Macrocycle/macrocyclic effect

Macrocyclic effect and specific character of complex formation with porphyrins 97MI8. 

A comparison between concave pyridines [13] monomacrocychc compounds [14] and [15] and open-chain analogues [16] shows a macrocyclic effect. The open-chain analogues [16] possess very small basicities [(log K)re = —1.3 to —1.6]. In the monomacrocychc systems, those which contain ether oxygens, [14] and [15b], had larger (log A)rei values. 

The 1,3-xylyl trick was also used for the incorporation of phenols into crown ethers. Three classes of phenols [46a]-[46c] have been investigated. They differ by their substituents in the 4-position. In Table 22 the pX a values of different macrocyclic phenols [46a]-[46c] are compared. The data obtained for the phenol-containing crowns [46a] and [46b] show very little evidence for a macrocyclic effect. No extra stabilization of the protonated (acidic) form by a macrocycle of appropriate ring size was found. The acidities of the macrocyclic phenols [46a] and [46b] were independent of the ring size and comparable to non-macrocyclic analogues. However, the azo-substituted crowns [46c] showed a difference of 0.8 pACg units which was not expected from the pAfa values of [46a] and [46b]. TTiis different behaviour of [46c] is not yet understood. 

Dicarbonyl functions have been built into macrocyclic structures, and pKa values for the resulting macrocycles [60] have been determined (Alberts and Cram, 1979). When the open-chain model [62] is compared with the macrocycles [60], identical first pK values were found (pKa = 8.6). Thus for the diketones [60], no macrocyclic effect is noticeable. But for the dissociation of a second proton from the mono-aniorts of [60] much higher pKa values are found. To a certain extent. Coulomb repulsions (see Section 2) are probably the reason for this behaviour, but the large difference in the pKa values (ApKa = 2.9, see Table 26) argues for a special stabilization of the mono-anion. Again hydrogen bonds are not unreasonable. 

Thioethers lack the capacity to neutralize positive charge and display weak donor properties. Consequently, they do not readily displace strong donor solvents (water) or strongly bonding anions (such as halides) from the coordination sphere. As a consequence, many thioether complex syntheses employ aprotic or alcoholic solvents and precursor complexes with weakly bound solvents (such as DMSO or acetone) or anions (such as C+3S03 ). Despite the synthetic challenges, a wide range of complexes has been reported, particularly with the cyclic poly-thioethers, where the macrocyclic effect overcomes many of the above difficulties. 

To study generality of SNAr-based macrocyclization, effects of leaving groups and bases have been examined in synthesis of 14-membered macrocycles (Eq. 9.8).11 Evidently, fluorides... 

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. 

The presence of the cyclic backbone in ligands of this type makes a substantial contribution to their metal-ion complexing ability even though coordination involves donors which are not directly incorporated in the ring fragment. The origins of the enhanced stability of the metal-containing species may be considered to reflect the operation of an indirect macrocyclic effect (see Chapter 6) in these systems. 

The stability of cryptate complexes. The cage topology of the cryptands results in them yielding complexes with considerably enhanced stabilities relative to the corresponding crown species. Thus the K+ complex of 2.2.2 is 105 times more stable than the complex of the corresponding diaza-crown derivative - such enhancement has been designated by Lehn to reflect the operation of the cryptate effect this effect may be considered to be a special case of the macrocyclic effect mentioned previously. 

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... 

Table 6.1. Parameters illustrating the macrocyclic effect for the high-spin Ni(n) complex of the tetraaza macrocycles L, L4, L6 and L8 (Micheloni, Paoletti Sabatini, 1983). 

Detailed analysis of a particular macrocyclic effect in the manner discussed so far is usually only justified if the open-chain and macrocyclic... 

Sulfur-containing ligands. Macrocyclic effects have also been documented in mixed donor systems. The Cu(ii) complex of the 14-mem-bered (cis) N2S2-donor analogue of cyclam exhibits a substantial macrocyclic effect with a log K difference of 4.6 relative to the corresponding open-chain species (Figure 6.2) (Micheloni, Paoletti, Siegfried-Hertli Kaden, 1985). The effect in this case is mainly due to a favourable... 

Crown polyethers. Macrocyclic effects involving complexes of crown polyethers have been well-recognized. As for the all-sulfur donor systems, the study of the macrocyclic effect tends to be more straightforward for complexes of cyclic polyethers especially when simple alkali and alkaline earth cations are involved (Haymore, Lamb, Izatt Christensen, 1982). The advantages include (i) the cyclic polyethers are weak, uncharged bases and metal complexation is not pH dependent (ii) these ligands readily form complexes with the alkali and alkaline earth cations... 

Finally, a discussion of the kinetic features of the macrocyclic effect (the kinetic macrocyclic effect ) mentioned in Chapter 1 is deferred until the next chapter. 

The dissociation kinetics of macrocyclic complexes have received considerable attention, especially during investigations of the nature of the macrocyclic effect. Before discussing the dissociation of cyclic ligand species, it is of benefit to consider some aspects of the dissociation of open-chain ligand complexes. 

---