Macrocyclic effect thermodynamic

It is important to note that, even when the coordination geometry prescribed by the macrocyclic cavity is ideal for the metal ion involved, unusual kinetic and thermodynamic properties may also be observed (relative to the corresponding open-chain ligand complex). For example, very often the macrocyclic complex will exhibit both enhanced thermodynamic and kinetic stabilities (kinetic stability occurs when there is a reluctance for the ligand to dissociate from its metal ion). These increased stabilities are a manifestation of what has been termed the macrocyclic effect - the multi-faceted origins of which will be discussed in detail in subsequent chapters. 

Consequences of unsaturation. Unsaturation in the macrocyclic ring may have major steric and electronic consequences for the nature of the ring. Extensive unsaturation will result in loss of flexibility with a corresponding restriction of the number of possible modes of coordination. Further, loss of flexibility tends to be reflected in an enhanced macrocyclic effect . For example, if the metal ion is contained in the macrocyclic cavity, the loss of flexibility reduces the possible pathways for ligand dissociation and this tends to increase the kinetic stability of the system. As explained in later chapters, enhanced thermodynamic stabilities will usually also result. 

Table 6.1 summarizes the thermodynamic parameters relating to the macrocyclic effect for the high-spin Ni(n) complexes of four tetraaza-macrocyclic ligands and their open-chain analogues (the open-chain derivative which yields the most stable nickel complex was used in each case) (Micheloni, Paoletti Sabatini, 1983). Clearly, the enthalpy and entropy terms make substantially different contributions to complex stability along the series. Thus, the small macrocyclic effect which occurs for the first complex results from a favourable entropy term which overrides an unfavourable enthalpy term. Similar trends are apparent for the next two systems but, for these, entropy terms are larger and a more pronounced macrocyclic effect is evident. For the fourth (cyclam) system, the considerable macrocyclic effect is a reflection of both a favourable entropy term and a favourable enthalpy term. 

Before considering further the thermodynamic nature of particular macrocyclic effects, it is necessary to consider the various components of a typical complexation reaction. These are best illustrated by the Born-Haber cycle illustrated in Figure 6.1. Each of the steps 1-5 has a AG, AH and a A5 term associated with it and the overall values of these parameters reflect the respective sums of the individual components. To understand fully the nature of a particular macrocyclic effect, it is necessary to have data available for each of these steps for both the macrocyclic system and open-chain (reference) system. Although some progress has been made... 

The thermodynamic origins of the enhanced stabilities of macrocyclic ligands over their acyclic counterparts have been the subject of considerable debate since the term macrocyclic effect was first coined.83 Comparison of thermodynamic data for the several metal ion complexes of the [18]crown-6 and its acyclic counterpart are shown in Table 1. Enthalpy contributions to stabilization appear strongest for the K+ complex, while entropic contributions are stronger for the Na+ complex. Undoubtedly, the factors responsible for the thermodynamics will vary according to ion size, charge, solvation effects and structural preference. Hence, a single definable source of the macrocyclic effect is, in these systems at least, probably nonexistent. 

Table 6-1. Thermodynamic stability data for copper(n) complexes of a series of nitrogen donor ligands, illustrating the macrocyclic effect.

The value of log K for the copper complex of 6.24 is 4.3, whilst for that of 6.23 it is 1.97. The macrocyclic complex is thus about 100 times more stable than the open-chain complex, and this is presumably due to the macrocyclic effect. In this case, thermodynamic measurements have shown that Afor the macrocyclic and open-chain complexes are almost identical, and so the macrocyclic effect is due almost entirely to the entropy term. However, even with these ligands the involvement of solvation may not be neglected entirely. The stability values given above are for the complexes in aqueous solution if the measurements are repeated in 80 % aqueous methanol, the value of log K for the formation of the macrocyclic complex is only 3.5. A hole-size effect (section 6.6) is also apparent if we move to the larger thioether macrocycle 6.26. For the formation of the copper complex of 6.26 (again in 80 % aqueous methanol) log K is found to be 0.95. 

Fig. 4 Thermodynamic macrocyclic effect complexation equilibria involving the Nin aqua.ion and the champions of non-cyclic tetra-amines 1 (2.3.2-tet) and of the tetra-amine macrocycles 2 (cyclam)...

According to the modular approach, components of the fluorosensor can be changed at will. For instance, it could be of some interest to replace the quad-ridentate receptors of systems 4 and 5 by their cyclic counterparts, to obtain 6 and 7 [8]. The reason of the interest is that, ceteris paribus, cyclic ligands form more stable metal complexes than their open-chain analogues (the thermodynamic macrocyclic effect [12]). The tetramine receptor in 6 has the skeleton of the classical 14-membered macrocycle cyclam, whereas the receptor subunit of 7 refers to the other well-known object of macrocyclic chemistry dioxocyclam. 

Thermodynamics - Ligands with multiple coordination sites are abundant as the gain in entropy from chelate and/or macrocyclic effects increase the thermodynamic stability of the system. 

The peraza macrocycles, in general, form more stable complexes with a variety of metal ions than do the open-chain polyamines containing the same number of amine groups. This characteristic is called the macrocyclic effect. Triaza-crowri macrocycles, in nearly every case, form 1 1 complexes with metal ions that are thermodynamically more stable than those with dieth-ylenetriamine. Only complexes of the open-chain triamine with and Hg- are more stable than those with the cyclic triamines (Bianchi et al., 1991). Triaza-9-crown-3 (23) forms stronger complexes with most cations than the larger triazacyclodecane (24), triazacycloundecane (25), or triazacyclo-dodecane (26) (Bhula et al., 1988 Chaudhuri and Wieghardt, 1987). 

The tetraazacycloalkanes, particularly the 14-membered cyclic tetraamine (cyclam) (10), exhibit the macrocyclic effect due to a more favorable enthalpy contribution to complex stability (Hancock and Martell, 1988). Complexes of the pentaaza-crown macrocycles have been studied extensively from a thermodynamic point of view (Bianchi et al., 1991). With the exception of Ni-, [15]Ns formed the most stable complexes with all the metal ions studied with the stability order as follows [15]N5(27) > [16]N5(28) > [17]N3(29) (Bianchi et al., 1991). 

Not only does chelation make the complex more stable, but it also forces the donor atoms to take up adjacent or cis sites in the resulting complex. Equation (2) shows how displacement of a chelating carbonate ion gives the unusual cis dichloride product instead of the thermodynamically more stable trans dichloride. Polydentate chelating ligands with three or more donor atoms also exist. Macrocyclic ligands, such as (4) and (5), confer an additional increment in the formation constant (the macrocyclic effect) they have been given trivial names, such as cryptates (4) and sepulchrates (5).i... 

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