Kinetically Inert and Labile Complexes

Metal complexes that undergo reactions with h min are described as being kinetically labile. If the reaction takes significantly longer than this, the complex is kinetically inert. 

There is no connection between the thermodynamic stability of a complex and its lability towards substitution. For example, values of AhydG° for Cr + and Fe are 

11n rate equations, [ ] stands for concentration of and should not be confused with use of square brackets around formulae of complexes in other contexts. For this reason, we omit [ ] in formulae in most reaction equations in this chapter. 

Average lesidraice time for H2O molecule in first hydration shell / s 10 10 10 10 lOr lOr 10  

Rates of water exchange for the group 1 metal ions vary over a small range from [Li(OH2)6l (least labile) to [Cs(OH2)g] (most labile). For the group 2 metal ions, k varies from 

---

The need to achieve high yield in one-pot synthesis, coupled to the relative kinetic inertness of rhenium complex (e.g. compared to technetium) and the mild conditions required has led to the development of useful versatile rhenium(V) intermediates that can be quickly prepared in quantitative yield, and are metastable, i.e. kinetically labile enough to react rapidly with the final chelator, again in high yield. The most widely used ligands suitable for this purpose are polydentate hydroxycarboxylic acids such as glucoheptonate [116a], citrate (47), tartrate (48), and 2-hydroxyisobutyric acid (49) [159]. Examples are discussed elsewhere in this chapter. They are typically used in the presence of Sn(II) to reduce Re(VII) to Re(V), at moderately elevated temperature (50-100 °C) at pH 2-3 (acid pH promotes reduction of perrhenate, presumably by facilitat-... 

According to Taube , complexes can be divided into two classes i.e. inert and labile depending on the rate at which the substitution reaction occurs. The author defines labile complexes as those which take part in substitution reaction without any delay ( 1 min) on coming into contact with other reagents under ordinary conditions. These conditions are room temperature and concentration of the reagents of about 0.1 M. In contrast, inert complexes are slower to react. In this article, the author discuss the reasons for the difference in the kinetic behaviour of various inorganic complexes and also attempts to classify them in terms of their lability. Another detailed x ount on the same topic can be found in the book by Basolo and Pearson... 

In terms of the development of an understanding of the reactivity patterns of inorganic complexes, the two metals which have been pivotal are platinum and cobalt. This importance is to a large part a consequence of each metal having available one or more oxidation states which are kinetically inert. Platinum is a particularly useful element of this pair because it has two kinetically inert sets of complexes (divalent and tetravalent) in addition to the complexes of platinum(O), which is a kinetically labile center. The complexes of divalent and tetravalent platinum show significant differences. Divalent platinum forms four-coordinate planar complexes which have a coordinately unsaturated 16-electron d8 platinum center, whereas tetravalent platinum is an 18-electron d6 center which is coordinately saturated in its usual hexacoordination. In terms of mechanistic interpretation one must therefore consider both associative and dissociative substitution pathways, in addition to mechanisms involving electron transfer or inner-sphere atom transfer redox processes. A number of books and articles have been written about replacement reactions in platinum complexes, and a number of these are summarized in Table 13. 

Complexes of (( Ir(III) are kinetically inert and undergo octahedral substitution reactions slowly. The rate constant for aquation of [IrBr(NH3)5]2+ [35884-02-7] at 298 K has been measured at -2 x 10-10 s-1 (168). In many cases, addition of a catalytic reducing agent such as hypophosphorous acid greatly accelerates the rate of substitution via a transient, labile Ir(H) species (169). Optical isomers can frequently be resolved, as is the case of ot-[IrCl2(en)2]+ [15444-47-0] (170). Ir(III) amine complexes are photoactive and undeigo rapid photosubstitution reactions (171). Other iridium complexes... 

In the case of inert cobalt(m) complexes it is possible to isolate the chelated products of the reaction. Let us return to the hydrolysis of the complex cations [Co(en)2(H2NCH2C02R)Cl]2+ (3.1), which contain a monodentate iV-bonded amino acid ester, that we encountered in Fig. 3-8. The chelate effect would be expected to favour the conversion of this to the chelated didentate AO-bonded ligand. However, the cobalt(iu) centre is kinetically inert and the chloride ligand is non-labile. When silver(i)... 

Work has been carried out in three broad areas using (a) labile metal ions particularly copper(Il), (b) metal ions of intermediate lability such as Pd(ll) which is a powerful Lewis acid and (c) kinetically inert cobalt(III) complexes. 

The complex [BF3(N(SiH3)3)] can be prepared and stored at low temperatures ( — 80 °C) since the decomposition then proceeds very slowly—at this temperature the complex is kinetically fairly stable. At room temperature the complex is kinetically unstable and the rate of decomposition is much greater. This is the key distinction made in Chapter 4 between kinetically inert and kinetically labile complexes. There it was pointed out that the species which crystallizes from a solution of a mixture of related labile complexes depends not only on the cation and ligand concentration but also on the solvent and crystallization temperature. Although it may be a relatively minor component in the solution, the least soluble complex is probably the one which crystallizes. In the solution there is a series of equilibria such that. 

Although in this chapter many aspects of stability have been discussed, there are many others that have not. It is now accepted that for some ligands, metal-ligand double bonding occurs. Just how are bond order and stability related Is the distinction between inert and labile transition metal complexes related in any way to the d-electron configuration of the transition metal (we shall have more to say about this in Chapter 14)7 In addition to the kinetic trans effect, discussed at the end of Chapter 4, there is a static trans effect, sometimes called the trans influence. In this, a metal-ligand bond... 

Although as a class the chelates are definitely bacteriostatic, the relative contributions of uptake and dissociation for both inert and labile species need to be more clearly defined before a full picture is obtained. The results suggest that kinetic reactivity may be more important than thermodynamic stability [30]. In the case of copper(II) complexes with 1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthrolines, more recent studies showed that the major mode of action on P. denitrificans in vitro was in fact inhibition of respiratory electron transport in the cytoplasmic membrane, no correlation with inhibition of macromolecular synthesis being apparent [31]. These results are relevant in view of the discrepancy in the reported antitumour activity of these species (see Section 6.2). 

Now that we have fairly well established that the dissociative mechanism generally applies for the substitution reactions of octahedral complexes, we are in a good position to begin to answer some of our earlier (p. 100) critical questions about inert versus labile complexes. As defined earlier,and inert-xro, kinetic terms describing the rates of reactions of coordination compounds. As you should recall from earlier courses, rates depend on the magnitude of the energy of activation, of the ratedetermining step. 

Rates of Reaction. The rates of formation and dissociation of displacement reactions are important in the practical appHcations of chelation. Complexation of many metal ions, particulady the divalent ones, is almost instantaneous, but reaction rates of many higher valence ions are slow enough to measure by ordinary kinetic techniques. Rates with some ions, notably Cr(III) and Co (III), maybe very slow. Systems that equiUbrate rapidly are termed kinetically labile, and those that are slow are called kinetically inert. Inertness may give the appearance of stabiUty, but a complex that is apparentiy stable because of kinetic inertness maybe unstable in the thermodynamic equihbrium sense. 

A further factor which must also be taken into consideration from the point of view of the analytical applications of complexes and of complex-formation reactions is the rate of reaction to be analytically useful it is usually required that the reaction be rapid. An important classification of complexes is based upon the rate at which they undergo substitution reactions, and leads to the two groups of labile and inert complexes. The term labile complex is applied to those cases where nucleophilic substitution is complete within the time required for mixing the reagents. Thus, for example, when excess of aqueous ammonia is added to an aqueous solution of copper(II) sulphate, the change in colour from pale to deep blue is instantaneous the rapid replacement of water molecules by ammonia indicates that the Cu(II) ion forms kinetically labile complexes. The term inert is applied to those complexes which undergo slow substitution reactions, i.e. reactions with half-times of the order of hours or even days at room temperature. Thus the Cr(III) ion forms kinetically inert complexes, so that the replacement of water molecules coordinated to Cr(III) by other ligands is a very slow process at room temperature. 

As already mentioned, complexes of chromium(iii), cobalt(iii), rhodium(iii) and iridium(iii) are particularly inert, with substitution reactions often taking many hours or days under relatively forcing conditions. The majority of kinetic studies on the reactions of transition-metal complexes have been performed on complexes of these metal ions. This is for two reasons. Firstly, the rates of reactions are comparable to those in organic chemistry, and the techniques which have been developed for the investigation of such reactions are readily available and appropriate. The time scales of minutes to days are compatible with relatively slow spectroscopic techniques. The second reason is associated with the kinetic inertness of the products. If the products are non-labile, valuable stereochemical information about the course of the substitution reaction may be obtained. Much is known about the stereochemistry of ligand substitution reactions of cobalt(iii) complexes, from which certain inferences about the nature of the intermediates or transition states involved may be drawn. This is also the case for substitution reactions of square-planar complexes of platinum(ii), where study has led to the development of rules to predict the stereochemical course of reactions at this centre. 

Cr2+ (d4) are kinetically labile, as are high-spin complexes of Co2+ (d7). However, complexes of Cr3+ (d3) and low-spin complexes of Co3+ (d6) are kinetically inert. For the exchange reaction (O represents lsO)... 

To describe the dynamics of metals at biological interphases in the presence of various ligands, the kinetics of dissociation of the complexes have to be taken into account in relation to the diffusion and to the uptake kinetics ([14] and Chapters 3 and 10 in this volume). Based on kinetic criteria, labile and inert complexes can be distinguished as limiting cases with regard to biological uptake ([14] and Chapter 3, this volume). 

Ir(IV), Pt(IV), with the states from Rh(III) being termed inert. Thus, kinetic factors tend to be more important, and reactions that should be possible from thermodynamic considerations are less successful as a result. On the other hand, the presence of small amounts of a kinetically labile complex in the solution can completely alter the situation. This is made even more confusing in that the basic chemistry of some of the elements has not been fully investigated under the conditions in the leach solutions. Consequently, a solvent extraction process to separate the precious metals must cope with a wide range of complexes in different oxidation states, which vary, often in a poorly known fashion, both in kinetic and thermodynamic stability. Therefore, different approaches have been tried and different flow sheets produced. 

There is a difference between the thermodynamic terms stable and unstable and the kinetic terms labile and inert. Furthermore, the differences between the terms stable and unstable, and labile and inert are relative. Thus, Ni(CN)4 and Cr(CN)6 are both thermodynamically stable in aqueous solution, yet kinetically the rate of exchange of radiocarbon-labeled cyanide is quite different. The half-life for exchange is about 30 sec for the nickel complex and 1 month for the chromium complex. Taube has suggested that those complexes that react completely within about 60 sec at 25°C be considered labile, while those that take a longer time be called inert. This rule of thumb is often given in texts, but is not in general use in the literature. Actual rates and conditions are superior tools for the evaluation of the kinetic and thermodynamic stability of complexes. 

---