β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding

Rianne M. Lord, James J. Mannion, Benjamin D. Crossley, Andrew J. Hebden, Max W. McMullon, Julie Fisher, Roger M. Phillips, Patrick C. McGowan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Herein, we report 30 new β-diketonate titanium compounds of the type [Ti(O,O)2X2], whereby O,O=asymmetric or symmetric β-diketonate ligand and X=Cl, Br, OEt or OiPr. Thirteen new crystal structures are discussed and show that these octahedral species all adopt cis geometries in the solid state. These compounds have been tested for their cytotoxicity using SRB and MTT assays, showing several of the compounds are as potent as cisplatin against a range of tumor cell lines. Results also show the [Ti(O,O)2Br2] complexes are more potent than [Ti(O,O)2Cl2], [Ti(O,O)2(OEt)2] and [Ti(O,O)2(OiPr)2]. Using a simple symmetrical heptane-3,5-dione (O,O) ligand bound to titanium, we observed more than a 50-fold increase in potency with the [Ti(O,O)2Br2] (28) when compared to [Ti(O,O)2Cl2] (27). One of the more potent compounds (6) has been added to three different sixmers of DNA, in order to analyse the potential DNA binding of the compound. NMR studies have been carried out on the compounds, in order to understand the structural properties and the species formed in solution during the in vitro cell assays.
Original languageEnglish
Pages (from-to)6598-6605
Number of pages8
JournalChemistrySelect
Volume1
Issue number20
Early online date15 Dec 2016
DOIs
Publication statusPublished - Dec 2016

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Titanium compounds
Assays
Ligands
Heptanes
DNA
Cytotoxicity
Titanium
Cisplatin
Structural properties
Tumors
Crystal structure
Cells
Nuclear magnetic resonance
Geometry

Cite this

Lord, R. M., Mannion, J. J., Crossley, B. D., Hebden, A. J., McMullon, M. W., Fisher, J., ... McGowan, P. C. (2016). β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding. ChemistrySelect, 1(20), 6598-6605. https://doi.org/10.1002/slct.201601290
Lord, Rianne M. ; Mannion, James J. ; Crossley, Benjamin D. ; Hebden, Andrew J. ; McMullon, Max W. ; Fisher, Julie ; Phillips, Roger M. ; McGowan, Patrick C. / β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding. In: ChemistrySelect. 2016 ; Vol. 1, No. 20. pp. 6598-6605.
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Lord, RM, Mannion, JJ, Crossley, BD, Hebden, AJ, McMullon, MW, Fisher, J, Phillips, RM & McGowan, PC 2016, 'β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding', ChemistrySelect, vol. 1, no. 20, pp. 6598-6605. https://doi.org/10.1002/slct.201601290

β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding. / Lord, Rianne M.; Mannion, James J.; Crossley, Benjamin D.; Hebden, Andrew J.; McMullon, Max W.; Fisher, Julie; Phillips, Roger M.; McGowan, Patrick C.

In: ChemistrySelect, Vol. 1, No. 20, 12.2016, p. 6598-6605.

Research output: Contribution to journalArticle

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T1 - β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding

AU - Lord, Rianne M.

AU - Mannion, James J.

AU - Crossley, Benjamin D.

AU - Hebden, Andrew J.

AU - McMullon, Max W.

AU - Fisher, Julie

AU - Phillips, Roger M.

AU - McGowan, Patrick C.

N1 - Not OA compliant; no AAM on ePrints. SH.

PY - 2016/12

Y1 - 2016/12

N2 - Herein, we report 30 new β-diketonate titanium compounds of the type [Ti(O,O)2X2], whereby O,O=asymmetric or symmetric β-diketonate ligand and X=Cl, Br, OEt or OiPr. Thirteen new crystal structures are discussed and show that these octahedral species all adopt cis geometries in the solid state. These compounds have been tested for their cytotoxicity using SRB and MTT assays, showing several of the compounds are as potent as cisplatin against a range of tumor cell lines. Results also show the [Ti(O,O)2Br2] complexes are more potent than [Ti(O,O)2Cl2], [Ti(O,O)2(OEt)2] and [Ti(O,O)2(OiPr)2]. Using a simple symmetrical heptane-3,5-dione (O,O) ligand bound to titanium, we observed more than a 50-fold increase in potency with the [Ti(O,O)2Br2] (28) when compared to [Ti(O,O)2Cl2] (27). One of the more potent compounds (6) has been added to three different sixmers of DNA, in order to analyse the potential DNA binding of the compound. NMR studies have been carried out on the compounds, in order to understand the structural properties and the species formed in solution during the in vitro cell assays.

AB - Herein, we report 30 new β-diketonate titanium compounds of the type [Ti(O,O)2X2], whereby O,O=asymmetric or symmetric β-diketonate ligand and X=Cl, Br, OEt or OiPr. Thirteen new crystal structures are discussed and show that these octahedral species all adopt cis geometries in the solid state. These compounds have been tested for their cytotoxicity using SRB and MTT assays, showing several of the compounds are as potent as cisplatin against a range of tumor cell lines. Results also show the [Ti(O,O)2Br2] complexes are more potent than [Ti(O,O)2Cl2], [Ti(O,O)2(OEt)2] and [Ti(O,O)2(OiPr)2]. Using a simple symmetrical heptane-3,5-dione (O,O) ligand bound to titanium, we observed more than a 50-fold increase in potency with the [Ti(O,O)2Br2] (28) when compared to [Ti(O,O)2Cl2] (27). One of the more potent compounds (6) has been added to three different sixmers of DNA, in order to analyse the potential DNA binding of the compound. NMR studies have been carried out on the compounds, in order to understand the structural properties and the species formed in solution during the in vitro cell assays.

U2 - 10.1002/slct.201601290

DO - 10.1002/slct.201601290

M3 - Article

VL - 1

SP - 6598

EP - 6605

JO - ChemistrySelect

JF - ChemistrySelect

SN - 2365-6549

IS - 20

ER -