Osmium(II)--versus ruthenium(II)--arene carbohydrate-based anticancer compounds: similarities and differences.
The synthesis and in vitro anticancer activity of Os(II)-arene complexes with carbohydrate-derived phosphite co-ligands are reported. The compounds were characterized by standard methods and the molecular structure of dichlorido(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)osmium(II) was determined by X-ray diffraction analysis. Complexes with chlorido leaving groups undergo hydrolysis by consecutive formation of aqua compounds, followed by cleavage of a P-O bond of sugar phosphite ligands, as demonstrated by NMR studies. These observations are similar to those of analogous Ru(II)-arene complexes; however the rate of hydrolysis is very slow for osmium compounds. The complexes with oxalato leaving groups resist hydrolysis; no hydrolytic species were detected by (31)P{(1)H} NMR spectroscopy over several days. Within this series of Os compounds, in vitro anticancer activity is highest for the most lipophilic chlorido complex dichlorido(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside)osmium(II).
Hanif
Muhammad
M
University of Vienna, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090, Vienna, Austria.
Nazarov
Alexey A
AA
Hartinger
Christian G
CG
Kandioller
Wolfgang
W
Jakupec
Michael A
MA
Arion
Vladimir B
VB
Dyson
Paul J
PJ
Keppler
Bernhard K
BK
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009992:Osmium / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D012428:Ruthenium / Q000737:chemistry*
D000970:Antineoplastic Agents; D002241:Carbohydrates; D056831:Coordination Complexes; D009992:Osmium; D012428:Ruthenium