Electron and proton transfer reactions inphotosynthetic reaction centers

Hiroshi Ishikita
石北 央

Low-barrier H-bonds
really exist?

Can we identify Low-barrier H-bond at the DFT level?
CH31050H3C
H3C15CH3HN

CH31051.0 1.5 2.0Odonor−H (Å) Calcd δH 18.9 ppm

0.5Exptl δH 18.5 ppm
H3C
H3C15+NH

CH31050O+ H

1.0 1.5 2.0Odonor−H (Å) Calcd δH 19.1 ppm

15H

10CH35CH31.0 1.5 2.0Odonor−H (Å) Calcd δH 20.8 ppm
Exptl δH 21.4 ppm

O15O10OHO51.0 1.5 2.0Odonor−H (Å) Calcd δH 23.0 ppm

0.5Exptl δH 14.1 ppm

Exptl δH 20.5 ppm

20OO

15-

HO

10O

50.5

1.0 1.5 2.0Odonor−H (Å) Calcd δH 22.1 ppm

1.0 1.5 2.0Odonor−H (Å) Calcd δH 22.6 ppm

OO

15

energyenergysingle well

OOO-

HOO

10O

500.5Exptl δH 21.0 ppm

1.0 1.5 2.0Calcd δH 21.4 ppm
Odonor−H (Å) Exptl δH 20.3 ppm

LBHB: pKa(donor) = pKa(acceptor)
LBHB

-

00.5

00.5Exptl δH 18.4 ppm

O520
O00.5H3C10

1.0 1.5 2.0Odonor−H (Å) Calcd δH 17.9 ppm

20

CH3N20+ H15Exptl δH 18.3 ppm∆E (kcal/mol)

20

O

000.5

∆E (kcal/mol)+N∆E (kcal/mol)

20

20

CH3

∆E (kcal/mol)∆E (kcal/mol)N∆E (kcal/mol)

H3C

15+ H

N

∆E (kcal/mol)

H3C∆E (kcal/mol)

20

LBHB can be unambiguously identified
in the potential-energy profile at the DFT level(with neither solving the nuclear Schrödinger equation
nor considering dynamics)

OIkeda, Saito, Hasegawa, Ishikita (2017) Angew. Chem. Int. Ed. Engl. 56, 9151

Does a low-barrier H-bond also exist
in a protein environment?
A short H-bond in photosystem II

Light-driven water-splitting enzyme Photosystem II
2H2O → O2 + 4H+ + 4e-

D1

D2

2 substrate water molecules are catalyzed
at the Mn4CaO5 cluster

QM/MM (Quantum Mechanics/ Molecular Mechanics)
QM/MM calculations (B3LYP / LACVP**+)(PDB) OTyr-NHis distance = 2.46 Å

OTyrZ(D1-Tyr161)

H(calc.) OTyr-NHis distance = 2.47 ÅNεD1-His190

NδHO

The unusually short H-bond seems tobe quantumchemically reasonable!

NUmena, Kawakami, Shen, Kamiya(2011) Nature 473, 55

OTyrZ-NHis190 = 2.46 ÅRemarkably short!

H+

This is why TyrZ…His can mediate proton-coupled electron transfer (PCET)
Saito, Shen, Ishida, Ishikita (2011) Biochemistry 50, 9836

What makes the TyrZ…His190 distance so short?
QM/MM calculations (B3LYP / LACVP**+)

OTyr-NHis distance = 2.47 Åpolar environment in PSII

OTyr-NHis distance = 2.71 Å

H+H+(uphill)(barrierless)Removal of waters
Single-well

A cluster of water molecules near Mn4Ca
 Matching pKa between TyrZ and His190

Standard(asymmetric double-well)

The barrier-less H-bond facilities PCET

Saito, Shen, Ishida, Ishikita (2011) Biochemistry 45, 9836

H+ release from H2O
in photosystem II

Identification of the H+ releasing site in the S0-to-S1 transition“O5 or O4”, which is the substrate?
Note: in the oxidation of the crystal structure, the substrate water is considered to be OH-.
1) Substrate = O52) Substrate = O4

Mn4O5O4 e-

HCaO4O5Mn3
III → IV

Mn2

[S0] O5 = OH-O5

Mn3

Mn3

III → IVIV

Mn1
Mn2

[S1] O5 = O2-

O4O5CaMn3
IV
Mn1

Mn4O4 e-

CaCa

Mn1

HMn4

Mn4

Mn1
Mn2

[S0] O4 = OH-

Mn2[S1] O4 = O2-

Identification of the H+ releasing site in the S0-to-S1 transition
1) Substrate = O5

Mn4

Mn4

O5O4 e-HCaO4O5Ca

Mn3
III → IV
Mn1

Mn3IV
Mn1

Mn2

[S0] O5 = OH-Mn2[S1] O5 = O2-

O5 is close to Ca2+ and is apparently interesting…
However, O5 has no H-bond partner in the crystal structures(Umena et al. Nature 2011, Suga et al. Nature 2015)

no proton transfer from O5(The activation energy for proton release must be high)H-bonds of the Mn4CaO5 cluster
D1-Asp612) Substrate = O4

OO

2.71 Å

OW1

HMn4

O4

O5Ca

Mn3
III → IV

OW539

Mn4eCaO5

O4 2.43-2.50 Å
Mn3

Mn1

Mn1

2.67 Å
Mn2

OW923 O1Mn2[S0] O4 = OHUmena, Kawakami, Shen, Kamiya (2011) Nature 473, 55

The O4…OW539 bond is very short (<2.5 Å!)
We focus on the O4…OW539 H-bond

Changes in the H-bond potential in the S0-to-S1 transition
O4 is linked with the O4-water chain
via W539

O4-water chain

X-ray
QM/MM

O4…OW539 distances:
2.43-2.50 Å (Umena 2011)
2.55 Å in S0 (Saito 2015)
2.45 Å in S1 (Saito 2015)
Low-barrier H-bond in S1HW539
HO4 H

S0Mn3(III)
Mn3(IV)

H+S1

[O4]

[W539]Saito, Rutherford, Ishikita. (2015) Nat. Commun. 6, 8488

H-bond pattern: before and after PT in the S0-to-S1 transition
pre-PT

post-PT

1047

H+545

399

477397
393

538

H+539

O4

pre-PT

post-PT

O atoms did not move during H+ transfer

superposition
The activation energy is low• O4 is the deprotonation site
• The O4-water chain is the proton transfer pathway
Saito, Rutherford, Ishikita. (2015) Nat. Commun. 6, 8488

Experimental support for the O4-water chain being used in S0-to-S1
Time-resolved infrared spectroscopy
The S0-to-S1 transition:“the highest rate among the four S-state transitions.”“The high PCET rate with a relatively small KIE value (∼1.2)”“This result is more consistent with the O4−H structure(Saito et al.) than the O5−H one.”
Simizu, Sugiura, Noguchi. (2018) J. Phys. Chem. B 122, 9460

The time-resolved infrared spectroscopy supports“O4 is the deprotonation site in the S0-to-S1 transition”
Conclusions:• O4 is the deprotonation site (= substrate water)• The O4-water chain is the proton transfer pathway
Saito, Rutherford, Ishikita. (2015) Nat. Commun. 6, 8488
Kawashima, Takaoka, Kimura, Saito, Ishikita. (2018) Nat. Commun. 9, 1247