Bulk and trace elements – bulk elements: C, H, O, N, S, P – maintaining the osmotic pressure body fluids Na, K, Ca, Mg, Cl – essential trace elements: F, I, Se, Si, Sn (main group elements) Fe, Zn, Cu, Mn, Mo, Co, V, Ni (transition metals) – potential trace elements: B, Ti, As, Pb, Cd, W, .... – toxic elements
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Bulk and trace elements – bulk elements: C, H, O, N, S, P– maintaining the osmotic pressure body fluids
Na, K, Ca, Mg, Cl
– essential trace elements:F, I, Se, Si, Sn (main group elements)Fe, Zn, Cu, Mn, Mo, Co, V, Ni (transition metals)
0.0642Mg0.1070Na0.16115Cl0.36250K2.421700CaBulk elements
Average amount of trace elements (70 kg individual)
Trace elements
1. The abundance of elements in different living organisms is in a given concentration range
2. The decreasing of abundance of elements causes physiological changes (diseases)
3. Administration of missing trace elements improve the physiological conditionThey take part in the metabolism.
4. The elements have defined biochemical functions
Trace elements
µg/day 10 50 Se 200 103 104
mg/day 0,5 2 F 10 20 100
survival deficiency optimal toxicity lethalit
therapeutic width
Roles of trace elements
1. Transport of biological small moleculespl. O2-transport: hemoglobin (Fe), hemocianin (Cu)
O2-storage: mioglobin (Fe)
2. Activation of molecules: metalloenzymes, enzymes activated by metal ionsa) catalysing of redox processes (Fe, Cu, Mn, Co, Mo, Ni)
biological oxidation, reduction of substrateb) catalysing of acid-base processes (Zn)
3. Secunder conformation of macromolecules– determination of conformation of enzymes– determination of conformation of proteins, nucleic acids
4. Metabolism of microelements– uptaking, transport, storage of trace elements
Roles of trace elements
Experimental methods for study of biological systems
− UV-visible (UV) spectroscopy (exited electron →groundstate)− electronspin resonance spectroscopy (ESR) (interaction between unpaired electron and magnetic field)− nuclear magnetic resonance spectroscopy (NMR) − X-ray diffraction (study of solid crystals)− Mössbauer spectroscopy (study of iron-, tin-complexes)− molecule modelling (computational modelling)
Abundance of trace elements in a caveman andtoday (ppm)
- circumstances of life origin- chemical factors(complex formation ability, solubility, reversibility of bound, hard-soft acid-base properties)
The origin of life
Chemical evolution: formation of simple and more complicate organic molecules from elementsPrebiological evolution: formation of living cells from group of complicate organic compoundsBiological evolution: the development of living world
Coordination chemistry of metal ions
Complex formation proecesses:M(H2O)n + L ML(H2O)n-1 + H2O
MLn-1(H2O) + L MLn + H2O
M(H2O)n + nL MLn + nH2Oβn = K1·K2· ... ·Kn
]L][)OH(M[])OH(ML[K
n2
1n21
−=
]L)][OH(ML[]ML[K
21n
nn
−
=
nn2
nn ]L][)OH(M[
]ML[=β
Complex formation processes
General equilibrium
pM + qA + rB + sH MpAqBrHs
M: metal ion (oxidation number: 1-3 (4)) or oxoanionA, B: ligands
Types of coordination compoundsa/ parent complexes: complex formed with one ligand:
MA, MA2, MA3 .... MAN (N: coordination number)b/ mixed ligand complexes: complex formed with two or more ligands:
M + A + B MAB orMA2 + MB2 2MAB
c/ protonated complexes: the non-coordinated donor groups of ligands are protonated
M + HnA M(AH) + n–1 H+
Coordination chemistry of metal ions
Types of coordination compoundsd/ deprotonated complexes: M + A M(AH–1) + H+
−deprotonation and coordination of ligands (e.g.: alcoholic group, amide group−deprotonation of coordinated water moleculeMA(H2O)n MA(H2O)n–1(OH) + H+
c/ polynuclear complexes: nM + mA MnAm
(A: bridge ligand or ligand containing more donor atoms)
Coordination chemistry of metal ions
Reactions of metal complexes 1. Substitution of ligands
MA + B MB + Ain solution:
M(H2O)n + nA MAn + nH2Othermodinamic aspect: stable, instable complexes (lg β)kinetic aspect: labile (fast exchange), inert (slow exchange)Biological importance:
MXY + L MXL + Y(X - polifuntional macromolecule, Y – small molecule)e.g.: Zn-carboxypeptidase, Fe-mioglobin
Factors influenced stability of complexes:• Type and charge of metal ion
- the complex of metal ion with +3 oxidation state is more stable- the stability of complexes of 3d elements with +2 oxidation state follow the Irving-Williams series
Mn(II) < Fe(II) < Co(II) < Ni(II) < Cu(II) > Zn(II)(related to the decrease in ionic radii)
Coordination chemistry of metal ions
Factors influenced stability of complexes:• Type of metal ions and ligands
- hard metal ions (Lewis-acids) form stable complexes with ligands containing hard donor atoms (F, O) - soft metal ions (Lewis-acids) form stable complexes with ligands containing soft donor atoms (I, S)
• Type of ligands- formation of chelate rings (five- or six-membered ring) →enhance the stability of complexes: chelate effect
Coordination chemistry of metal ions
Potential donor atoms in biological systems
• Hard-soft acid-base groups of metal ions and ligands
Alkali and alkali earth metal ions:biological roles
Membrantransportprocesses
Alkali and alkali earth metal ions:biological roles
Membrantransport processesTransport across the membrane
Diffusion: non-selective, in direction of concentrationgradient
Facilated passive transport: by means of carriers (ionophors)energy is not required
Active transport: in opposite direction of contentrationgradient, energy is requiredenergy source: hydrolysis of ATP
Alkali and alkali earth metal ions:biological roles
Membrantransport processesTransport across the membrane
Alkali and alkali earth metal ions:biological roles
Membrantransport processesTransport across the membrane
Diffusion: non-selective, in direction of concentrationgradient
Facilated passive transport: by means of carriers (ionophors)energy is not required
Active transport: in opposite direction of contentrationgradient, energy is requiredenergy source: hydrolysis of ATP
Alkali and alkali earth metal ions:biological roles
Membrantransport processesTransport across the membrane
Alkali and alkali earth metal ions:biological roles
Membrantransport processesPassiv transportLigands: carrier ionophors: e.g. Valinomicin
Alkali and alkali earth metal ions:biological roles
Chanel ionophorse.g. Gramicidin A
Membrantransport processesTransport across the membrane
Diffusion: non-selective, in direction of concentrationgradient
Facilated passive transport: by means of carriers (ionophors)energy is not required
Active transport: in opposite direction of contentrationgradient, energy is requiredenergy source: hydrolysis of ATP
Alkali and alkali earth metal ions:biological roles
Membrantransport processesTransport across the membrane
Alkali and alkali earth metal ions:biological roles
Biological rolesNa+, K+:• maintaining of osmotic pressure of cells• take part in acid-base processes• regulation of membrane potentials• K+: take part in determination of conformation of biomolecules, in activation of enzymes, in synthesis of acetilcoline• Na+: take part in activation of enzymes, in secondary active transport
Alkali and alkali earth metal ions:biological roles
Biological roles of alkali metals
Na+, K+: regulation of membrane potentials
Na+, K+: regulation of membrane potentials
Biological roles of alkali metals
Ca2+:• regulation the processes of nerve transmission• regulation the muscle contraction• regulation electrolyte balance• blood coagulation• building up bones and theeths
Biological roles of alkali earth metals
Ca2+: regulation the processes of nerve transmission
Mg2+:• activation of enzymes, determination of conformation of proteins• take part in hydrolysis of ATP, universal source of energy → metabolism of energy • building up of bones• part of chlorophyll (photosynthesis)
Biological roles of alkali earth metals
Mg2+ - photosynthesis
6 CO2 + 6 H2O = C6H12O6 + 6 O2
Two photosystemI. reduction of CO2 (dark reaction)CO2 + NADPH + H+ + ATP → C6H12O6
+ ADP + Pi + NADP+
II. photolysis of water (light reaction)H2O + NADP+ + Pi + ADP
O2 + NADPH + H+ + ATP⎯⎯→⎯light
chlorophyll
Biological roles of alkali earth metals
Mg2+ - photosynthesis
Biological roles of alkali earth metals
Mg2+ - photosynthesis
90Sr – radioactive, t½ = 28 year, can be built up in bonesBaSO4 – contrast compound (X-ray)
Biological roles of alkali earth metals
Complexes of iron(II)
Complexes:• in solution: [Fe(H2O)6]2+ (octahedral, pale green)• easy oxidation to iron(III) (in basic solution)• redoxpotential of Fe(III)/Fe(II) is changed by formation of complexesFe3+/Fe2+ : CN– +0,36 V
H2O +0,77 VPhen +1,12 V
Complexes:• intermediate (hard/soft) acid: binding to O-, N- and S-donor-atoms
• most important ligands: aromatic nitrogen donors in chelatable position• bipiridine, fenantroline, porphyrins
• usually octahedral complexes (some tetrahedral complexes)
Complexes of iron(II)
Complexes:• in solution: [Fe(H2O)6]3+ (pale violet)• stable complexes in acid and basic pH range• characteristic reaction: hydrolysis
• usually octahedral complexes• hard acid: • binding to F– and O-donors containing ligands• [Fe(SCN)4]– + 6 F– [FeF6]3– + 4 SCN–
intensive red colorless
Complexes of iron(III)
Biological role of iron
Iron proteins
Hem proteins Non-hem proteins~ 70 % ~ 30 %
iron-sulphur othersproteins
• Human body: cca. 4 g iron (~3 g in hemoglobin)• uptaking of iron: 1 mg/day
Iron proteins
Hem proteins Non-hem proteinsoxygen transport, storage
hemoglobin hemerythrinmyoglobin
electron transfercytochromes iron-sulphur proteins
oxidases, oxygenasescytochrome c oxidase
iron transport transferriniron storage ferritin
Biological role of iron
Globin: contains153 amino acidsHem: Fe-porphyrin
Hem is bound to globin protein via iron ion (without covalent bound)
5. coordination side:imidazole N
Myoglobin (oxygen storage)
Hemoglobin (oxygen transport)
It contains 4 globin units
Fe(II) + O2: iron ion passes to porphyrin ring
uptaking of oxygen: high partial pressure of oxygengiving down of oxygen: low partial pressure of oxygenCO2 + H2O HCO3
– + H+
Hemoglobin (oxygen transport)
parital pressure of oxygen in the lungs
partial pressure of oxygen in the muscle
– oxygen transporter in molluscs
– 4 part, one part contain two iron, it binds one O2
Hemerythrin
• transfer electrons (redox proteins and enzymes)• insert oxygen atoms or dioxygen into organic substrates or catalyse other important organic reaction• coordination number: 5 or 6• interaction between protein and hem moiety: covalent or van der Waals bound
Cytochromes
Cytochrome C
provide electrons via following reaction:
Fe2+ Fe3+ + e–
Cytochrome P450• part of monooxygenase enzymes • activation of dioxygen molecule
• Metalloproteins, which take part in the DNA transcription• Zn: regulation of structure• 9-10 zinc ions, • Zn2+: tetrahedral geometry (His N, Cys S) →the conformation is similar to a finger
Zinc fingers
Pharmaceutical application of metals
Administration of trace elements• treatment of deficiency diaseses Remove of toxic elements• treatment of toxicity of heavy metals
Important aspects:• metal complexes of chelatable or macrocyclic ligands have high stability• neither ligands nor complex are not toxic• ligand is selective