[OsIVCl5(Hazole)]− Complexes: Synthesis, Structure, Spectroscopic Properties, and Antiproliferative Activity

Büchel, Gabriel E.; Stepanenko, Iryna N.; Hejl, Michaela; Jakupec, Michael A.; Arion, Vladimir B.; Keppler, Bernhard K.

doi:10.1021/ic901671j

Cited by 23 publications

(30 citation statements)

References 46 publications

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“…The uncontracted DZ basis set of Dyall [88,89,90] − anion has been taken from the X-ray structure [91]. The geometry of the water radical cation had the H-O-H angle of 101.41098 degrees and the O-H bond distance of 0.99192Å.…”

Section: Computational Detailsmentioning

confidence: 99%

Spin contamination analogy, Kramers pairs symmetry and spin density representations at the 2-component unrestricted Hartree–Fock level of theory

Bučinský

Malček

Biskupič

et al. 2015

Computational and Theoretical Chemistry

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Abstract"Kramers pairs symmetry breaking" is evaluated at the 2-component (2c) Kramers unrestricted and/or general complex Hartree-Fock (GCHF) level of theory, and its analogy with "spin contamination" at the 1-component (1c) unrestricted Hartree-Fock (UHF) level of theory is emphasized. The GCHF "Kramers pairs symmetry breaking" evaluation is using the square of overlaps between the set of occupied spinorbitals with the projected set of Kramers pairs. In the same fashion, overlaps between α and β orbitals are used in the evaluation of "spin contamination" at the UHF level of theory. In this manner, UHFŜ 2 expectation value is made formally extended to the GCHF case. The directly evaluated GCHF expectation value of theŜ 2 operator is considered for completeness. It is found that the 2c GCHF Kramers pairs symmetry breaking has a very similar extent in comparison to the 1c UHF spin contamination. Thus higher excited states contributions to the 1c so 2c unrestricted wave functions of open shell systems have almost the same extent and physical consequences. Moreover, it is formally shown that a single determinant wave function in the restricted open shell Kramers case has the expectation value ofK 2 operator equal to the negative number of open shell electrons, while the eigenvalue ofK 2 for the series of simple systems (H, He, He*-triplet, Li and Li*-quartet) are found to be equal to minus the square of the number of open shell electrons. The concept of unpaired electron density is extended to the GCHF regime and compared to UHF and restricted open shell Hartree-Fock spin density. The "collinear" and "noncollinear" analogs of spin density at the GCHF level of theory are considered as well. Spin contamination and/or Kramers pairs symmetry breaking, spin

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Section: Computational Detailsmentioning

confidence: 99%

Spin contamination analogy, Kramers pairs symmetry and spin density representations at the 2-component unrestricted Hartree–Fock level of theory

Bučinský

Malček

Biskupič

et al. 2015

Computational and Theoretical Chemistry

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“…These complexes were studied for their antiproliferative activity in vitro and in vivo (Scheme 2). 16, 57 …”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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The relationship between cis-trans isomerism and anticancer activity has been mainly addressed for square-planar metal complexes, in particular, for platinum(II), e.g., cis- and trans-[PtCl2(NH3)2], and a number of related compounds, of which, however, only cis-counterparts are in clinical use today. For octahedral metal complexes, this effect of geometrical isomerism on anticancer activity has not been investigated systematically, mainly because the relevant isomers are still unavailable. An example of such an octahedral complex is trans-[RuCl4(Hind)2]−, which is in clinical trials now as its indazolium (KP1019) or sodium salt (NKP1339), but the corresponding cis-isomers remain inaccessible. We report the synthesis of Na[cis-OsIIICl4(κN2-1H-ind)2] (Na[1]) to show that cis-isomer of NKP1339 can in principle be prepared as well. The procedure involves heating (H2ind)[OsIVCl5(κN1-2H-ind)] in a high boiling point organic solvent resulting in an Anderson rearrangement with formation of cis-[OsIVCl4(κN2-1H-ind)2] ([1]) in high yield. The transformation is accompanied by an indazole coordination mode switch from κN1 to κN2 and stabilization of the 1H-indazole tautomer. Fully reversible spectroelectrochemical reduction of [1] in acetonitrile at 0.46 V vs NHE is accompanied by a change in electronic absorption bands indicating formation of cis-[OsIIICl4(κN2-1H-ind)2]− ([1]−). Chemical reduction of [1] in methanol with NaBH4 followed by addition of nBu4NCl afforded the osmium(III) complex nBu4N[cis-OsIIICl4(κN2-1H-ind)2] (nBu4N[1]). Metathesis reaction of nBu4N[1] with an ion exchange resin led to isolation of the water-soluble salt Na[1]. The X-ray diffraction crystal structure of [1]·Me2CO was determined and compared with that of trans-[OsIVCl4(κN2-1H-ind)]·2Me2SO (2·2Me2SO), also prepared in this work. EPR spectroscopy was performed on the OsIII complexes and the results analyzed by ligand-field and quantum chemical theories. We furthermore assayed effects of [1] and Na[1] on cell viability and proliferation in comparison to trans-[OsIVCl4(κN1-2H-ind)] [3] and cisplatin and found a strong reduction of cell viability at concentrations between 30 and 300 µM in different cancer cell lines (HT29, H446, 4T1 and HEK293). HT-29 cells are less sensitive to cisplatin than 4T1 cells, but more sensitive to [1] and Na[1], as shown by decreased proliferation and viability as well as an increased late apoptotic/necrotic cell population.

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“…All complexes displayed good to excellent cytotoxicity towards the human glioblastoma cell line A172 and the most active complex 10 ( Figure 1) showed IC50 values in the high nM range. In contrast to the Os(III) azole complexes [30], excellent correlation between the Os III/II redox potential and the antiproliferative activity was observed. It appeared that compounds that were more lipophilic and stable towards ligand substitution reactions before cellular uptake were the most cytotoxic.…”

mentioning

confidence: 81%

Development of anticancer agents: wizardry with osmium

Hanif

Babak

Hartinger

2014

Drug Discovery Today

149

103

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[Os^IVCl₅(Hazole)]⁻ Complexes: Synthesis, Structure, Spectroscopic Properties, and Antiproliferative Activity

Cited by 23 publications

References 46 publications

Spin contamination analogy, Kramers pairs symmetry and spin density representations at the 2-component unrestricted Hartree–Fock level of theory

Spin contamination analogy, Kramers pairs symmetry and spin density representations at the 2-component unrestricted Hartree–Fock level of theory

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

Development of anticancer agents: wizardry with osmium

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