Kinetic enhancement in macrocycles

Kinetic enhancement and kinetic depression has been discussed recently by the authors of this review d  

Let us imagine a macromolecule growing by a cationic mechanism and having a chain end X, formed upon initiation, and which is much more reactive (rate constant ke) toward a cationic growing end than the heteroatoms along the chain (rate constant kb), e.g. in the case of a polyether  

If we now assume that kg kb, and simultaneously ke kp, and that only the strained oxonium ions can propagate (164c), then, at least at the early stages of polymerizatton, the large mqority of macromolecules (the proportion given by the ratio of the correspondir rate constants) will exist in the form of the non-reactive macroQfcles. If X = H, then the proton transfer to monoma  

Indeed, for longer chains (and, thus, for higher degrees of conversion for living systems with kj kp) the rate constant kg (which decreases with n) may become lower than the rate constants of back-biting to doset located oxygen atoms. At this point, the kinetic enhancement vanishes and the kinetically controlled proportion of macrocycles decreases, eventually reaching its thermodynamically controlled proportions. 

It has only recently been experimentally shown that the cyclic living (with H-0 ions) 

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Consequently, linear polymer cannot be usually obtained because of kinetic enhancement in macrocycles connected with conversion of the active center of oxirane propagation to more stable nonstrained oxonium cations. Dale et have... 

A special case of kinetic enhancement in macrocycles is observed when a zwitterionic polymerization of lactide was carried out. Waymouth and co-workers have observed formation of cyclic polymer of up to 3 x 10" and dispersity below 1.3 when polymerization was initiated by heterocyclic carbene (l,3-dimesitylimidazol-2-ylidene). It stems probably from propagation being much faster than cyclization and end-biting being much faster than backbiting. The latter can be explained by the reaction of oppositely charged chain-ends, located close to each other more frequently than can be expected for neutral chains (Scheme 12). 

Thus, we first discuss thermodynamics, paying attention to features that are important for polymer synthesis (e.g., dependence of equilibrium monomer concentration on polymerization variables) then we describe kinetics and thermodynamics of macrocyclization, trying to combine these two related problems, usually discussed separately. In particular we present the new theory of kinetic enhancement and kinetic reduction in macrocyclics. Thereafter, we describe the polymerization of several groups of monomers, namely cyclic ethers (oxiranes, oxetanes, oxolanes, acetals, and bicyclic compounds) lactones, cyclic sulfides, cyclic amines, lactams, cyclic iminoethers, siloxanes, and cyclic phosphorus-containing compounds, in this order. We attempted to treat the chapters uniformly we discuss practical methods of synthesis of the corresponding polymers (monomer syntheses and polymer properties are added), and conditions of reaching systems state and reasons of deviations. However, for various groups of monomers the quality of the available information differ so much, that this attempt of uniformity can not be fulfilled. 

The differences in end- and backbiting rates result in phenomena known as kinetic enhancement of macrocycles or linear polymer. The former occurs when endbiting is more effective than backbiting and manifests itself in formation of maaocycles during polymerization in concentrations higher than the equilibrium values. 

We have shown in the previous sections that in certain systems (e.g. polymerization of cyclic formals studied by Schulz 7 8) and Y amashita 20>) one can use kinetic enhancement to obtain higher proportions of macrocyclics. This is mostly due to the enhanced contribution of the end-to-end closure. There are systems (THF2- 3), cyclic sulfides 25y) in which kinetic ring-depression was observed due to a slow rate of cyclization and thus the equilibrium concentration of the rings was attained only slowly. These two extreme cases are depicted in Fig. 3.9. 

The combination of a calixarene subunit and the bicyclic guanidinium in macrocycle 15 demonstrates affinities for dicatonal-L-x-phosphatidylcholine (Kn = 7.5 x 10" M ) and acetylcholine (ATa = 7.3 x 10 M ) in chloroform. These affinities are reduced in CDCI3/ CD3OD (99 1). Kinetic studies were performed on the hydrolysis of p-nitrophenylcholine carbonate in the presence of 15, which showed a 149-fold rate enhancement over methanolysis. The guanidinium is thought to piay a role in the stabilization of the BAc2-type transition state. This provides an example of an artificial acetylcholinesterase. 

However, the authors of both simulation works mentioned above analyzed systems with high DP of linear polymer. When critical concentration (total equilibrium concentration of cyclics for infinite DP of linear polymer, expressed in monoma units) for a given monomer is high in comparison to the initial monomer concentration and the concentration of initiator DP is also relatively high, the resulting equilibrium linear polymer is of low DP . Consequently, the effect of kinetic enhancement of maaocycles, that is, passing of the macrocycle concentrations through maxima, is observed not only for systems with... 

Recent kinetic studies have shown that the aquation of trans-[CoL(N02)C1] and trans-[C6LC 2 ] (L = a tetra-aza macrocycle) show large variations in rates. The dependence of the aquation rates on conformational strain energy only appears to apply to a limited number of compounds. The rate enhancements are best rationalized in terms of the ability of the macrocycle to fold toward the leaving group. These studies also show that very large rate enhancements in cobalt (III) complexes of 14-membered macrocycles only occur when w-dialkyl groups are present. 

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. 

In this article the design, synthesis and d-block metal ion chemistry of some more recent examples of covalently-linked, macrocyclic ligand systems are discussed. The use of macrocyclic rings in such systems is not surprising given that the resulting macrocyclic complexes often exhibit both enhanced kinetic and thermodynamic stabilities and hence tend to retain their integrity under a variety of conditions - a lesson that nature knows well. 

Covesicles of the cationic nitrobenzoate 6 and DODAC, or corresponding DPP-analogues, e.g. 7, are hydrolysed at pH 8. Nitrophenolate absorption appears at 400 nm. The outer benzoate esters at the outer vesicle surface are hydrolysed within minutes and the same head groups on the inner surface survive for 1-15 hours (Figure 4.9). Detailed kinetics of flip-flop dynamics and OH permeation have been evaluated in these systems. Monolayer lipid membranes made of macrocyclic bolaamphiphiles showed enhanced dynamic stability. ... 

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