiotics. Cultures were maintained at 37 °C in a humidified atmosphere containing 5% CO2 and 95% air.
Table 1. Crystal Data and Details of Data Collection for 1, 2, 3·2DMSO, 4, and 5·11.25H2O
 123·2DMSO45·11.25H2O
empirical formulaC6H8Cl4N4OsC14H12Cl4N4OsC10H20Cl4N4O2OsS2C14H12Cl4N4OsC48H72.5Cl4N32O25.25Os
fw468.16568.28624.42568.281833.88
space groupPP21/cP21/cP21/cPca21
a [Å]6.5110(4)9.925(3)9.2546(3)9.8508(3)31.5673(9)
b [Å]7.1695(5)12.022(3)14.6087(5)12.1309(4)16.9392(6)
c [Å]7.4983(5)6.9802(15)7.6323(3)6.9496(2)14.3896(5)
α [deg]115.562(4)    
β [deg]110.932(4)108.128(11)99.294(2)108.036(2) 
γ [deg]92.719(4)    
V3]286.36(3)791.5(3)1018.32(6)789.66(4)7694.5(4)
Z12224
λ [Å]0.710730.710730.710730.710730.71073
ρcalcd [g cm–3]2.7152.3842.0362.3901.583
crystal size [mm3]0.20 × 0.06 × 0.040.20 × 0.06 × 0.010.50 × 0.25 × 0.030.44 × 0.20 × 0.020.20 × 0.18 × 0.04
T [K]100100100100100
μ [mm–1]12.0358.7327.0018.7531.890
R1a0.02370.03130.02050.01840.0486
wR2b0.05520.07290.04620.04500.1310
GOFc1.0710.9491.0671.0901.050
a

R1 = ∑∣∣Fo∣ – ∣Fc∣∣/∑∣Fo∣.

b

wR2 = {∑w(Fo2Fc2)2/∑w(Fo2)2}1/2.

c

GOF = {∑[w(Fo2Fc2)2]/(np)}1/2, where n is the number of reflections and p is the total number of parameters refined.

Cytotoxicity in Cancer Cell Lines

Cytotoxicity in the cell lines mentioned above was determined by the colorimetric MTT assay (MTT = 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, purchased from Fluka). For this purpose, cells were harvested from culture flasks by trypsinization and seeded in 100 μL/well aliquots in MEM supplemented with 10% heat-inactivated fetal bovine serum, 1 mM sodium pyruvate, 4 mM l-glutamine, and 1% nonessential amino acids (100 × stock solution) into 96-well microculture plates (Iwaki/Asahi Technoglass) in the following densities to ensure exponential growth of untreated controls throughout the experiment: 1.5 × 103 (CH1), 4.0 × 103 (A549), and 2.5 × 103 (SW480) viable cells per well. Cells were allowed to settle and resume proliferation for 24 h and were then exposed to the test compounds by addition of 100 μL/well aliquots of appropriate dilutions in the same medium. For this purpose, compounds were dissolved in DMSO first and diluted in medium such that the effective DMSO content did not exceed 0.5% whenever necessary. After exposure for 96 h, the medium was replaced by 100 μL/well RPMI 1640 medium (supplemented with 10% heat-inactivated fetal bovine serum and 4 mM l-glutamine) plus 20 μL/well solution of MTT in phosphate-buffered saline (5 mg/mL) (all purchased from Sigma-Aldrich). After incubation for 4 h, medium/MTT mixtures were removed, and the formazan precipitate formed by viable cells was dissolved in DMSO (150 μL/well). Optical densities at 550 nm (corrected for unspecific absorbance at 690 nm) were measured with a microplate reader (Tecan Spectra Classic) to yield relative quantities of viable cells as percentage of untreated controls, and 50% inhibitory concentrations (IC50) were calculated by interpolation. Evaluation is based on at least two (in case of inactivity) or three independent experiments, each comprising triplicate samples.

Results and Discussion

ARTICLE SECTIONS
Jump To

Synthesis

By exploring further the Anderson type rearrangement reactions, which already enabled the synthesis of (azole)pentachloridoosmate(IV) complexes, (5) we obtained trans-bis(azole)tetrachloridoosmium(IV) complexes following the reaction scheme:
The reactions were performed in suspensions of the starting compounds (H2azole)2[OsIVCl6], where Hazole = 1H-pyrazole, 1H-imidazole, and 1H-benzimidazole, in 1-hexanol at 160 °C to yield 1, 3, and 4. The indazole product 2 was obtained by heating the indazolium hexachloridoosmate(IV) in the solid state at 150 °C. The liberation of two molecules of hydrochloric acid was followed by thermogravimetric analysis and the formation of bis-azole complexes by NMR spectroscopy. The trans-[OsIVCl4(Hazole)2] complexes can also be prepared starting from (H2azole)[OsIVCl5(Hazole)] providing further evidence for Anderson type rearrangement reaction in the solid state (Supporting Information, Figure S1). The complexes 14 were synthesized in yields ranging from 19 to 82%. It is worth noting that in the case of indazole the only product isolated was trans-[OsIVCl4(2H-ind)2]. All four compounds are nonelectrolytes and hence show poor solubility in aqueous media. Therefore, attempts to encapsulate them in a cucurbit[7]uril host molecule to improve the aqueous solubility and use the latter as a vehicle for drug delivery (23) to the cell, as reported for platinum (24, 25) and metallocene (26) anticancer agents, have been undertaken. However, instead of inclusion complexes adduct 5 resulted from reaction of 1 with cucurbit[7]uril, as described for other metal chlorido complexes. (27-30)

Crystal Structures

The results of X-ray diffraction studies of complexes 1, 2, 3·2DMSO, 4, and 5·11.25H2O are shown in Figures 1 and 2, respectively. Selected bond lengths and angles are quoted in Table 2. To our knowledge 14 are the first bis(azole)tetrachloridoosmium(IV) complexes characterized by X-ray crystallography as individual compounds.

Figure 1

Figure 1. ORTEP view of [OsIVCl4(Hpz)2] (1), [OsIVCl4(Hind)2] (2), [OsIVCl4(Him)2] in 3·2DMSO, and [OsIVCl4(Hbzim)2] (4). Thermal ellipsoids are drawn at 50% probability level.

Complex 1 crystallized in the triclinic centrosymmetric space group P1̅, while compounds 2, 3·2DMSO, and 4 crystallized in the monoclinic space group P21/c. There is one molecule of 1 and two molecules of 24 in the corresponding unit cells. In addition, complex 3 contains one molecule of cocrystallized DMSO per asymmetric unit. The osmium ion in all four complexes lies on a center of symmetry, and the centrosymmetric molecules are of point group symmetry Ci. The osmium atom displays distorted octahedral coordination geometry with four chlorido ligands in the equatorial positions and two azole ligands bound axially. Comparison of the bond lengths in the coordination environment of osmium in 14 shows (Table 2) that the longer the axial bonds, the shorter are the equatorial ones.
Table 2. Selected Bond Lengths (Å) and Angles (deg) in the Coordination Polyhedron of Osmium(IV) in 14
 123·2DMSO4
Atom1–Atom2
Os–N12.059(5)2.050(5)2.069(2)2.073(2)
Os–Cl12.3301(14)2.3439(16)2.3381(6)2.3250(7)
Os–Cl22.3326(14)2.3395(15)2.3139(6)2.3280(7)
Atom1–Atom2–Atom3
Cl1–Os–Cl290.58(5)90.22(6)89.67(2)88.75(3)
N1–Os–Cl190.03(14)91.73(15)90.34(6)90.47(7)
N1–Os–Cl289.16(14)89.32(15)89.41(6)90.13(7)
Both trans-azole ligands in 14 lie in one plane in contrast to what was found in (Ph4P)[trans-RuIIICl4(1H-ind)2], where the 1H-indazole ligands are significantly twisted. (31) The plane through both azole ligands crosses the equatorial plane between chloride ligands, the torsion angles ΘCl1–Os–N1–N2, ΘCl2–Os–N2–N1, ΘCl1–Os–N1–C2, and ΘCl1–Os–N1–C1 being −30.4(4), −33.2(6), −31.6(2), and −47.8(2)°, respectively.
Of particular interest is the structure of indazole derivative 2 (Figure 1), in which the indazole is stabilized in a quinoid tautomeric form coordinating to osmium via nitrogen atom N1. This mode of coordination has not been documented for any transition metal yet. Indazole acts mainly as a monodentate neutral ligand in metal complexes binding to metal ions via N2. In a few cases, it was found to be deprotonated, acting as a bridging ligand in polynuclear metal complexes (32) or even more rarely as a monodentate indazolate ligand coordinated via N1 or N2. (3e, 33)
The molecules of 1 in the crystal structure form a chain running almost parallel to axis a (Supporting Information, Figure S2). Hydrogen bonding interactions between the pyrazole nitrogen atom N2 as a proton donor and chloride ligand Cl2i as a proton acceptor are evident [N2···Cl2i 3.270, N2–H 0.88, H···Cl2i 2.511 Å, N2–H···Cl2i 144.86°; symmetry code i: x – 1, y, z]. The unit cell packing diagram for 2 is shown in Supporting Information, Figure S3. A bifurcated hydrogen bond between N2 as proton donor and chloride ligands Cl1i and Cl2ii as proton acceptors is present in the crystal structure [N2···Cl1i 3.444, N2···Cl2ii 3.143 Å]. In addition, stacking interaction between indazole ligands of neighboring molecules of 2 is also evident. The interplanar separation is about 3.4 Å (Supporting Information, Figure S4). Intermolecular hydrogen bonding interaction between the imidazole nitrogen N4 and the oxygen atom O1i (2.698 Å) of cocrystallized DMSO is shown in Supporting Information, Figure S5. A bifurcated hydrogen bonding interaction between atom N2 of benzimidazole ligand in one molecule with chloride ligands Cl1i and Cl2ii of two adjacent molecules of 4 [N2···Cl1i 3.541, N2···Cl2ii 3.504 Å], along with π–π* stacking interactions between heteroaromatic rings separated at about 3.4 Å are displayed in Supporting Information, Figure S6.
In contrast to 14, trans-[OsIVCl4(Hpz)2]·cucurbit[7]uril (5·11.25H2O) crystallizes in a noncentrosymmetric orthorhombic space group Pca21. The result of X-ray diffraction study of this complex is shown in Figure 2. The bond lengths Os–N1 and Os–N6 of 2.076(7) and 2.077(7) Å, respectively, along with Os–Cl1, Os–Cl2, Os–Cl3, and Os–Cl4 [2.386(2), 2.357(2), 2.382(2) and 2.386(2), correspondingly] are significantly longer than the Os–N1, Os–Cl1, and Os–Cl2 bond lengths in 1 (Table 2). The atom N2 is involved in a hydrogen bond N2–H···Cl3i with the following geometrical parameters: N2···Cl3i 3.242 Å, N2–H···Cl3i 133.6°, while atom N7 forms a hydrogen bond with a cocrystallized water molecule [N7···O11 2.899 Å, N7–H···O11 133.6°].

Figure 2

Figure 2. ORTEP view of trans-[OsIVCl4(Hpz)2]·cucurbit[7]uril in 5·11.25H2O. Thermal ellipsoids are drawn at 50% probability level.

Passage of trans-[OsIVCl4(Hpz)2] through the portal of cucurbit[7]uril could experience strong repulsive forces at distances less than the sums of van der Waals radii (portal diameter 5.4 Å, (23) cavity width 7.3 Å, (23) and Cl2···Cl4 vector in 5 of 4.74 Å). Although the cucurbit[7]uril does form an inclusion complex with a metal halide, namely, cis-[SnCl4(H2O)2], a more sophisticated mechanism of portal passage and formation of the complex was suggested. (34) First a tetrahedral SnCl4 molecule enters the host molecule, which then undergoes hydration. Partial inclusion of oxaliplatin into cucurbit[7]uril has been also reported. (35)

NMR Spectra

The 1H, 13C and 15N NMR spectra show signals due to coordinated azole heterocycles (14). The assignment of the protons and carbon atoms of the azole heterocycle is in some cases hindered by the temperature-independent paramagnetism of low-spin d4 osmium(IV) which causes some broadening of the signals and large shifts relative to uncoordinated azoles at room temperature. Protons close to the metal center generally show larger shifts to negative values. However, it should be noted that signals are remarkably sharp for the majority of the compounds studied. We succeeded to obtain two-dimensional NMR spectra for the compounds 1, 3, and 4 (13C,1H HSQC, 15N,1H HSQC (1, 3), 13C,1H HMBC, 1H,1H COSY).

trans-[OsCl4(Hpz)2]

The H1 proton in 1 at 19.21 ppm was identified from the 15N,1H HSQC plot with a chemical shift for N1 at 115.50 ppm. Because of the Cs local symmetry of the coordinated pyrazole, the H3 and H5 signals do not overlap as is the case for the metal-free pyrazole. The resonance signal H5 is observed as a singlet at −2.97 ppm, while H3 is observed as a doublet at −5.59 ppm. The assignment of the H3 and H5 signals was enabled by a homonuclear decoupling experiment. H4 shows a broad signal at 6.48 ppm. In the 13C{1H} NMR spectra of 1 the carbon resonances of C4, C5, and C3 appear at 73.52, 181.14, and 218.41 ppm, respectively.

trans-[OsCl4(Him)2]

The H1 proton in 3 at 12.29 ppm was identified from the 15N,1H HSQC plot with the chemical shift for N1 at 157.08 ppm. The H4 and H5 resonances do not overlap as is the case for the metal-free imidazole. The singlets at −0.51, 7.29, and 7.86 ppm were attributed to H2, H4, or H5; a more precise assignment failed. The corresponding carbon resonances of C2, C4, and C5 were found at 119.52 {7.29}, 114.45 {7.86}, and 188.36 {−0.51} ppm. The 13C,1H HMBC plot does not enable the assignment of C2, C4, C5 and H2, H4, H5 because of the same number of cross peaks.

trans-[OsCl4(Hbzim)2]

Compound 4 shows two singlets, two doublets, and two triplets in the 1H NMR spectrum. The H1 proton is found as a singlet at 9.00 ppm, while a strongly shifted singlet at −5.58 ppm was assigned to H2, which is in close proximity to the coordination site. The two doublets were attributed to H4 and H7, whereas the two triplets to H5 and H6. In the 13C{1H} NMR spectra the carbon resonances of C4 and C7 are seen at 122.64 {6.71} and 133.73 {4.58} ppm, while those for C5, C6 at 127.45 {6.74}, 135.48 {5.55} and C2 at 200.46 ppm, respectively. There are two signals at 114.64 and 159.43 ppm for the quarternary carbons C8 and C9. Neither the 13C,1H HMBC nor the 1H,1H COSY allowed to differentiate between H4/H7 (C4/C7) and H5/H6 (C5/C6).

Electrochemical Behavior

The cyclic voltammograms (CVs) of the complexes 14 in DMSO (0.2 M (n-Bu4N)[BF4]/DMSO) at a carbon disk working electrode, recorded with a scan rate of 0.2 V/s, display a reversible one-electron reduction wave attributed to the OsIV → OsIII process with potential values ranging from 0.31 to 0.50 V and an irreversible single electron reduction wave (Ired) attributed to the OsIII → OsII process with Ep potential values between −1.17 and −1.55 V versus NHE (Figure 3, Table 3). The redox waves OsIV/OsIII are characterized by a peak-to-peak separation (ΔEp) of 68–71 mV and an anodic peak current (ipa) that is almost equal to the cathodic peak current (ipc), as expected for reversible electron transfer processes. The one-electron nature of these processes was verified by comparing the peak current height (ip) with that of standard ferrocene/ferrocenium couples under identical experimental conditions. The reduction potentials OsIV/OsIII are in the following order: E1/2(1) > E1/2(2) > E1/2(4) > E1/2(3), which agrees quite well with the relative electron-donating character of the azole ligands [EL(Hpz) > EL(2H-ind) > EL(Hbzim) > EL(Him)]. (36, 37) The reduction potential for OsIII → OsII was calculated using Lever’s equation (38) (eq 1) [EL(Cl) = −0.24, (37)EL(2H-ind) = 0.18, (39)EL(Hpz) = 0.20, (37)EL(Hbzim) = 0.1, (37)EL(Him) = 0.09, (40)SM(OsIII/OsII) = 1.01, (37)IM(OsIII/OsII) = −0.40 (37)].
The values of Ecalc for OsIII/OsII obtained by using this formula are quoted for comparison with the Ep values measured for OsIII/OsII in Table 3.
Table 3. Cyclic Voltammetric Data for 14
complexEp Os(III/II)EcalcE1/2 Os(IV/III)a, (ΔEp)b
1–1.22–0.970.50 (68)
2–1.17–1.010.42 (69)
3–1.55–1.190.31 (68)
4–1.41–1.170.37 (71)
a

Potentials E1/2 (E1/2 = (Epa + Epc)/2, where Epa and Epc are the anodic and cathodic peak potentials) are given in V and measured at a scan rate of 0.2 V/s in DMSO, using ferrocene as internal standard, and are quoted relative to NHE.

b

ΔEp values (ΔEp = EpaEpc) are given in mV.

Figure 3

Figure 3. Cyclic voltammogram of 0.2 M solution of 3 in DMSO at a carbon disk working electrode at a scan rate of 0.2 V/s, starting the scan in cathodic direction.

Aqueous Solubility and Resistance to Hydrolysis

The solubility of the complexes 14 in water containing 1% DMSO at 298 K varies from 1.9 (1 and 3) to 2.1 mM (4). The complexes remain intact in this medium for at least 24 h as is shown for complex 4 in Figure 4 by UV–vis spectroscopy. The optical spectra of 14 in DMSO are shown in Supporting Information, Figure S7.

Figure 4

Figure 4. UV–vis spectra of an aqueous solution (containing 1% DMSO) of 4, measured immediately after dissolution and 24 h thereafter.

Cytotoxicity in Cancer Cell Lines

The cytotoxicity of compounds 14 was assessed by means of the MTT assay in three human cell lines originating from different malignant tumors. A 96 h exposure yielded the concentration–effect curves depicted in Figure 5 and IC50 values listed in Table 4. IC50 values are mostly in the 10–5 M range in the rather chemosensitive ovarian cancer cell line CH1, but mostly higher than 100 μM or even higher than the maximally applicable concentrations (because of limited solubility) in the less chemosensitive colon cancer (SW480) and nonsmall cell lung cancer (A549) cells. Best of the four compounds, the indazole complex 2 retains cytotoxic properties in those two cell lines. The cytotoxicity of this compound is in a range well comparable with that of the clinically studied ruthenium complex (H2ind)[RuIIICl4(Hind)2] (KP1019). (12) Furthermore, this compound is similarly potent as or up to 2.4 times more potent than the corresponding monoindazole complex (H2ind)[OsIVCl5(2H-ind)], depending on the cell line, while the cytotoxicity of the bispyrazole analogue 1 is comparable to that of the monopyrazole complex (H2pz)[OsIVCl5(Hpz)], (5) all based on IC50 values. The fact that comparisons of 14 do not yield uniform structure–activity relationships in the three cell lines employed suggest that variation of the azole ligands in the compounds does not affect cytotoxic potency in a generally valid way but that the consequences for the biological effects are more complex.
Table 4. Cytotoxicity of Compounds 14 and the Reference Compound KP1019 in Three Human Cancer Cell Lines
 IC50, μMa
compoundA549CH1SW480
1>160115 ± 14120 ± 5
2181 ± 1153 ± 441 ± 14
3>64046 ± 1173 ± 9
4>16036 ± 16>160
KP1019 44 ± 11b79 ± 5b
a

50% inhibitory concentrations (means ± standard deviations from at least three independent experiments), as obtained by the MTT assay (exposure time: 96 h).

b

C. Bartel, M. A. Jakupec, unpublished results.

Figure 5

Figure 5. Concentration–effect curves of compounds 14 in (A) A549, (B) CH1, and (C) SW480 cells, obtained by the MTT assay (96 h exposure).

Final Remarks

Anderson type transformation of (H2azole)2[OsIVCl6] in 1-hexanol and in the solid state resulted in complexes with the general formula trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole, 1H-imidazole, 2H-indazole, or 1H-benzimidazole. Comparison of the described complexes with their ruthenium analogues (H2azole)[RuIIICl4(Hazole)2] provides further evidence for the higher oxidation state preference of the heavier congener. Despite the nonelectrolyte character of the prepared compounds, the solubility in water containing 1% DMSO was borderline to allow the assessment of their antiproliferative activity in vitro against human cancer cell lines. An attempt to improve the solubility of the complexes by encapsulation in cucurbit[7]uril was described. The importance of this work consists in preparation of precursors, which can be suitable for the synthesis of osmium(III) analogues of KP1019, a potent investigational anticancer drug in clinical trials. In addition, a notable crystallographic contribution has been made. The complexes trans-[OsIVCl4(Hazole)2] are characterized for the first time as individual compounds by X-ray crystallography. A remarkable finding is the stabilization of the quinoid-type 2H-indazole in 2 coordinated to metal via N1. Further attempts to prepare osmium(IV) complexes with 1H-indazole tautomer and inclusion complexes with cucurbit[8]uril and cucurbit[10]uril are underway in our laboratory.

Supporting Information

ARTICLE SECTIONS
Jump To

Thermogravimetric data for (H2ind)2[OsCl6] and (H2ind)[OsCl5(1H-ind)] (Figure S1), the unit cells for 1 and 2 (Figures S2, S3) as well as hydrogen bonding interactions in the crystal structures of 2, 3·2DMSO and 4 (Figures S4–S6), UV–vis spectra of 14 in DMSO (Figure S7). Crystallographic data for 1, 2, 3·2DMSO, 4, and 5·11.25H2O in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org.

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

ARTICLE SECTIONS
Jump To

  • Corresponding Author
    • Vladimir B. Arion - University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria Email: [email protected]
  • Authors
    • Gabriel E. Büchel - University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria
    • Iryna N. Stepanenko - University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria
    • Michaela Hejl - University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria
    • Michael A. Jakupec - University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria
    • Bernhard K. Keppler - University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria

Acknowledgment

ARTICLE SECTIONS
Jump To

We thank Marcel Wieland, Institute of Organic Chemistry, University of Vienna, for providing us with cucurbit[7]uril, Alexander Roller for collecting the X-ray diffraction data, Prof. Dr. Markus Galanski for recording 2D NMR spectra, and Dr. Peter Unfried for thermogravimetric measurements. We are also indebted to the Austrian Science Fund (FWF) for financial support of the project I 374-N19.

References

ARTICLE SECTIONS
Jump To

This article references 40 other publications.

  1. 1
    Allardyce, C. S.; Dorcier, A.; Scolaro, C.; Dyson, P. J. Appl. Organomet. Chem. 2005, 19, 1 10
    Dorcier, A.; Ang, W. H.; Bolaño, S.; Gonsalvi, L.; Juillerat-Jeannerat, L.; Laurenczy, G.; Peruzzini, M.; Phillips, A. D.; Zanobini, F.; Dyson, P. J. Organometallics 2006, 25, 4090 4096
    Dyson, P. J. Chimia 2007, 61, 698 703
    Renfrew, A. K.; Phillips, A. D.; Egger, A. E.; Hartinger, C. G.; Bosquain, S. S.; Nazarov, A. A.; Keppler, B. K.; Gonsalvi, L.; Peruzzini, M.; Dyson, P. J. Organometallics 2009, 28, 1165 1172
  2. 2
    Peacock, A. F. A.; Habtemariam, A.; Fernandez, R.; Walland, V.; Fabbiani, F. P. A.; Parsons, S.; Aird, R. E.; Jodrell, D. I.; Sadler, P. J. J. Am. Chem. Soc. 2006, 128, 1739 1748
    Peacock, A. F. A.; Melchart, M.; Deeth, R. J.; Habtemariam, A.; Parsons, S.; Sadler, P. J. Chem.—Eur. J. 2007, 13, 2601 2613
    Peacock, A. F. A.; Habtemariam, A.; Moggach, S. A.; Prescimone, A.; Parsons, S.; Sadler, P. J. Inorg. Chem. 2007, 46, 4049 4059
    Peacock, A. F. A.; Parsons, S.; Sadler, P. J. J. Am. Chem. Soc. 2007, 129, 3348 3357
    van Rijt, S. H.; Peacock, A. F. A.; Johnstone, R. D. L.; Parsons, S.; Sadler, P. J. Inorg. Chem. 2009, 48, 1753 1752
  3. 3
    Cebrián-Losantos, B.; Krokhin, A. A.; Stepanenko, I. N.; Eichinger, R.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Inorg. Chem. 2007, 46, 5023 5033
    Stepanenko, I. N.; Krokhin, A. A.; John, R. O.; Roller, A.; Arion, V. B.; Jakupec, M. A.; Keppler, B. K. Inorg. Chem. 2008, 47, 7338 7347
    Schmid, W. F.; John, R. O.; Arion, V. B.; Jakupec, M. A.; Keppler, B. K. Organometallics 2007, 26, 6643 6652
    Schmid, W. F.; John, R. O.; Mühlgassner, G.; Heffeter, P.; Jakupec, M. A.; Galanski, M.; Berger, W.; Arion, V. B.; Keppler, B. K. J. Med. Chem. 2007, 50, 6343 6355
    Schuecker, R.; John, R. O.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Organometallics 2008, 27, 6587 6595
  4. 4
    Dorcier, A.; Dyson, P. J.; Gossens, C.; Rothlisberger, U.; Scopelliti, R.; Tavernelli, I. Organometallics 2005, 24, 2114 2123
    Dorcier, A.; Hartinger, C. J.; Scopelliti, R.; Fish, R. H.; Keppler, B. K.; Dyson, P. J. J. Inorg. Biochem. 2008, 102, 1066 1076
  5. 5
    Büchel, G. E.; Stepanenko, I. N.; Hejl, M.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Inorg. Chem. 2009, 48, 10737 10747
  6. 6
    Stepanenko, I. N.; Cebrián-Losantos, B.; Arion, V. B.; Krokhin, A. A.; Nazarov, A. A.; Keppler, B. K. Eur. J. Inorg. Chem. 2007, 400 411
  7. 7
    Singh, P.; Sarkar, B.; Sieger, M.; Niemeyer, M.; Fiedler, J.; Zališ, S.; Kaim, W. Inorg. Chem. 2006, 45, 4602 4609
  8. 8
    Peacock, A. F. A.; Sadler, P. J. Chem.—Asian. J. 2008, 3, 1890 1899
  9. 9
    Chiorescu, I.; Stepanenko, I. N.; Arion, V. B.; Krokhin, A. A.; Keppler, B. K. The 13th International Conference on Biological Inorganic Chemistry (ICBIC XIII), Vienna, Austria, July 15–20, 2007; J. Biol. Inorg. Chem. (2007) 12 (Suppl. 1); P456, S 226.
  10. 10
    Chiorescu, I.; Stepanenko, I. N.; Arion, V. B.; Krokhin, A. A.; Scaffidi-Domianello, Y. Y.; Keppler, B. K. The 8th European Biological Chemistry Conference (EUROBIC 8), Aveiro, Portugal, July 2–7, 2006, PS7.17, p 333.
  11. 11
    Davies, J. A.; Hockensmith, C. M.; Kukushkin, V. Yu.; Kukushkin, Yu. N. Synthetic Coordination Chemistry – Principles and Practice; World Scientific Pub. Co.: Hackensack, NJ, 1995; pp 392 396.
  12. 12
    Jakupec, M. A.; Reisner, E.; Eichinger, A.; Pongratz, M.; Arion, V. B.; Galanski, M.; Hartinger, C. G.; Keppler, B. K. J. Med. Chem. 2005, 48, 2831 2837
  13. 13
    Lipponer, K.-G.; Vogel, E.; Keppler, B. K. Met.-Based Drugs 1996, 3, 243 260
  14. 14
    Smith, C. A.; Sutherland-Smith, A. J.; Kratz, F.; Baker, E. N.; Keppler, B. K. J. Biol. Inorg. Chem. 1996, 1, 424 431
  15. 15
    Keppler, B. K.; Wehe, D.; Endres, H.; Rupp, W. Inorg. Chem. 1987, 26, 844 846
  16. 16
    Brauer, G. Handbuch der Präparativen Anorganischen Chemie, III; Ferdinand Enke Verlag: Stuttgart, Germany, 1981; pp 1742 1744.
  17. 17
    Rudnitskaya, O. V.; Buslaeva, T. M.; Lyalina, N. N. Zh. Neorg. Khim. 1994, 39, 922 924
  18. 18
    Barrette, W. C., Jr.; Johnson, H. W., Jr.; Sawyer, D. T. Anal. Chem. 1984, 56, 1890 1898
  19. 19
    SAINT-Plus, version 7.06a, and APEX2; Bruker-Nonius AXS Inc.: Madison, WI, 2004;
  20. 20
    Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467 473
  21. 21
    Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112 122
  22. 22
    Johnson, G. K. Report ORNL-5138; OAK Ridge National Laboratory; Oak Ridge, TN, 1976.
  23. 23
    Isaacs, L. Chem. Commun. 2009, 619 629
  24. 24
    Wheate, B. J. J. Inorg. Biochem. 2008, 102, 2060 2066
  25. 25
    Goldoni, L.; Grugni, M.; De Munari, S.; Cassin, M.; Bernardini, R. Chem. Lett. 2010, 39, 676 677
  26. 26
    Buck, D. P.; Abeysinghe, P. M.; Cullinane, C.; Day, A. I.; Collins, J. G.; Harding, M. M. Dalton Trans. 2008, 2328 2334
  27. 27
    Yan, K.; Huang, Z.-Y.; Liu, S.-M.; Liang, F.; Wu, C.-T. Wuhan Univ. J. Nat. Sci. 2004, 9, 99 101
  28. 28
    Samsonenko, D. G.; Sokolov, M. N.; Virovets, A. V.; Pervukhina, N. V.; Fedin, V. P. Eur. J. Inorg. Chem. 2001, 167 172
  29. 29
    Virovets, A. V.; Samsonenko, D. G.; Dybtsev, D. N.; Fedin, V. P.; Clegg, W. Zhur. Strukt. Khim. 2001, 42, 384 387
  30. 30
    Virovets, A. V.; Samsonenko, D. G.; Sokolov, M. N.; Fedin, V. P. Acta Crystallogr. 2001, E57, M33 M34
  31. 31
    Peti, W.; Pieper, T.; Sommer, M.; Keppler, B. K.; Giester, G. Eur. J. Inorg. Chem. 1999, 1551 1555
  32. 32
    Rendle, D. F.; Storr, A.; Trotter, J. Can. J. Chem. 1975, 53, 2930 2943
    Cortes-Llamas, S. A.; Hernández-Pérez, J. M.; Hó, M.; Munoz-Hernández, M.-A. Organometallics 2006, 25, 588 595
  33. 33
    Fackler, J. P., Jr.; Staples, R. J.; Raptis, R. G. Z. Kristallogr. 1997, 212, 157 158
  34. 34
    Lorenzo, S.; Day, A.; Craig, D.; Blanch, R.; Arnold, A.; Dance, I. CrystEngComm 2001, 49, 1 7
  35. 35
    Jeon, Y. J.; Kim, S.-Y.; Ko, Y. H.; Sakamoto, S.; Yamaguchi, K.; Kim, K. Org. Biomol. Chem. 2005, 3, 2122 2125
  36. 36
    Reisner, E.; Arion, V. B.; Keppler, B. K.; Pombeiro, A. J. L. Inorg. Chim. Acta 2008, 361, 1569 1583
  37. 37
    Lever, A. B. P. Inorg. Chem. 1990, 29, 1271 1285
  38. 38
    Lever, A. B. P.; Dodsworth, E. S. Inorganic Electronic Structure and Spectroscopy; Wiley: New York, 1999; pp 277 290.
  39. 39
    Büchel, G. E.; Stepanenko, I. N.; Heffeter, P.; Hejl, M.; Jakupec, M. A.; Keppler, B. K.; Berger, W. E.; Arion, V. B. manuscript in preparation.
  40. 40
    Reisner, E.; Arion, V. B.; Eichinger, A.; Kandler, N.; Giester, G.; Pombeiro, J. A. L.; Keppler, B. K. Inorg. Chem. 2005, 44, 6704 6716

Cited By

ARTICLE SECTIONS
Jump To

This article is cited by 48 publications.

  1. Mark V. Sigalov, Andrey V. Afonin, Irina V. Sterkhova, Bagrat A. Shainyan. 2H-Indazole Tautomers Stabilized by Intra- and Intermolecular Hydrogen Bonds. The Journal of Organic Chemistry 2019, 84 (14) , 9075-9086. https://doi.org/10.1021/acs.joc.9b01021
  2. Russell J. Needham, Abraha Habtemariam, Nicolas P. E. Barry, Guy Clarkson, and Peter J. Sadler . Halide Control of N,N-Coordination versus N,C-Cyclometalation and Stereospecific Phenyl Ring Deuteration of Osmium(II) p-Cymene Phenylazobenzothiazole Complexes. Organometallics 2017, 36 (22) , 4367-4375. https://doi.org/10.1021/acs.organomet.7b00501
  3. Paul-Steffen Kuhn, Gabriel E. Büchel, Katarina K. Jovanović, Lana Filipović, Siniša Radulović, Peter Rapta, and Vladimir B. Arion . Osmium(III) Analogues of KP1019: Electrochemical and Chemical Synthesis, Spectroscopic Characterization, X-ray Crystallography, Hydrolytic Stability, and Antiproliferative Activity. Inorganic Chemistry 2014, 53 (20) , 11130-11139. https://doi.org/10.1021/ic501710k
  4. Gabriel E. Büchel, Anatolie Gavriluta, Maria Novak, Samuel M. Meier, Michael A. Jakupec, Olesea Cuzan, Constantin Turta, Jean-Bernard Tommasino, Erwann Jeanneau, Ghenadie Novitchi, Dominique Luneau, and Vladimir B. Arion . Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles. Inorganic Chemistry 2013, 52 (11) , 6273-6285. https://doi.org/10.1021/ic400555k
  5. Naresh Kumar, Nidhi Goel. Recent development of imidazole derivatives as potential anticancer agents. Physical Sciences Reviews 2023, 8 (10) , 2903-2941. https://doi.org/10.1515/psr-2021-0041
  6. John R. Kromer, Alan J. Oberley, Lava R. Kadel, Derek Vonarx, Jared McNeil, Joan Haskin, Ryan M. Steinert, Katie R. Mitchell-Koch, Curtis E. Moore, David M. Eichhorn. Synthesis and X-ray crystal structures of mononuclear and multinuclear metal complexes of 3-substituted 4-cyanopyrazole ligands. Polyhedron 2023, 243 , 116546. https://doi.org/10.1016/j.poly.2023.116546
  7. Pramod Kumar Shah, Nihar R. Jena, Pradeep Kumar Shukla. A theoretical characterization of mechanisms of action of osmium(III)-based drug Os-KP418: hydrolysis and its binding with guanine. Structural Chemistry 2023, 34 (3) , 995-1003. https://doi.org/10.1007/s11224-022-02064-1
  8. Galdina V. Suárez-Moreno, Delia Hernández-Romero, Óscar García-Barradas, Óscar Vázquez-Vera, Sharon Rosete-Luna, Carlos A. Cruz-Cruz, Aracely López-Monteon, Jesús Carrillo-Ahumada, David Morales-Morales, Raúl Colorado-Peralta. Second and third-row transition metal compounds containing benzimidazole ligands: An overview of their anticancer and antitumour activity. Coordination Chemistry Reviews 2022, 472 , 214790. https://doi.org/10.1016/j.ccr.2022.214790
  9. Jana Hildebrandt, Norman Häfner, Daniel Kritsch, Helmar Görls, Matthias Dürst, Ingo B. Runnebaum, Wolfgang Weigand. Highly Cytotoxic Osmium(II) Compounds and Their Ruthenium(II) Analogues Targeting Ovarian Carcinoma Cell Lines and Evading Cisplatin Resistance Mechanisms. International Journal of Molecular Sciences 2022, 23 (9) , 4976. https://doi.org/10.3390/ijms23094976
  10. B A Shainyan, M V Sigalov. Hydrogen bonding-assisted transformations of cyclic chalcones: E/Z-isomerization, self-association and unusual tautomerism. Russian Chemical Reviews 2022, 91 (5) , RCR5035. https://doi.org/10.1070/RCR5035
  11. Liviu Ungur, Katharina Pallitsch, Zeid A. AlOthman, Abdullah A. S. Al-Kahtani, Vladimir B. Arion, Liviu F. Chibotaru. Towards understanding the magnetism of Os( iv ) complexes: an ab initio insight. Dalton Transactions 2021, 50 (36) , 12537-12546. https://doi.org/10.1039/D1DT01558C
  12. Angelina Z. Petrović, Dušan C. Ćoćić, Dirk Bockfeld, Marko Živanović, Nevena Milivojević, Katarina Virijević, Nenad Janković, Andreas Scheurer, Milan Vraneš, Jovana V. Bogojeski. Biological activity of bis(pyrazolylpyridine) and terpiridine Os( ii ) complexes in the presence of biocompatible ionic liquids. Inorganic Chemistry Frontiers 2021, 8 (11) , 2749-2770. https://doi.org/10.1039/D0QI01540G
  13. Małgorzata Biedulska, Aleksandra Królicka, Andrea D. Lipińska, Marta Krychowiak-Maśnicka, Michał Pierański, Kinga Grabowska, Dawid Nidzworski. Physicochemical profile of Os (III) complexes with pyrazine derivatives: From solution behavior to DNA binding studies and biological assay. Journal of Molecular Liquids 2020, 316 , 113804. https://doi.org/10.1016/j.molliq.2020.113804
  14. Russell J. Needham, Hannah E. Bridgewater, Isolda Romero-Canelón, Abraha Habtemariam, Guy J. Clarkson, Peter J. Sadler. Structure-activity relationships for osmium(II) arene phenylazopyridine anticancer complexes functionalised with alkoxy and glycolic substituents. Journal of Inorganic Biochemistry 2020, 210 , 111154. https://doi.org/10.1016/j.jinorgbio.2020.111154
  15. Natalia Sanz del Olmo, Riccardo Carloni, Paula Ortega, Sandra García-Gallego, F. Javier de la Mata. Metallodendrimers as a promising tool in the biomedical field: An overview. 2020, 1-52. https://doi.org/10.1016/bs.adomc.2020.03.001
  16. Priyaranjan Kumar, Swati Swagatika, Srikanth Dasari, Raghuvir Singh Tomar, Ashis K. Patra. Modulation of ruthenium anticancer drugs analogs with tolfenamic acid: Reactivity, biological interactions and growth inhibition of yeast cell. Journal of Inorganic Biochemistry 2019, 199 , 110769. https://doi.org/10.1016/j.jinorgbio.2019.110769
  17. M. Saeed Mirzaei, Avat Arman Taherpour. Tautomeric preferences of the cis and trans isomers of axitinib. Chemical Physics 2018, 507 , 10-18. https://doi.org/10.1016/j.chemphys.2018.04.006
  18. Massimiliano Francesco Peana, Serenella Medici, Maria Antonietta Zoroddu. The Intriguing Potential of “Minor” Noble Metals: Emerging Trends and New Applications. 2018, 49-72. https://doi.org/10.1007/978-3-319-74814-6_2
  19. Samuel M. Meier-Menches, Christopher Gerner, Walter Berger, Christian G. Hartinger, Bernhard K. Keppler. Structure–activity relationships for ruthenium and osmium anticancer agents – towards clinical development. Chemical Society Reviews 2018, 47 (3) , 909-928. https://doi.org/10.1039/C7CS00332C
  20. Chilaluck C. Konkankit, Sierra C. Marker, Kevin M. Knopf, Justin J. Wilson. Anticancer activity of complexes of the third row transition metals, rhenium, osmium, and iridium. Dalton Transactions 2018, 47 (30) , 9934-9974. https://doi.org/10.1039/C8DT01858H
  21. Kousik Ghosh, Abhisek Banerjee, Antonio Bauzá, Antonio Frontera, Shouvik Chattopadhyay. One pot synthesis of two cobalt( iii ) Schiff base complexes with chelating pyridyltetrazolate and exploration of their bio-relevant catalytic activities. RSC Advances 2018, 8 (49) , 28216-28237. https://doi.org/10.1039/C8RA03035A
  22. Gabriella Tamasi, Antonello Merlino, Federica Scaletti, Petra Heffeter, Anton A. Legin, Michael A. Jakupec, Walter Berger, Luigi Messori, Bernhard K. Keppler, Renzo Cini. {Ru(CO) x }-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo. Dalton Transactions 2017, 46 (9) , 3025-3040. https://doi.org/10.1039/C6DT04295C
  23. Gabriel E. Büchel, Susanne Kossatz, Ahmad Sadique, Peter Rapta, Michal Zalibera, Lukas Bucinsky, Stanislav Komorovsky, Joshua Telser, Jörg Eppinger, Thomas Reiner, Vladimir B. Arion. cis-Tetrachlorido-bis(indazole)osmium( iv ) and its osmium( iii ) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339. Dalton Transactions 2017, 46 (35) , 11925-11941. https://doi.org/10.1039/C7DT02194A
  24. Maria S. Novak, Gabriel E. Büchel, Bernhard K. Keppler, Michael A. Jakupec. Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles. JBIC Journal of Biological Inorganic Chemistry 2016, 21 (3) , 347-356. https://doi.org/10.1007/s00775-016-1345-z
  25. José Elguero. Tautomerism: A Historical Perspective. 2016, 1-10. https://doi.org/10.1002/9783527695713.ch1
  26. Paul‐Steffen Kuhn, Samuel M. Meier, Katarina K. Jovanović, Isolde Sandler, Leon Freitag, Ghenadie Novitchi, Leticia González, Siniša Radulović, Vladimir B. Arion. Ruthenium Carbonyl Complexes with Azole Heterocycles – Synthesis, X‐ray Diffraction Structures, DFT Calculations, Solution Behavior, and Antiproliferative Activity. European Journal of Inorganic Chemistry 2016, 2016 (10) , 1566-1576. https://doi.org/10.1002/ejic.201501393
  27. Emilia Păunescu, Patrycja Nowak‐Sliwinska, Catherine M. Clavel, Rosario Scopelliti, Arjan W. Griffioen, Paul J. Dyson. Anticancer Organometallic Osmium(II)‐ p ‐cymene Complexes. ChemMedChem 2015, 10 (9) , 1539-1547. https://doi.org/10.1002/cmdc.201500221
  28. Lara C. Sudding, Prinessa Chellan, Preshendren Govender, Gregory S. Smith. Cyclometalated Benzaldimine-Terminated Rhodium and Iridium Dendrimers: Synthesis, Characterization and Molecular Structures of Mononuclear Analogues. Journal of Inorganic and Organometallic Polymers and Materials 2015, 25 (3) , 457-465. https://doi.org/10.1007/s10904-015-0184-7
  29. Begoña Verdejo, Laura Acosta-Rueda, M. Paz Clares, Almudena Aguinaco, Manuel G. Basallote, Concepción Soriano, Roberto Tejero, Enrique García-España. Equilibrium, Kinetic, and Computational Studies on the Formation of Cu 2+ and Zn 2+ Complexes with an Indazole-Containing Azamacrocyclic Scorpiand: Evidence for Metal-Induced Tautomerism. Inorganic Chemistry 2015, 54 (4) , 1983-1991. https://doi.org/10.1021/ic5029004
  30. Serenella Medici, Massimiliano Peana, Valeria Marina Nurchi, Joanna I. Lachowicz, Guido Crisponi, Maria Antonietta Zoroddu. Noble metals in medicine: Latest advances. Coordination Chemistry Reviews 2015, 284 , 329-350. https://doi.org/10.1016/j.ccr.2014.08.002
  31. Lara C. Sudding, Richard Payne, Preshendren Govender, Fabio Edafe, Catherine M. Clavel, Paul J. Dyson, Bruno Therrien, Gregory S. Smith. Evaluation of the in vitro anticancer activity of cyclometalated half-sandwich rhodium and iridium complexes coordinated to naphthaldimine-based poly(propyleneimine) dendritic scaffolds. Journal of Organometallic Chemistry 2014, 774 , 79-85. https://doi.org/10.1016/j.jorganchem.2014.10.003
  32. O. V. Rudnitskaya, E. K. Kultyshkina, E. V. Dobrokhotova, I. V. Anan’ev. Synthesis and structure of [H(DMSO)2]2[OsX6] (X = Cl, Br). Russian Journal of Coordination Chemistry 2014, 40 (12) , 911-917. https://doi.org/10.1134/S1070328414120124
  33. Muhammad Hanif, Maria V. Babak, Christian G. Hartinger. Development of anticancer agents: wizardry with osmium. Drug Discovery Today 2014, 19 (10) , 1640-1648. https://doi.org/10.1016/j.drudis.2014.06.016
  34. Gabriella Tamasi, Alice Carpini, Daniela Valensin, Luigi Messori, Alessandro Pratesi, Federica Scaletti, Michael Jakupec, Bernhard Keppler, Renzo Cini. {Ru(CO)x}-core complexes with selected azoles: Synthesis, X-ray structure, spectroscopy, DFT analysis and evaluation of cytotoxic activity against human cancer cells. Polyhedron 2014, 81 , 227-237. https://doi.org/10.1016/j.poly.2014.05.067
  35. Waseem A. Wani, Zeid Al-Othman, Imran Ali, Kishwar Saleem, Ming-Fa Hsieh. Copper(II), nickel(II), and ruthenium(III) complexes of an oxopyrrolidine-based heterocyclic ligand as anticancer agents. Journal of Coordination Chemistry 2014, 67 (12) , 2110-2130. https://doi.org/10.1080/00958972.2014.931947
  36. Gajendra Gupta, Jerald Mahesh Kumar, Amine Garci, Nandini Rangaraj, Narayana Nagesh, Bruno Therrien. Anticancer Activity of Half‐Sandwich Rh III and Ir III Metalla‐Prisms Containing Lipophilic Side Chains. ChemPlusChem 2014, 79 (4) , 610-618. https://doi.org/10.1002/cplu.201300425
  37. Ling Zhang, Xin-Mei Peng, Guri L. V. Damu, Rong-Xia Geng, Cheng-He Zhou. Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry. Medicinal Research Reviews 2014, 34 (2) , 340-437. https://doi.org/10.1002/med.21290
  38. Preshendren Govender, Fabio Edafe, Banothile C.E. Makhubela, Paul J. Dyson, Bruno Therrien, Gregory S. Smith. Neutral and cationic osmium(II)-arene metallodendrimers: Synthesis, characterisation and anticancer activity. Inorganica Chimica Acta 2014, 409 , 112-120. https://doi.org/10.1016/j.ica.2013.05.025
  39. Samuel M. Meier, Maria S. Novak, Wolfgang Kandioller, Michael A. Jakupec, Alexander Roller, Bernhard K. Keppler, Christian G. Hartinger. Aqueous chemistry and antiproliferative activity of a pyrone-based phosphoramidate Ru(arene) anticancer agent. Dalton Transactions 2014, 43 (26) , 9851. https://doi.org/10.1039/c4dt00569d
  40. Sabine H. van Rijt, Isolda Romero-Canelón, Ying Fu, Steve D. Shnyder, Peter J. Sadler. Potent organometallic osmium compounds induce mitochondria-mediated apoptosis and S-phase cell cycle arrest in A549 non-small cell lung cancer cells. Metallomics 2014, 6 (5) , 1014. https://doi.org/10.1039/c4mt00034j
  41. J. Elguero, I. Alkorta, R. M. Claramunt, P. Cabildo, P. Cornago, M. Ángeles Farrán, M. Ángeles García, C. López, M. Pérez-Torralba, D. Santa María, D. Sanz. Structure of NH-benzazoles (1H-benzimidazoles, 1H- and 2H-indazoles, 1H- and 2H-benzotriazoles). Chemistry of Heterocyclic Compounds 2013, 49 (1) , 177-202. https://doi.org/10.1007/s10593-013-1237-x
  42. Richard Payne, Preshendren Govender, Bruno Therrien, Catherine M. Clavel, Paul J. Dyson, Gregory S. Smith. Neutral and cationic multinuclear half-sandwich rhodium and iridium complexes coordinated to poly(propyleneimine) dendritic scaffolds: Synthesis and cytotoxicity. Journal of Organometallic Chemistry 2013, 729 , 20-27. https://doi.org/10.1016/j.jorganchem.2013.01.009
  43. Gabriel E. Büchel, Iryna N. Stepanenko, Michaela Hejl, Michael A. Jakupec, Bernhard K. Keppler, Petra Heffeter, Walter Berger, Vladimir B. Arion. Osmium(IV) complexes with 1H- and 2H-indazoles: Tautomer identity versus spectroscopic properties and antiproliferative activity. Journal of Inorganic Biochemistry 2012, 113 , 47-54. https://doi.org/10.1016/j.jinorgbio.2012.04.001
  44. Nicolas P.E. Barry, Olivier Zava, Paul J. Dyson, Bruno Therrien. Encapsulation of inorganic and organic guest molecules into an organometallic hexacationic arene osmium metalla-prism: Synthesis, characterisation and anticancer activity. Journal of Organometallic Chemistry 2012, 705 , 1-6. https://doi.org/10.1016/j.jorganchem.2011.12.009
  45. Muhammad Hanif, Alexey A. Nazarov, Christian G. Hartinger. Synthesis of [RuII(η6-p-cymene)(PPh3)(L)Cl]PF6 complexes with carbohydrate-derived phosphites, imidazole or indazole co-ligands. Inorganica Chimica Acta 2012, 380 , 211-215. https://doi.org/10.1016/j.ica.2011.10.007
  46. Simon A. Cotton. Iron, ruthenium and osmium. Annual Reports Section "A" (Inorganic Chemistry) 2012, 108 , 186. https://doi.org/10.1039/c2ic90010f
  47. Wen-Xiu Ni, Wai-Lun Man, Shek-Man Yiu, Man Ho, Myra Ting-Wai Cheung, Chi-Chiu Ko, Chi-Ming Che, Yun-Wah Lam, Tai-Chu Lau. Osmium(vi) nitrido complexes bearing azole heterocycles: a new class of antitumor agents. Chemical Science 2012, 3 (5) , 1582. https://doi.org/10.1039/c2sc01031c
  48. Ying Fu, María J. Romero, Abraha Habtemariam, Michael E. Snowden, Lijiang Song, Guy J. Clarkson, Bushra Qamar, Ana M. Pizarro, Patrick R. Unwin, Peter J. Sadler. The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes. Chemical Science 2012, 3 (8) , 2485. https://doi.org/10.1039/c2sc20220d
  • Abstract

    Chart 1

    Chart 1. Compounds Reported in This Worka

    Chart aAll complexes have been characterized by X-ray crystallography; atom labeling was introduced for assignments of resonances in NMR spectra.

    Figure 1

    Figure 1. ORTEP view of [OsIVCl4(Hpz)2] (1), [OsIVCl4(Hind)2] (2), [OsIVCl4(Him)2] in 3·2DMSO, and [OsIVCl4(Hbzim)2] (4). Thermal ellipsoids are drawn at 50% probability level.

    Figure 2

    Figure 2. ORTEP view of trans-[OsIVCl4(Hpz)2]·cucurbit[7]uril in 5·11.25H2O. Thermal ellipsoids are drawn at 50% probability level.

    Figure 3

    Figure 3. Cyclic voltammogram of 0.2 M solution of 3 in DMSO at a carbon disk working electrode at a scan rate of 0.2 V/s, starting the scan in cathodic direction.

    Figure 4

    Figure 4. UV–vis spectra of an aqueous solution (containing 1% DMSO) of 4, measured immediately after dissolution and 24 h thereafter.

    Figure 5

    Figure 5. Concentration–effect curves of compounds 14 in (A) A549, (B) CH1, and (C) SW480 cells, obtained by the MTT assay (96 h exposure).

  • References

    ARTICLE SECTIONS
    Jump To

    This article references 40 other publications.

    1. 1
      Allardyce, C. S.; Dorcier, A.; Scolaro, C.; Dyson, P. J. Appl. Organomet. Chem. 2005, 19, 1 10
      Dorcier, A.; Ang, W. H.; Bolaño, S.; Gonsalvi, L.; Juillerat-Jeannerat, L.; Laurenczy, G.; Peruzzini, M.; Phillips, A. D.; Zanobini, F.; Dyson, P. J. Organometallics 2006, 25, 4090 4096
      Dyson, P. J. Chimia 2007, 61, 698 703
      Renfrew, A. K.; Phillips, A. D.; Egger, A. E.; Hartinger, C. G.; Bosquain, S. S.; Nazarov, A. A.; Keppler, B. K.; Gonsalvi, L.; Peruzzini, M.; Dyson, P. J. Organometallics 2009, 28, 1165 1172
    2. 2
      Peacock, A. F. A.; Habtemariam, A.; Fernandez, R.; Walland, V.; Fabbiani, F. P. A.; Parsons, S.; Aird, R. E.; Jodrell, D. I.; Sadler, P. J. J. Am. Chem. Soc. 2006, 128, 1739 1748
      Peacock, A. F. A.; Melchart, M.; Deeth, R. J.; Habtemariam, A.; Parsons, S.; Sadler, P. J. Chem.—Eur. J. 2007, 13, 2601 2613
      Peacock, A. F. A.; Habtemariam, A.; Moggach, S. A.; Prescimone, A.; Parsons, S.; Sadler, P. J. Inorg. Chem. 2007, 46, 4049 4059
      Peacock, A. F. A.; Parsons, S.; Sadler, P. J. J. Am. Chem. Soc. 2007, 129, 3348 3357
      van Rijt, S. H.; Peacock, A. F. A.; Johnstone, R. D. L.; Parsons, S.; Sadler, P. J. Inorg. Chem. 2009, 48, 1753 1752
    3. 3
      Cebrián-Losantos, B.; Krokhin, A. A.; Stepanenko, I. N.; Eichinger, R.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Inorg. Chem. 2007, 46, 5023 5033
      Stepanenko, I. N.; Krokhin, A. A.; John, R. O.; Roller, A.; Arion, V. B.; Jakupec, M. A.; Keppler, B. K. Inorg. Chem. 2008, 47, 7338 7347
      Schmid, W. F.; John, R. O.; Arion, V. B.; Jakupec, M. A.; Keppler, B. K. Organometallics 2007, 26, 6643 6652
      Schmid, W. F.; John, R. O.; Mühlgassner, G.; Heffeter, P.; Jakupec, M. A.; Galanski, M.; Berger, W.; Arion, V. B.; Keppler, B. K. J. Med. Chem. 2007, 50, 6343 6355
      Schuecker, R.; John, R. O.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Organometallics 2008, 27, 6587 6595
    4. 4
      Dorcier, A.; Dyson, P. J.; Gossens, C.; Rothlisberger, U.; Scopelliti, R.; Tavernelli, I. Organometallics 2005, 24, 2114 2123
      Dorcier, A.; Hartinger, C. J.; Scopelliti, R.; Fish, R. H.; Keppler, B. K.; Dyson, P. J. J. Inorg. Biochem. 2008, 102, 1066 1076
    5. 5
      Büchel, G. E.; Stepanenko, I. N.; Hejl, M.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Inorg. Chem. 2009, 48, 10737 10747
    6. 6
      Stepanenko, I. N.; Cebrián-Losantos, B.; Arion, V. B.; Krokhin, A. A.; Nazarov, A. A.; Keppler, B. K. Eur. J. Inorg. Chem. 2007, 400 411
    7. 7
      Singh, P.; Sarkar, B.; Sieger, M.; Niemeyer, M.; Fiedler, J.; Zališ, S.; Kaim, W. Inorg. Chem. 2006, 45, 4602 4609
    8. 8
      Peacock, A. F. A.; Sadler, P. J. Chem.—Asian. J. 2008, 3, 1890 1899
    9. 9
      Chiorescu, I.; Stepanenko, I. N.; Arion, V. B.; Krokhin, A. A.; Keppler, B. K. The 13th International Conference on Biological Inorganic Chemistry (ICBIC XIII), Vienna, Austria, July 15–20, 2007; J. Biol. Inorg. Chem. (2007) 12 (Suppl. 1); P456, S 226.
    10. 10
      Chiorescu, I.; Stepanenko, I. N.; Arion, V. B.; Krokhin, A. A.; Scaffidi-Domianello, Y. Y.; Keppler, B. K. The 8th European Biological Chemistry Conference (EUROBIC 8), Aveiro, Portugal, July 2–7, 2006, PS7.17, p 333.
    11. 11
      Davies, J. A.; Hockensmith, C. M.; Kukushkin, V. Yu.; Kukushkin, Yu. N. Synthetic Coordination Chemistry – Principles and Practice; World Scientific Pub. Co.: Hackensack, NJ, 1995; pp 392 396.
    12. 12
      Jakupec, M. A.; Reisner, E.; Eichinger, A.; Pongratz, M.; Arion, V. B.; Galanski, M.; Hartinger, C. G.; Keppler, B. K. J. Med. Chem. 2005, 48, 2831 2837
    13. 13
      Lipponer, K.-G.; Vogel, E.; Keppler, B. K. Met.-Based Drugs 1996, 3, 243 260
    14. 14
      Smith, C. A.; Sutherland-Smith, A. J.; Kratz, F.; Baker, E. N.; Keppler, B. K. J. Biol. Inorg. Chem. 1996, 1, 424 431
    15. 15
      Keppler, B. K.; Wehe, D.; Endres, H.; Rupp, W. Inorg. Chem. 1987, 26, 844 846
    16. 16
      Brauer, G. Handbuch der Präparativen Anorganischen Chemie, III; Ferdinand Enke Verlag: Stuttgart, Germany, 1981; pp 1742 1744.
    17. 17
      Rudnitskaya, O. V.; Buslaeva, T. M.; Lyalina, N. N. Zh. Neorg. Khim. 1994, 39, 922 924
    18. 18
      Barrette, W. C., Jr.; Johnson, H. W., Jr.; Sawyer, D. T. Anal. Chem. 1984, 56, 1890 1898
    19. 19
      SAINT-Plus, version 7.06a, and APEX2; Bruker-Nonius AXS Inc.: Madison, WI, 2004;
    20. 20
      Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467 473
    21. 21
      Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112 122
    22. 22
      Johnson, G. K. Report ORNL-5138; OAK Ridge National Laboratory; Oak Ridge, TN, 1976.
    23. 23
      Isaacs, L. Chem. Commun. 2009, 619 629
    24. 24
      Wheate, B. J. J. Inorg. Biochem. 2008, 102, 2060 2066
    25. 25
      Goldoni, L.; Grugni, M.; De Munari, S.; Cassin, M.; Bernardini, R. Chem. Lett. 2010, 39, 676 677
    26. 26
      Buck, D. P.; Abeysinghe, P. M.; Cullinane, C.; Day, A. I.; Collins, J. G.; Harding, M. M. Dalton Trans. 2008, 2328 2334
    27. 27
      Yan, K.; Huang, Z.-Y.; Liu, S.-M.; Liang, F.; Wu, C.-T. Wuhan Univ. J. Nat. Sci. 2004, 9, 99 101
    28. 28
      Samsonenko, D. G.; Sokolov, M. N.; Virovets, A. V.; Pervukhina, N. V.; Fedin, V. P. Eur. J. Inorg. Chem. 2001, 167 172
    29. 29
      Virovets, A. V.; Samsonenko, D. G.; Dybtsev, D. N.; Fedin, V. P.; Clegg, W. Zhur. Strukt. Khim. 2001, 42, 384 387
    30. 30
      Virovets, A. V.; Samsonenko, D. G.; Sokolov, M. N.; Fedin, V. P. Acta Crystallogr. 2001, E57, M33 M34
    31. 31
      Peti, W.; Pieper, T.; Sommer, M.; Keppler, B. K.; Giester, G. Eur. J. Inorg. Chem. 1999, 1551 1555
    32. 32
      Rendle, D. F.; Storr, A.; Trotter, J. Can. J. Chem. 1975, 53, 2930 2943
      Cortes-Llamas, S. A.; Hernández-Pérez, J. M.; Hó, M.; Munoz-Hernández, M.-A. Organometallics 2006, 25, 588 595
    33. 33
      Fackler, J. P., Jr.; Staples, R. J.; Raptis, R. G. Z. Kristallogr. 1997, 212, 157 158
    34. 34
      Lorenzo, S.; Day, A.; Craig, D.; Blanch, R.; Arnold, A.; Dance, I. CrystEngComm 2001, 49, 1 7
    35. 35
      Jeon, Y. J.; Kim, S.-Y.; Ko, Y. H.; Sakamoto, S.; Yamaguchi, K.; Kim, K. Org. Biomol. Chem. 2005, 3, 2122 2125
    36. 36
      Reisner, E.; Arion, V. B.; Keppler, B. K.; Pombeiro, A. J. L. Inorg. Chim. Acta 2008, 361, 1569 1583
    37. 37
      Lever, A. B. P. Inorg. Chem. 1990, 29, 1271 1285
    38. 38
      Lever, A. B. P.; Dodsworth, E. S. Inorganic Electronic Structure and Spectroscopy; Wiley: New York, 1999; pp 277 290.
    39. 39
      Büchel, G. E.; Stepanenko, I. N.; Heffeter, P.; Hejl, M.; Jakupec, M. A.; Keppler, B. K.; Berger, W. E.; Arion, V. B. manuscript in preparation.
    40. 40
      Reisner, E.; Arion, V. B.; Eichinger, A.; Kandler, N.; Giester, G.; Pombeiro, J. A. L.; Keppler, B. K. Inorg. Chem. 2005, 44, 6704 6716
  • Supporting Information

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    Thermogravimetric data for (H2ind)2[OsCl6] and (H2ind)[OsCl5(1H-ind)] (Figure S1), the unit cells for 1 and 2 (Figures S2, S3) as well as hydrogen bonding interactions in the crystal structures of 2, 3·2DMSO and 4 (Figures S4–S6), UV–vis spectra of 14 in DMSO (Figure S7). Crystallographic data for 1, 2, 3·2DMSO, 4, and 5·11.25H2O in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org.


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect