TY - JOUR
T1 - Synthesis and reactivity of the aquation product of the antitumor complex trans-[RuIIICl4(indazole)2]-
AU - Cebrián-Losantos, Berta
AU - Reisner, Erwin
AU - Kowol, Christian R.
AU - Roller, Alexander
AU - Shova, Sergiu
AU - Arion, Vladimir B.
AU - Keppler, Bernhard K.
N1 - CAN 149:166632 78-7 Inorganic Chemicals and Reactions Institute of Inorganic Chemistry,University of Vienna,Vienna,Austria. Journal 1038862-74-6P Role: PEP (Physical, engineering or chemical process), PRP (Properties), SPN (Synthetic preparation), PREP (Preparation), PROC (Process) (chain polymer; prepn. and crystal and mol. structure and cyclic voltammetry); 328238-76-2; 1038862-81-5; 1038862-82-6; 1038862-83-7; 1038862-84-8; 1038862-86-0; 1038862-87-1; 1038862-88-2; 1038862-89-3 Role: FMU (Formation, unclassified), PEP (Physical, engineering or chemical process), PRP (Properties), FORM (Formation, nonpreparative), PROC (Process) (formation in electrochem. redox couple); 1038862-76-8P; 1038862-77-9P; 1038862-78-0P; 1038862-79-1P; 1038862-80-4P Role: PRP (Properties), SPN (Synthetic preparation), PREP (Preparation) (prepn. and crystal and mol. structure); 1038862-72-4P Role: PEP (Physical, engineering or chemical process), PRP (Properties), SPN (Synthetic preparation), PREP (Preparation), PROC (Process) (prepn. and cyclic voltammetry); 1038862-70-2P Role: PEP (Physical, engineering or chemical process), PRP (Properties), RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), PROC (Process), RACT (Reactant or reagent) (prepn. and cyclic voltammetry and reactivity); 75-05-8 (Acetonitrile); 75-18-3 (Dimethyl sulfide); 100-47-0 (Benzonitrile); 700-00-5 (9-Methyladenine); 938-55-6 (6,6-Dimethyladenine); 197723-00-5 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. and reactivity and iminoacylation of aquation product of ruthenium indazole chloro antitumor complex); 835616-91-6P; 835616-92-7P; 835616-94-9P; 835616-96-1P; 1038862-68-8P; 1038862-69-9P; 1038862-71-3P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and reactivity and iminoacylation of aquation product of ruthenium indazole chloro antitumor complex); 328238-75-1P Role: PEP (Physical, engineering or chemical process), PRP (Properties), RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), PROC (Process), RACT (Reactant or reagent) (prepn., crystal and mol. structure, cyclic voltammetry, solvation kinetics and reactivity)
PY - 2008/7/21
Y1 - 2008/7/21
N2 - Aquation of the investigational anticancer drug trans-[Ru IIICl4(Hind)2]- (1, KP1019) results in the formation of mer,trans-[RuIIICl3(Hind) 2(H2O)] (2), which was isolated in high yield (85%) and characterized by spectroscopic methods and X-ray crystallography. Dissolution of 2 in acetone, led to its dimerization into [RuIII 2(μ-Cl)2Cl4(Hind)4]·2(Me) 2CO (3) in 79% yield, with release of two water molecules. Complex 2 reacts readily with nucleophilic organic molecules, viz., methanol or dimethyl sulfide, at room temperature by replacement of the aqua ligand to give mer,trans-[RuIIICl3(Hind)2(MeOH)] (4) and mer,trans-[RuIIICl3(Hind)2(Me2S)] (5) in 58 and 64% yield, respectively. By reaction of 2 with DMSO at room temperature or dimethyl sulfide at elevated temperatures trans,trans,trans- [RuIICl2(Hind)2(Me2S)2] (6) and trans,trans,trans-[RuIICl2(Hind) 2(S-DMSO)2] (7) were prepared in 64 and 75% yield, respectively. Dissolution of 2 in acetonitrile or benzonitrile gave rise to mer,trans-[RuIIICl3(Hind)(HN=C(Me)ind)] (8a), mer,trans-[RuIIICl3(Hind)(HN=C(Ph)ind)] (8b), and trans,trans-[RuIIICl2(HN=C(Me)ind)2]Cl (9) in 67, 50, and 23% yield, respectively, upon metal-assisted iminoacylation of indazole, which is unprecedented for ruthenium(III). Furthermore, complex 2 reacts with the DNA-model bases 9-methyladenine (9-meade) and N6,N6-dimethyladenine (6-me2ade) to yield mer,trans-[Ru IIICl3(Hind)2(9-meade)] (10) and mer,trans-[RuIIICl3(Hind)2(6-me 2ade)] (11) with the purine bases bound to the Ru(III) center via N7 and N3, respectively. Complex 11 represents the first ruthenium complex in which the coordination of the purine ligand N6,N6-dimethyladenine occurs via N3. In addition, the polymer [Na(EtOAc)2RuIII(μ-Cl) 4(Hind)2]n (12) was crystallized from ethyl acetate/diethyl ether solutions of Na[trans-RuIIICl 4(Hind)2]·1.5H2O (1a). The reported complexes were characterized by elemental analysis, IR and UV-vis spectroscopy, ESI mass spectrometry, cyclic voltammetry, and X-ray crystallography. Electrochemical investigations give insight into the mechanistic details of the solvolytic behavior of complex 2. The lability of the aqua ligand in 2 suggests that this complex is a potential active species responsible for the high antitumor activity of trans-[RuIIICl4(Hind) 2]-. © 2008 American Chemical Society.
AB - Aquation of the investigational anticancer drug trans-[Ru IIICl4(Hind)2]- (1, KP1019) results in the formation of mer,trans-[RuIIICl3(Hind) 2(H2O)] (2), which was isolated in high yield (85%) and characterized by spectroscopic methods and X-ray crystallography. Dissolution of 2 in acetone, led to its dimerization into [RuIII 2(μ-Cl)2Cl4(Hind)4]·2(Me) 2CO (3) in 79% yield, with release of two water molecules. Complex 2 reacts readily with nucleophilic organic molecules, viz., methanol or dimethyl sulfide, at room temperature by replacement of the aqua ligand to give mer,trans-[RuIIICl3(Hind)2(MeOH)] (4) and mer,trans-[RuIIICl3(Hind)2(Me2S)] (5) in 58 and 64% yield, respectively. By reaction of 2 with DMSO at room temperature or dimethyl sulfide at elevated temperatures trans,trans,trans- [RuIICl2(Hind)2(Me2S)2] (6) and trans,trans,trans-[RuIICl2(Hind) 2(S-DMSO)2] (7) were prepared in 64 and 75% yield, respectively. Dissolution of 2 in acetonitrile or benzonitrile gave rise to mer,trans-[RuIIICl3(Hind)(HN=C(Me)ind)] (8a), mer,trans-[RuIIICl3(Hind)(HN=C(Ph)ind)] (8b), and trans,trans-[RuIIICl2(HN=C(Me)ind)2]Cl (9) in 67, 50, and 23% yield, respectively, upon metal-assisted iminoacylation of indazole, which is unprecedented for ruthenium(III). Furthermore, complex 2 reacts with the DNA-model bases 9-methyladenine (9-meade) and N6,N6-dimethyladenine (6-me2ade) to yield mer,trans-[Ru IIICl3(Hind)2(9-meade)] (10) and mer,trans-[RuIIICl3(Hind)2(6-me 2ade)] (11) with the purine bases bound to the Ru(III) center via N7 and N3, respectively. Complex 11 represents the first ruthenium complex in which the coordination of the purine ligand N6,N6-dimethyladenine occurs via N3. In addition, the polymer [Na(EtOAc)2RuIII(μ-Cl) 4(Hind)2]n (12) was crystallized from ethyl acetate/diethyl ether solutions of Na[trans-RuIIICl 4(Hind)2]·1.5H2O (1a). The reported complexes were characterized by elemental analysis, IR and UV-vis spectroscopy, ESI mass spectrometry, cyclic voltammetry, and X-ray crystallography. Electrochemical investigations give insight into the mechanistic details of the solvolytic behavior of complex 2. The lability of the aqua ligand in 2 suggests that this complex is a potential active species responsible for the high antitumor activity of trans-[RuIIICl4(Hind) 2]-. © 2008 American Chemical Society.
KW - Solvolysis kinetics (of aquation product of ruthenium indazole chloro antitumor complex)
KW - Reduction
KW - Reduction potential (of aquation product of ruthenium indazole chloro antitumor complex and its iminoacylation products and dimethyladenine complex)
KW - Crystal structure
KW - Molecular structure (of ruthenium chloro complexes with indazole and its iminoacylation products and dimethyladenine)
KW - Amidation (prepn. and reactivity and iminoacylation of aquation product of ruthenium indazole chloro antitumor complex)
KW - ruthenium indazole adenine complex prepn structure reactivity iminoacylation
KW - crystal structure ruthenium indazole adenine complex
KW - electrochem redn ruthenium indazole adenine complex
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrhd&sid=DataCite
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrkg&sid=DataCite
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrjf&sid=DataCite
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrmj&sid=DataCite
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrlh&sid=DataCite
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrnk&sid=DataCite
UR - https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccrfrgc&sid=DataCite
U2 - 10.1021/ic800506g
DO - 10.1021/ic800506g
M3 - Article
SN - 0020-1669
VL - 47
SP - 6513
EP - 6523
JO - Inorganic Chemistry: including bioinorganic chemistry
JF - Inorganic Chemistry: including bioinorganic chemistry
IS - 14
ER -
