Macrocycle stability constants

The macrocyclic hexamine [18]aneN6 was further found to recognize catechol, catecholamines and biologically relevant compounds (see Chart II)64). It interacts with all of these donor compounds in neutral pH solutions to form 1 1 complexes, which were determined polarographically. The stability constants pL are summarized in Table 6. 

In the case of macrocyclic tacn side arms, stability constants of type (820) dinickel complexes are considerably higher and six-coordination can be achieved due to the binding of additional coligands, either at both Ni11 (in (828))2031 or at only one of them (in (829)).2082... 

The complexation of other mixed oxa aza macrocycles has been studied, and protonation and stability constants of the zinc complexes of macrocycles l,4,10,13-tetraoxa-7,16-diazacycloocta-decane-7,16-bis(malonate), the -7-malonate derivative and -7,16-bis(methylacetate) derivative have been determined by potentiometry at a 1 1 ligand-to-metal ratio.730... 

Complex stability constants are most often determined by pH-potentiometric titration of the ligand in the presence and absence of the metal ion.100 This method works well when equilibrium is reached rapidly (within a few minutes), which is usually the case for linear ligands. For macrocyclic compounds, such as DOTA and its derivatives, complex formation is very slow, especially for low pH values where the formation is not complete, therefore a batch method is... 

Thermodynamic aspects of the interaction of metal ions with macrocyclic ligands have been well studied. In many instances such studies have involved a comparison of the behaviour of cyclic ligand systems with that of their open-chain analogues. In this manner, information concerning the thermodynamic consequences arising from the cyclic nature of the macrocyclic ligand has been obtained. Frequently these studies have been restricted to stability constant (log K) measurements and, for such studies, a variety of techniques has been employed (Izatt etal., 1985). 

In the preceding chapter, thermodynamic aspects of macrocycle complexation were treated in some detail. In this chapter, kinetic aspects are discussed. Of course, kinetic and thermodynamic factors are interrelated. Thus, in terms of a simple complexation reaction of the type given below (charges not shown), the stability constant (/CML) may be expressed directly as the ratio of the second-order formation constant (kf) to the first-order dissociation rate constant (kd) ... 

Lamb, J. D., Izatt, R. M. Christensen, J. J. (1981). Stability Constants of Cation-Macrocycle Complexes and Their Effect on Facilitated-Transport Rates, Ch 2 in Progress in Macrocyclic Chemistry, Volume 2, ed. R. M. Izatt J. J. Christensen. Wiley-Interscience, New York. 

Rate constants for reaction of Ca2+aq with macrocycles and with cryptands (281,282,291) reflect the need for conformational changes, considerably more difficult for cryptands than for crown ethers, which may be considerably slower than formation of the first Ca2+-ligand bond. Ca2+aq reacts with crown ethers such as 18-crown-6 with rate constants of the order of 5 x 107M 1 s, with diaza crown ethers more slowly (286,326). The more demanding cryptands complex Ca2+ more slowly than crown ethers (kfslow reaction for cryptands with benzene rings fused to the macrocycle. The dominance of kA over kt in determining stability constants is well illustrated by the cryptates included in Table X. Whereas for formation of the [2,1,1], [2,2,1], and [2,2,2] cryptates kf values increase in order smoothly and gently, the k( sequence Ca[2,l,l]2+ Ca[2,2,l]2+ Ca[2,2,2]2+ determines the very marked preference of Ca2+ for the cryptand [2,2,1] (290). 

Similar results were obtained for analogous complexes of the de-( er -butyl)ated macrocycle (L24)2-. The ter7-butyl substituents do not affect the regiochemistry of this particular Diels-Alder reaction, but they clearly increase its rate. The observed trend is indicative of a small stabilization of the transition-state by hydrophobic effects (AAG 3 kJ/mol k coinpiex/k l) lckgr(nin(i = expiAAG /RT)). This would be consistent with our earlier observation that complexes bearing less polar carboxylate anions have the higher stability constants (see Section III.E). 

For monocyclic crown ethers the data presented in Table 4 and the stability constants for glymes [43]—[46] determined by Chaput et al. (1975) can be combined to calculate the macrocyclic effect (Table 7). The data indicate that the gain in binding energy on ring closure shows the same pattern as the ion selectivity of the crown ether, being highest for Na+/15-crown-5, K+/18-... 

Stability constants represent primary data when considering a ligand type for use in a medical application. Stability constant determinations have been undertaken for the N4 donor macrocyclic ligand derivatives (180) and (18H with a range of divalent first-row transition and post-transition metal ions (including Mn )." In all cases the natural (Irving-Williams) stability order was observed to obtain for the 1 1 (M L) complexes. 

The stability constant (7=0.1, 25 °C) has been reported for the 1 1 manganese(II) complex of the related amide-containing, 15-membered macrocycle l,4,7-trimethylcarboxy-9,14-dioxo-1,4,7,10,13-pentaazacyclopentadecane as 14.7 (log value). ... 

Much more pronounced is the macrocyclic or [l]-cryptate effect found in 10 as compared with 2 the stability constant for K+ complexation increases by about 104 (in methanol) on ring formation. A similar increase has been observed between copper-(II) complexes of acyclic and macro-cyclic tetra-aza ligands (139). 

More than 50 macrocyclic crown ethers were synthesised by Pedersen, and many were found to solublise alkali metal salts in non-polar solvents. He isolated 1 1 complexes with metal salts (87) and also showed that if the cation was too large to fit in the central hole, complexes with ratios of 1 2 or 2 3 (metal ether) could be obtained (88). Some of the larger ethers have been shown to complex two metal atoms simultaneously (89). Stability constants in solution are affected by the nature of the anion and the solvent. Both are also important in obtaining crystalline products. 

Stability constants, from which AG° values are calculated, provide a direct measure of the extent of complexing in solution, and these values have been used to determine cation selectivity by macrocyclic compounds. Several of the methods commonly used to determine log K values cannot be used with many of these systems. Thus, procedures based on change in hydrogen ion concentration (pH titration, hydrogen electrode, etc.) cannot be used in those cases where the ligand is uncharged and its concentration is not pH dependent. Spectral methods generally have not been used because of the usual lack of favorable absorption characteristics by the compounds, cations or cation-complexes in the cases studied. 

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