Basics of

Basics of
Bioinorganic
Bioinorganic
Chemistry
Chemistry
Handout- part 1
Lorenz Kienle
Max-Planck-Institut fr
Festkrperforschung
Stuttgart
Outline
Outline
1. Very important terms of coordination chemistry
2. General aspects of bioinorganic chemistry
3. Coordination for uptake, transport and storage (Fe)
4. Hard ions: Na
+
, K
+
, Mg
2+
, Ca
2+
5. Cobalamines
6. Metals in Photosynthesis
7. Fe in bio systems
8. Function of Zn
9. Fixation of nitrogen
Resources
Resources
Text books
W. Kaim, B. Schwederski: Bioinorganic Chemistry: Inorganic Elements
in the Chemistry of Life, Wiley 1994, German edition: Teubner 1995
S. J. Lippard, J. M. Berg: Bioanorganische Chemie, Spektrum- Akademischer Verlag
D. Shriver, P. Atkins: Inorganic Chemistry, Freeman and Comp. 1999 (Chapter 19)
Internet resources
Lectures of Prof. Rehder (University Hamburg), doc-files (german)
Internet resources, e. g. Uni Siegen (KomplexeMaster7Sem.ppt, etc.)
Bonding: http://wwwchem.uwimona.edu.jm:1104/courses/CFT.html
Lectures of Prof. Klfers (LMU, see homepage)
Papers
S. Busch et al., Eur. J. Inorg. Chem. 1999, 1643
E. Buerlein, Angew. Chem. Int. Ed. 2003, 42, 614
Quiz
Quiz
What is the function of an enzyme?
What is a coenzyme, what are vitamins?
Describe the function of Hb and Mb
Do you know any Zn-containing enzyme?
Is there any metal-organic compound in-vivo?
Can you describe the effect of -bonding on
0
?
Describe the function of Mn in photosynthesis
What are cytochromes?
Do you know any redox-active cluster compound?
Describe the biological nitrogen fixation
1.
Very important terms
of coordination chemistry
Coordination compound (complex)
Coordination compound (complex)
-
-
basics
basics
Central atom is bound to unexpectedly large number of ligands
Usually discrete species in solution and solid
Examples: K
4
[Fe(CN)
6
], CoCl
2
* 6 H
2
O
Properties of central atoms (transition metals):
Large charge/radius ratio
Variable oxidation states (d-electrons available)
(Meta)stable high oxidation states, s- electrons are removed first
Compounds are often paramagnetic (unpaired electrons)
Formation of colored ions and compounds
Compounds with profound catalytic activity
Formation of stable complexes (Lewis acids, see HSAB)
Trend to metal-metal bonding (clusters, not important in biology)
Properties of ligands
Monodentate or polydentate ligand
Ambidentate ligands (nitro-, nitrito)
Coordination number
Coordination number
-
-
examples
examples
CN 2: linear (Cu
+
, Ag
+
, Au
+
, Hg)
CN 3: trigonal planar (HgI
3
-
, [Pt(P{C
6
H
5
}
3
]
3
),
trigonal pyramid
CN 4: tetrahedron ([Al(OH)
4
]-, [Cd(CN)
4
]
2-
)
square planar (d
8
, [PtCl
4
]
2-
, [AuF
4
]
-
)
bisphenoidal (-trigonal bipyramid, [AsF
4
]
-
[SbCl
4
]
-
)
tetragonal pyramid (-octahedron)
CN 5: trigonal bipyramid (Fe(CO)
5
, [SnCl
5
]
-
)
tetragonal pyramid
Higher CNs are favoured:
Complexes containing central atoms of the periods 5 and 6, small ligands (size)
Single bonds metal-ligand (see MnO
4
-
)
On the left of a row of the d-block (size and small number of d-electrons)
Central atoms with a high oxidation number (size and small number of d-electrons)
Coordination number
Coordination number
-
-
examples
examples
Pseudorotation
Exchange of a- and e-ligand, see MgATpase
[Ni(CN)
5
]
3-
: b) and a) in crystal structure
Fe(CO)5: fast pseudorotation in solution
CN 6: octahedron ([Cr(H
2
O)
6
]
3+
, [Fe(CN)
6
]
3-
)
distorted octahedron
trigonal prism
Coordination number
Coordination number
-
-
examples
examples
CN 7:
pentagonal bipyramid monocapped trigonal prism monocapped octahedron
[UO
2
F
5
]
3-
, [HfF
7
]
3-
[TaF
7
]
3-
[IF
6
]
-
, [NbOF
6
]
3-
CN 8: cube ([UF
8
]
3-
)
square antiprism
[TaF
8
]
3-
, [ReF
8
]
3-
dodecahedron
[Mo(CN)
8
]
4-
Isomerism
Isomerism
Two or more molecules or ions have the same molecular formula but
the atoms are arranged differently
The structures of isomers are not super imposable
Isomers have different physical (color) and/or chemical properties.
Stereoisomerism
Optical isomerism: Enantiomers
Geometrical isomerism:
cis-, trans; meridional, facial
Structural isomerism
Ionization isomerism ([CoCl(NH
3
)
5
]SO
4
/ [CoSO
4
(NH
3
)
5
]Cl)
Coordination isomerism ([Co(NH
3
)
6
] [Cr(CN)
6
] / [Cr(NH
3
)
6
] [Co(CN)
6
)
Linkage isomerism (cyano / isocyano)
HSAB concept
HSAB concept
Pearsons concept, 1963
Lewis concept: metal ions are acids because they accept electrons
ligands are bases because they donate electrons
Hard acids tend to form complexes with hard bases (ionic bonds)
Soft acids tend to form complexes with soft bases (covalent bonds)
Hard acids: H
+
, Li
+
(> Na
+
), Cr
6+
(> Cr
3+
)
Intermediate acids: Fe
2+
, Mn
2+
, Cu
2+
, Zn
2+
Soft acids: Au
+
(> Ag
+
, Cu
+
), Hg
2+
, Pt
2+
Hard bases: F
-
, OH
-
, NH
3
, PO
4
3-
(> HPO
4
2-
), MoO
4
2-
Intermediate bases: Cl
-
Soft bases: I
-
(> Br
-
), S
2-
(> HS
-
, > H
2
S), AsS
2
-
Chelates
Chelates
Structure
Multidentate ligands (more than one bond with the central atom or ion)
Ring structures
Properties
Multidentate ligands are much stronger complex formers than monodentate ligands
Chelates remain stable even at very dilute concentrations (less dissociation)
Chelate effect: Increase of entropy
G = H - TS, H ~ for multi- and mono-dentate complexes
Cu(H
2
O)
4
2+
+ 4NH
3
Cu(NH
3
)
4
2+
+ 4H
2
O
Cu(H
2
O)
4
2+
+ N
4
Cu(N
4
)
2+
+ 4H
2
O
Chelate therapy (detoxification)
EDTA
en
N
N
HO O
OH
O
OH
O
HO O
NH
2
NH
2
Ni
H
2
N
H
2
N
O
Pb
O
N
N
O
O
Co
N
N
N
N
N
N
Bonding in coordination compounds
Bonding in coordination compounds
Simple electrostatic model (problem: square complexes)
18 Val. el.-rule (problem: no information about geometry, magnetism)
Related to octet rule, no. of el. on metal ion = number of el. on a noble gas, [Ar] + 18 Val. el
[Co(NO
2
)
6
]
3-
, but [Cr(NH
3
)
6
]
3+
, carbonyls obey EAN (Fe(CO)
5
, Ni(CO)
4
)
Valence Bond Theory (Pauling)
Hybridization of the metals orbitals, -bond with ligand orbitals
sp
3
(tetrahedral), d
2
sp
3
(octahedral), dsp
3
(trigonal bipyramid), dsp
2
(square planar)
inner- and outer orbital complexes, e. g. Co
3+
(consequences for magnetism)
inner (rearrangement of electrons)
4s
4p 4d
3d
outer
Bonding in complexes
Bonding in complexes
-
-
CTF
CTF
Crystal Field Theory (Electrostatic guide to splitting of d-levels)
Ligand field splitting
0
, LFSE (Ligand Field Stabilization Energy)
Spectrochemical series:
I
-
< Br
-
< S
2-
< Cl
-
< NO
3-
< OH
-
< H
2
O < NH
3
< en < NO
2
-
< CN
-
< CO
Metal:
0
increases with increasing oxidation number and down a group
Mn(II) < Ni(II) < Fe(II) < V(II) < Fe(III) < Co(III) < Mn(IV) < Mo(III) < Pd(IV) < Pt(IV)
Electronic configuration (h.s., l.s.) depend on LFSE and P (pairing energy)
Trends for l.s:
ligands: right end of spectrochemical series
central atoms: 4d, 5d metals
geometry: octahedral coordination
Jahn-Teller distortion: remove of degeneracy, increase of LFSE
Splitting e
g
(d
z2
lower energy) and t
2g
(d
xy
higher energy)
Square coordination: d
xy
higher energy than d
z2
large
0
Bonding in complexes
Bonding in complexes
-
-
LFT
LFT
-bonding
Ligand field theory (Interaction in terms of atomic and molecular orbitals)
Overlap atomic orbitals of similar symmetry to form molecular orbitals
-bonding
SALC of metal t
2g
and -orbitals of the ligand
Non-bonding t
2g
become antibonding ( -donor)
Non-bonding t
2g
become bonding ( -acceptor)
Interconnection CFT-LFT
2.
General aspects of
bioinorganic chemistry

Bioinorganic Chemistry
Bioinorganic Chemistry

a contradiction?
a contradiction?
Organic chemistry: restricted to carbon compounds
Biochemistry: chemical components of living systems
Inorganic chemistry: no covalent carbon components
Bioinorganic chemistry: biochemical function of inorganic elements
Consequence: interdisciplinary research, synthesis and analysis of model systems
Profit from Bioinorganic Chemistry: learning from nature
Nature: optimized system by evolution
Efficient collection, conversion and storage of energy
Moderate conditions during catalytic processes supported by metal proteins
Stereoselective synthesis
Three main fields of research
Enzymes, biological relevant complexes: biochemistry and coordination chemistry
Biomineralization: biochemistry and solid state (materials) chemistry
Synthesis and characterization of model systems
Methods for characterization
Methods for characterization
Diffraction methods (3d structure)
Problem: crystallization of proteins
Complex structures, high resolution (ca. 0.2 nm), no identification of hydrogen atoms
NMR (local structure and dynamical properties of species )
Electron microscopy (3d structure with medium resolution)
ESR (electronic properties of species containing unpaired electrons)
Mssbauer spectroscopy (identification of species with quadrupol moment)
Optical spectroscopy (color, electronic properties)
X-ray absorption techniques (local structure)
SQUID (characterization of magnetic materials)
Cyclovoltammetry (characterization of electron transfer)

Periodic table of life

Periodic table of life
Metals Essential elements for humans (daily requirement: 25 mg)
Non metals Presumably essential elements
Symptoms of deficiency: Mg (muscle cramps), Fe (animea), Mn (infertility)
Toxic effects in case of high doses (therapeutic width)
Occurrence of non essential elements (e.g. Rb: 1.1 g / 70 kg) and of contaminations (e.g. Hg)
Metal content of a human body (70 kg)
Metal content of a human body (70 kg)
Ca 1000 g Sn 20 mg
K 140 g V 20 mg
Na 100 g Cr 14 mg
Mg 25 g Mn 12 mg
Fe 4.2 g Mo 5 mg
Zn 2.3 g Co 3 mg
Cu 72 mg Ni 1 mg
Non metals: O (45500 g), C (12600 g), H (7000 g), N (2100 g), P (700 g)
Metal content of a human body (70 kg)
Metal content of a human body (70 kg)
Earths Crust Human Body
Element % Element %
O 47 O 63
Si 28 C 25.5
Al 7.9 H 9.5
Fe 4.5 N 1.4
Ca 3.5 Ca 0.31
Na 2.5 P 0.22
K 2.5 K 0.08
Mg 2.2 S 0.06
Week correlation to distribution of the elements in the earths crust (there: O > Si > Al > Fe)
Good correlation to distribution of the elements in sea water
Functions of
Functions of

inorg
inorg
. elements
. elements

summary
summary
Assembly of structures (DNA, biomineralization), endo- and
exoskeletons. Ca, Mg, Zn, Si
Information carriers (muscle contractions, nerve function). Na, K, Ca, Mg
Activation of enzymes. Mg, Ca
Formation, metabolism and degradagation of organic compounds by
Lewis acid/base catalysis. Zn, Mg
Transfer of electrons (energy conversion), FeII/FeIII/FeIV, stable due to
bioligands
Uptake, transport, storage and conversion of small molecules

3
O
2
: Fe, Cu (conversion), Mn (generation)
N
2
: Fe, Mo, V (conversion to ammonia)
CO
2
: Ni, Fe (reduction to methane)
Most prominent
Most prominent

bioelements
bioelements

Na
+
,K
+
: Electrolytes
Mg
2+
: Chlorophyll, energy production (ATP ADP), skeleton
Ca
2+
: muscle functions, Hydroxylapatite Ca
5
(PO
4
)
3
(OH), CaCO
3
V
IV/V
, Mo
IV/VI
, W
IV/VI
, Mn
II/III/IV
, Fe
II/III
, Ni
I/II/III
, Cu
I/II
: electron transfer
Fe and Cu: transport and storage of oxygen
Fe
II
, Fe
III
: Magnetite (Fe
3
O
4
)
Co: Cobalamine, e.g. Vitamin-B
12
Zn
2+
: Enzymes, zincfinger (gen. transcription), stabilization of proteins
Si
IV
: bones; SiO
2
/silicagel
P
V
: Hydroxylapatite, ATP, cell membrane, DNA
Se
-II
: Selenocysteine
F
-
: Fluorapatit (Ca
5
(PO
4
)
3
F) teeth; Cl
-
: besides HCO
3
-
most important free
anion, I
-
: hormones of the thyroid, radiation therapy
Application of metals in medicine
Application of metals in medicine
Li
+
: Treatment of depression (Li
2
CO
3
, low doses)
Gd
3+
: Contrast agent (NMR)
BaSO
4
: Contrast agent (radiography)

99
mTc: radio diagnostics (thyroid)
Au(I): Rheumatism
Sb(III): Eczema
Bi(III): Gastric ulcer
Cd: Carboanhydrase
(Thalassiosira weissflogii)
Health
Concentration
Dead
Well
Application of metals in medicine
Application of metals in medicine
Pt(II): Cisplatin (cis-[Pt(NH
3
)
2
Cl
2
]), chemotherapy
(inhibition of cell division, not cell growth)
O
H
H
CH
2
H
P
-
O O
H H
N NH
H
2
N
O
N
N
O
O
H
H
CH
2
H
P
O
-
O
O
H
H
N
NH
H
2
N
O
N
N
Pt
NH
3
NH
3
N7 of guanine
O
O
Filamentous growth of bacteria
Terms related to bioinorganic chemistry
Terms related to bioinorganic chemistry
See: http://www.chem.qmul.ac.uk/iupac/bioinorg/: glossary terms
Active center: Location in an enzyme where the specific reaction takes place
Allosteric enzyme: Can bind a small regulatory molecule that influences catalytic activity
Apo-enzyme: An enzyme that lacks its metal center or prosthetic groups
ATP: Adenosine 5-triphosphate
Biomembrane: Sheet like assemblies of proteins and lipids (bilayer)
Calmodulin: Cabinding protein involved in metabolic regulation
Carboanhydrase: Zn-containing enzyme that catalyzes the reversible decomposition of
carbonic acid to carbon dioxide and water
Charge-transfer complex: An aggregate of two or more molecules in which charge is
transferred from a donor to an acceptor.
Chlorin: 2,3-Dihydroporphyrin, reduced porphyrin with two non-fused saturated carbon
atoms (C-2, C-3) in one of the pyrrole rings.
Chlorophyll: Magnesium complex of a porphyrin in which a double bond in one of the
pyrrole rings (17-18) has been reduced. A fused cyclopentanone ring is also present
Cisplatin: Cis-diamminedichloroplatinum(II), antitumor drug. Of major importance in the
antitumor activity of this drug is its interaction with the nucleic acid bases of DNA
Terms related to bioinorganic chemistry
Terms related to bioinorganic chemistry
Cluster: Metal centers grouped close together which can have direct metal bonding
or through a bridging ligand, e.g. ferredoxin
Cobalamin: Vitamin B12, substituted corrin-Co(III) complex
Coenzyme: A low-molecular-weight, non-protein organic compound (often a nucleotide)
participating in enzymatic reactions
Cofactor: An organic molecule or ion (usually a metal ion) that is required by an enzyme for
its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
Cooperativity: The phenomenon that binding of an effector molecule to a biological system
either enhances or diminishes the binding of a successive molecules, e.g. hemoglobin
Corrin: Ring-contracted porphyrin derivative that is missing a carbon
Cytochrome: Heme protein that transfers electrons, and exhibits intense absorption
bands. The iron undergoes oxidation-reduction between oxidation states Fe(II) and Fe(III).
Cytochrome-c oxidase: The major respiratory protein of animal and plant mitochondria. It
catalyzes the oxidation of Fe(II)-cytochrome c, and the reduction of dioxygen to water.
Contains two hemes and three copper atoms, arranged in three centers.
Terms related to bioinorganic chemistry
Terms related to bioinorganic chemistry
Cytochrome P-450: General term for a group of heme-containing monooxygenases The
reaction with dioxygen appears to involve higher oxidation states of iron, such as Fe(IV)=O
Cytoplasm: The part of protoplasm in a cell outside of and surrounding the nucleus
Dehydrogenase: An oxidoreductase which catalyzes the removal of hydrogen
Desferrioxamine (dfo): Chelating agent used world-wide in the treatment of iron overload
conditions, such as hemochromatosis and thalassemia.
Dismutase: Enzyme that catalyzes a disproportionation reaction
Entatic state: A state of an atom or group which has its geometric or electronic condition
adapted for function. Derived from entasis (Greek) meaning tension
Enzyme: A macromolecule that functions as a biocatalyst by increasing the reaction rate
FeMo-cofactor: An inorganic cluster found in the FeMo protein of the molybdenum-
nitrogenase, essential for the catalytic reduction of N
2
to ammonia
Ferredoxin: A protein containing more than one iron and acid-labile sulfur, that displays
electron-transferactivity but not classical enzyme function
Ferritin: An iron storage protein consisting of a shell of 24 protein subunits, encapsulating
up to 4500 iron atoms in the form of a hydrated iron(III) oxide.
Terms related to bioinorganic chemistry
Terms related to bioinorganic chemistry
Heme: A near-planar coordination complex obtained from iron and dianionic porphyrin
Hemerythrin: A dioxygen-carrying protein from marine invertebrates, containing an oxo-
bridged dinuclear iron center
Hemocyanin: A dioxygen-carrying protein (from invertebrates, e.g arthropods and
molluscs), containing dinuclear type 3 copper sites
Hemoglobin: A dioxygen-carrying heme protein of red blood cells
HiPIP: High-Potential Iron-sulfur Protein (ferredoxin). Cluster which undergoes oxidation-
reduction between the [4Fe-4S]
2+
and [4Fe-4S]
3+
states
Holoenzyme: An enzyme containing its characteristic prosthetic group(s) and/or metal(s)
Ion channel: Enable ions to flow rapidly through membranes in a thermodynamically
downhill direction after an electrical or chemical impulse. Their structures usually consist
of 4-6 membrane-spanning domains. This number determines the size of the pore and thus
the size of the ion to be transported
Ionophore: A compound which can carry specific ions through membranes
Ion pumps: Enable ions to flow through membranes in a thermodynamically uphill
direction by the use of an energy source. They open and close upon the binding and
subsequent hydrolysis of ATP, usually transporting more than one ion towards the outside
or the inside of the membrane
Terms related to bioinorganic chemistry
Terms related to bioinorganic chemistry
Metalloenzyme: An enzyme that, in the active state, contains one or more metal ions
Mitochondria: Cytoplasmic organelles, produce ATP by oxidative phosphorylation
Model: A synthetic coordination entity that closely approaches the properties of a metal ion
in a protein and yields useful information concerning biological structure and function
Myoglobin: A monomeric dioxygen-binding hemeprotein of muscle tissue, structurally
similar to a subunit of hemoglobin
Nucleic acids: Macromolecules composed of sequences of nucleotides that perform
several functions in living cells, e.g. the storage of genetic information
Nucleosides: Compounds in which a purine or pyrimidine base is beta-N-glycosidically
bound to C-1 of either 2-deoxy-D-ribose or of D-ribose, but without any phosphate groups
Nucleotides: Nucleosides with one or more phosphate groups esterified mainly to the 3'- or
the 5'- position of the sugar moiety
OEC: Oxygen-Evolving Complex
Photosynthesis: A metabolic process in plants and certain bacteria, using light energy
absorbed by chlorophyll and other photosynthetic pigments for the reduction of CO
2
,
followed by the formation of organic compounds
Terms related to bioinorganic chemistry
Terms related to bioinorganic chemistry
Plastocyanin: An electron transferprotein, containing a type 1 copper site, involved in plant
and cyanobacterial photosynthesis, which transfers electrons to Photosystem 1
Rieske protein: An iron-sulfur protein of the mitochondrial respiratory chain, containing a
[2Fe-2S] cluster
Rubredoxin: An single iron-sulfur protein, function as an electron carrier
SOD: See superoxide dismutase, cataysis of disproportionation of superoxide
Soret band: Strong absorption band in the blue region of the optical absorption spectrum
of a heme protein
Substrates: A compound that is transformed under the influence of a catalyst
Trace elements: Elements required for physiological functions in very small amounts, e.g.
Co, Cu, F, Fe, I, Mn, Mo, Ni, Se, V, W, and Zn
Type 1,2,3 copper: Different classes of copper-binding sites in proteins, classified by their
spectroscopic properties as Cu(II). Type 1, or blue copper centers the copper is
coordinated to at least two imidazole nitrogens from His and one sulfur from Cys. In type 2,
or non-blue copper sites, the copper is mainly bound to imidazole nitrogens from His. Type
3 copper centers comprise two spin-coupled copper ions, bound to imidazole nitrogens
Zinc finger: A domain, found in certain DNA-binding proteins, comprising a helix-loop
structure in which a zinc ion is coordinated to 2 - 4 Cys sulfurs, the remaining ligands
being His
Basics of enzyme reactions (catalysis)
Basics of enzyme reactions (catalysis)
Catalysts
Accelerate chemical reactions (rate enhancement)
Participate in reactions but are not consumed
Stabilize the transition state (lower activation energy)
DO NOT alter the chemical equilibrium, (E) ~ reaction rate
Reduce the amount of time required to attain the equilibrium
Principle of complementarity
The active sites of enzymes tend to be more complementary to the transition states than they
are to the actual substrates
Preformation of the transition state by strained enzyme (entactic state)
Energy aspect: small activation energy, statistical aspect: more productive encounters
between reaction partners, kinetic aspect: faster reaction
Ligands
Ligands
-
-
Proteins
Proteins
Proteins consist of -amino acids, connected via peptide bonds
Metal coordination by functional groups in the side chain (R)
Histidine (both N atoms available, metal-metal briding
possible, pKa ~6)
Methionine
Cysteine
(metal-metal bridging, pKa ~ 8)
Selenocystein
(non-innocent ligand)
Aspartic acid
Tyrosine
(non-innocent ligand)
Glutamic acid
C
C
N
C
O
H
C
-
O
O
R
1
R
3
N
+
H
H
H
H
H
N-terminus
C-terminus
H
C C
H
N
H
2
C
O
N
N
M
M
pKa ~ 4
Excursus: biochemistry of Se
Excursus: biochemistry of Se
Related to S-containing biomolecules
More reactive, function as antioxidant (anti-aging)
Deactivation of radicals and lipohydroperoxides
RH +
3
O
2
R* + HO
2
*
R* + O
2
ROO*
ROO* + RH R* + ROOH
H
+
ROOH + E-Se
-
E-SeOH + ROH
G-SH/-H
2
O
E-Se-S-G
G-SH/-G-S-S-H, H
+
Ligands
Ligands
-
-
Proteins
Proteins
Coordination of metals by carboxylates:
1
(syn and anti),
2
, briding
Characteristic affinities of R to defined oxidation states of metals
Metal centers are undersaturated (bonding of substrate)
Coordination geometry frequently distorted (entatic state theory)
bond stability CN R typical coordn. geometry
Zn(II) high 3 His, Cys
-
dis. tetrahedron
Cu(I) high 3,4 His, Cys
-
, Met dis. tetrahedron
Cu(II) high 3,4 His dis. square
Fe(II), Ni(II), low 4-6 His, Glu
-
, Asp
-
dis. octahedron
Co(II), Mg(II)
Fe(III) high 4-6 Glu, Asp
-
, Tyr
-
, Cys
-
dis. octahedron
Structure of Proteins
Primary structure: Sequence of amino acids
Secondary structure: Shapes formed within regions of the protein
Tertiary structure: Shape of entire protein
Quaternary structure: Structures formed by interaction of several subunit
Cyclic
Cyclic
ligands
ligands
-
-
Porphyrin
Porphyrin
complexes
complexes
Unsaturated tetradentate macrocyclic ligands
Coordination of otherwise labile divalent metal ions
Porphyrin complexes: chelate-effect and size selective as host
Porphyrin: very stable, Hckel-aromatic (18 el = 4n +2), colored
Porphyrin
Hemoglobin
Myoglobin
Peroxidases
Chlorin
Chlorophyll (Mg
2+
)
Tunichlorine (Ni
2+
)
Corrin
Cobalamin (Co
2+
)
Metallaporphyrin
complex
Fe
Cyclic
Cyclic
ligands
ligands
-
-
Porphyrin
Porphyrin
complexes
complexes
N
C o
+
N H
2
C O C H
2
C H
2
H
H
H C H
2
O H
O H
H
C H
3
C H
3
H
3
C C H
C H
2
N H
C O
C H
2
C H
2
H
3
C
H
H
C H
3
N H
2
C O C H
2
H
H
3
C
N H
2
C O C H
2
H
3
C
C H
3
C H
2
C O N H
2
C H
3
H
H
C H
2
C H
2
C O N H
2
C H
3
C H
3
C H
2
C H
2
C O N H
2
N
N
N
N
N
O
O
O
P
O
O
N C
N
Fe
N
N N
R R'
R
R'
R R"
R
R"
Vitamine B
12
Cyclic
Cyclic
ligands
ligands
-
-
Porphyrin
Porphyrin
complexes
complexes
Bonding
Most complexes are (nearly) planar two open coordination sites (e.g. substrate)
Usually low spin complexes Fe(II) high spin in deoxy-hemoglobin out-of-plane position
Fine tuning of electronic configuration by conformation and axial ligands
Splitting of d orbitals (CFT):
octahedron
tetragonal bipyramide
square
Cyclic
Cyclic
ligands
ligands
-
-
Ionophores
Ionophores
Bonding of hard cations by macrocycles or quasi-macrocycles
Coordination by O, N
Production of a lipophilic shell around hard cations
Size, charge selective
Monesin A
Nucleobases
Nucleobases
-
-
building units of DNA, RNA
building units of DNA, RNA
DNA, RNA: macromolecules consisting of nucleotides as building units
Nucleotides: Pentose, pyrimindine- or purine base, phosphate group (1:1:1)
Information carriers as ligands (oligo- and polynucleotides)
Coordination by nucleobases or by phosphate groups (Zn
2+
, Mg
2+
)
N
N
N
O
HN
H
2
N
Sugar
N
HN
O
O
CH
3
Sugar
N
N O
NH
2
Sugar
N
N
N
N
NH
2
Sugar
Thymine Cytosine Adenine Guanine
P
O O
O
X
H
H
OH
Base
O
CH
2
H H
O
HO
X
H
H
OH
Base
O
CH
2
H H Nucleotide
X = OH: Ribose
X = H Desoxiribose
Nucleoside
Nucleobases
Nucleobases

pairing
pairing
Metals influence pairing of nucleic acid polymers (H-bonding)
Pairing of nucleobases inside DNA, complementarity of A-T and G-C
Metal atoms: Mispairing possible (carcinogenic effect), e.g. T-G
H
H
H
O
Base
P
O O
O
O
O CH
2
H
H
H
O
Base
P
O O
O
O
CH
2
H
H
H
O
Base
P
O
O
O
O
CH
2
H H
H H
H H
A-T
G-C
A-T
G-C
3.
Coordination for uptake,
transport and storage (Fe)
Some basic properties of Fe
Some basic properties of Fe
Usually oxidation of Fe(II)aq to Fe(III)aq under in-vivo conditions
Insalubrious function of Fe(II) high spin: formation of radicals, e.g. Fe(II) h.s. +
3
O
2
Fe(III) +O
2

Fe(III) non soluble at pH ~7, coordination of Fe(III) by complexing agents unambiguous

Condensation to clusters and colloids
Related affinity to different ligands (S, O, N)
Switching from high- to low spin configuration (medium strength of ligand)
Complexation interconnected with electron and proton transfer:
[Fe
3+
(Ligand)
3-
] +3 H
+
+ el Fe
2+
+ H
3
(Ligand)
Fe
H
2
O
H
2
O
OH
2
OH
2
O
O
Fe
OH
2
OH
2
OH
2
OH
2
H
H
Fe
O
Fe
O
O
Fe
O
Fe
H
H
2+
-2H
+
4+
Fe
H
2
O
H
2
O
OH
2
OH
2
O
O
Fe
OH
2
OH
2
OH
2
OH
2
-H
2
O, -2H
+
2[Fe(H
2
O)
6
]
3+ Colloids
Siderophores
Siderophores
(microorganisms)
(microorganisms)
Two groups of chelating agents
Hydroxamate
Catecholate
Antibiotic function, highly active (!), octahedral coordination of Fe(III)
-
-
HN
O
NH
O O O
O
NH
O
O
O
O
-
O
O
O
-
O
-
O
-
O
O
O
O
O
O
O
Fe
3-
Catecholate
O
-
O
-
R
Apoenterobactin
NH
NH
NH
NH
NH
NH
O O O
O O O
(CH2)3 (CH2)3 (CH2)3
N N N
C C C
CH
3
CH
3
CH
3
O O O
O
-
O
-
O
-
Mycobactin
Different M-X interactions
Hydroxamate
R-C
O
N O
-
R'
Ferrichrome
Proteins (complex organisms)
Proteins (complex organisms)
Transport: Transferrin
Coordination of Fe by caboxy- and phenolate groups of residues
Uptake of two Fe(III) and one HCO
3
-
Stability of complexes decrease with decreasing pH
High affinity of Apotransferrin, protection against infections
Not very specific (Cr
3+
, Al
3+
, Cu
2+
, Mn
2+
)
Release of Fe(III): Reduction to Fe(II) and binding by porphyrine
N
NH
O
O
O
O
O
O
Fe
O
NH
2
NH
2
HN
Arg
His
Tyr
Tyr
Asp
Storage: Ferritin
High symmetry of Apoferritin: F432
Hollow sphere built from proteins (inner dia.: ~ 7 nm, outer dia. ~ 13 nm)
Capacity: up to 4500 Fe
3+
, biomineralization (?)
Carboxylate groups for Fe(III) binding, core-structure related to Ferrihydrite Fe
10
O
6
(OH)
18
Exchange via channels (dia. 1nm), tuning of hydrophilic/hydrophobic character via residues
Release of Fe as Fe(II) via hydrophilic channels
Basics of
Basics of
Bioinorganic
Bioinorganic
Chemistry
Chemistry
Handout- part 2
Lorenz Kienle
Max-Planck-Institut fr
Festkrperforschung
Stuttgart
4.
Hard ions: Na
+
, K
+
,
Mg
2+
, Ca
2+
Basic characteristics
Basic characteristics
2.5 1.5 5 152 Extracellular
0.1 2.5 92 11 Intracellular
Concentration (mmol/kg)
O N,O O O Preferred donors
6-8 6 6-8 6 Coordination number
1.75 2.32 0.66 0.86 Charge/radius ratio
1.14 0.86 1.52 1.16 Ionic radius,
Ca
2+
Mg
2+
K
+
Na
+
Antagonism
multidentate chelates bidentate chelates
Labile bonding in solution, fast diffusion along a concentration gradient
Na, K:
Na, K:
Inhom
Inhom
. distributed electrolytes
. distributed electrolytes
Function
Stabilization (membrane, nucleotides, enzymes)
Fast information transfer by diffusion (highly volatile, diffusion control)
Maintenance of the concentration gradient
Pump storage model
Active Transport:
Ion pumps, proteins triggered by enzymes
Passive transport:
Ionophores, chelating ligands
Ion channels, proteins
Active
m
e
m
b
r
a
n
e
energy
Pump-storage model
Passive
spatial coordinate
Passive Ion transport
Passive Ion transport
-
-
summary
summary
lipophilic membran intracellular
extracellular
Ionophores
Carrier
mechanism
(very slow)
Channel
pore
Gated
Channel
Neurotransmitters, toxins, Ca
2+
, voltage gated
Passive transport:
Passive transport:
Ionophores
Ionophores
Analogs from the lab: crown ethers, cryptands (macrocycles)
Chelate effect (thermodyn. and kinet. stable)
Size/charge selectivity
Distinct polarity inside / outside the complex
Template effect of alkali metal (conformational change of ionophore)
Selectivity depending on number of coordination centers of ligand
Selectivity adjusted by optimum conformation
Natural ionophores act as antibiotics
Transport of alkali metal through biological membranes (carrier mechanism)
Perturbation of electrolyte level in bacteria
Nonactin
K-Valinomycine
3d coordination by folding
O
O
O
O
O
O
O O
N
N
O O
O O
Higher selectivity
Passive transport: Ion channels
Passive transport: Ion channels
Transmembrane protein with tube structure
Gramicidin A: a simple example
Formed from integral membrane proteins
Length 3 nm, two tubes in a row can perorate a membrane
Antiparallel helical aggregate of proteins
More complex channels
Building units: 4-5 homologous membrane proteins (helices)
Immediate lining contains polar groups (fixed charges)
Specific due to diameter, and chemistry inside the channel
Gates of the channels
Gate functioning important subject of pharmaceutical research
Opening by neurotransmitters, Ca
2+
, electrical pulses
Blocking as important biological function,
e.g. blocking of K
+
channels by H
+
sensing of sour
Active transport: Ion pumps
Active transport: Ion pumps
-
-
overview
overview
Transmembrane protein acting against concentration gradient
Structure, function:
Carboxylate groups (hydrophilic) for binding the active species
Selectivity by formation of E1 and E2 which are produced via (de)phosphorylation
Energyconsuming ion transport mechanism, energy production by hydrolysis of ATP
Symport: simultaneous transport of anions and cations (K
+
/Cl
-
) in same direction
Antiport: transport of ions of the same charge in opposite direction (H
+
/K
+
)
Example: Na
+
/K
+
/MgATPase (Mg
2+
-catalysis)
3 Na
+
(ic) + 2 K
+
(ic) + ATP
4-
+H
2
O 3 Na
+
(ec) + 2 K
+
(ic) + ADP
3-
+H
2
PO
4
-
ic: intracellular, ec: extracellular
Na
Na
+ +
/K
/K
+ +
/
/
MgATPase
MgATPase
: Flip
: Flip
-
-
Flop
Flop
-
-
mechanism
mechanism
Phosphorylation, conformational change to E2
Binding of Na
+
Conformation E1
Release of Na
+
Conformation E2
Binding of K
+
Conformation E2
Release of K
+
Conformation E1
Dephosphorylation, conformational change to E1
Toxins affecting ion transport (examples)
Toxins affecting ion transport (examples)
Digitoxigenine (Foxglove): Blocking of Na
+
/K
+
/ATPase
Inhibition of dephosphorylization
Increase of Na
+
and Ca
2+
due to antiport system
Consequence: Muscle contraction (heart!)
Poison of Fugu fish (Tetrodotoxin): Blocking of Na
+
channels
Mg: Catalysis of phosphate transfer
Mg: Catalysis of phosphate transfer
Mg
2+
: very hard, CN = 6, prefers multiple charged ligands (phosphates)
Functions:
Charge compensation, e.g. ATP (reduction of the high concentration of negative charges)
Polarization, increase of nucleophilic character: Mg
2+
+ OH
2
[MgOH]
+
+ H
+
Fixation of the reactants
Mechanism: S
N
2 with pseudorotation
Conformational changes during Na/K pumping
On the average a human adult synthesizes and uses an amount of ATP per day
which corresponds to the body weight!
Mg: phosphate transfer
Mg: phosphate transfer
-
-
examples
examples
ATP activated for hydrolysis ATP protected
HO
P
O
P
O
O
O
O
P
O
O
adenosyl
O
O
Mg
2+
HO
P
O
P
O
O
O
O
P
O
O
adenosyl
O
O
Mg
2+
HO
P
OH
O
O-Nu
P
O
O
O
P
O
O
adenosyl
O
Mg
2+
HO
Nucleophile
Hydrolysis of ATP (Na/K/ATPase pump)
Phosphate transfer to creatine via MgATP
Phosphate transfer to glycerate (formation of 2-phosphoglycerate)
H
2
C CO
2
-
N
H
3
C
NH
2
NH
2
MgATP/MgADP
Ca: great variety of functions
Ca: great variety of functions
Structural function
Biomineralization (1 kg), 10g/70kg in non-solid form
Strong influence on protein folding
Second messenger-, trigger-, activation funftion
Binding to acidic
2
-carboxy groups of proteins
High coordination numbers (7, 8), irregular coordination geometry
Lability of complexes allows fast structural changes
High concentration gradient (Ca
2+
pumps in sarcoplasmic reticulum)
Interconnections of electrolyte transport
membrane
2K
+
3Na
+
K
+
Na
+
2Na
+
Ca
2+
active
ATP ADP + P
extrac.
intrac.
passive
active
ADP + P ATP
Ca: Activation of enzymes, energetic processes
Ca: Activation of enzymes, energetic processes
Enzyme
(inactive)
Enzyme (active)
Substrate
can be fixed by
enzyme
Calmodulin (inactive)
Calmodulin (active)
Activation
Calmodulin = calcium modulating protein
Conformational change of Apo-Calmodulin by Ca-binding
Recognition and activation of enzymes
Muscle contraction (Translation of electrical stimulus into chemical stimulus)
Depolarization of membrane, opening of Na-channels
Release of Ca
2+
from acidic storage protein: Calsequestrin
Calsequestrin contains up to 50 Ca-binding sites, carboxylate groups (Glu, Asp)
Uptake of Ca
2+
by Troponin C, coupling with ATP Hydrolysis
Biomineralization
Biomineralization
: CaCO
: CaCO
3 3
-
-
Modifications
Modifications
Occurrence e.g. in shells, otholiths
Control of morphology and orientation by organic component
Carboxy-groups of peptide side chains (Asp, Glu)
Oxidized carbohydrates
Lab-examples:
Spindel-shaped calcite crystals in presence of malonic acid
Presence of stearic acid supports the formation of disc shaped Vaterite crystals
Four important modifications of CaCO
3
Aragonite
metastable, otholithes of fishes,
coral reef, pearls
Calcite, Calcite, {104}
stable, structural relation to rock salt
{104} frequently at the surface of shells
Vaterit
metastable, disordered (?), rare
formation of sperolithes
Amorphous CaCO
3
formation of spherolites
Biomineralization
Biomineralization
: Apatite Ca
: Apatite Ca
5 5
(PO
(PO
4 4
)
)
3 3
X
X
Occurrence e.g. in bones and teeth (enamel: larger crystals, F-substituted)
Highly effective mechanisms for Ca-transport (humans: 0.7g/day)
Collagen: template function, serves for defined orientation of apatite crystals
Binding of Ca via carboxy groups of osteocalcin or via phospho-proteins (?)
Hydroxyapatite
Collagen
Three left handed helices combined to
one right handed super helix
[001](Apatite) parallel to collagen helices
Composite material, no binding sites for Ca
Disordered structure
OH shifted from mirror plane
Non-polar structure (P6
3
/m)
c
o
l
l
a
g
e
n

f
i
b
e
r
Osteocalcin
Perfect match with apatite
Biomimetic
Biomimetic
morphogenisis
morphogenisis
(S. Busch)
(S. Busch)
Growth of apatite on gelatine in the lab
Observations:
Formation of a hexagonal seed (no crystal)
Formation of dumbbell
Formation of closed spheres
Principles of crystal growth
Fractal growth with self-similarity
Maximum aperture: (45 5), down scaling by 0.7
Discussion of internal electrical fields
Switch to polar space group (?), ordering of OH-groups (?)
Umbrella tree model
Biomineralization
Biomineralization
: SiO
: SiO
2 2
-
-
diatoms
diatoms
Polymers of silicid acid SiO
n
(OH)
4-2n
, no silicates, related to opal
Aggregation of silicid acid in SVD (silica deposition vesicles)
Inhibition of spontaneous polycondensation by ionophores (?)
Polycondensation via Proteins, e.g. silaffines: engaged condensation
Intermediates: D6R, D4R (see zeolites)
Formation of nanospheres, micro-morphogenesis