Factors Affecting the Stability of Complexes

The formation of a coordinate bond is the result of the donation and acceptance of a pair of electrons. This in itself suggests that if a specific electron donor interacts with a series of metal ions (electron acceptors) there will be some variation in the stability of the coordinate bonds depending on the acidity of the metal ion. Conversely, if a specific metal ion is considered, there will be a difference in stability of the complexes formed with a series of electron pair donors (ligands). In fact, there are several factors that affect the stability of complexes formed between metal ions and ligands, and some of them will now be described. 

Establishing correlations between the stability of complexes and factors related to the characteristics of the metal ion and ligands involved is not a new endeavor. One of the earliest correlations established showed that for many types of ligands, the stability of the complexes that they form with +2 ions of first-row transition metals varies in the order 

The effect of the nature of the metal ion on the stability of EDTA4 complexes. 

A measure of the Lewis acidity of a metal ion is determined by its affinity for a pair of electrons, and the greater this affinity, the more stable the complexes formed by the metal ion will be. However, removing electrons from a metal to produce an ion is also related to the attraction the metal atom has for electrons. Therefore, it seems reasonable to seek a correlation between the stability constants for complexes of several metals with a given ligand and the total energy necessary for ionization to produce the metal ions. The first-row transition metal ions react in solution with ethylenediamine, en, to form stable complexes. We will consider only the first two steps in complex formation, which can be shown as follows  

Another type of correlation involving a metal ion with a series of ligands has been established for complexes between Ag+ and numerous amines, for which the reactions can be shown as 

---

Many factors affect the stability of complexes. One important factor, the multiple-bond character of the M—X bonds, will be discussed in Section 9-7. 

Factors affecting the stabilities of complexes containing only monodentate ligands... 

Factors Affecting the Stability of Donor-Acceptor Complexes ... 

The object of this chapter is to provide some background for the appreciation of the pharmaceutics of proteins, peptides DNA, oligonucleotides and monoclonal antibodies as therapeutic entities. From an understanding of the nature of amino acids and their physical properties comes an appreciation of the physical nature and properties of peptides, polypeptides and proteins, defined below. The solution properties of proteins in simple and complex media should be understood, together with the factors affecting the stability of proteins in solution. Problems in the formulation of proteins to be overcome will then become clearer. 

In formulation studies, all the factors affecting the stability of the pharmaceutical product have to be considered. Because the stability of pharmaceuticals is generally affected by numerous and complex factors, quantitative analysis of the role of each would involve a very large and complex series of experiments. The effect of each individual factor would have to be tested under conditions in which all other factors are maintained constant. Factorial analysis attempts to minimize the number of experiments needed to get meaningful results and, therefore, to save time and labor. 

In many of their complexes PF3 and PPI13 (for example) resemble CO (p. 926) and this at one time encouraged the belief that their bonding capabilities were influenced not only by the factors (p. 198) which affect the stability of the a P M interaction which uses the lone-pair of elecU"ons on p and a vacant orbital on M, but also by the possibility of synergic n back-donation from a nonbonding d , pair of electrons on the metal into a vacant 3d , orbital on P. It is, however, not clear to what extent, if any, the a and n bonds reinforce each other, and more recent descriptions are based on an MO approach which uses all (cr and n) orbitals of appropriate symmeU"y on both the phosphine and the metal-containing moiety. To the extent that a and n bonding effects on the stability of metal-phosphorus bonds can be isolated from each otlier and from steric factors (see below) the accepted sequence of effects is as follows ... 

Another factor that affects trends in the stability constants of complexes formed by a series of metal ions is the crystal field stabilization energy. As was shown in Chapter 17, the aqua complexes for +2 ions of first-row transition metals reflect this effect by giving higher heats of hydration than would be expected on the basis of sizes and charges of the ions. Crystal field stabilization, as discussed in Section 17.4, would also lead to increased stability for complexes containing ligands other than water. It is a pervasive factor in the stability of many types of complexes. Because ligands that form tt bonds... 

It is apparent that Am3+ forms a stronger complex than Eu3+ with the same ligand. The main factors that may affect the stability of europium and americium complexes are ionic radii and the availability of the /-electrons. In the present case the /-electron participation of the 5/ orbital of Ams+ is possibly more important than the radius factor. If the radius factor was the more important one, Eu3+ with its smaller ionic size would be expected to form a stronger complex than Am3+. However, it is well-known that the 5/ orbitals are more polarizable than the wellshielded 4/ ones. 

---