STERIC AND ELECTRONIC EFFECTS IN OXYGEN BINDING AND ACTIVATION WITH BIOMIMETIC COMPLEXES

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STERIC AND ELECTRONIC EFFECTS IN OXYGEN BINDING
AND ACTIVATION WITH BIOMIMETIC COMPLEXES

• Elena V. Rybak-Akimova

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Acknowledgements
Tufts University
Collaborators

• Prof. Larry Que and Prof. William Tolman, and
  their group members (University of Minnesota)
• Prof. William Reiff (Northeastern University)
  Mossbauer and magnetic susceptibility
• Prof. Alexander Nazarenko (SUNY College at
  Buffalo), Dr. Richard Staples (Harvard), Prof.
  Terry Haas (Tufts) - crystallography

• Dr. Sergei Kryatov
• Sonia Taktak
• Ivan Korendovych
• Dr. Olga Kryatova
• Dr. Aida Herrera
• Jeffrey Wikstrom
• Asli Ovat
• Wanhua Ye
• Prof. Rebecca Roesner and Phil Butler (visitors
  from Illinois Wesleyan University)

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NATURAL AND SYNTHETIC OXYGEN CARRIERS
O2, MeIm
D.H. Busch et al. Inorg. Chem. 1994, 33, 910
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Reversible O2 binding vs. Dioxygen activation in
non-heme systems
Reversible O2 binding
Coordinated superoxide is unreactive in substrate
oxidations
Oxygen activation peroxo- and high-valent oxo-
intermediates may be involved is substrate
oxidations
Non-heme iron chemistry
Copper chemistry
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APPROACH
Their reactivity was investigated by (a)
analyzing the products of catalytic reactions
(b) quantum chemistry computations.
CHEMICAL SYSTEMS

• Oxygen binding to
• (a) sterically hindered dinuclear iron(II)
  complexes
• (b) mononuclear copper(I) complexes
• Peroxo species in substrate oxidations
• (a) mechanism of phosphine oxidation with
  diiron(III)-peroxo intermedinate
• (b) designing mononuclear iron oxidation
  catalysts

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Oxygenation of a functional model of RNR
Oxygen activation at the dinuclear non-heme
iron(II) center of Class 1 Ribonucleotide
Reductase
Dioxygen reactivity of the diferrous synthetic
model complex (V. L. MacMurdo and L. Que, Jr.
Inorg. Chem. 2000, 39, 2254)
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Oxygenation of the Fe(II) TLA Dimer
CH2Cl2, -60 C Fe2 0.221 mM, O2 3.22 mM
Six-coordinate iron(II) slow reaction S.V.
Kryatov, E.V. Rybak-Akimova, V.L. MacMurdo, L.
Que, Jr. Inorg. Chem.2001, 2220
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Kinetics of oxygenation of the Fe(II) TLA dimer
Method of initial rates
Dichloromethane, -50 C O23.18 mM
Dichloromethane, -50 C Fe0.23 mM
Simple second-order reaction (1st order in
diferrous complex, 1st order in O2) v k
Fe2O2, k 1.9 M-1s-1 (-40 0C, CH3CN)
Activation parameters
?H 17 kJ/mol, ?S -175 J/K mol
ASSOCIATIVE, LOW-BARRIER, ENTROPICALLY
CONTROLLED PROCESS
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Oxidation of diiron(II) complex with
unsubstituted TPA ligand
(TPA)2Fe2(OH)22 O2 no peroxide!
½ O2
k 8.6(6) M-1s-1 ?H 32(4) kJ mol-1 ?S
-87(10) J/K mol
(TPA)FeIII products
Time interval between the spectra is 1 s. Fe20
0.25 mM, O20 4.4 mM, T ?40 ?C CH3CN
Spectrophotometric titration of
(TPA)2Fe2(OH)22 with dioxygen. CH2Cl2, 25 oC
S.V. Kryatov et al. Submitted
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Reaction of Fe2(OH)2(BQPA)22 with O2
Oxygenation vs. Oxidation
v k Fe2O2
Formation of a peroxo complex and oxidation into
Fe(III)Fe(III) species proceed via a common
bimolecular reaction between the Fe(II)Fe(II)
dimer and O2.
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Peroxo intermediate in diiron-BQPA systemis
stabilized by additions of bases
The kinetic parameters of Fe2(OH)2(BQPA)22
reactions with O2 do not depend on the presence
of a base. The yields of the peroxo species
increase dramatically
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Steric Effects in Oxygenation of Diiron(II)
complexes with TPA derivatives
S.V. Kryatov J. Kaizer, L. Que, Jr.
Fe2(OH)2(TLA)22
Fe2(OH)2(BQPA)22
O2
O2
L BQPA
L TLA
d(Fe - O) 1.984 and 2.101 Å
d(Fe - O) 1.973 and 2.168 Å
?H, kJ mol-1 17 ? 2 36 ? 4 ?S,
J mol-1 K-1 ?175 ? 20 ?80 ? 10 k, M-1s-1
2.34(20) 1.8(5) (-35 0C,
CH3CN)
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Rapid Oxygenation at a Vacant Site
Fe2(OH)2(BnBQA)22
k 2670 M-1s-1
spectra acquired every 10 ms
k 1.07 M-1s-1
(-40 0C, CH3CN)
Clean, rapid formation of the peroxo
species 1000-fold acceleration of O2 binding
S.V. Kryatov et al. Submitted
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Oxygenation of the Diferrous Complex with a
Tridentate Ligand BnBQA
?H 16(2) kJ mol-1 ?S -108(10) J K-1 mol-1
d(Fe - O) 1.985 and 2.090 A
Associative rate-limiting step
Labile monodentate CH3CN is coordinated to each
Fe((II)
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Rapid Oxygenation of Diferrous Complex with a
Tridentate Ligand Is Not an Electronic Effect
E1/2(O2/O2-) -1220 mV in CH3CN outer sphere
electron transfer is unlikely
S.V. Kryatov, S. Taktak
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Oxygen binding by copper(I) complexes
THF -80 oC
Irreversible oxygenation
Two reaction pathways A) direct
oxygenation B) solvent (THF) assisted
oxygenation.
S.V. Kryatov with N. Aboelella, W. Tolman et
al. JACS, submitted
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ELECTRONIC EFFECTS IN OXYGENATION OF COPPER(I)
COMPLEXES LCuI(RCN)
Hammett correlations for the oxygenation rates
Electron-withdrawing substituents in nitrile
ligands retard the oxygenation of Cu(I)L(RCN)
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Oxygenation of Five-Coordinate Diiron(II,II)
Paddlewheel Complexes with Sterically Hindered
Carboxylates
FeIIFeIIA4L2 O2 ? (FeIIFeIII) (FeIIIFeIV)
FeII2B4L2 O2 ? peroxo intermediate(s) L -
py MeIm THF
Lee, D. Lippard, S.J. J. Am. Chem.Soc. 1998,
120, 12153 Lee, D. DuBois, J. Petasis, D.
Hendrich, M.P. Krebs, C. Huynh, B.H. J. Am.
Chem. Soc. 1999, 121, 9893 Lee, D. Krebs, C.
Huynh, B.H. Hendrich, M.P. Lippard, S.J. J. Am.
Chem. Soc. 2000, 122, 6399 Lee, D. Pierce, B.
Krebs, C. Hendrich, M.P. Huynh, B.H. Lippard,
S.J. J. Am. Chem. Soc. 2002, 124, 3993
Hagadorn, J.R. Que Jr., L. Tolman, W.B. J. Am.
Chem. Soc. 1998, 120, 13531 Hagadorn, J.R. Que
Jr., L. Tolman, W.B. J. Am. Chem. Soc. 1999,
121, 9760. Chavez, F.A. Ho, R.Y.N. Pink, M.
Young Jr., V.G. Kryatov, S.V. Rybak-Akimova,
E.V. Andres, H. Münck, E. Que Jr., L. Tolman,
W.B. Angew. Chem. Int. Ed. Engl. 2002, 41, 149.
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Kinetic Parameters of the Oxygenation of
Diiron(II) Paddlewheel Complexes
v k Fe2 O2
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Activation parameters for the formation of
diiron(III) peroxide complexes from diiron(II)
precursors and O2
Low activation enthalpies large negative
activation entropies
ASSOCIATIVE PROCESSES
Small electronic effect of the capping ligands
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Isokinetic Relationships in the Oxygenation of
Iron(II) Paddlewheel Complexes
Three paddlewheel complexes with different
capping ligands (L py, MeIm, or THF) react
with dioxygen via similar rate-limiting steps.
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Reactivity of paddlewheel peroxo intermediates
Double-mixing experiments
S.V. Kryatov, F.A. Chavez, A.M. Reynolds, E.V.
Rybak-Akimova, L. Que, Jr., W.B. Tolman. Inorg.
Chem. 2004, 2141
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Kinetics of substrate oxidation with a
paddlewheel diiron peroxo intermediate
Influence of the substrate concentration Saturati
on behavior (Michaelis-Menten kinetics)
Influence of the capping ligand concentration
Reaction is retarded by adding THF
-800 C, CH2Cl2
Dissociation of a capping ligand and coordination
of the substrate are necessary for triphenyl
phosphine oxidation
Saturation kinetics in substrate oxidations with
peroxo- or high-valent oxo-species Y. Mekmouche
et al. Chem. Eur. J. 2002, 8, 1196 M. Taki, S.
Itoh, S. Fukuzumi. J. Am. Chem. Soc. 2002, 124,
998 M. Costas, C.W. Cady, S.V. Kryatov, M. Ray,
M.J. Ryan, E.V. Rybak-Akimova, L. Que, Jr. Inorg.
Chem. 2003, 7519.
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Possible reaction pathways in triphenyl phosphine
oxidation with diiron peroxo species
?H 52 kJ/mol ?S 15 J/K mol
k1 0.17?0.03 s-1 k2/k-1 1.7 ? 0.2
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Reactions of Fe2(O2)(THF)2 with different
substrates
PPh3
Py
Eyring plots of the pseudo-first-order
rate constants (kobs) for the reaction of
Fe2(O2)(THF)2 with excess PPh3 (solid line) and
excess Py (dotted line). Fe20 0.3 mM, PPh30
or Py0 9.5 mM, CH2Cl2
a Saturation rate constants at 193 K in CH2Cl2
Dissociative Ligand Substitution Limits
Inner-Sphere Phosphine Oxidation
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Possible reaction pathways in triphenyl phosphine
oxidation with diiron peroxo species
?H 52 kJ/mol ?S 15 J/K mol
k1 0.17?0.03 s-1 k2/k-1 1.7 ? 0.2
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Oxygen and Peroxide Activation in Mononuclear
System Iron Bleomycin
Pdb 1MTG
R.M.Burger, Chem.Rev., 1998, 98, 1153.
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IRON(II) COMPLEXES WITH PENTADENTATE
AMINOPYRIDINE LIGANDS
High-spin, five-coordinate Fe(II) in
square-pyramidal environment
Sonia Taktak, Aida Herrera
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Peroxide activation with iron(II) aminopyridine
macrocycles
Possible role of acid
Terminal olefins also undergo epoxidation
Sonia Taktak
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RELATIVE STABILIZATION OF Fe(III) STATE BY
DEPROTONATED AMIDE GROUPS
Fe(III)
Fe(II)
EFe3/Fe2 -0.57 V
-0.26 V a
-0.08 V b vs. SCE
a D.H. Busch et al Inorg. Chem. 14 (1975), 1194 b
G. Ferraudi Inorg. Chem. 19 (1980), 438
Stability constant of the amide complex is larger
than that of the amine complex by a factor of
105 and that of the Schiff base complex by a
factor of 108
I.V. Korendovych, R.J. Staples, W.M. Reiff, E.V.
Rybak-Akimova. Inorg. Chem. 2004, 43, 3930
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Rapid reaction between iron(II) amidopyridine
macrocycle and O2
t1/2 20 s (CN3CN) t1/2 gt 200 s (CN3CN/
MeIm) at room temp.
X-ray structure of the final oxidation
product (in the presence of MeIm)
-40 oC
Future work Activate
Ivan Korendovych, Olga Kryatova
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Conclusions

• Oxygen binding to a series of diiron(II)
  complexes is an associative bimolecular process
• Oxygenation of investigated dinuclear iron(II)
  complexes is a low-barrier, entropically
  controlled process
• Rapid oxygenation of dinuclear iron(II) complexes
  occurs at vacant or labile coordination sites
• Oxygen binding to low-coordinate copper(I) is
  facilitated by electron-donating substituents
• Peroxo intermediates in diiron systems can
  transfer an oxygen atom to substrates
  (phosphines). Coordination of the substrate to
  one of the iron centers is necessary for
  productive oxidation.
• Mononuclear iron(II) bleomycin mimics catalyze
  olefin epoxidation with H2O2, and react with O2,
  yielding peroxo intermediates. Electron-donating
  substituents (deprotonated amides) greatly
  facilitate reaction with dioxygen.
• Acknowledgments
• NSF the Research Corporation