Embed Size (px)
Citation preview
By: Seth Cory and Trang Nguyen CHEM 462 – Dr. Marcetta Y. Darensbourg 1
Acetyl CoA Synthase: Nature’s Monsanto Acetic Acid Catalyst
Outline
2
Industrial Process: Monsanto Acetic Acid Catalysis Reaction Mechanism Advantages & Other Routes
Biological Mechanism: ACS/CODH Catalysis Overview of Structure Proposed Mechanisms & Biomimetic Complexes Survey of Mechanisms at the A-Cluster Analysis of Synthetic Biomimetic Complexes Computational Analysis
Conclusion Current Directions Summary
Monsanto Acetic Acid Process Acetic acid used by many chemists Converted to acetic anhydride and used for synthesis of
acetate films and aspirin
Mid 1960s: BASF cobalt catalyst used for methanol carbonylation Reaction conditions: 250 oC and 680 bar
Late 1960s: Monsanto rhodium catalyst discovered Reaction conditions: 150-200 oC and 30-60 bar
3 Miessler, G; Spessard, G. Organometallic Chemistry. 1996. Jones, J. Platinum Metals Rev. 2000, 3, 94-105.
HI
H2O
CH3IRh3+
COI
OC II
CH3
Rh3+CI
OC II
O
CH3
Rh3+CI
OC II
O
CH3CO
Rh+ COI
OC I
CH3CO
I
H2O
CH3CO
OH
CO
CH3OH
Start HereMonsanto Acetic Acid Process
4
Rate = k[[Rh(CO2)I2-]][CH3I]
Adapted from: Miessler, G; Spessard, G. Organometallic Chemistry. 1996.
E.C. = 18 e-
E.C. = 16 e-
E.C. = 18 e-
E.C. = 16 e-
Monsanto Acetic Acid Process
5 Jones, J. Platinum Metals Rev. 2000, 3, 94-105.
6
Benefits: Uses a more efficient metal complex to synthesize a C-C bond Increased yield selectivity to >99% based upon methanol Milder conditions needed for the synthesis
(150-200 oC and 30-60 bar) Plant capacity: 500,000 tons annually
Challenges: Rhodium: expensive and precipitates under low water concentrations Large production of high boiling point by-products
Replaced by an Iridium catalyst in the late 1990s by BP Chemicals
How can nature do this chemistry at atmospheric pressures and low temperatures?
Monsanto Acetic Acid Process
Sunley, G; Watson, D. Catal. Today. 2000, 58, 293-307. Sava, X; et al. Ullmann’s Encyclopedia of Industrial Chemistry. 2007.
Outline
7
Industrial Process: Monsanto Acetic Acid Catalysis Reaction Mechanism Advantages & Other Routes
Biological Mechanism: ACS/CODH Catalysis Overview of Structure Proposed Mechanisms & Biomimetic Complexes Survey of Mechanisms at the A-Cluster Analysis of Synthetic Biomimetic Complexes Computational Analysis
Conclusion Current Directions Summary
8
Natural Sources of ACS
Chemoautotropic: grow on CO2/H2 or CO
Major role in the global carbon (CO2/CO) cycle
Tan, S; et al. Biochem. 2007, 46, 11606 -11613
Bacteria
Bacteria have developed intricate chemical processes to survive based on their environments!
ACS/CODH: Overview of Structure
9 Ragsdale, S; et al. Chem. Rev. 2014, 114, 4149-4174.
ACS/CODH: Overview of Reactions
10
Active site of C-cluster Proposed Mechanism of C-cluster
How CO is delivered from C-cluster to A-cluster?
Macharak, P; Harrop, T. Coord. Chem. Rev. 2005, 249, 3007-3024. Lindahl, P. Met. Ions Life Sci. 2009, 6, 133-150. Wolfgang, K; Schwederski, B; Klein, A. Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life. 2013.
ACS/CODH: Overview of Structure
11 Ragsdale, S; et al. Chem. Rev. 2014, 114, 4149-4174.
12
A Cluster: active site of ACS reaction
Proximal Ni: (trigonal planar) + where substrate binds + very labile can be removed by phenanthroline
Proximal Ni: (trigonal pyramid) can be replaced by Zn and Cu inactivates ACS activity
Ni
Lindahl, P. Coordination & Bioinorganic Chemistry Lectures, Nickel Enzyme, Texas A&M University, College Station. TX, USA, 2014
A-Cluster: Nid Site (Tight)
13
Ni2+
N
S N
S
HN
O
Ni2+
O
O
2-
*signifies an attachment to the protein backbone
N
S N
S
HN
O
O
O
4-
cys
gly
cys
Spectroscopic Properties of A-cluster
14
Electronic Properties Oxidized = diamagnetic 1 e- Reduced =
paramagnetic Under CO atmosphere gives
EPR signal
Vibrational Properties νCO = 1996 cm-1
Macharak, P; Harrop, T. Coord. Chem. Rev. 2005, 249, 3007-3024. Fontecilla-Camps, J; et al. Nat. Struct. Biol. 2003, 10, 217-278.
Outline
15
Industrial Process: Monsanto Acetic Acid Catalysis Reaction Mechanism Advantages & Other Routes
Biological Mechanism: ACS/CODH Catalysis Overview of Structure Proposed Mechanisms & Biomimetic Complexes Survey of Mechanisms at the A-Cluster Analysis of Synthetic Biomimetic Complexes Computational Analysis
Conclusion Current Directions Summary
How can we study the chemistry of the A-cluster?
16
Goals: Provide mechanistic insight at the A-Cluster Use the model to synthesize acetyl-CoA from CH3 and CO
Biophysical Methods Starting materials: How to obtain the A-cluster of ACS/CODH enzyme? Protein biochemistry: purify proteins from living organisms Active-site mimicking organometallic complexes
Experimental techniques: How to study the activity of A-cluster? Biophysical Techniques: X-ray Crystallography & Spectroscopy Organometallic synthesis coupled with spectroscopy and redox studies Structural & Spectroscopic vs. Functional
Computationally using DFT calculations
Diamagnetic Mechanism Paramagnetic Mechanism
17
Relies on Nip(0) Ni(II) square planar species
NiFeC EPR signal results from a side-reaction
Relies on Nip (I) Ni(III) square pyramidal species
NiFeC EPR signal results from a Ni(I)-CO species
Crabtree, R. The Organometallic Chemistry of the Transition Metals. 2005. Ragsdale, S; et al. Chem. Rev. 2014, 114, 4149-4174.
Ni0: d10
Ni+: d9
18
Lindahl Mechanism (Diamagnetic)
Adapted from: Lindahl, P. Met. Ions Life Sci. 2009, 6, 133-150. Lindahl, P; Barondeau, D. J. Am. Chem. Soc. 1997, 119, 3959-3970.
Ni2+N
S N
S
O
Ni0S
2+/1+[Fe4S4]
Ni2+N
S N
S
O
Ni2+S2+/1+[Fe4S4]
Ni2+N
S N
S
O
Ni2+
S2+/1+[Fe4S4]
Ni2+N
S N
S
O
Ni2+
S2+/1+[Fe4S4]
CO
CH3Co3+-CoFeSP Co1+-CoFeSP
CO
H3C
Migratory InsertionH3C
O
CoAS-
H3C S
O
CoA
H3C
Camps Mechanism (Diamagnetic)
19 Adapted from: Fontecilla-Camps, J; et al. Nat. Struct. Biol. 2003, 10, 217-278.
Ni2+N
S N
S
O
Ni0S
2+/1+[Fe4S4]
Ni2+N
S N
S
O
Ni0S
2+/1+[Fe4S4]
Ni2+N
S N
S
O
Ni2+
S2+/1+[Fe4S4]
Ni2+N
S N
S
O
Ni2+
S2+/1+[Fe4S4]
CO
CH3Co3+-CoFeSP
Co1+-CoFeSP
CO
CO
H3C
Migratory InsertionH3C
O
H3C S
O
CoA
CoAS-
Does CO withdraw e- density from Ni0?
Ragsdale Mechanism (Paramagnetic)
20
Ragsdale, S; Murakami, J. Biol. Chem. 2000, 275, 4699-4707. Ragsdale, S; et al. Biochemistry. 2002, 41, 1807-1819. Adapted from: Ragsdale, S; et. al. Chem. Rev. 2014, 114, 4149-4174.
Ni2+N
S N
S
O
Ni1+S2+[Fe4S4]
Ni2+N
S N
S
O
Ni1+S2+[Fe4S4]
Ni2+N
S N
S
O
Ni2+
S2+[Fe4S4]
Ni2+N
S N
S
O
Ni3+S
2+[Fe4S4]
CO
CH3Co3+-CoFeSP
Co1+-CoFeSP
CO
CO
H3CMigratory Insertion
H3C
O
CoAS-
H3C
S
O
CoA
Ni2+ is activated by a 1e-
reduction by ferredoxin
Ni2+N
S N
S
O
Ni2+S
2+[Fe4S4]
CO
H3C
Internal e- transfer
Outline
21
Industrial Process: Monsanto Acetic Acid Catalysis Reaction Mechanism Advantages & Other Routes
Biological Mechanism: ACS/CODH Catalysis Overview of Structure Proposed Mechanisms & Biomimetic Complexes Survey of Mechanisms at the A-Cluster Analysis of Synthetic Biomimetic Complexes Computational Analysis
Conclusion Current Directions Summary
Nip Biomimetic Complexes
Neither complex can be reduced Sulfur lone pairs prevent reduction Catalytically incompetent with
respect to ACS-type activity
22
Ni2+
S
N
S
N
Adapted from: Darensbourg, M; et al. Inorg. Chem. 1990, 29, 4366-4368. Adapted from: Darensbourg, M; et al. Organomettalics. 1993, 12, 870-875. Lindahl, P; J. Biol. Inorg. Chem. 2004, 9, 516-524.
Ni2+
P S
S P
Ph
Ph
Ph Ph
Ni2+,1+,0
P S
S P
Ph
Ph
Ph Ph
CH3
H3C
Nip Biomimetic Complexes
23
Ni2+,1+
S
N
S
N
CH3 CH3
σ-donors to the metal No π-acceptors to delocalize electrons
Phosphine ligands delocalize electrons Good π-acceptors allow for reduction to Ni0
Catalyzes formation of acetyl group Adapted from: Darensbourg, M; et al. Inorg. Chem. 1990, 29, 4366-4368. Adapted from: Darensbourg, M; et al. Organomettalics. 1993, 12, 870-875. Lindahl, P; J. Biol. Inorg. Chem. 2004, 9, 516-524.
Functional Biomimetic Complex
24 Adapted from: Holm, R; et al. J. Am. Chem. Soc. 1991, 113, 8485-8492.
Ni2+,1+
N
SS
S RR
RCH3MgX
Ni2+
N
SS
S RR
R
H3C
CO
Ni2+
N
SS
S RR
R
CO CH3
H3CSR
O
Ni0RS
-
• Can be reduced to Ni1+
• Thioethers cannot stabilize low oxidation state of Ni • After reductive elimination, the Ni0 dissociates and precipitates • v(CO) = 2026 cm-1 (only when CO binds first)
R = i-Pr or t-Bu
Biomimetic Complexes
25 Adapted from: Schröder; et al. Chem. Commun. 2003, 24, 3012-3013.
Nid-like site: N2S2 square-planar coordinated
Nip-like site: 2 bridging thiolates with 2 phosphines
{Nip2+ Nid2+} {Nip+ Nid2+} {Nip0 Nid2+} e- e-
Ni2+,1+
Ni2+
P P
S S
Ph
Ph Ph
Ph
NN
Biomimetic Complexes
26 Adapted from: Schröder; et al. Chem. Commun. 2003, 24, 3012-3013. Adapted from: Rauchfuss, T; et al. J. Am. Chem. Soc. 2003, 125, 8700-8701.
Ni2+
N
S
N
S
O O
Ni0
OC CO
Nid-like site:
2 amide nitrogens
Able to reduce to Ni0
Nid-like site:
2 tertiary amine nitrogens
Unable to reduce to Ni0
Ni2+,1+
Ni2+
P P
S S
Ph
Ph Ph
Ph
NN
Biomimetic Complexes
27
Nip-like site:
3rd bridging ligands
3 coordination sites
Nip-like site:
2 phosphine ligands
4 coordination sites
No ACS activity
(6) (6)
(5)
(5)
(5)
(5)
Adapted from: Riordan, C; Krishnan, R. J. Am. Chem. Soc. 2004, 126, 4484-4485. Lindahl, P. Coordination & Bioinorganic Chemistry Lectures, Nickel Enzyme, Texas A&M University, College Station. TX, USA, 2014
Ni2+,1+,0
P
S
P
S
Ni2+
N N
O
O
R
R
R
R
NH2
O
H3C(O)CHN
Outline
28
Industrial Process: Monsanto Acetic Acid Catalysis Reaction Mechanism Advantages & Other Routes
Biological Mechanism: ACS/CODH Catalysis Overview of Structure Proposed Mechanisms & Biomimetic Complexes Survey of Mechanisms at the A-Cluster Analysis of Synthetic Biomimetic Complexes Computational Analysis
Conclusion Current Directions Summary
Hall’s Theoretical Model
29
Calculated Cu1+(CO)(CH3) as unstable and CO likely dissociates upon CH3 addition in a competitive mechanism
Showed CH3 addition to Ni0 prior to CO retains thiolate ligands
Calculated an unstable Ni3+(CO )(CH3) that dissociates from thiolate ligands
Provided insight on a nickel-assisted thioacetyl reductive elimination
Adapted from: Hall, M; et. al. J. Am. Chem. Soc. 2004, 126, 3410-3411.
MS
L
S
S
N
N
O
O
Ni2+
CH3
Fe
HS
HSHS
Hall’s Theoretical Model
30 Adapted from: Hall, M; et. al. J. Am. Chem. Soc. 2004, 126, 3410-3411.
S Ni0S
S
Ni2+
+CH3
[1: 0 kcal mol-1]
S
Ni2+
S
S
Ni2+
[2: 0 kcal mol-1]
H3C
CO S
Ni2+
S
S
Ni2+
[3: -14.8 kcal mol-1]
H3C CO
S
Ni2+
S
S
Ni2+
[4: -21.0 kcal mol-1]
C
[TS: -5.0 kcal mol-1]
O
H3CSCH3
S
Ni2+
S
S
Ni2+
[5: -40.3 kcal mol-1]
COH3C
H3CS
[TS: -28.3 kcal mol-1] -25.5 kcal mol-1
H3CS CH3
O
+-
Outline
31
Industrial Process: Monsanto Acetic Acid Catalysis Reaction Mechanism Advantages & Other Routes
Biological Mechanism: ACS/CODH Catalysis Overview of Structure Proposed Mechanisms & Biomimetic Complexes Survey of Mechanisms at the A-Cluster Analysis of Synthetic Biomimetic Complexes Computational Analysis
Conclusion Summary Current Directions
Ni(0) has never been observed
Ni(0) in a highly electropositive environment formed by Nid2+ and [Fe4S4]2+
Reduction potential for Ni2+−CO/Ni+− CO is already negative, below −550 mV
SN2 addition of methyl cation to the Nip+ should result in a Nip3+
Nip3+ state is highly oxidizing and unstable
Further reduced to a more stable state Nip2+
Requires e- transfer from a redox carrier protein, which has not also been observed
32
Questions: Diamagnetic Vs. Paramagnetic
Ragsdale, S; et al. Chem. Rev. 2014, 114, 4149-4174. Macharak, P; Harrop, T. Coord. Chem. Rev. 2005, 249, 3007-3024.
Conclusion
33
The closed state is required to promote the oxidative
addition of a Ni0/1+ to form Ni2+/3+(CO)CH3 followed by a
methyl migration to form an acetyl C-C bond formation
Reductive elimination drives the formation of acetyl-CoA
Similar to Monsanto Acetic Acid Process
34
Current Work: Ni-Ni bond roles in catalysis?
Lindahl, P; J. Inorg. Biochem. 2012, 106, 172-178. M., Matsumoto, et al. Proc. Nat. Acad. Sci. USA. 2009, 106, 111862–111866.
Harvesting the Power of ACS
35 Dalton. Trans. 2010,12, 2949-3136. M., Matsumoto, et al. Proc. Nat. Acad. Sci. USA. 2009, 106, 111862–111866.
