Why no  -H species into the enzyme? - no thermodynamic stabilization of terminal-H intermediates terminal-H corresponds to a kinetic product? But if this is true.... Can interconversion from terminal- to  -H 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. Formation of synthetic Fe(II)Fe(II)-H - species Terminal hydride species can be transiently formed and are more reactive than corresponding  -H species in H 2 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] H cluster. DFT results. (dppv)(CO)Fe(edt)Fe(PMe 3 )(CO) 2, Fe(I)Fe(I) redox state dppv = cis-1,2-C 2 H 2 (PPh 2 ) 2 Stereo-electronic similarity to [2Fe] H  possibility to verify theoretical predictions (Illinois, Brest) J-F Capon, F Gloaguen, F Y Petillon, P Schollhammer, J Talarmin 2009, 253,

Protonation regiochemistry Reaction with triflic acid in acetonitrile: looking for transition states and intermediate species

Protonation of synthetic models of the [2Fe] H cluster. DFT results Reaction Coordinate Kinetic control: terminal-H Thermodynamic control:  -H E (kcal/mol)

Protonation of synthetic models of the [2Fe] H cluster. DFT results. In the protonation of (dppv)(CO)Fe(edt)Fe(PMe 3 )(CO) 2 steric factor plays a key role Importance of intramolecular proton relay! S Ezzaher, J-F Capon, F Gloaguen, F Y Petillon, P Schollhammer, J Talarmin 2009, 48, 2-4

Protonation of synthetic models of the [2Fe] H cluster. Proximal or distal protonation?

 -protonation terminal-protonation on Fe d GG G≠G≠ GG G≠G≠ [(dppv)(CO)Fe(edt)Fe(PMe 3 )(CO) 2 ] (1) (CO) 3 Fe(edt)Fe(CO) 3 (2) a-a - (dppv)(CO)Fe(edt)Fe(CO) 3 (3) (PH 3 ) 2 (CO)Fe(edt)Fe(CO) 3 (4) a - (PMe 3 ) 2 (CO)Fe(edt)(CO)(PMe 3 ) 2 (5) (dppv)(CO)Fe(pdt)Fe(dppv)(CO) (6) (PH 3 ) 2 (CO)Fe(edt)(CO)(PH 3 ) 2 (7) (PH 3 ) 3 Fe(edt)(PH 3 )(CO) 2 (7a) 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] H cluster. 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  -H 3Int 4 Pseudo C3 rotations

Interconversion from terminal- to  -H: Pseudo C 3 rotations 4 Reaction Coordinate Int Int 4 E (kcal/mol)

Design of synthetic catalysts Easy H 2 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 H 2 production 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, k f =10 4 k f =4

Intermediates in the electrocatalytic H 2 production FeFe FeFe COCO COCO COCO COCO S S COCO COCO H FeFe FeFe COCO COCO COCO COCO S S COCO COCO H H ? Transient species

The DFT structure of the  -CO species Methodology: BP-86/TZVP, vibrational analysis (harmonic approximation)

DFT characterization of intermediate catalytic species: 1H - and 1H 2 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 H 2 production  -pdt)Fe 2 (CO) 5 P(NC 4 H 8 ) 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 species Possible formation of an intermediate species (2B) resembling the structure observed in the enzymatic cofactor?

DFT 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 species Coexistence of b1 e b2 leads to six non superimposed IR bands (1741, 1846, 1879, 1903, 1914, 1959 cm -1 ). (R 2 = 0.970)

DFT characterization of intermediate species (protonated intermediates) a-  Ha-tH1  G a-  H - a-tH1 = 34.7 kJ/mol b-H1b-H2  G b-H1 - b-H2 = 48.9 kJ/mol

Therefore… - The P(NC 4 H 8 ) 3 ligand does not lead to  -CO species resembling the H-cluster - The P(NC 4 H 8 ) 3 does not lead to terminal hydride species such as those most probably formed in the catalytic cycle of the enzyme... Because P(NC 4 H 8 ) 3 is too bulky  -pdt)Fe 2 (CO) 5 P(NC 4 H 8 ) 3