2. Contents
Introduction
Chemistry of transition metals
General aspect of coordination chemistry
Crystal field theory and Ligand field theory
Properties of metal complexes
Stability of metal complexes
Chemical kinetics
Complexation and Substitution Reactions
Organometallic of Transition metals
Reaction of organometallic compounds
Labeling chemistry and Labeled compound of 99mTc
Labeling chemistry and Labeled compound of 11C
Labeling chemistry and Labeled compound of 18F
Labeling chemistry and Labeled compound of 125I and 131I
Labeling chemistry and Labeled compound of 68Ga
5. Metals in medicine
Periodic Table of the bio-elements: elements building up bio-mass,
additional essential elements, essential for some groups of
organisms, medicinally important elements
Enzo Alessio, Bioinorganic Medicinal Chemistry, 2011 Wiley-VCH Verlag & Co. KGaA,
Boschstr. 12, 69469 Weinheim, Germany
14. Metals in the Body
The elemental composition of a typical human
15. Metals in the Body
Zinc in transcription
Zinc fingers are protein folds
that form a sequence able to A pair of zinc fingers interacting with a
bind to DNA. A typical finger is section of DNA.
formed by the coordination
of Zn(II) to two pairs of amino
acid side chains located either
side of the ‘fingertip
16. Metals in the Body
Selective transport and storage of iron
(a) Siderophores (b) Fe-transferritin (c) Ferritin
Protein shell
Structure of the Fe-transport protein transferrin
Iron core
17. Metals in the Body
Oxygen transport and storage
(a) Myoglobin
Reversible binding of O2 to myoglobin:
Structure of myoglobin,showing
coordination by O2 causes the Fe to
the Fe porphyrin group located
become low spin and move into the plane
between helices E and F.
of the porphyrin ring.
18. Metals in the Body
Oxygen transport and storage
(b) Haemoglobin
Key point: Haemoglobin consists of a tetramer of myoglobin-like subunits, with four
Fe sites that bind O2 cooperatively.
Haemoglobin is an α2β2 tetramer. Its α and β
subunits are very similar to myoglobin.
19. Metals in the Body
Others
Cytochromes
The plastocyanin molecule.
Iron–sulfur clusters
20. Diagnostic and Therapeutic Medicine
Features of metals and metal complexes that can be used in the
design of therapeutic and diagnostic agents.
22. Diagnostic and Therapeutic Medicine
Cancer treatment
Key points: The complex cis-[PtCl2(NH3)2] results in the inhibition of DNA replication and
prevention of cell division; other drugs cause DNA to be degraded by oxygenation.
Cisplatin
Carboplatin Trinueclear Pt (II)
Structure of an adduct formed between —
Pt(NH3)2 and two adjacent
guanine bases on an oligonucleotide.. Satraplatin
25. Diagnostic and Therapeutic Medicine
Imaging agents
Key point; Radiopharmaceuticals are drugs containing a radionuclide in their composition
Dotarem (MRI)
Cardiolyte (heart imaging) Tc-MAG-3 (kidney imaging)
Bone imaging Ceretec (Brain imaging)
26. Diagnostic and Therapeutic Medicine
Imaging agents
Key point: Particular organs and tissues are targeted according to the ligands that are
present.
A highly promising candidate for bone-imaging: a clear visualization
of the skeleton with low uptake in any other organ.
27. Diagnostic and Therapeutic Medicine
Imaging agents
Schematic representation of perfusion and target-specific
radiopharmaceuticals.
Organometallics 2012, 31, 5693−5714
28. Diagnostic and Therapeutic Medicine
Imaging agents
0 M 0 M 25 M 25 M
50 M 50 M 125 M 125 M
250 M 250 M 500 M 500 M
10 m
HeLa cells incubated 7 h at 37 oC with [Eu2(LC2)3]
lexc = 330 nm, exposure time 60 s, x40
29. Diagnostic and Therapeutic Medicine
Imaging agents
Hacat
Imaging other
cell lines
Hela Cells incubated
5 h at 37 oC
on plastic with
500 mM [Eu2(LC2)3]
MCF 7
-
lexc = 330 nm
exposure time 60 s
x40
10 mm
30. Diagnostic and Therapeutic Medicine
Imaging agents
Imaging with other lanthanides
250 mM 250 mM
[Tb2(LC2)3]
10 mm
500 mM
Q = 0.38 % !
[Sm2(LC2)3]
lex = 330 nm (BP 80 nm), exposure time 60 s, lens x40
HeLa cells incubated 7h (Tb) or 24 h Sm) at 37 oC
