Principles of Bioinorganic Chemistry - 2004

Lecture Date Lecture Topic Reading Problems1 9/9 (Th) Intro; Choice, Uptake, Assembly of Mn+ Ions Ch. 5 Ch. 12 9/14 (Tu) Metalloregulation of Gene Expression Ch. 6 Ch. 23 9/16 (Th) Metallochaperones; Mn+-Folding, X-linking Ch. 7 Ch. 34 9/21 (Tu) Med. Inorg. Chem./MetalloneurochemistryCh. 8 Ch. 45 9/23 (Th) Mössbauer, EPR, IR Spectral FundamentalsCh. 9 Ch. 56 9/28 (Tu) Electron Transfer; Fundamentals Ch. 9 Ch. 67 9/30 (Th) Long-Distance Electron Transfer Ch. 10 Ch. 78 10/5 (Tu) Hydrolytic Enzymes, Zinc, Ni, Co Ch. 109 10/7 (Th) CO and Bioorganometallic Chemistry TBA Ch. 810 10/12 (Tu) Dioxygen Carriers: Hb, Mb, Hc, Hr Ch. 11 Ch. 911 10/14 (Th) O2 Activation, Hydroxylation: MMO, ToMOCh. 11 Ch. 1012 10/19 (Tu) Model Chemistry for O2 Carriers/ActivatorsCh. 12 Ch. 1113 10/21 (Th) Complex Systems: cyt. oxidase; nitrogenase Ch. 12 Ch. 1214 TBA Term Examination

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Magnetic Splitting of Line in 63/65Cu EPR Spectroscopy

The Research Yard at SLAC

Electron Transfer (ET) in Living Systems

PRINCIPLES:

•M-binding sites tailored to minimize structural changes upon ET•One-electron transfer processes preferred•Coupling of H+ with electron transfer controls redox potential•ET can occur over long distances; ~ 11-13 Å is most common•Parameters: distance, driving force, reorganizational energy, path

TOPICS:

•Three major bioinorganic ET units: FenSn clusters; Cu; hemes•Long-distance electron transfer: dependence on distance, driving force, reorganization energy•Electron supply in the methane monooxygenase system

The Major Metal Units in ET Proteins (1)

Iron-SulfurClusters

Properties of Iron-Sulfur Clusters(A) Rubredoxin Fe–S, 2.25 - 2.30 Å in oxidized (FeIII) and reduced (FeII) states Reduction potentials: - 50 to + 50 mV

(B) 2Fe-2S Ferredoxins (Fd)FeII FeII FeII FeIII FeIII FeIII

reduced mixed-valent oxidized

all physiological uses

Reduction potentials: -490 to - 280 mV

(C) 3Fe-4S Ferredoxins (cube missing a corner)

FeIII 3S4 FeIII

2 FeII S4

Reduction potentials: -700 to - 100 mV

Reminder:

o =-RT/nF lnQ + pH,where Q = [Mn]/[Mn-1]

Thus, at pH 7, the biological H2/2H+

standard coupleis - 420 mV.

Properties of Iron-Sulfur Clusters, cont’d

(D) 4Fe-4S Ferredoxins and High-potential Iron Proteins (HiPIPs)

FeII3

FeIII FeII2

FeIII2 FeII FeIII

3

HiPIP

Reduction potentials: -650 to - 280 mV (Fd); + 350 mV (HiPIP)

The three state hypothesis:

Ferredoxin

minimal reorganizational energy

The Physical Properties of Iron-Sulfur Clusters

Primary structure (sequence) does not dictate the tertiary structure of a metalloprotein, as revealed by this 8-iron ferredoxin crystal structure.

Structure of an 8Fe-8S Ferredoxin

The Major Metal Units in ET Proteins (2)

Blue Copper and CuA

Depicted at the right are the three copper sites in the enzyme ascorbate oxidase. Type 1, or blue, copper is the ET center. Below is depicted CuA .

Blue Copper

SCu

SS

Cu

O

NN

NN

HisGlu

Cys

HisMet CysCuA

The Physical Properties of Blue Copper Centers

The deep sky bluecolor of theseproteins facilitated their purification on columns; the opticalband is Cu–S C.T.

Structure of Poplar Plastocyanin

The oxidized, reduced and apo plastocyanin structures are nearly identical.

The copper(II) thiolate center is difficult to model.

EPR Spectra Distinguish the Three Types of Copper Found in Metalloproteins

CuA Model Chemistry: Reversible 1-Electron Transfer

-2.5-2.0-1.5-1.0-0.500.00.501.01.5

-0.6-0.4-0.200.20.40.6 ( ) . E V vs Cp2Fe+/Cp2Fe

Cu Cu

N

N

N N

N N

N N

SCu Cu

SN

N

His

NN

HisCys

Cys

O

S

Me

O

O OCu

O

CuO O

O O

N N

NN

Cu Cu

O O

R

3+

Met

Glu

CuA

+

+

= R Ph3 -C

-Cu Cu ( )dist Å

2.5-2.7

2.448

2.4246(12)

2.4500(15)

These complexes demonstrate that constrained dicopper(I/II) units afford good 1-electron reversible transfer centers and display the possible environments that could be encountered in biology.

LeCloux

Chuan He

The Major Metal Units in ET Proteins (3)

Cytochrome c from tuna showing coordination of the iron porphyrin group by the protein side chains from Met (left) and His (right) residues.

Electronic Properties of Low-Spin Metalloporphyrins

Note again, minimal reorganization energy upon electron transfer

For [Fe(N4-porphyrin)(N-His)(S-Met)]

- e-

low spin ferrous low spin ferric

N

N

N

N

COO-

COO-

Fe

protoporphyrin IX