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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' level of the ion, CF theory focuses on the change in energy of the d-orbitals when charges representing the ligands approach the metal ion and form salt-like bonds.

Figure 1.2 Transition metal ions and their electronic configurations for various oxidation states.

The spatial arrangements of the five d-orbitals on a Cartesian coordinate system are shown in Figure 1.3. The shapes shown represent the probability of finding an electron in a volume of space about the nucleus of the metal ion. If the metal ion has no bonded ligands - this is referred to as a free ion - the energies of all five d-orbitals will be the same and are said to be five-fold degenerate in energy. This situation is shown on the left side of Figure 1.4. Let's suppose that instead of existing as a free ion, the metal ion is part of a stable complex consisting of six negatively charged ligands bound to the metal ion in an octahedral array. The way that crystal field theory approaches this situation is to consider what happens to the five d-orbitals in the electrostatic field set that is up by the ligands. The first thing that the theory does is to consider a situation in which the total negative charge of the ligands is 'smeared' equally over the surface of a sphere with a radius equal to the metal-ligand bond distance and with the metal ion at its center. Since the d-orbitals have electrons in them and the surface of the sphere is negatively charged, the energies of the d-orbitals will be raised; that is, they will become less stable relative to the free ion, due to electrostatic repulsion between the d-electrons and the negatively charged surface of the sphere. Since the charge on the sphere has no 'directionality' - that is, the negative charges are equally distributed over the entire surface of the sphere - all five d-orbitals must experience the same electrostatic perturbation from the sphere and move as a group to a new energy, Eo (see Figure 1.4). The next step is to redistribute the charge on the surface of the sphere and concentrate it at the six points where the axes penetrate the sphere. If the charge at each of the six points is identical, this will produce a perfect octahedral crystal field about the central metal ion and simulate what the d-orbitals experience in an octahedral metal complex. It should be evident that since and are pointed directly at the charges (ligands), they must experience a different perturbation than the three orbitals, dxz, dyz, dxy, that are directed between the charges. While it may not be obvious that both and should experience an identical perturbation from the octahedral field, quantum mechanics shows that , which has a ring of electron density in the xy plane (Figure 1.3), is actually a composite of two orbitals that are identical to , except that they lie in the yz and xz planes. Thus, since is a composite of two orbitals that look like , it makes sense that the crystal field will affect and identically, as shown in Figure 1.4. It should also be evident that since these orbitals are pointed directly at the ligands, they feel the electrostatic repulsion directly, and thus their energies are raised relative to the energy of the spherical field, Eo. It is possible to show that if the total charge on the sphere is simply rearranged or 'localized' to certain positions on the sphere, the energy of the system cannot change; that is, Eo for the sphere and the octahedral field must be the same. This is the center of gravity rule, which applies to electrostatic models of this type. The consequences of this is that if two orbitals, and , are raised by a certain amount, the remaining three, dxz, dyz, dxy, must be lowered by a certain amount. Inspection of the shapes and orientations of dxz, dyz, dxy shows that since these orbitals are directed 45° to the axes of the system, and each is related to the others by a simple rotation, all must experience exactly the same perturbation from the charges which are on the axes of the system. This set of orbitals, which are 'triply degenerate', is often referred to as the 't2g' set due to its symmetry properties. In a similar fashion, the orbitals, and which are 'doubly degenerate' are referred to as the 'eg' set. The labels t2g and eg are products of the application of group theory, a mathematical tool for characterizing the symmetry properties of molecules.

Figure 1.3 Boundary surfaces of the five d-orbitals.

Figure 1.4 Generation of the octahedral crystal field from the free ion.

Simple electrostatic arguments show that the spacing between the t2g and eg levels depends on the distance that the charge is from the origin of the system and the magnitude of the charge. If the distance is decreased, or if the magnitude of the negative charge is increased, the splitting between t2g and eg will increase. As we will see, metal complexes can be made with a wide variety of attached ligands, some of which are negatively charged, for example, CI-, CN- and so on, and some of which are electrically neutral, for example, H2O, NH3, and so on. However, one thing that all ligands have in common is that they direct electrons - usually a lone pair - toward the metal ion, and these electrons become the 'point charges' in the crystal field model describing the electronic structure of the complex. Since the ability of different ligands to perturb the d-orbitals varies considerably, the spitting between the t2g and eg sets of orbitals can be quite different for different complexes. In order to address this, CF theory denotes the splitting between the t2g and...