Metal Complexes for Therapeutic Applications

Abstract

Metal complexes have been widely used for applications in the chemical and physical sciences due to their unique electronic and stereochemical properties. For decades the use of metal complexes for medicinal applications has been postulated and demonstrated. The distinct characteristics of metal complexes, including their molecular geometries (that are not readily accessed by organic molecules), as well as their ligand exchange, redox, catalytic, and photophysical reactions, give these compounds the potential to interact and react with biomolecules in unique ways and by distinct mechanisms of action. Herein, the potential of metal complexes to act as components bioactive therapeutic compounds is discussed.

Keywords: Bioinorganic Chemistry; Chemical Biology; Coordination Compounds; Enzyme Inhibitors; Metals in Medicine.

Figure 1.

Geometries of carbon and metal containing complexes. a) Linear, planar, and tetrahedral geometry of carbon centers; b) Square planar, trigonal bipyramidal, square pyramidal, octahedral, sandwich and half sandwich geometries of metal complexes; c) X-ray crystal structure of Λ-OS1 bound to GSK3β. Λ-OS1 shows a highly complementary molecular surface that is able to form a novel interaction with the glycine rich loop via an induced fit binding mode; d) Structures of Λ-OS1 and staurosporine. PDB accession codes 3PUP and 1Q3D for protein-bound Λ-OS1 and staurosporine, respectively [19].

Figure 2.

Representation of diverse chemical space occupied by metal complexes. a) Structures of plotted sandwich, half sandwich, and octahedral metal complexes. b) Principle moment of inertia plot showing FDA approved drugs (blue circles) and metal complexes (orange diamonds) from part ‘a’ of the figure. Adapted with permission from [36].

Figure 3.

Ligand exchange activity of metal complexes. Mechanism of action of: a) the clinically approved anticancer drug cisplatin, and b) a coordinationally covalent bound Au(I) complex as an enzyme inhibitor.

Figure 4.

Redox bioactive of metal complexes. a) Chemical structures of Tamoxifen, Ferrocifen, Ferrocerone, and Ferroquine; b) Redox activation mechanism of Ferrocifen; c) chemical structures of redox active Pt(IV) complexes that have entered clinical trials.

Figure 5.

Catalytic metal complexes. a) Proposed catalytic cycle for the oxidation of GSH to GSSH; b) Enantioselective conversion of pyruvate to d-lactate with the proposed transitions state of the chiral Os(II) complex.

Figure 6.

Photophysical activity of metal complexes. a) Structure of a peptoid-Ru(II) polypyridine complex conjugate; b) Dual mechanism of action of the peptoid as an enzyme inhibitor and a Ru(II) polypyridine complex as a photosensitizer for light activated protein inactivation.