hindered rotation?

FeS

Fe

S

N

OCCO

ONC

CN

H

H

[Fe4S4]

NH3+

Why no Why no -H species into the enzyme?-H species into the enzyme?

- no thermodynamic stabilization of terminal-H intermediates...- no thermodynamic stabilization of terminal-H intermediates...- - ...terminal-H corresponds to a kinetic product?...terminal-H corresponds to a kinetic product?

But if this is true....But if this is true....Can interconversion from terminal- to Can interconversion from terminal- to -H-Hspecies take place into the protein?species take place into the protein?

•Hindered rotation?

Relevance of studies of protonation regiochemistry in synthetic models!- Brest laboratory- Illinois laboratory

[FeFe]-hydrogenases models and catalysis. [FeFe]-hydrogenases models and catalysis. Formation of synthetic Fe(II)Fe(II)-HFormation of synthetic Fe(II)Fe(II)-H- - speciesspecies

• Terminal hydride species can be transiently formed and are more reactive than corresponding -H species in H2 production.

• Spontaneously convert to -H species

Van der Vlugt J, Whaley C, Wilson S, Rauchfuss T. J. Am. Chem. Soc., 2005, 127, 16012;

Ezzaer S, Capon J-F, Gloaguen F, Petillon F Y, Schollhammer P, Talarmin J. Inorg. Chem., 2007, 46, 3426

Protonation of synthetic models of the [2Fe]Protonation of synthetic models of the [2Fe]HH

cluster. DFT results.cluster. DFT results.

• (dppv)(CO)Fe(edt)Fe(PMe3)(CO)2, Fe(I)Fe(I) redox state

dppv = cis-1,2-C2H2(PPh2)2

• Stereo-electronic similarity to [2Fe]H

Fe

S

FeS

OC

P

P

OP(CH3)3

CO

H

Fe

S

FeS

OC

Cys-S

O

CO

H

NC

CN

possibility to verify theoretical predictions (Illinois, Brest)

J-F Capon, F Gloaguen, F Y Petillon, P Schollhammer, J Talarmin 2009, 253, 1476-1494

Protonation regiochemistry

Fe

S

FeS

CO

P(CH3)3

CO

P

POC

Fe

S

FeS

CO

P(CH3)3

CO

P

POC H

Fe

S

FeS

H

P(CH3)3

CO

P

POC

O

Fe

S

FeS

CO

P(CH3)3

CO

H

PP

O

+ CF3SO3H

TS(1a-1Ha+)

TS(1c-1Hc+)

TS(1a-1Hb+)

1Ha+

1Hc+

1Hb+

Reaction with triflic acidin acetonitrile: looking for transition statesand intermediate species

Protonation of synthetic models of the [2Fe]Protonation of synthetic models of the [2Fe]HH

cluster. DFT results.cluster. DFT results.

Fe

S

Fe

S

P

P

COO

H

P(CH3)3

CO

SO

O O

CF3

Fe

S

Fe

S

P

P

CO

OP(CH3)3

CO

SO

O O

CF3

H

Fe

S

Fe

S

P

P

COCO

P(CH3)3

CO SO

O O

CF3

H

Fe

S

Fe

S

P

P

COCO

P(CH3)3

CO

H

SO

O O

CF3

2

1

3

4 4

-28.5

3

2

-5.8

15.2

-0.610.7

1

Reaction Coordinate

• Kinetic control: terminal-H• Thermodynamic control: -H

E (kcal/mol)

Protonation of synthetic models of the [2Fe]Protonation of synthetic models of the [2Fe]HH

cluster. DFT results.cluster. DFT results.

• In the protonation of (dppv)(CO)Fe(edt)Fe(PMe3)(CO)2

steric factor plays a key role

Importance of intramolecular proton relay!

Fe

S

Fe

S

P

P

COCO

P(CH3)3

CO

SOH

O O

CF3

Fe

S

Fe

S

P

P

COCO

P(CH3)3

CO

H

SO

O O

CF3

S Ezzaher, J-F Capon, F Gloaguen, F Y Petillon, P Schollhammer, J Talarmin 2009, 48, 2-4

Fe

S

FeS H

R3POC

R3P

PR3

CO

O

O

FeFe

SSH

R3PR3P

CO

PR3

CO

Fe

S

FeS

R3POC

R3P

PR3

CO

O

O

FeFe

SS

R3PR3P

CO

PR3

CO

Fe

S

FeS

R3POC

R3P

PR3

CO

CO

+

+

H+

H+

Transition state is stabilized when bridging CO moves towards the more electron-rich iron atom

Product is stabilized when the CO ligands are more evenly distributed among the iron atoms

Protonation of synthetic models of the [2Fe]Protonation of synthetic models of the [2Fe]HH

cluster. Proximal or distal protonation?cluster. Proximal or distal protonation?

-protonation terminal-protonation on Fed

G G≠ G G≠

[(dppv)(CO)Fe(edt)Fe(PMe3)(CO)2] (1) -13.3 15.2

-4.9 6.4

(CO)3Fe(edt)Fe(CO)3 (2) 11.3

17.1 -a -

(dppv)(CO)Fe(edt)Fe(CO)3 (3) -1.0 18.3 9.2 -

(PH3)2(CO)Fe(edt)Fe(CO)3 (4) -2.3 18.9 - a -

(PMe3)2(CO)Fe(edt)(CO)(PMe3)2 (5) -26.3 7.9 -23.5 5.6

(dppv)(CO)Fe(pdt)Fe(dppv)(CO) (6) -19.5 19.6

-15.7 16.6

(PH3)2(CO)Fe(edt)(CO)(PH3)2 (7) -13.3 8.1 -3.4 10.9

(PH3)3Fe(edt)(PH3)(CO)2 (7a) -19.4 6.0 -8.1 0.0

a. The reaction product does not correspond to an energy minimum structure and evolves back to reactant (the FeFe complex + triflic acid).

Protonation of synthetic models of the [2Fe]Protonation of synthetic models of the [2Fe]HH

cluster. Extending the seriescluster. Extending the series

Brief summary

• Terminal-H species are easily formed but spontaneously convert to (less reactive) mu-H species

• Relevance of the investigation of the mechanism of t-H -> mu-H conversion

Interconversion from terminal- to Interconversion from terminal- to -H -H

Fe

S

Fe

S

LL

HP

PL

O

Fe

S

Fe

S

HL

LP

PL

O

Fe

S

Fe

S

HL

LP

PL

O

Fe

S

Fe

S

HL

CO

LP

PL

120°

120°

3 Int

Int 4

Pseudo Pseudo CC3 rotations3 rotations

Interconversion from terminal- to Interconversion from terminal- to -H:-H:Pseudo Pseudo CC33 rotations rotations

Fe

S

Fe

S

LL

HP

PL

O

Fe

S

Fe

S

HL

LP

PL

O

Fe

S

Fe

S

HL

LP

PL

O

Fe

S

Fe

S

HL

CO

LP

PL

4

Reaction Coordinate

-28.5

3

Int

-5.6

6.2

15.83 Int

Int 4

E (kcal/mol)

Fe Fe

S

S

H

O

P

P

CO

L

L'

Fe Fe

S

SH

O

P

P

CO

FeS

Fe

S

H

P

PCO CO

L

L'

Fe

P

P

SFe

H

S

CO L' CO

Fe

H

FeP

PS

S

L'CO

CO

FeS

Fe

SH

P

P

COOC

Fe Fe

S

S

H

O

P

P

CO

L

FeS

Fe

SP

P HCO

L

L'CO

H

Fe

S

FeS

P

PCO

L'

CO

L

L

L'

L

L

L'

L'

L

trigonal (Bailar) twisttransition state

rhombic (Ray-Dutt) twisttransition state

trigonal (Bailar) twisttransition state

rhombic (Ray-Dutt) twisttransition state

Design of synthetic catalystsDesign of synthetic catalysts

• Easy H2 formation from Fe(II)Fe(I)-H species (terminal-H)

• In synthetic complexes (and in the isolated cofactor): Isomerization of Fe(II)Fe(II) terminal-H to -H coordination compounds is thermodinamically favoured...

• ... is it always kinetically unhindered?

• Do we really need Fe(I)Fe(I) like this:

Electrocatalytic HElectrocatalytic H2 2 productionproduction

1 = Fe(I)Fe(I) redox state

Borg S, Behrsing T, Best S, Razavet M, Liu X, Pickett C, J. Am. Chem. Soc., 2004, 126, 16988

kf=104

kf=4

FeS

Fe

S CO

COOC

OC

OC

CO

Intermediates in the electrocatalytic HIntermediates in the electrocatalytic H22 production production

Fe

FeC

OC

O

CO

CO

SSC

OCO

H

Fe

FeC

OC

O

CO

CO

SSC

OCO

HH?

Transient species

The DFT structure of the The DFT structure of the -CO species-CO species

Methodology: BP-86/TZVP, vibrational analysis (harmonic approximation)

Fe

HS

Fe

S CO

COOC

CO

OCO

H

DFT characterization of intermediate catalytic DFT characterization of intermediate catalytic species: 1Hspecies: 1H-- and 1H and 1H22

1-H and 1-H- are -H species:

Protonation of 1-H- leads to an intermediate species featuring two hydrogen atoms coordinated to the two iron centres:

Another example of a catalyst designed for HAnother example of a catalyst designed for H22

productionproduction

-pdt)Fe2(CO)5P(NC4H8)3

Hou J, Peng X, Zhou Z, Sun S, Zhao X, Gao S, J. Org. Chem., 2006, 71, 4633

Transient formation of a -CO species during turnover (IR absorption at 1768 cm-1)

Exp. characterization of intermediate speciesExp. characterization of intermediate species

Possible formation of an intermediate species (2B) resembling the structure observed in the enzymatic cofactor?

DFT characterization of intermediate speciesDFT characterization of intermediate species

b1 and b2 (-CO species) are almost isoenergetic and might coexist in solution. No other isomers could be characterized by DFT

b2b1

DFT characterization of intermediate speciesDFT characterization of intermediate species

Coexistence of b1 e b2 leads to six non superimposed IR bands (1741, 1846, 1879, 1903, 1914, 1959 cm-1).

(R2 = 0.970)

DFT characterization of intermediate speciesDFT characterization of intermediate species(protonated intermediates)(protonated intermediates)

a-H a-tH1

Ga-H - a-tH1= 34.7

kJ/mol

b-H1 b-H2Gb-H1 - b-H2= 48.9

kJ/mol

Therefore…Therefore…

- The P(NC4H8)3 ligand does not lead to -CO species

resembling the H-cluster

- The P(NC4H8)3 does not lead to terminal hydride species

such as those most probably formed in the catalytic cycle of the enzyme

... Because P(NC4H8)3 is too bulky

-pdt)Fe2(CO)5P(NC4H8)3