Metals in Medicine

James C. Dabrowiak

• Editore: Wiley
• Anno: 2017
• ISBN:
  9781119191346
• Edizione: 2
• Argomento: Biological Sciences
• Categoria: Biochemistry

Working from basic chemical principles, Metals in Medicine, 2nd Edition describes a wide range of metal-based agents for treating and diagnosing disease. Thoroughly revised and restructured to reflect significant research activity and advances, this new edition contains extensive updates and new pedagogical features while retaining the popular feature boxes and end-of-chapter problems of the first edition.

Topics include:

• Metallo-Drugs and their action
• Platinum drugs for treating cancer
• Anticancer agents beyond cisplatin including ruthenium, gold, titanium and gallium
• Responsive Metal Complexes
• Treating arthritis and diabetes with metal complexes
• Metal complexes for killing bacteria, parasites and viruses
• Metal ion imbalance and its links to diseases including Alzheimer's, Wilson's and Menkes disease
• Metal complexes for detecting disease
• Nanotechnology in medicine

Now in full colour, Metals in Medicine, 2nd Edition employs real-life applications and chapter-end summaries alongside feature boxes and problems. It provides a complete and methodical examination of the use of metal complexes in medicine for advanced undergraduate and postgraduate students in medicinal inorganic chemistry, bioinorganic chemistry, biochemistry, pharmacology, biophysics, biology and bioengineering. It is also an invaluable resource for academic researchers and industrial scientists in inorganic chemistry, medicinal chemistry and drug development.

1
Inorganic Chemistry Basics

1.1 Introduction

No description of the metal-containing compounds that have found their way into medicine would be useful without first providing basic information on the bonding in metal complexes, their spectral and magnetic properties and, most importantly, the manner in which they react with water and biological targets in the cell. The approach taken in this chapter assumes background knowledge of general and organic chemistry with no previous exposure to inorganic chemistry, as would occur in a junior- or senior-level course at most universities. The concepts presented are for the most part intuitive, requiring basic knowledge of chemistry and physics, but sometimes more abstract issues like quantum mechanics – which explains the spectral properties of metal complexes – will also need to be covered. The overall goal of this chapter is to bring all readers to a common level, providing them with the ‘core’ of information needed to understand how and why, from the chemical perspective, metal complexes play important roles in medicine.

1.2 Crystal Field Theory

The bonding that exists in metal complexes, their spectral and magnetic properties and their chemical reactivity are not easily explained using a single theory. However, one approach that is often used in a basic presentation of bonding concepts in transition metal chemistry is crystal field theory (abbreviated CF theory), which because it is based on simple electrostatic arguments, is relatively easy to understand. In CF theory, the interactions between the metal ion (M) and the groups attached to it (called ligands and denoted by L) are considered to be electrostatic in nature, and the bonding in the compound is described as being salt-like in character. The metal ion, a cation, electrostatically interacts with a series of surrounding ligands, which are usually negatively charged or, if they are uncharged, have the negative end of a dipole directed toward the metal ion. Barring any serious steric interactions between the ligands, the arrangements about the metal ion generally have high-symmetry geometries. For example, a six-coordinate complex – that is, a compound with six ligands attached to the metal ion – has an octahedral arrangement of ligands, while five-coordinate complexes have square or trigonal bipyramidal arrangements, four-coordinate structures are tetrahedral and square planar, and so on. These geometries, along with compounds and intermediates commonly encountered in metal complexes used in medicine, are shown in Figure 1.1.

Figure 1.1 Common geometries of metal complexes and intermediates found in inorganic chemistry.

1.2.1 Octahedral Crystal Field

The first-row transition metal series, which begins with scandium, Sc, fills the 3d level of the atom, while the second- and third-row transition metal series, which begin with yttrium, Y, and lanthanum, La, respectively, fill the 4d (second row) and 5d (third row) orbitals of the atom. The transition metal ions and the electronic configurations of common oxidation states are shown in Figure 1.2. Since ions of these elements have electron occupancies in the d level, which is considered the ‘valence’ lev...