Download - BIOINORGANIC CHEMISTRY discipline at the interface between inorganic chemistry and biology
BIOINORGANIC CHEMISTRY
discipline at the interface between inorganic chemistry and biology
BIOINORGANIC CHEMISTRY
discipline at the interface between inorganic chemistry and biology
Resources
Biological Inorganic Chemistry: Structure and ReactivityH. B. Gray, E. I. Stiefel, J. Selverstone Valentine, I. Bertini, Eds., University Science Books, 2006
The long history of iron in the Universe and in health and diseaseBiochim. Biophys. Acta, 2012, 1820, 161-187
THE ELEMENTS OF LIFE
24 elements are essential to life
H through Zn – excluding He, Ne, Ar, Li, Be, Al, Sc, Ti
Se, Mo, I
7 additional elements are essential to certain organisms
Sr, Ba, W, As, Br, Cd, Sn
THE ELEMENTS OF LIFE
bulk elements
C, H, N, O, P, S
macrominerals and ions
Na, K, Mg, Ca, Cl, PO43-, SO4
2-
trace elements
Fe, Zn, Cu
ultratrace nonmetals and metals
F, I, Se, Si, As, B Mn, Mo, Co, Cr, V, Ni, Cd, Sn
ELEMENTAL FUNCTIONALITY
charge carriers – Na, K, Cl
structure and templating – Ca, Zn, Si, S
signaling – Ca, B, N, O, Zn
buffering – P, C
catalysis – Zn, Fe, Ni, Mn, V, Co, Cu, W, S, Se
electron transfer – Fe, Cu, Mo
energy storage – H, P, S, Na, K, Fe
biomineralization – Ca, Mg, Fe, Si, Sr, Cu, P
THE ELEMENTS OF LIFE
bulk elements
C, H, N, O, P, S
macrominerals and ions
Na, K, Mg, Ca, Cl, PO43-, SO4
2-
trace elements
Fe, Zn, Cu
ultratrace nonmetals and metals
F, I, Se, Si, As, B Mn, Mo, Co, Cr, V, Ni, Cd, Sn
ELEMENTAL MASS ABUNDANCE IN A 70 kg HUMAN
SYMPTOMS OF ELEMENTAL DEFICIENCY IN HUMANS
ELEMENTAL ABUNDANCE IN THE UNIVERSE
TERRESTRIAL ELEMENTAL ABUNDANCE
TERRESTRIAL ELEMENTAL ABUNDANCE
ELEMENTAL ABUNDANCE
TERRESTRIAL ELEMENTAL ABUNDANCE
TERRESTRIAL ELEMENTAL ABUNDANCE
ELEMENTAL MOLAR ABUNDANCE OF TRANSITION METALS
TRAPS FOR BIOLOGICAL ELEMENTS
CARRIERS IN BLOOD PLASMA
ELEMENTAL MOLAR ABUNDANCE OF TRANSITION METALS
ELEMENTAL ABUNDANCE IN THE UNIVERSE
EVOLUTIONARY TIMELINE
HYDROLYSIS REACTIONS OF Fe3+
ELEMENTAL MASS ABUNDANCE IN A 70 kg HUMAN
AVERAGE IRON DISTRIBUTION IN HUMANS
BINDING OF O2 BY MYOGLOBIN
HEME REDUCTION POTENTIALS
Fe3+/Fe2+
IRON REDUCTION POTENTIALS
PROTEINS – CLASSES AND FUNCTIONS
dynamic
catalysis enzymes
transport hemoglobin
protection antibodies
muscle contraction actin and myosin
metabolic control hormones
gene transcription histones
storage ferritin
structural
matrices for bone collagen and elastinand connective tissue
PROTEINS
proteins are polymers of 20 different -amino acids, known as the common amino acids, which have a specific codon in the DNA genetic code
properties of 20 genetically coded amino acids
-amino group – except proline, which has an imino
group
-carboxyl group
unique R side chain and a hydrogen bound at the
central carbon
possess at least one asymmetric carbon (L form)
except glycine
HOOC – C – NH2
H
R
PROTEINS
at neutral pH, the amino and carboxyl groups are ionized, and the amino acids thus exist as zwitterions
proteins are produced by enzymatic polymerization of the 20 common amino acids, connected by peptide bonds formed by dehydration
AMINO ACIDS – ALIPHATIC
AMINO ACIDS – POLAR
AMINO ACIDS – AROMATIC
AMINO ACIDS – SULFUR OR SELENIUM
H
AMINO ACIDS – SECONDARY AMINE
AMINO ACIDS – CHARGED
PROTEINSproteins are produced by enzymatic polymerization of the 20 common amino acids, connected by peptide bonds formed by dehydration
the specific sequence of amino acids in the polypeptide chain is called the primary structure of the protein and is determined from the genetic information
PROTEINS
apoprotein – amino acids only
cofactors – small organic (e.g., vitamins, ATP, NAD, FAD) or inorganic molecules (particularly metal ions) that are required for activity; can be loosely bound (coenzymes) or tightly bound (prosthetic groups)
prosthetic group – tightly bound group (e.g., heme) to apoprotein
holoprotein – active protein with cofactors and prosthetic groups attached
COFACTORS
may participate directly in catalytic processes or carry other small molecules; binding to proteins may be weak or strong
are required in small quantities, may have to be supplied in diet and are either water or fat soluble
functions
metal ions maintain protein conformation through electrostatic interactions
prosthetic groups like heme may bind to active site and change the conformation to control bonding
may accept a substrate during reaction
METAL LIGATION
metal ions are bound in mononuclear or polynuclear coordination units in which amino acid side chains function as endogenous multidentate chelating ligands (protein)
often protein ligation does not coordinately saturate metals – catalysis
common bridging ligands
O2-, OH-, -CH2S-, S2-, -CH2CO2-, imidazole
exogenous terminal ligands are also often bound to metals
H2O, OH-, O2-, HS-, S2-
ENDOGENOUS METAL LIGATION
Oxygen atoms of peptide carbonyls, nitrogen atoms of deprotonated backbone amides, and lysine side chains are also available for metal coordination.
Protein residues as ligands for metal ions
ENDOGENOUS METAL LIGATION
ENDOGENOUS METAL LIGATION
PROTEINS
apoprotein – amino acids only
cofactors – small organic (e.g., vitamins, ATP, NAD, FAD) or inorganic molecules (particularly metal ions) that are required for activity; can be loosely bound (coenzymes) or tightly bound (prosthetic groups)
prosthetic group – tightly bound group (e.g., heme) to apoprotein
holoprotein – active protein with cofactors and prosthetic groups attached
PROSTHETIC GROUPS
biosynthesized groups that may participate directly in catalytic processes or carry other small molecules; binding to proteins is strong
functions
bind metal cations tightly
may accept a substrate
may participate in electron transfer
may bind to active site and change the conformation to control bonding
MACROCYCLIC LIGANDS
tetrapyrroles most common, best known bioinorganic compounds
study of structure/function and organic synthesis of these complexes led to several Nobel prizes
1915 – Willstätter (extraction of pigments, relationship between
chlorophyll and heme)
1930 – Fischer (formula of heme and chlorophyll, first synthesis of
tetrapyrroles)
1962 – Kendrew & Perutz (X-ray structure of hemoglobin and
myoglobin)
1964 – Crowfoot Hodgkin (X-ray structure of vitamin B12)
1965 – Woodward (total synthesis of vitamin B12 and chlorophyll)
1988 – Deisenhofer, Huber, & Michel (X-ray structure of photosynthetic
reaction centers containing heme and chlorophyll in bacteria)
TETRAPYRROLESpartially unsaturated, tetradentate, macrocyclic ligands
stable, rigid, planar or nearly planar ring system
deprotonated forms bind metal ions tightly and size selectively
extensive conjugation leads to very intense colors (pigments of life) and potentially to redox activity
PORPHYRINS
PORPHYRINS
PORPHYRINS
CHLORINS – CHLOROPHYLL a
chlorophyll a
CORRINS – VITAMIN B12
SPECIAL COFACTOR LIGANDS – PTERINS FOR Mo AND W
M = Mo or WR = H or adenosine
M = Mo or WR = H, adenosine, cytosine, guanosine, hypoxanthine
SPECIAL COFACTOR LIGANDS FOR MoMo NITROGENASE
A few families of bacteria and archea are the only organisms that can produce nitrogen-containing compounds from atmospheric dinitrogen (N2 fixation). All other fixed-nitrogen derives from abiological processes.
Current nitrogen fixation :
-Abiological natural processes (lightning, volcanic eruptions): ≈10%-Haber-Bosch process: ≈30%-Biological nitrogen fixation: ≈60%
The most common nitrogen-fixing enzyme is Mo-nitrogenase
SPECIAL COFACTOR LIGANDS FOR Mo – NITROGENASE
His
homocitrate
In fact, recent evidence indicates that there is a carbon in the middle of the FeMo cofactor of nitrogenase:
Science 2011, 334, 940Science 2011, 334, 974
Typical textbook drawing:
SPECIAL COFACTOR LIGANDS – IRON SULFUR CLUSTERS
SPECIAL COFACTOR LIGANDS – IRON SULFUR CLUSTERS
SPECIAL COFACTOR LIGANDS – IRON SULFUR CLUSTERS
Dark gray: Fe(III)Light gray: Fe(II)Dual color circle: Fe centers with +2.5 oxidation state
Localized and delocalized charges possibleFerromagnetic and antiferromagnetic coupling possible
FERREDOXINS