Development, Synthesis and Characterization of Biomimetic Model Complexes
Elizabeth Brandes, Kristin Sahr and Ariel Schuelke and Dr. Roslyn M. Theisen
Department of Chemistry, University of Wisconsin - Eau Claire
Introduction
Characterization
Metalloenzymes are proteins that catalyze a specific reaction and contain
metals that are tightly bound at the active site. Hemoglobin is a common
metalloprotein that transfers O2 in the blood.
A subclass of metalloenzymes are dioxygenases. Dioxygenases transfer
both oxygen atoms of O2 into substrate. They have the ability to cleave and
degrade aromatic compounds and play an important role in many
biological functions, such as mammalian metabolism.1
A specific dioxygenase, Quercetin 2,3 Dioxygenase (QDO), is unique in that
it is the only known dioxygenase that is copper dependent. The copper
center is bound to 3 histidines, 1 glutamate, and the antioxidant quercetin.2
QDO is found in bacteria, where they use the enzyme to degrade aromatic
compounds. Aromatic compounds are one of the most prevalent and
persistent pollutants in the environment. A synthetic model that mimics the
active site of QDO, could be used for possible bioremediation purposes.
Characterization of Ligands
SalenH2 and BPG were characterized by 1H NMR. 1H NMR is used elucidate the
structure of compound by measuring the number and chemical shift of protons.
SalenH2:
BPG:
Characterization of Metal Complexes
UV-Visible Spectra of Copper Complexes
OH
OH
OH
O2
OH
HO
O
O
CO2H
CO
OH O
1.4
1.2
1.2
1
N
1
O
OH
N
N
N
O
0.6
O
0.6
λ =351nm
Cu(BPG)
0.2
Cu(BPG)(Quercetin)
λ =265 and 302nm
0.2
O
0.4
λ =255 and 287nm
N
CuII
0.8
2PF6-
0.8
0.4
Research Goals
CuII
0
0
200
• Synthesize ligands that mimic the 3-His-1-Carboxylate coordination
• Synthesize and characterize metal complexes
• Study reactivity of metal complexes and substrates
300
400
500
Wavelength(nm)
600
700
200
800
300
400
500
Wavelength (nm)
600
700
800
UV-Visible and IR Spectra of Manganese Complex
Synthesis
UV/Vis Spectrum of Mn(Salen) in MeOH
FT-IR Spectrum of Mn(Salen) in mineral oil
1.2
100.00
90.00
1
Synthesis of Ligands
SalenH24:
80.00
N
N
O
70.00
ν(C=N) = 1540cm-1
60.00
0.6
50.00
40.00
0.4
M 2+
M 2+ salt
NaOH, MeOH
Absorbance (AU)
0.8
30.00
λ = 394nm
O
20.00
0.2
10.00
0
200
N,N-bis(2-pyridlymethyl)glycine)(BPG)3:
400
500
600
700
Wavelength (nm)
M 2+ salt
N
NaOH, MeOH
AgPF6 or NaBPh 4
O
M
N
N
O
References
300
1. Que, Lawrence; Ho, R. Y. N. Dioxygen Activation by Enzymes with Mononuclear Non-Heme Iron Active
Sites. Chem. Rev. 1996, 96, 2607–2624.
2. Fusetti, F.; Schröter, K. H.; Steiner, R. A.; van Noort, P. I.; Pijning, T.; Rozeboom, H. J.; Kalk, K. H.; Egmond, M.
R.; Dijkstra, B. W. Crystal Structure of the Copper-Containing Quercetin 2,3-Dioxygenase from Aspergillus
Japonicus. Struct. Lond. Engl. 1993 2002, 10, 259–268. Steiner, R. A.; Kalk, K. H.; Dijkstra, B. W. Anaerobic
Enzyme⋅substrate Structures Provide Insight into the Reaction Mechanism of the Copper-Dependent
Quercetin 2,3-Dioxygenase. Proc. Natl. Acad. Sci. 2002, 99, 16625–16630.
3. Cox, D.; Benkovic, J.; Bloom, L.M.; Bradley, F.C.; Nelson, M.J.; Que, L.; Wallick. J.M. Chem. Soc. 1998, 110,
2027
4. Shaabani S.; Darbari R. Elixir Org. Chem. 2013, 55, 12764-12766
800
2,400
2,200
2,000
1,800
1,600
1,400
0.00
1,200
Frequency (cm-1)
Future Work
• Synthesize and characterize Fe2+(BPG) complex to model the active site of
quercetin dioxygenase.
• Study reactivity of Fe2+(BPG) and substrates.
Acknowledgements
University of Wisconsin – Eau Claire Chemistry Department
University of Wisconsin – Eau Claire Material Science Program
Student Blugold Commitment Differential Tuition funds through the
UW- Eau Claire Faculty/Student Research Collaboration Grants program
% Transmittance
O
Absorbance
HO
Quercetin
2,3 dioxygenase
[Cu(II)(Salen)] (green) in MeOH
Cu(BPG) (blue) and Cu(BPG)(Quercetin)(green) in MeOH
Absorbance (AU)
OH