CURSO QUMICA BIOINORGNICA

UNAM Octobre 24/29, 2012

PETER M.H. KRONECK, Lab 212

[email protected]

Qumica Bioinorganic bsica de Manganeso en todo

a fotosntesis

Los Colores de Vida

Artculos que introducen

R.R. Crichton (2008)
Biological Inorganic Chemistry (chapter 16). Elsevier.
C.F Yocum, V.L Pecoraro (1999)
Current Opinion in Chemical Biology, 3,182-l 87Recent advances in the understanding of
the biological chemistry of manganese
A.J. Wu , J.E. Penner-Hahn, V.L. Pecoraro (2004)
Chemical Reviews, 104, 908-938. Structural, Spectroscopic, and Reactivity Models for the
Manganese Catalases
J.P. McEvoy, G.W. Brudvig (2006)
Chemical Reviews, 106, 4455-4483. Water-Splitting Chemistry of Photosystem II
T. M Iverson (2006)
Current Opinion in Chemical Biology, 10, 91100. Evolution and unique bioenergetic
mechanisms in oxygenic photosynthesis
J. Barber (2006)
Biochemical Society Transactions, 34, 619-631. Photosystem II: an enzyme of global
significance
http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookps.html
http://www.phschool.com/science/biology_place/biocoach/photosynth/overview.html

Repeticin: ROS = Reactive Oxygen Species

Especies de Oxgeno reactivas
sp

133 pm
1145 cm-1
O
2
-0.33V

p*

O2
sp

112 pm
1554 cm-1

+0.94V
149 pm

H2O2

842 cm-1

+0.38V

ss

OH+H2O

+2.31V

ss
3S+

Eo vs NHE, pH 7.25

2H2O
3

Conservacin de la energa de hoy: Reduccin de O2 a H2O

Gente es Aerobes

Los elementos de vida

H
Li

He

www.webelements.com
Be

Ne

Na Mg

Al

Si

Cl

Ar

Cu Zn Ga Ge As Se Br

Kr

Ca Sc Ti

Rb Sr

Zr

Cs Ba La Hf

Cr

Mn Fe Co Ni

Nb Mo Tc

Ta

Ru Rh Pd Ag Cd In

Re Os Ir

Pt

Au Hg Tl

Abundancia en el cuerpo (75 kg)

Ca: 1.2 kg
Fe: 4-7 g
K: 150 g
Zn: 2-3 g
Na: 70 g
Cu: 70-100 mg
Mg: 20-30 g
Mn: 10-12 mg

Sn Sb Te

Pb Bi

Po At

Xe

Rn

S: 140 g
P: 780 g
5

Metales de transicin - Funciones Biolgicas

Na

Charge Carrier, Osmolysis/equilibrium

Charge Carrier, Osmolysis/equilibrium

Mg

Structure, ATP/ThDP Binding, Photosynthesis,...

Ca

Structure, Signaling, Charge Carrier

Nitrogen Fixation, Oxidases, O2 Carrier

Cr

Unknown! (glucose metabolism ???)

Mo

Nitrogen Fixation, Oxidoreductase, O-Transfer

Oxidoreductases, Acetylene Hydratase

Mn

REDOX/ACID-BASE CATALYSIS
Photosynthesis, Oxidases, Structure,...

Fe

Oxidoreductase, O2 Transport + Activation,e--Transfer,...

Co

Oxidoreductase, Vitamin B12 (Alkyl Group Transfer)

Ni

Hydrogenase, CO Dehydrogenase, Hydrolases, Urease

Cu

Oxidoreductases, O2 Transport, e- -Transfer

Zn

Structure, Hydrolases, Acid-Base Catalysis...

6

Estados de oxidacin de Metales de Transicin

Na

Na(I)

K(I)

Mg

Mg(II)

Ca

Ca(II)

V(V)=(d0), V(IV)=(d1), V(III)=(d2)

Cr

Cr(III)=(d3),Cr(IV)=(d2),Cr(V)=(d1)

Mo

Mo(III)=(d3),Mo(IV)=(d2),Mo(V)=(d1), Mo(VI)=(d0)

W(IV)=(d2) ,W(V) =(d1), W(VI)=(d0)

Mn

Mn(IV)=(d3), Mn(III)=(d4), Mn(II) =(d5)

Fe

Fe(V)=(d3), Fe(IV)=(d4),Fe(III)=(d5),Fe(II)=(d6), Fe(I)?=(d7)

Co

Co(III)=(d6), Co(II)=(d7), Co(I)=(d8)

Ni

Ni(III)=(d7), Ni(II)=(d8), Ni(I)=(d9)

Cu

Cu(III)=(d8), Cu(II)=(d9), Cu(I)=(d10)

Zn

Zn(II) =(d10)

Mn Biochemistry R.R. Crichton, Chap. 16

The importance of Mn for living organisms is considerable:
(i) the tetranuclear Mn cluster involved in O2 production in photosynthetic
plants, algae and cyanobacteria
(ii) mammalian enzymes, arginase and mitochondrial superoxide dismutase.
(iii)Most of Mn biochemistry can be explained by its redox activity, and by
its analogy to Mg2+.
In contrast to other redox active metals (Fe) is that Mn is less reducing than
Fe under most biological conditions; Fe3+ is stable relative to Fe2+, Mn2+
relative to Mn3+ (Why ?). Two important consequences of this redox
chemistry are that Mn2+ can participate in useful redox catalysis on many
similar substrates to Fe3+, whereas the higher redox potential of Mn2+ makes
free Mn2+ harmless under conditions where free Fe2+ would produce
hydroxyl radicals. Cells (notably bacterial cells) can tolerate very high
cytoplasmic concentrations of Mn2+ with no negative consequences; this is
certainly not the case with redox metal ions like Fe and Cu.
8

Bioqumica de Mn R.R. Crichton, Chap. 16

La importancia de Mn para organismos vivos es considerable:
(i) el Mn tetranuclear cluster que est implicado en la produccin de oxgeno en
fbricas fotosintticas, algas y cyanobacteria
(ii) enzimas mamferas como arginase y superxido mitochondrial dismutase.
(iii) la mayor parte de la bioqumica de Mn puede ser explicada por su actividad
redox, y en otro por su analoga con Mg2+.
En contraste con otros metales activos redox (Fe) es que Mn tiene el potencial
menos que reduce que Fe en la mayor parte de condiciones biolgicas; Fe3+ es
estable con relacin a Fe2+, Mn2+ con relacin a Mn3+ (Por qu ?). Dos
consecuencias importantes de esta qumica redox son que Mn2+ puede
participar en la catlisis redox til en muchos substrates similares a Fe3+,
mientras que ms alto redox potencial de Mn2+ hace Mn2+ libre inocuo en
condiciones donde liberado Fe2+ producira a radicales hydroxyl. Las clulas
(notablemente clulas bacterianas) pueden tolerar concentraciones
citoplsmicas muy altas de Mn2+ sin consecuencias negativas; esto no es
9
seguramente el caso con iones metlicos redox como Fe y Cu.

Mn Biochemistry R.R. Crichton, Chap. 16

Mn is the cofactor for superoxide dismutases, catalases and some
peroxidases. These enzymes are all used for the detoxification of
ROS.

An important property of Mn in its (2+)-oxidation state, which has

important consequences, is that is a close but not exact surrogate of
Mg2+. Mn2+ with its relatively similar ionic radius can readily
exchange with Mg2+ in most structural environments, and exhibits
much of the labile, octahedral coordination chemistry. However, it can
more easily accommodate the distortions in coordination geometry in
progressing from the substrate-bound to the transition state and to the
bound product. Consequently, Mn2+ in the active site of a Mg2+enzyme often results in improved enzyme efficacy.
10

Mn Biochemistry R.R. Crichton, Chap. 16

Mn es el cofactor para el superxido dismutases, catalases y algn
peroxidases. Estas enzimas son todos usadas para el detoxification de
ROS.
Una propiedad importante de Mn en su (2+) estado de oxidacin, que
tiene consecuencias importantes, es un final, pero no sustituto exacto
de Mg2+. Mn2+ con su radio inico relativamente similar puede
cambiar fcilmente con Mg2+ en la mayor parte de ambientes
estructurales, y expone la mayor parte de los labile, octahedral
qumica de coordinacin. Sin embargo, esto puede acomodar ms
fcilmente la deformacin en la geometra de coordinacin en la
progresin del substrate-ligado al estado de transicin y al producto
atado. Por consiguiente, Mn2+ con el sitio activo de un Mg2+-enzyme a
menudo causa la eficacia de enzima mejorada.
11

Formas de Vida De Anaerobio a Aerobio

condiciones anxicas (-O2) contra condiciones xicas (+O2)
H.D. Holland (2006), Phil. Trans. R. Soc. B, 361, 903-915

Estimated evolution of atmospheric O2

The red and green lines represent the range of the estimates: stage1: 3.852.45 Gyr (Ga),
stage2: 2.451.85 Ga, stage3: 1.850.85 Ga, stage4: 0.850.54Ga, stage5: 0.54 Gapresent
www.globalchange.umich.edu/globalchange1/current/lectures/Perry_Samson_lectures/evolution_atm/index.html
12

Activacin de O2 Tipos de Reaccin

Reversible binding of O2 Myoglobin, Hemoglobin (Fe), Hemocyanin
(Cu-Cu)
O2.- dismutation Superoxide Dismutase (Mn, Fe, Ni, Cu, Zn)
O2.- + O2.- +2H+ O2 + H2O2
H2O2 decomposition Catalase (Mn, heme-Fe)
2 H2O2 2 H2O + O2
Oxygenases (Mn, Fe, Cu, Cytochrome P450)
R-H + O2 + NADPH + H+ R-OH + H2O + NADP+
Oxidases (2-electron reduction to H2O2; Fe, Cu)
O2 + 2e- +2H+ H2O2 (focus on Cu enzyme Galactose Oxidase)
Oxidases (4-electron reduction to H2O; heme-Fe, Cu)
O2 + 4e- +4H+ 2 H2O (focus on Cu enzyme Ascorbic Acid Oxidase
and Fe,Cu enzyme Cytochrome c Oxidase)
13

No protena Ligantes
Acid/base

Ligand
H2O/OH-,O2-

pKa
14,~34

10.3
12.7
4.7
11.6
9.3
4.8
3.5, -7, -9, -11

Neutral

HCO3-/CO32HPO42-/PO43H3CCOO-/H3CCOOH
HO2- /H2O2
NH3 /NH4+
N3- /N3H
F-, Cl- Br-, I-/XH
O2, CO, NO, RNC
Mn+

d-

Hd+
14

Hd+

Modulacin de acidez (pKa)

-H+

H2O + Mn+

+H+
Metal
pKa
none
14.0
Ca2+
13.4
Mn2+
11.1
Cu2+
10.7
Zn2+
10.0
Mn+

d-

HO- -Mn+

4 orders of
magnitude !

Hd+
Hd+

15

Control cintico
[Mn+(H2O)m]

-H2O

[Mn+(H2O)m-1]

+H2O
Metal
k (s-1)
K+
1x109
Ca2+
3x108
Mn2+
2x107
Fe2+
4x106
Co2+
3x106
Ni2+
4x104
Fe3+
2x102
Co3+
<10-6

15 orders of
magnitude!

16

Velocidades de cambio acuticos

M. Eigen, Nobel Prize Lecture 1967

Expresado como vida de complejos

til para mirar la reactividad en
ligand cambian reacciones - catlisis

inert

labile

17

Estabilidad de Complejos de In Metlicos:

Irving-Williams Series

Stability order for high-spin divalent metal ion

complexes: Peak at Cu(II), Minimum at Mn(II)
18

Protena Ligantes Residuos de Aminocido

Mn prefiere ligar el oxgeno ligantes
N

Tyr
Cys

His

Glu(+Asp)
Met
Lys
Ser

19

La superposicin de estructura del metal se centra en in Fehomoprotocatechuate 2,3-dioxygenase (PDB 2IG9) y Mn-HPCD
(PDB 3BZA) Atoms: gray C; blue N; red O; magenta Mn
J.P. Emerson et al. (2008) PNAS, 105, 73477352

20

Humano Mn SOD Tetramer

Borgstahl et al. (1996) Biochemistry, 35, 4287-4297; Quint et al. (2006) Biochemistry, 45,
82098215

21

Mn SOD
PDB 1VAR
http://en.wikipedia.org/wiki/Superoxide_dismutase

The dismutation of superoxide

may be written as:
M(n+1)+-SOD + O2 Mn+SOD + O2
Mn+-SOD + O2 + 2H+
M(n+1)+-SOD + H2O2.
M = Cu (n=1); Mn (n=2) ; Fe
(n=2) ; Ni (n=2).
The oxidation state of the
metal cation oscillates between
n and n+1.
22

El sitio activo de Lactobacillus plantarum Mn-catalase

(Hexamer, PDB 1JKV and 1JKU; V.V. Barynin et al.(2001), Structure, 2001, 9, 725738)

2 H2O2 2 H2O + O2
23

Azide (N3-) ligando en el sitio activo de Lactobacillus

plantarum Mn-catalase

24

Mn Ribonucleotide Reductase
J.E. Martin, J.A. Imlay (2011), Mol Microbiol., 80, 319334; J.A. Stubbe, J. A. Cotruvo
(2011), Curr Opin Chem Biol., 15, 284290

25

Ribonucleotide Reductase Chemistry

http://en.wikipedia.org/wiki/Ribonucleotide_reductase

26

Qumica Bioinorganic bsica de Manganeso en todo a fotosntesis

Luz conducida en evolucin de dioxygen

A.W. Rutherford, A. Boussac (2004)

Science, 303, 1782-1784; S. Merchant, M.
Sawaya (2005) Plant cell 17, 648-663;
D. A. Bryant, N.-U. Frigaard (2006) TRENDS
in Microbiology, 14, 488-496; T. M. Iverson
(2006) Current Opinion in Chemical
Biology , 10, 91100; D.G. Nocera (2012)
ACCOUNTS OF CHEMICAL RESEARCH, 45,
767776.

27

Introduccin a Fotosntesis
(Britannica Enciclopedia en Lnea)
http://www.britannica.com/EBchecked/topic/458172/photosynthesis

28

Punto para recordar: Relase de oxgeno, la

respuesta puede ser encontrada en las rocas
Mineral Hollandite:
Ba0.8Pb0.2Na0.1Mn4+6.1Fe3+1.3Mn2+0.5Al0.2Si0.1O16

BaMn8O16
O2 Evolving Complex (OEC), a Mn4CaO5
Cluster

29

(a) End-on view of the Hollandite lattice (tunnel

type) consisting of Mn (red) and O (blue) atoms
and showing the proposed location of Ba2+ cations
(gray) in the 2 2 tunnels (57, 58).
There are two kinds of bridging O atoms, and one
of each kind is designated by vertical stripes (sp3like) or horizontal stripes (sp2-like).
(b) Oblique view of the hollandite lattice shows the
difference in the mode of bridging of the sp3-like
(apical) and sp2-like (planar) O atoms between
three Mn atoms.
(c) Expanded oblique view shows more clearly the
differences between the sp3-like (vertical stripes)
and sp2-like (horizontal stripes) bridging O atoms.
Sauer K , Yachandra VK (2002) PNAS, 99, 8631-8636

2002 by National Academy of Sciences

30

El centro de reaccin Fotosinttico (PS I) de bacterias moradas

Luz conducida en sntesis de ATP
(C.D. Lancaster and H. Michel, Handbook of Metalloproteins 2001)

Robert Huber, Premio Nobel

1988 (con Deisenhofer y
Michel)

31

El centro de reaccin Fotosinttico (PS I) de bacterias moradas

(C.D. Lancaster and H. Michel, Handbook of Metalloproteins 2001)

32

El centro de reaccin Fotosinttico de bacterias moradas y

Transferencia electrnica
(C.D. Lancaster and H. Michel, Handbook of Metalloproteins 2001)

33

Mdulos fundamentales del Aparato de Fotosntesis

Light-dependent reactions of photosynthesis at the thylakoid membrane
http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookps.html
http://www.phschool.com/science/biology_place/biocoach/photosynth/intro.html
http://en.wikipedia.org/wiki/Photosynthesis

34

34

Respiracin de Mitochondrial & Sntesis de Centro de Reaccin

Fotosinttica de ATP transferencia de electrn/protn
Conectada fuerza de Protonmotive

35

Mdulos fundamentales del Aparato de Fotosntesis

The "Z scheme"
http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookps.html
http://www.phschool.com/science/biology_place/biocoach/photosynth/intro.html
http://en.wikipedia.org/wiki/Photosynthesis

36

3D estructura de Fotosistema II de alga Synechococcus elongatus

(3.8 resolution, Zouni et al. (2001), NATURE, 409, 739)

37

Cofactors de Fotosistema de Photosystem II (Synechococcus elongatus)

(water-oxidizing, OEC = oxygen-evolving complex, a 4 Mn cluster)

38

Estructura de Clorofila. La estructura de clorofila b es mostrada con la Unin internacional de

enumeracin de Qumica Pura y Aplicada

39
2005 by American Society of Plant Biologists

Merchant S, Sawaya M. Plantcell 2005;17:648-663

Chlorophyll (Mg) y Heme (Fe)

Porphyrin ring y Phytol chain

40

La oxidacin de la agua, complejo que desarrolla el oxgeno,

un 3Mn+1Mn cluster ???

41

Estructura total de PSII dimer de T. vulcanus en una

resolucin de 1.9
Umena1 et al. (2011), Nature, 473, 55-60

42
Y Umena et al. Nature (2011) doi:10.1038/nature09913

Organizacin de chlorophylls

43
Y Umena et al. Nature (2011) doi:10.1038/nature09913

Structure of the Mn4CaO5 cluster (OEC).

Y Umena et al. Nature (2011) doi:10.1038/nature09913

44

The Mn4CaO5 Cluster (OEC)

45

Hydrogen-bond network around YZ.

Y Umena et al. Nature (2011) doi:10.1038/nature09913

46

The S-state (Kok) cycle showing how the absorption of four photons of light (h) by
P680 drives the splitting of two water molecules and formation of O2 through a
consecutive series of five intermediates (S0, S1, S2, S3, and S4). The S-states
represent the various oxidation states of Mn in PSII-OEC. Electron donation from
the PSII-OEC to P680+ is mediated by tyrosine, YZ.
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

47

La Hoja artificial

48
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

The solar photons are stored by photosynthesis to split water to oxygen and four
protons and four electrons, which are utilized in the conversion of carbon
dioxide to carbohydrates.
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

49

A simplified scheme of the light-driven reactions of photosynthesis. Solar photons

create a wireless current that is harnessed by redox cofactors at the terminus of the
charge-separating network to translate the wireless current into a solar fuel by
performing the water splitting reaction at OEC. The initial reductant, plastoquinol
(PQH2), is translated into NADPH in PSI, which transfers hydrogen to the Calvin
cycle where it is fixed with CO2 to produce carbohydrates.

50
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

(left) Schematic of cubane structure of PSII-OEC. (middle) Structure of the CoOEC as determined from EXAFS (Pi not shown). Co-OEC is the head-to-tail
dimer of the cubane of PSII-OEC. (right) Co-OEC structure rotated by 45 to
more clearly shows edge sharing octahedra. The alkali metal ions, which are not
shown, likely reside above the 3-fold triangle defined by the -bridging oxygens.
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

51

Proposed pathway for water splitting by Co-OEC. A PCET equilibrium proceeds

the turnover-limiting OO bond-forming step. Curved lines denote phosphate or
terminal oxygen (from water or hydroxide). The oxyl radical in the far right
structure is shown for emphasis. If the hole is completely localized on oxygen,
then the Co oxidation state is Co(III) and not Co(IV).
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

52

Schematic of a Co-OEC functionalized npp+-silicon single-junction PEC cell.

The buried junction performance characteristics are Isc = 26.7 mA/cm2 and Voc
= 0.57 V.
53
Published in: Daniel G. Nocera; Acc. Chem. Res. 2012, 45, 767-776.
DOI: 10.1021/ar2003013
Copyright 2012 American Chemical Society

Resumen Viviendo en una Mundo de Oxgeno

Respiracin & Fotosntesis
(energy conservation ATP synthesis proton-coupled-electron transfer)

The use of the electron acceptor dioxygen and the photosynthetic

production of dioxygen (water-oxidizing, oxygen-evolving complex) are
two elementary processes of life which depend on a complex network of
multi-site proteins and enzymes. Redox and light driven reactions are
used for energy conservation (proton pumping; ATP synthesis).
The 3Cu-2Fe, multi-subunit enzyme cytochrome c oxidase is the terminal
oxidase of mitochondrial respiration, whereas the Mn4CaO5 cluster (with
a tyrosine nearby) constitutes the oxygen evolving complex.

The reduction of dioxygen to water proceeds without the release of ROS.

COX receives the electrons via cytochrome c from where they are
transferred to the dinuclear mixed valence electron transfer center CuA.
The dinuclear heme-CuB center constitutes the reduction site of dioxygen,
which carries a covalently attached tyrosine at the active site.
54

Resumen Viviendo en una Mundo de Oxgeno

Respiracin & Fotosntesis
(energy conservation ATP synthesis coupled electron-proton transfer)

COX represents a redox driven proton pump, with defined electron and
proton transfer pathways (redox protons vs protons).
The mechanism of dioxygen reduction is relatively well understood, its
mechanism has been characterized both by spectroscopic and structural
techniques at high resolution. It appears that a tyrosine (radical), in
addition to Fe and Cu centers, is involved in catalysis.
The dioxygen production (PS II) is a light-driven metalloradical enzyme
process. The splitting of water and formation of dioxygen at the Mn4CaO5
cluster is still less understood despite a huge amount of spectroscopic and
biochemical studies. For Mn, cycling between oxidation states +2, +3, and
+4, has been suggested (S-state model).

New techniques have been employed to grow better crystals of these

extremely large membrane-bound molecules to achieve a resolution below
2 , to understand their function on an atomic level.
55