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Dinuclear metal complexes modelling active sites of metallohydrolases

Jarenmark, Martin LU (2009)
Abstract
To study the active sites of dinuclear metallohydrolases new metal complexes that model these sites both in structure and function have been synthesized using two new phenol based dinucleating ligands, 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2-pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP) and 2,6-Bis[N-(N-(carboxymethyl)-N-(pyridylmethyl)amine)methyl]-4-methylphenolate (BCPMP). Both ligands contain pyridyl, tertiary amine and carboxylate groups but in IPCPMP one carboxylate donor is exchanged for a non-coordinating group yielding an unsymmetric ligand while BCPMP is symmetric with identical sets of ligands on either side of the phenol group. Zinc complexes of both these ligands have been structuraly... (More)
To study the active sites of dinuclear metallohydrolases new metal complexes that model these sites both in structure and function have been synthesized using two new phenol based dinucleating ligands, 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2-pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP) and 2,6-Bis[N-(N-(carboxymethyl)-N-(pyridylmethyl)amine)methyl]-4-methylphenolate (BCPMP). Both ligands contain pyridyl, tertiary amine and carboxylate groups but in IPCPMP one carboxylate donor is exchanged for a non-coordinating group yielding an unsymmetric ligand while BCPMP is symmetric with identical sets of ligands on either side of the phenol group. Zinc complexes of both these ligands have been structuraly characterized revealing tetratetranuclear complexes are formed when reacting IPCPMP with zinc acetate or ZnCl2 and sodium pivalate. Infrared spectroscopy indicate that the tetranuclear complexes dissociate in solution yielding two dinuclear complexes. The symmetric ligand BCPMP only yielded a dinuclear complex. Complexes of both ligand enhance the rate of phosphoester cleavage. For the substrate 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) an in situ prepared complex of the unsymmetric ligand yielded higher activity than the corresponding complex of the symmetric ligand. A zinc complex of the unsymmetric ligand also enhanced the hydrolysis of bis(2,4-dinitrophenyl)-phophate (BDNPP) and displayed saturation behaviour with respect to both pH and substrate concentration. Potentiometric studies support the formulation of the active catalyst as a dinuclear zinc complex with two terminally coordinated hydroxides where one act as nucleophile in the hydrolysis of BDNPP. The unsymmetric ligand has also been used to form a mononuclear Fe(III) complex that systematically and selectively can be used to synthesize heterodinuclear metalcomplexes. Several of these have been characterized by X-ray crystallography revealing close to identical structures for complexes of the fomula [Fe(III)M(II)(IPCPMP) (OAc)2(CH3OH)][PF6] (M = Zn, Co, Ni). A FeMn complex of the same formula is believed to have a very similar structure. The complexes have been studied by a range of different methods in both solid state (IR and Mössbauer spectroscopy as well as Magnetic susceptibility) and solution (IR and UV-vis spectroscopy) These complexes enhance the transesterification of HPNP but display different reactivities with the highest for the FeCo complex. They also enhance the hydrolysis of BDNPP and display significantly different pH dependencies. The results are used to discuss various mechanistic possibilities and it appears that the complexes use slightly different mechanisms partly depending on the pH of the solution. A FeCu derivative with the formula [{FeCu(IPCPMP)(OAc)}2(m-O)][PF6]2 has also been structurally characterized and has a tetranuclear structure where two heterodinuclear parts are bridged by a m-oxido group. Its structure and spectroscopic properties have been used to explain peculiarities in the reactivity and spectroscopic properties of the FeZn derivative. (Less)
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author
supervisor
opponent
  • Professor Casella, Luigi, Department of General Chemistry, University of Pavia
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Bioinorganic chemistry, enzymes, hydrolases, models, dinuclear, heterodinuclear, phosphotriesterase, purple acid phophatase
pages
155 pages
defense location
Centre for chemistry and chemical engineering, Lecture Hall B
defense date
2009-06-12 13:15
ISBN
978-91-7422-224-1
language
English
LU publication?
yes
id
3d431835-2cb4-4592-bd0b-e73c8b670860 (old id 1396745)
date added to LUP
2009-05-19 08:09:46
date last changed
2016-09-19 08:45:19
@phdthesis{3d431835-2cb4-4592-bd0b-e73c8b670860,
  abstract     = {To study the active sites of dinuclear metallohydrolases new metal complexes that model these sites both in structure and function have been synthesized using two new phenol based dinucleating ligands, 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2-pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP) and 2,6-Bis[N-(N-(carboxymethyl)-N-(pyridylmethyl)amine)methyl]-4-methylphenolate (BCPMP). Both ligands contain pyridyl, tertiary amine and carboxylate groups but in IPCPMP one carboxylate donor is exchanged for a non-coordinating group yielding an unsymmetric ligand while BCPMP is symmetric with identical sets of ligands on either side of the phenol group. Zinc complexes of both these ligands have been structuraly characterized revealing tetratetranuclear complexes are formed when reacting IPCPMP with zinc acetate or ZnCl2 and sodium pivalate. Infrared spectroscopy indicate that the tetranuclear complexes dissociate in solution yielding two dinuclear complexes. The symmetric ligand BCPMP only yielded a dinuclear complex. Complexes of both ligand enhance the rate of phosphoester cleavage. For the substrate 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) an in situ prepared complex of the unsymmetric ligand yielded higher activity than the corresponding complex of the symmetric ligand. A zinc complex of the unsymmetric ligand also enhanced the hydrolysis of bis(2,4-dinitrophenyl)-phophate (BDNPP) and displayed saturation behaviour with respect to both pH and substrate concentration. Potentiometric studies support the formulation of the active catalyst as a dinuclear zinc complex with two terminally coordinated hydroxides where one act as nucleophile in the hydrolysis of BDNPP. The unsymmetric ligand has also been used to form a mononuclear Fe(III) complex that systematically and selectively can be used to synthesize heterodinuclear metalcomplexes. Several of these have been characterized by X-ray crystallography revealing close to identical structures for complexes of the fomula [Fe(III)M(II)(IPCPMP) (OAc)2(CH3OH)][PF6] (M = Zn, Co, Ni). A FeMn complex of the same formula is believed to have a very similar structure. The complexes have been studied by a range of different methods in both solid state (IR and Mössbauer spectroscopy as well as Magnetic susceptibility) and solution (IR and UV-vis spectroscopy) These complexes enhance the transesterification of HPNP but display different reactivities with the highest for the FeCo complex. They also enhance the hydrolysis of BDNPP and display significantly different pH dependencies. The results are used to discuss various mechanistic possibilities and it appears that the complexes use slightly different mechanisms partly depending on the pH of the solution. A FeCu derivative with the formula [{FeCu(IPCPMP)(OAc)}2(m-O)][PF6]2 has also been structurally characterized and has a tetranuclear structure where two heterodinuclear parts are bridged by a m-oxido group. Its structure and spectroscopic properties have been used to explain peculiarities in the reactivity and spectroscopic properties of the FeZn derivative.},
  author       = {Jarenmark, Martin},
  isbn         = {978-91-7422-224-1},
  keyword      = {Bioinorganic chemistry,enzymes,hydrolases,models,dinuclear,heterodinuclear,phosphotriesterase,purple acid phophatase},
  language     = {eng},
  pages        = {155},
  school       = {Lund University},
  title        = {Dinuclear metal complexes modelling active sites of metallohydrolases},
  year         = {2009},
}