Half-sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands

Structural studies and preliminary investigation of in vitro and in vivo anti-tumour activities

Narasinga Rao Palepu, Sanjay Adhikari, Richard Premkumar J, Akalesh K. Verma, Samantha L. Shepherd, Roger M. Phillips, Werner Kaminsky, Mohan Rao Kollipara

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere3640
Pages (from-to)1-10
Number of pages10
JournalApplied Organometallic Chemistry
Volume31
Issue number7
Early online date11 Oct 2016
DOIs
Publication statusPublished - Jul 2017

Fingerprint

Iridium
Rhodium
Oximes
Ruthenium
Tumors
Ligands
Bearings (structural)
Cells
Chelation
Benzene
Cisplatin
Density functional theory
Energy gap
Nitrogen
Metals
Apoptosis
Experiments

Cite this

Palepu, Narasinga Rao ; Adhikari, Sanjay ; J, Richard Premkumar ; Verma, Akalesh K. ; Shepherd, Samantha L. ; Phillips, Roger M. ; Kaminsky, Werner ; Kollipara, Mohan Rao. / Half-sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands : Structural studies and preliminary investigation of in vitro and in vivo anti-tumour activities. In: Applied Organometallic Chemistry. 2017 ; Vol. 31, No. 7. pp. 1-10.
@article{496431f72c604d0c9269d17286fb44cf,
title = "Half-sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands: Structural studies and preliminary investigation of in vitro and in vivo anti-tumour activities",
abstract = "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.",
keywords = "Aldoximes, Amidoxime, Anti-tumour, Iridium, Ruthenium",
author = "Palepu, {Narasinga Rao} and Sanjay Adhikari and J, {Richard Premkumar} and Verma, {Akalesh K.} and Shepherd, {Samantha L.} and Phillips, {Roger M.} and Werner Kaminsky and Kollipara, {Mohan Rao}",
note = "No full text in Eprints. HN 27/10/2017",
year = "2017",
month = "7",
doi = "10.1002/aoc.3640",
language = "English",
volume = "31",
pages = "1--10",
journal = "Applied Organometallic Chemistry",
issn = "0268-2605",
publisher = "John Wiley and Sons Ltd",
number = "7",

}

Half-sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands : Structural studies and preliminary investigation of in vitro and in vivo anti-tumour activities. / Palepu, Narasinga Rao; Adhikari, Sanjay; J, Richard Premkumar; Verma, Akalesh K.; Shepherd, Samantha L.; Phillips, Roger M.; Kaminsky, Werner; Kollipara, Mohan Rao.

In: Applied Organometallic Chemistry, Vol. 31, No. 7, e3640, 07.2017, p. 1-10.

Research output: Contribution to journalArticle

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

VL - 31

SP - 1

EP - 10

JO - Applied Organometallic Chemistry

JF - Applied Organometallic Chemistry

SN - 0268-2605

IS - 7

M1 - e3640

ER -