Metal Compounds In Medicine

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Early diagnosis of diseases (e.g., cancer) and detection of curative progress after therapeutic treatments play an important role in medicine and health care.

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This Demonstration illustrates the molecules for 15 organometallic drugs. Shown are the basic characteristics (the metal center, the code-ID for the crystallography open database, medical usage, known agents for the same usage, and the coordination polyhedron), and four 3D views (molecule, molecule and polyhedron, molecule and polyhedron around the metal atom, and idealized polyhedron).

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Contributed by: Guenther Gsaller (November 2012)
(Institute of Organic Chemistry, Johannes Kepler University, Linz, Austria, http://www.jku.at/orc/)
Open content licensed under CC BY-NC-SA


Snapshots


Details

Types of Agents

The following groups of agents were selected:

1. SOD mimetic, 2. insulin mimetic, 3. radiopharmaceutical, 4. anti-tumor, 5. MRI contrast

1. SOD mimetic agents

The active center of superoxide dismutase is manganese. In humans three forms of the enzyme (SOD1, SOD2, and SOD3) are present. Mn(II) macrocycle M40403 has been (animal) tested as a catalytic SOD mimic.

The Mn(II) complexes Mn-7106426 and Mn-7106427, illustrated in this Demonstration, show promising in vitro SOD activity [3].

The coordination number for manganese in these complexes is 6 and the coordination polyhedra are slightly distorted octahedra.

2. Insulin mimetic agents

Bis(maltolato)oxovanadium(IV) or BMOV is the most frequently tested substance and has been proposed as an insulin mimic.

The V(IV) complexes and , illustrated in this Demonstration, did not exhibit an insulin-mimetic effect in the lipogenesis assay and in the gylcerol release lipolysis assay. They did show some effect for the release of free fatty acids [4].

The coordination number for vanadium in these complexes is 6 and the coordination polyhedra are slightly distorted octahedra.

3. Radiopharmaceuticals

Technetium-99m is a radionuclide and widely used in diagnostic medicine. Tc-imaging procedures are used regularly in a nuclear medicine department. Ceretec is a radiotracer to image the cerebral blood stream. Cardiotec is an approved cardiac imaging agent.

The three complexes , , and , illustrated in this Demonstration, are examples of a general synthetic method for the production of radiopharmaceuticals containing technetium or rhenium [5].

The coordination number for rhenium, technetium in these complexes is 4 and the coordination polyhedra are slightly distorted tetrahedra.

4. Anti tumor agents

Cisplatin was the first platinum anticancer drug. The problem of resistance limits its applicability. Oxaliplatin has no cross-resistance with Cisplatin.

The four complexes , , , and , illustrated in this Demonstration, are examples of a study of palladium/platinum nucleobase complexes [6]. The Cisplatin-analogue was tested against Cisplatin with different human tumor cell lines. It showed promising results.

The coordination number for palladium, platinum in these complexes is 4 and the coordination polyhedra are slightly distorted square planes.

5. MRI contrast agents

These agents shorten the relaxation time of nearby water molecules. Contrast with background tissues is enhanced. Magnevist and Dotarem are well-known commercial products for clinical use. The central ion for most agents is gadolinium(III). MRI contrast agents have one (or more) water sites ready for quick exchange.

The four lanthanide tetraalkyne DOTAM complexes Dy-1, Nd-1, Tb-1, and Yb-1, illustrated in this Demonstration, are part of a study with the aim to deliver a flexible toolbox for creating MRI contrast agents [7].

The coordination number for dysprosium, neodymium, terbium, and yttrium in these complexes is 9 and the coordination polyhedra are slightly distorted trigonal prisms with three caps.

Source of Crystal Data

The ball and stick figures are derived from crystal structures found via Crystallography Open Database. The code-IDs for each used structure are listed in the Demonstration.

References

[1] M. Gielen and E. Tiekink, eds., Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine, Chichester: John Wiley & Sons, Ltd., 2005.

[2] R. M. Roat-Malone, Bioinorganic Chemistry: A Short Course, Hoboken: John Wiley & Sons, Inc., 2002.

[3] M. Clares, S. Blasco, M. Inclán, L. del Castillo Agudo, B. Verdejo, C. Soriano, A. Doménech, J. Latorre, and E. Garcia-España, "Manganese(II) Complexes of Scorpiand-Like Azamacrocycles as MnSOD Mimics," Chemical Communications, 47(21), 2011 pp. 5988–5990. doi:10.1039/C1CC10526D.

[4] J. Nilsson, E. Degerman, M. Haukka, G. Lisensky, E. Garribba, Y. Yoshikawa, H. Sakurai, E. Enyedy, T. Kiss, H. Esbak, D. Rehder, and E. Nordlander, "Bis- and Tris(pyridyl)amine-oxidovanadium Complexes: Characteristics and Insulin-Mimetic Potential," Dalton Transactions, 38, 2009 pp. 7902–7911. doi:10.1039/B903456K.

[5] J. Bernard, K. Ortner, B. Spingler, H.-J. Pietzsch, and R. Alberto, "Aqueous Synthesis of Derivatized Cyclopentadienyl Complexes of Technetium and Rhenium Directed toward Radiopharmaceutical Application," Inorganic Chemistry, 42(4), 2003 pp. 1014–1022. doi:10.1021/ic0204575.

[6] J. Ruiz, M. Villa, N. Cutillas, G. Lopez, C. de Haro, D. Bautista, V. Moreno, and L. Valencia, "Palladium(II) and Platinum(II) Organometallic Complexes with 4,7-dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine. Antitumor Activity of the Platinum Compounds," Inorganic Chemistry, 47(11), 2008 pp. 4490–4505. doi:10.1021/ic701873b.

[7] M. Milne, K. Chicas, A. Li, R. Bartha, and R. Hudson, "ParaCEST MRI Contrast Agents Capable of Derivatization via “click” Chemistry," Organic & Biomolecular Chemistry, 10(2), 2012 pp. 287–292. doi:10.1039/C1OB06162C.



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