Osmium(III) analogues of KP1019: Electrochemical and chemical synthesis, spectroscopic characterization, x-ray crystallography, hydrolytic stability, and antiproliferative activity

Handle URI:
http://hdl.handle.net/10754/563803
Title:
Osmium(III) analogues of KP1019: Electrochemical and chemical synthesis, spectroscopic characterization, x-ray crystallography, hydrolytic stability, and antiproliferative activity
Authors:
Kuhn, Paul-Steffen; Büchel, Gabriel E. ( 0000-0002-5055-7099 ) ; Jovanović, Katarina K.; Filipović, Lana; Radulović, Siniša S.; Rapta, Peter; Arion, Vladimir B.
Abstract:
A one-electron reduction of osmium(IV) complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole ([1]0), 2H-indazole ([2]0), 1H-imidazole ([3]0), and 1H-benzimidazole ([4]0), afforded a series of eight new complexes as osmium analogues of KP1019, a lead anticancer drug in clinical trials, with the general formula (cation)[trans-OsIIICl4(Hazole)2], where cation = H2pz+ (H2pz[1]), H2ind+ (H2ind[2]), H2im+ (H2im[3]), Ph4P+ (Ph4P[3]), nBu4N+ (nBu4N[3]), H2bzim+ (H2bzim[4]), Ph4P+ (Ph4P[4]), and nBu4N+ (nBu4N[4]). All complexes were characterized by elemental analysis, 1H NMR spectroscopy, electrospray ionization mass spectrometry, UV-vis spectroscopy, cyclic voltammetry, while H2pz[1], H2ind[2], and nBu4[3], in addition, by X-ray diffraction. The reduced species [1]- and [4]- are stable in aqueous media in the absence of air oxygen and do not react with small biomolecules such as amino acids and the nucleotide 5′-dGMP. Cell culture experiments in five different human cancer cell lines (HeLa, A549, FemX, MDA-MB-453, and LS-174) and one noncancerous cell line (MRC-5) were performed, and the results were discussed and compared to those for KP1019 and cisplatin. Benzannulation in complexes with similar structure enhances antitumor activity by several orders of magnitude, implicating different mechanisms of action of the tested compounds. In particular, complexes H2ind[2] and H2bzim[4] exhibited significant antiproliferative activity in vitro when compared to H2pz[1] and H2im[3]. (Chemical Equation Presented).
KAUST Department:
KAUST Catalysis Center (KCC); Physical Sciences and Engineering (PSE) Division; Chemical Science Program
Publisher:
American Chemical Society (ACS)
Journal:
Inorganic Chemistry
Issue Date:
20-Oct-2014
DOI:
10.1021/ic501710k
Type:
Article
ISSN:
00201669
Sponsors:
We thank A. Dobrov for ESI mass spectra measurements, A. Roller for collection of the X-ray data, and M. Malarek for reading the manuscript and helpful discussion. We are thankful to the Ministry of Science and Technology of Serbia for financial support from Grant No. III41026. P.R. thanks the Science and Technology Assistance Agency (Contract No. SK-AT-0027-12) and Slovak Grant Agency VEGA (Grant No. 1/0307/14) for financial support.
Is Supplemented By:
Kuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049111: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146p9b; DOI:10.5517/cc146p9b; HANDLE:http://hdl.handle.net/10754/624407; Kuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049112: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146pbc; DOI:10.5517/cc146pbc; HANDLE:http://hdl.handle.net/10754/624408; Kuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049113: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146pcd; DOI:10.5517/cc146pcd; HANDLE:http://hdl.handle.net/10754/624409
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Chemical Science Program; KAUST Catalysis Center (KCC)

Full metadata record

DC FieldValue Language
dc.contributor.authorKuhn, Paul-Steffenen
dc.contributor.authorBüchel, Gabriel E.en
dc.contributor.authorJovanović, Katarina K.en
dc.contributor.authorFilipović, Lanaen
dc.contributor.authorRadulović, Siniša S.en
dc.contributor.authorRapta, Peteren
dc.contributor.authorArion, Vladimir B.en
dc.date.accessioned2015-08-03T12:10:40Zen
dc.date.available2015-08-03T12:10:40Zen
dc.date.issued2014-10-20en
dc.identifier.issn00201669en
dc.identifier.doi10.1021/ic501710ken
dc.identifier.urihttp://hdl.handle.net/10754/563803en
dc.description.abstractA one-electron reduction of osmium(IV) complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole ([1]0), 2H-indazole ([2]0), 1H-imidazole ([3]0), and 1H-benzimidazole ([4]0), afforded a series of eight new complexes as osmium analogues of KP1019, a lead anticancer drug in clinical trials, with the general formula (cation)[trans-OsIIICl4(Hazole)2], where cation = H2pz+ (H2pz[1]), H2ind+ (H2ind[2]), H2im+ (H2im[3]), Ph4P+ (Ph4P[3]), nBu4N+ (nBu4N[3]), H2bzim+ (H2bzim[4]), Ph4P+ (Ph4P[4]), and nBu4N+ (nBu4N[4]). All complexes were characterized by elemental analysis, 1H NMR spectroscopy, electrospray ionization mass spectrometry, UV-vis spectroscopy, cyclic voltammetry, while H2pz[1], H2ind[2], and nBu4[3], in addition, by X-ray diffraction. The reduced species [1]- and [4]- are stable in aqueous media in the absence of air oxygen and do not react with small biomolecules such as amino acids and the nucleotide 5′-dGMP. Cell culture experiments in five different human cancer cell lines (HeLa, A549, FemX, MDA-MB-453, and LS-174) and one noncancerous cell line (MRC-5) were performed, and the results were discussed and compared to those for KP1019 and cisplatin. Benzannulation in complexes with similar structure enhances antitumor activity by several orders of magnitude, implicating different mechanisms of action of the tested compounds. In particular, complexes H2ind[2] and H2bzim[4] exhibited significant antiproliferative activity in vitro when compared to H2pz[1] and H2im[3]. (Chemical Equation Presented).en
dc.description.sponsorshipWe thank A. Dobrov for ESI mass spectra measurements, A. Roller for collection of the X-ray data, and M. Malarek for reading the manuscript and helpful discussion. We are thankful to the Ministry of Science and Technology of Serbia for financial support from Grant No. III41026. P.R. thanks the Science and Technology Assistance Agency (Contract No. SK-AT-0027-12) and Slovak Grant Agency VEGA (Grant No. 1/0307/14) for financial support.en
dc.publisherAmerican Chemical Society (ACS)en
dc.titleOsmium(III) analogues of KP1019: Electrochemical and chemical synthesis, spectroscopic characterization, x-ray crystallography, hydrolytic stability, and antiproliferative activityen
dc.typeArticleen
dc.contributor.departmentKAUST Catalysis Center (KCC)en
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentChemical Science Programen
dc.identifier.journalInorganic Chemistryen
dc.contributor.institutionFaculty of Chemistry, Institute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42Vienna, Austriaen
dc.contributor.institutionInstitute for Oncology and Radiology of Serbia, Pasterova 14Belgrade, Serbiaen
dc.contributor.institutionDepartment of Physical Chemistry, Slovak University of Technology, Radlinského 9Bratislava, Slovakiaen
kaust.authorBüchel, Gabriel E.en
dc.relation.isSupplementedByKuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049111: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146p9ben
dc.relation.isSupplementedByDOI:10.5517/cc146p9ben
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624407en
dc.relation.isSupplementedByKuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049112: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146pbcen
dc.relation.isSupplementedByDOI:10.5517/cc146pbcen
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624408en
dc.relation.isSupplementedByKuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049113: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146pcden
dc.relation.isSupplementedByDOI:10.5517/cc146pcden
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624409en
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