TY - JOUR
T1 - Half-sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands
T2 - Structural studies and preliminary investigation of in vitro and in vivo anti-tumour activities
AU - Palepu, Narasinga Rao
AU - Adhikari, Sanjay
AU - J, Richard Premkumar
AU - Verma, Akalesh K.
AU - Shepherd, Samantha L.
AU - Phillips, Roger M.
AU - Kaminsky, Werner
AU - Kollipara, Mohan Rao
N1 - No full text in Eprints. HN 27/10/2017
PY - 2017/7
Y1 - 2017/7
N2 - Half-sandwich ruthenium, rhodium and iridium complexes (1-12) were synthesized with aldoxime (L1), ketoxime (L2) and amidoxime (L3) ligands. Ligands have the general formula [PyC(R)NOH], where R = H (L1), R = CH3 (L2) and R = NH2 (L3). Reaction of [((arene)MCl2)2] (arene = p-cymene, benzene, Cp*; M = Ru, Rh, Ir) with ligands L1-L3 in 1:2 metal precursor-to-ligand ratio yielded complexes such as [((arene)MLκ2 (N∩N)Cl)]PF6. All the ligands act as bidentate chelating nitrogen donors in κ2 (N∩N) fashion while forming complexes. In vitro anti-tumour activity of complexes 2 and 10 against HT-29 (human colorectal cancer), BE (human colorectal cancer) and MIA PaCa-2 (human pancreatic cancer) cell lines and non-cancer cell line ARPE-19 (human retinal epithelial cells) revealed a comparable activity although complex 2 demonstrated greater selectivity for MIA PaCa-2 cells than cisplatin. Further studies demonstrated that complexes 3, 6, 9 and 12 induced significant apoptosis in Dalton's ascites lymphoma (DL) cells. In vivo anti-tumour activity of complex 2 on DL-bearing mice revealed a statistically significant anti-tumour activity (P = 0.0052). Complexes 1-12 exhibit HOMO-LUMO energy gaps from 3.31 to 3.68 eV. Time-dependent density functional theory calculations explain the nature of electronic transitions and were in good agreement with experiments.
AB - Half-sandwich ruthenium, rhodium and iridium complexes (1-12) were synthesized with aldoxime (L1), ketoxime (L2) and amidoxime (L3) ligands. Ligands have the general formula [PyC(R)NOH], where R = H (L1), R = CH3 (L2) and R = NH2 (L3). Reaction of [((arene)MCl2)2] (arene = p-cymene, benzene, Cp*; M = Ru, Rh, Ir) with ligands L1-L3 in 1:2 metal precursor-to-ligand ratio yielded complexes such as [((arene)MLκ2 (N∩N)Cl)]PF6. All the ligands act as bidentate chelating nitrogen donors in κ2 (N∩N) fashion while forming complexes. In vitro anti-tumour activity of complexes 2 and 10 against HT-29 (human colorectal cancer), BE (human colorectal cancer) and MIA PaCa-2 (human pancreatic cancer) cell lines and non-cancer cell line ARPE-19 (human retinal epithelial cells) revealed a comparable activity although complex 2 demonstrated greater selectivity for MIA PaCa-2 cells than cisplatin. Further studies demonstrated that complexes 3, 6, 9 and 12 induced significant apoptosis in Dalton's ascites lymphoma (DL) cells. In vivo anti-tumour activity of complex 2 on DL-bearing mice revealed a statistically significant anti-tumour activity (P = 0.0052). Complexes 1-12 exhibit HOMO-LUMO energy gaps from 3.31 to 3.68 eV. Time-dependent density functional theory calculations explain the nature of electronic transitions and were in good agreement with experiments.
KW - Aldoximes
KW - Amidoxime
KW - Anti-tumour
KW - Iridium
KW - Ruthenium
UR - http://www.scopus.com/inward/record.url?scp=84991093570&partnerID=8YFLogxK
U2 - 10.1002/aoc.3640
DO - 10.1002/aoc.3640
M3 - Article
AN - SCOPUS:84991093570
VL - 31
SP - 1
EP - 10
JO - Applied Organometallic Chemistry
JF - Applied Organometallic Chemistry
SN - 0268-2605
IS - 7
M1 - e3640
ER -