On the Electronic Structure ofmer,trans‐[RuCl3(1H‐indazole)2(NO)], a Hypothetical Metabolite of the Antitumor Drug Candidate KP1019: An Experimental and DFT Study

Bučinský, Lukáš; Büchel, Gabriel E.; Ponec, Robert; Rapta, Peter; Breza, Martin; Kožı́šek, Jozef; Gall, Marián; Biskupič, Stanislav; Fronc, Marek; Schiessl, Katharina; Cuzan, Olesea; Prodius, Denis; Turta, Constantin; Shova, Sergiu; Zając, D.; Arion, Vladimir B.

doi:10.1002/ejic.201201526

Cited by 18 publications

(21 citation statements)

References 104 publications

(135 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In other words, when the equatorial H 2 O ligand is replaced by NO, the coordination of NO to Ru(III) produces the [Ru III (NO) 0 ] structure product. This outcome is in agreement with the result obtained by Bučinský and his coworkers . They showed that the closed‐shell structure [Ru III (NO)] 6 fits better with the physical/spectroscopic properties of mer,trans ‐[RuCl 3 (Hind) 2 (NO)].…”

Section: Resultssupporting

confidence: 91%

“…Several ruthenium dimethyl sulfoxide nitrosyls have been synthesized and characterized by Alessio et al They indicated that the spectroscopic features are consistent with the [Ru(NO)] 6 formulation for all complexes because the ruthenium nitrosyls are formed by a diamagnetic Ru II nucleus bound to NO + . Experimental and DFT studies on the electronic structure of mer,trans ‐[RuCl 3 (1 H‐indazole) 2 (NO)] have been done by Bučinský and his coworkers . They showed that the physical/spectroscopic properties of mer,trans ‐[RuCl 3 (Hind) 2 (NO)] are better attributed to the closed‐shell structure [Ru III (NO)] 6 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reaction mechanism of NO with hydrolysates of NAMI‐A: an MD simulation by combining the QM/MM(ABEEM) with the MD‐FEP method

Wang

Zhao

et al. 2018

J Comput Chem

View full text Add to dashboard Cite

Nitrosylation reaction mechanisms of the hydrolysates of NAMI-A and hydrolysis reactions of ruthenium nitrosyl complexes were investigated in the triplet state and the singlet state. Activation free energies were calculated by combining the QM/MM (ABEEM) method with free energy perturbation theory, and the explicit solvent environment was simulated by an ABEEMσπ polarizable force field. Our results demonstrate that nitrosylation reactions of the hydrolysates of NAMI-A occur in both the triplet and the singlet states. The Ru-N-O angle of the triplet ruthenium nitrosyl complexes is in the range of 132.0 -138.2 . However, all the ruthenium nitrosyl complexes at the singlet state show an almost linear Ru-N-O angle. The nitrosylation reaction happens prior to the hydrolysis reaction for the firststep hydrolysates. The activation free energies of the nitrosylation reactions show that the H 2 O-NO exchange reaction of [RuCl 4 (Im)(H 2 O)] in the singlet spin sate is the most likely one. Comparing with the activation free energies of the hydrolysis reactions of the ruthenium nitrosyl complexes, the results indicate that the rate of the DMSO-H 2 O exchange reaction of [RuCl 3 (NO)(Im)(DMSO)] is faster than that of [RuCl 3 (H 2 O)(Im) (DMSO)] in both the triplet spin state and the singlet spin state.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Reaction mechanism of NO with hydrolysates of NAMI‐A: an MD simulation by combining the QM/MM(ABEEM) with the MD‐FEP method

Wang

Zhao

et al. 2018

J Comput Chem

View full text Add to dashboard Cite

show abstract

“…38 (H 2 ind) 2 [RuCl 5 (NO)] (Hind = 1 H -indazole) was prepared by heating the sodium salt with indazole in a 1:2 molar ratio in 6 M HCl. The starting compound ( n -Bu 4 N) 2 [OsCl 5 (NO)] was synthesized as previously reported in the literature.…”

Section: Methodsmentioning

confidence: 99%

Mechanism Elucidation of thecis–transIsomerization of an Azole Ruthenium–Nitrosyl Complex and Its Osmium Counterpart

et al. 2013

Self Cite

View full text Add to dashboard Cite

Synthesis and X-ray diffraction structures of cis and trans isomers of ruthenium and osmium metal complexes of general formulas (nBu4N)[cis-MCl4(NO)(Hind)], where M = Ru (1) and Os (3), and (nBu4N)[trans-MCl4(NO)(Hind)], where M = Ru (2) and Os (4) and Hind = 1H-indazole are reported. Interconversion between cis and trans isomers at high temperatures (80–130 °C) has been observed and studied by NMR spectroscopy. Kinetic data indicate that isomerizations correspond to reversible first order reactions. The rates of isomerization reactions even at 110 °C are very low with rate constants of 10–5 s–1 and 10–6 s–1 for ruthenium and osmium complexes, respectively, and the estimated rate constants of isomerization at room temperature are of ca. 10–10 s–1. The activation parameters, which have been obtained from fitting the reaction rates at different temperatures to the Eyring equation for ruthenium [ΔHcis-trans‡= 122.8 ± 1.3; ΔHtrans-cis‡= 138.8 ± 1.0 kJ/mol; ΔScis-trans‡= −18.7 ± 3.6; ΔStrans-cis‡= 31.8 ± 2.7 J/(mol·K)] and osmium [ΔHcis-trans‡= 200.7 ± 0.7; ΔHtrans-cis‡= 168.2 ± 0.6 kJ/mol; ΔScis-trans‡= 142.7 ± 8.9; ΔStrans-cis‡= 85.9 ± 3.9 J/(mol·K)] reflect the inertness of these systems. The entropy of activation for the osmium complexes is highly positive and suggests the dissociative mechanism of isomerization. In the case of ruthenium, the activation entropy for the cis to trans isomerization is negative [−18.6 J/(mol·K)], while being positive [31.0 J/(mol·K)] for the trans to cis conversion. The thermodynamic parameters for cis to trans isomerization of [RuCl4(NO)(Hind)]−, viz. ΔH° = 13.5 ± 1.5 kJ/mol and ΔS° = −5.2 ± 3.4 J/(mol·K) indicate the low difference between the energies of cis and trans isomers. The theoretical calculation has been carried out on isomerization of ruthenium complexes with DFT methods. The dissociative, associative, and intramolecular twist isomerization mechanisms have been considered. The value for the activation energy found for the dissociative mechanism is in good agreement with experimental activation enthalpy. Electrochemical investigation provides further evidence for higher reactivity of ruthenium complexes compared to that of osmium counterparts and shows that intramolecular electron transfer reactions do not affect the isomerization process. A dissociative mechanism of cis↔trans isomerization has been proposed for both ruthenium and osmium complexes.

show abstract

“…26 RuCl 3 and OsO 4 were purchased from Johnson Matthey. NH 2 OH·HCl, K 2 C 2 O 4 ·H 2 O, NaNO 2 , 1 H -indazole (Hind), 1 H -benzimidazole (Hbzim), 1 H -pyrazole (Hpz), and 1 H -imidazole (Him) were from Aldrich and Acros, while Na 15 NO 2 was from Cambridge Isotope Laboratories.…”

Section: Experimental Sectionmentioning

confidence: 99%

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

et al. 2013

Self Cite

View full text Add to dashboard Cite

Ruthenium nitrosyl complexes of the general formulas (cation)+[cis-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (Hind) (1c), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (Hpz) (2c), (cation)+ = (H2bzim)+, Hazole = 1H-benzimidazole (Hbzim) (3c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (Him) (4c) and (cation)+[trans-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (1t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (2t), as well as osmium analogues of the general formulas (cation)+[cis-OsCl4(NO)(Hazole)]−, where (cation)+ = (n-Bu4N)+, Hazole =1H-indazole (5c), 1H-pyrazole (6c), 1H-benzimidazole (7c), 1H-imidazole (8c), (cation)+ = Na+; Hazole =1H-indazole (9c), 1H-benzimidazole (10c), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11c), (cation)+ = H2pz+, Hazole = 1H-pyrazole (12c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (13c), and (cation)+[trans-OsCl4(NO)(Hazole)]−, where (cation)+ = n-Bu4N+, Hazole = 1H-indazole (5t), 1H-pyrazole (6t), (cation)+ = Na+, Hazole = 1H-indazole (9t), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (12t), have been synthesized. The compounds have been comprehensively characterized by elemental analysis, ESI mass spectrometry, spectroscopic techniques (IR, UV–vis, 1D and 2D NMR) and X-ray crystallography (1c·CHCl3, 1t·CHCl3, 2t, 3c, 6c, 6t, 8c). The antiproliferative activity of water-soluble compounds (1c, 1t, 3c, 4c and 9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c) in the human cancer cell lines A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma) has been assayed. The effects of metal (Ru vs Os), cis/trans isomerism, and azole heterocycle identity on cytotoxic potency and cell line selectivity have been elucidated. Ruthenium complexes (1c, 1t, 3c, and 4c) yielded IC50 values in the low micromolar concentration range. In contrast to most pairs of analogous ruthenium and osmium complexes known, they turned out to be considerably more cytotoxic than chemically related osmium complexes (9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c). The IC50 values of Os/Ru homologs differ by factors (Os/Ru) of up to ∼110 and ∼410 in CH1 and SW480 cells, respectively. ESI-MS studies revealed that ascorbic acid may activate the ruthenium complexes leading to hydrolysis of one M–Cl bond, whereas the osmium analogues tend to be inert. The interaction with myoglobin suggests nonselective adduct formation; i.e., proteins may act as carriers for these compounds.

show abstract

On the Electronic Structure ofmer,trans‐[RuCl₃(1H‐indazole)₂(NO)], a Hypothetical Metabolite of the Antitumor Drug Candidate KP1019: An Experimental and DFT Study

Cited by 18 publications

References 104 publications

Reaction mechanism of NO with hydrolysates of NAMI‐A: an MD simulation by combining the QM/MM(ABEEM) with the MD‐FEP method

Reaction mechanism of NO with hydrolysates of NAMI‐A: an MD simulation by combining the QM/MM(ABEEM) with the MD‐FEP method

Mechanism Elucidation of thecis–transIsomerization of an Azole Ruthenium–Nitrosyl Complex and Its Osmium Counterpart

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

Contact Info

Product

Resources

About