bulk and trace elements
TRANSCRIPT
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
Average abundance of trace elements(70 kg individual)
0.15100S1.0680P2.61815N9.76780H18.012590C65.145550OOrganic elements%weight (g)element
0.000014 mgMo0.0000312-20 mgMn0.0001480-120 mgCu0.0042-4Zn
0.0074.2-4.6FeTrace elements(<100 mg/body kg)
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)
1701,70,01Pb> 2000,19<0,001Hg7000,70,001Cd1,00,40,4Ti2,30,90,4Al2,30,70,3B1,00,030,03Co1,00,10,1Mo1,21,21,0Cu1,03333Zn1,06060Fe
ratiotodaycavemanelement
Composition of earth crust and see water (ppm)
5⋅10–70,00355Cu∼10–8∼10–71-100Ln0,010,011,5Mo∼10–60,0005100Cr∼10–70,0014400Ti∼10–53,0277000Si∼10–70,0181300Al14619000130Cl0,371005028300Na
see/earthsee waterearth crustelement
- 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
Coordination chemistry of metal ions
Reactions of metal complexes2. Redox reactions
ε(oxidated form) < εo < ε(reduced form)
Fe(III)/Fe(II) ε (V) Cu(II)/Cu(I) ε (V)εo H2O +0,77 H2O +0,17
OH– –0,56 glycine –0,16oxalate +0,02CN– +0,22 bipiridine +0,96 pyridine +0,27fenantroline +1,10 imidazole +0,35
CN– +1,10
Coordination chemistry of metal ions
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
Oxigen containing ligands: H2O, CO3
2–, NO3–, PO4
3–, ROPO3
2–, (RO)2PO3–,
CH3COO–, OH–, RO–, R2O, crownethersNitrogen containing ligands:NH3, N2H4, RNH2,Cl–
H+, Na+, K+
Mg2+, Ca2+, Mn2+, VO2+
Al3+, Co3+, Cr3+, Ga3+, Fe3+, Tl3+, Ln3+, MoO3+
hard bases (ligands)hard acids (metal ions)
,
Sulphur containing ligands:RSH, RS–, R2S, S2O3
2–
R3P, (RS)2PO2–,
(RO)2P(O)S–,RNC, CN–, CO, R–, H–, I–
Cu+, Au+, Tl+, Ag+, Hg22+
Pt2+, Pb2+, Hg2+, Cd2+, Pd2+, Pt4+,
soft bases (ligands)soft acids (metal ions)
Br–, SO32–,
Nitrogen containing ligands:NO2
–, N3–, N2,
Fe2+, Ni2+, Zn2+, Co2+, Cu2+,Pb2+, Sn2+, Ru2+, Au3+
intermediate bases(ligands)
intermediate acids (metal ions)
NH2
NNH
Potential donor atoms in biological systems
The most important ligands in biological systems
• amino acid, peptide, protein• nucleic acid base, nucleoside, nucleotide• porfirins• polyphenols, carbohydrates, glycerides
Metal complexes of amino acids and peptides• -COO–-coordination: Na+, Ca2+, Al3+
• -NH2-coordination: Ag+, Hg2+
• (NH2,COO–) coordination: M2+ (M+, M3+) transition metal ions
amino acid dipeptide
coordination is influenced: • by R1-Rn sidechain• pl: Asp, Glu – carboxylate group,• His – imidazole ring, • Cys – SH-group
Nukleinsavak és alkotórészeik
N
N N
N
O CH2 O P
O
-O
O P
O
O-
O P
O
O-
O-
NH2
HO OH
nukleobázis: N-donorok soft fémek
foszfát: O-donor hard fémek
Nucleic acids and their components
nucleic base: N-donors
phosphate: O-donors
soft metal ions
hard metal ions
N
N N
N
MM2+ + H2P MP + 2 H+
Order of stabilitiesMg(II) < Zn(II) < Cu(II) < Fe(II) < Ni(II) < Pd(II) < Pt(II)
N = 4 (Ni(II), Pt(II), Pd(II)) – all coordination sites are occupiedN = 6 (Fe(II), Co(II), Mg(II), Zn(II)) – axial coordination site
Metalloporphyrines
Complexes of alkali metal ions
No stable complexes with “normal” ligands
Crown ethers: macrocyclic polyethers
18-crown-6 Dibenzo-crown-6
OO
O
OO
O OO
O
OO
O
cryptand e.g. 2,2,2 NO O
NO OO O
Li+ complex of 12-crown-4
Complexes of alkali metal ions
Factors influencing the stability of alkali complexes
O
O O
O
OO
O
OO
O
a) the size of cavity
K+> Rb+> Cs+ > Na+> Li+
lgβNa(I) = 2.2 (methanol)lgβK(I) = 1.3 (methanol)
lgβNa(I) = 4.1 (methanol)lgβK(I) = 5.9 (methanol)
NO O
NO OO O
( )m( )n
( )n(vízben) lgβLi(I) lgβNa(I) lgβK(I)
m=0, n=1 5,3 2,8 <2,0
m=1, n=0 2,5 5,4 3,9
m=n=1 <2,0 3,9 5,4
m=1, n=2 <2,0 1,65 2,2
m=2, n=1 <2,0 <2,0 <2,0
m=n=2 <2,0 <2,0 <2,0
a) the size of cavity
Factors influenced the stability of alkali complexes
c) number of binding side
lgβNa(I)=6,95 lgβK(I)=9,45
NO O
NO OO O N
O ON
O O
lgβNa(I)=3,0 lgβK(I)=4,35
Factors influenced the stability of alkali complexes
methanol/water = 95/5
d) type of binding side
OO
O
OO
O
ON
O
ON
O
CH3
CH3
Factors influenced the stability of alkali complexes
lgβNa(I) = 4.3 (methanol)lgβK(I) = 6.1 (methanol)
lgβNa(I) = 3.7 (methanol)lgβK(I) = 5.3 (methanol)
d) type of binding side
NO O
NO OO O N
N NN
O OO
CH3 CH3
O
Factors influenced the stability of alkali complexes
lgβNa(I) = 3.9 (water)lgβK(I) = 5.4 (water)
lgβNa(I) = 2.5 (water)lgβK(I) = 2.6 (water)
Selectivity of ligands
NO O
NO OO O
Importance• specific chelators (diagnostic, therapy)• phasetransfer: transport of KMnO4 in organic phase
Complexes of alkali earth metals
O-donor ligands are preferred• crown ethers, macrocyclic• edta
NCOOH
COOHHOOC
HOOCCH2CH2N
ON
O
O
N O
O
O
O
O
Alkali and alkali earth metal ions:biological roles
Abundance in human body• cca 1 % of body (trace elements < 0,01 %)• e.g. 170 g potassium/ 70 kg, 1000-1250 g Ca, 26 g Mg
• bulk elements: C, H, O, N, S, PNa, K, Ca, Mg, Cl
Distribution (mmol/1000 g)
22.0440.0Extracellular fluid of neuron
410.049.0Intracellular fluid of neuronCalamary
2.51.55.0152.0blood plasma0.12.592.011.0blood cell
Ca2+Mg2+K+Na+
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
Biological roles of alkali earth metals
P1
ADP
Ca2+: muscle contraction
Ca2+-binding proteins• trigger proteins: e.g.: calmodulin
Buffer proteins: pl. calbindin• Ca-storage proteins: calreticulin, calsequestrin• blood coagulation: prothrombin• building up bones: osteocalcin: Ca5(PO4)3OH
Ca2+-binding proteins: blood coagulation - protrombin
Biological roles of alkali earth metals
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
pH > 1: [Fe(H2O)6]3+ + H2O [Fe(H2O)5(OH)]2+ + H3O+
Ks = 1,8⋅10–3
• Dimerization → structure with oxo bridges (yellow)[(H2O)5Fe–O–Fe(H2O)5]4+
Complexes of iron(III)
Complexes:pH > 2: polynuclear structures, mixed hydroxo complexes →Fe(OH)3 precipitation
• 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
RH + O2 + 2 e– + 2 H+ → ROH + H2O
• 5. coordination side: cysteine S • 6. coordination side: H2O
Cytochromes
Cytochrome P450
Catalase– catalysing the disproportion of H2O2
2 H2O2 → 2 H2O + O2
– it contains four same units– 5. coordination side: tyrosine O–
– mechanism:
Fe(III)
O-(Tyr)
Fe(IV)
O-(Tyr)
H2O2 H2O
H2O2H2O + O2
Catalase
• Tetrahedral geometry of iron• Iron binding to inorganic and organic sulphur donors (Cys) S• one e–-pass
• reduced ferredoxin oxidized ferredoxin • unusually low redox potenctial: –0,05 - –0,49 V → they behave as a reduction agents
Iron-sulphur proteins
• rubredoxin: [1Fe]3+(RS–)4 (–0,06 V)• ferredoxins: [2Fe-2S]2+(RS–)4 (–0,3 - –0,4 V)
[4Fe-4S]2+(RS–)4 (–0,4 V)HIPIP: [4Fe-4S]2+(RS–)4 (0,35 V)
– e–
+ e–
Iron-sulphur protein (HIPIP)
Iron-sulphur proteins
Transferrin:Transport: iron(III) form, at neutral pHStructure: M ~ 80.000, 0,15 % irontwo structural units:
one unit: 2 iron(III) + protein
Transport of iron
Siderophores:iron transporter in microorganisms
C
N
R
R
O
O-
Fe+3
3
O-
O-
Fe+3
3
Rhydroxamate-type
e.g. ferrichromcatecholate-type
e.g. enterobactin
Transport of iron
FerritinIt contains 24 protein units (~ 175 amino acids/unit)4500 iron atoms/ferritin (25 %)iron micelle (7 nm diameter) : (FeOOH)8⋅FeO⋅H2PO4
uptaking: iron(II) form, it is followed by oxidation to iron(III)Hemosiderinstorage of excess of ironcca. 45 % iron
Storage of iron
Biological role of copper
• Essential for every living organisms• 80-120 mg / 70 kg body• uptaking: 1,5-3,0 mg/day, < 10 mg• toxicity: > 15 mg• diseases caused by copper:
excess of copper: Wilson diseasemissing of copper: Menke’s disease
Functions of copper proteins
• Oxygen transport, storage: hemocyanin (mollusc)
• Catalysing of redox processesoxidases (blue-copper oxydase), oxygenases, superoxide dismutase
• Copper transport, storage: ceruloplasmin, metallothionein
Biological role of copper
Superoxide dismutase (SOD)2 O2
– + 2 H+ H2O2 + O2⎯⎯→⎯SOD
His 61
His 78
His 69
H2O
Zn2+
Cu2+
His 44
His 46His 118
Asp 81
Biological role of copper
Superoxide dismutase (SOD)Zn: regulation of structureCu: takes part in redox processes
Reactions:Cu2+(His–)Zn2+ + O2
– + H+ → Cu+ + (HisH)Zn2+ + O2
Cu+ + O2– + H+ + (HisH)Zn2+ → Cu2+(His–)Zn2+ + H2O2
Biological role of copper
Ceruplasmine:1005 amino acid (single protein chain), 6 copper
Function: • oxidase• ferrioxidase: Fe2+ → Fe3+
• transport of copper• metabolism of copper → missing of ceruloplasmine →Wilson disease, Menke’s disease
Biological role of copper
Zinc metalloproteins1940 – first zinc enzyme: carbonic anhydrase1985 – 100 zinc containing enzymes1995 – 300 enzymes + > 100 zinc containing proteins
Role of zinc: • active centrum (catalysing of acid-base processes)• regulating of structure
The second most abundant trace element The least toxic elementEssential for every living organism2-4 g zinc / 70 kg body
Biological role of zinc
Carboanhydrase
• Process:CO2 + H2O HCO3
– + H+
k = 3·10–2 s–1, with enzyme: k = 6·105 s–1
• Zn: tetrahedral geometry, • coordination: 3 histidine + 1 H2O• Zn – H2O → Zn-OH– → interact with CO2
Carboxypeptidase A• Process: hydrolysis of peptide bound at C-termini • 1 Zn + 307 amino acids (M ~ 34.000) • coordination: 2 histidine + 1 glutamate COO– + 1 H2O
Glu 117
His 119
Thr 199
His 96
His 94
His 64
Glu 106
H2O
Gln 92
Zn2+
Carboanhydrase
Carboxypeptidase A
Zinc fingers
• 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
Metal complexes in therapy
Anticancer pharmaceuticals, medicines:cisplatin complexes
cisplatin carboplatin
Pharmaceutical application of metals
H3NPt
H3N
Cl
Cl
H3NPt
H3N
O
O
C
C
O
O
Mechanism of cisplatin
Pharmaceutical application of metals
H3N (II)Pt
H3N
Cl
Cl
H3N (II)Pt
H3N
Cl
OH2
NH3
Pt(II)H3N Guanin (DNA)
Cl
H3N (II)Pt
H3N
G
G
hydrolysis
DNA
Metal complexes in therapyLithium: maniac depression: Li2CO3
Vanadium: insulin mimic (oral) pharmaceuticals
bis(picolinato)oxovanadium(IV) bis(maltolato)oxovanadium(IV)
OV
N
N
OO
O O OV
O
O
O
OO
O
CH3
CH3
Pharmaceutical application of metals
Metal complexes in therapy• Bismuth: gastric ulcer: Bi(NO3)3
• zinc: treatment of ulcers
Pharmaceutical application of metals
Metal complexes in therapy• gold: rheumatoid arthritis
Pharmaceutical application of metals
+Na-O
S
O-Na+
O
OAu
n
O
H
HO
H
HO
H
HOHH
S
OH
Au
Au S CH2
HC
H2C SO3Na
OH
nMyochrysine
Solganol
Allochrysine
Metal complexes in therapysilver: treatment of infection
Pharmaceutical application of metals
SHN
N
N
H2N
O O
sulfadiazin
Contrast compounds• X-ray contrast:
heavy metal salts: e.g.: BaSO4
organic iodine compounds• NMR tomography: Gd-polycarboxylate complexes
Pharmaceutical application of metals
Contrast compounds• NMR tomography: Gd-polycarboxylate complexes
NN
N
COO-
-OOC
-OOC
COO-
COO-
N N
NNCOO-
COO-
-OOC
-OOC
DTPA - Magnevist
DOTA - Dotaterm
Pharmaceutical application of metals
Radioactive isotopesDiagnosis• > 80 %, 99mTc, γ-ray (t1/2(γ) = 6 hours, t1/2(β) = 212000 years)
Therapy• outer ray source• Injection: 186Re, 188Re
Pharmaceutical application of metals