Micellar reactions

Micelles not only can alter rate constants of reactions but they can alter the conformation of molecules and thus affect the outcome of a reaction [8]. Selfassociation of alkyl tyrosines enhances the population of one conformer (Fig. 11.1) (a) over conformer (b) and (c) (Table 11.1). The special aspect of conformer (a) is that it is the only one which has a trans carboxylate co-planar with the hydrocarbon and could expose its ionic group to the water phase while the alkyl group points to the centre of the aggregate, thus it will be preferred. Self-associating solutes are a special class of compounds (so called functional micelles ) which are dealt with separately. It is more common to experience solutes which are more simply 

The subject of micellar catalysis and inhibition of reactions can be divided into the types of reaction occurring, e.g. base-catalysed and acid-catalysed hydrolyses, oxidation, etc., or in terms of mechanisms, e.g. juxtaposition of reactive groups in micelles, attraction of counterions to an oppositely charged micellar surface, protection by solubilization within non-ionic micelles, etc. It is not possible to adhere rigidly to either scheme but we will attempt here to consider, in turn, hydrolysis, oxidation in aqueous micelles, reactions in inverse micelles, reactions involving drugs and miscellaneous reactions of interest. Bunton s summary of the topic in his recent review of the subject is worth repeating here [12]  

Hartley [13] formulated a sign rule to explain shifts of indicator equilibria in the presence of anionic or cationic surfactant micelles, to which a corollary has been added for kinetic systems which says reactions involving anions are catalysed by cationic micelles and inhibited by anionic ones. Reactions involving cations are catalysed by anionic micelles and inhibited by cationic ones... [14]. These concepts have been illustrated on many occasions, as we will see below. The acid-catalysed hydrolysis of benzylideneaniline to benzaldehyde is 

One of the most comprehensive studies has been carried out by Bruice et al. [19] who studied the rate of solvolysis of neutral, positively and negatively charged esters when incorporated into non-functional and functional micelles of neutral, positive and negative charges. The second-order rate constants for alkaline hydrolysis, /cqh [0H ] were found to decrease with increasing concentration of surfactant for all cases studied. The association of the esters with non-nucleophilic micelles must either decrease the availability of the esters to OH attack or provide a less favourable medium for the hydrolysis reaction to occur. This is another circumvention of the simple electrostatic rules as the kinetic effect seems to have nothing to do with the concentration or restriction of access of the hydroxyl ions in the Stern layer of the micelles. Presumably the labile ester bond is not positioned near the surface of these micelles, but the molecules are oriented as shown in Fig. 11.2. 

They consider the interaction between a monovalent alkylsulphate ion, A , and a monovalent cation. This will be governed by the solubility product (K ) between the two ions, thus  

---

The rates of this micellar reaction are also dependent on both metal ion and ligand concentration (Scheme 1 and Eq. 1-4) 36. ... 

However, there is an important difference between these two systems in the ligand-metal ion ratio in complexation. Namely, micellar reactions require a more generalized reaction Scheme 3, where the molarity of ligand n is either 1 or 2 depending upon the structure of the ligands. This scheme gives rates Eq. 2-4 for n = 1 and Eq. 3, 5, 6 for n = 2. The results of the kinetic analysis are shown in Table 3. 

Figure 4 indicates the effect of the CTAB concentration on the rate constant of the complexes of 29 and 32. The CMC of CTAB is near 1 x 10 3 M. Below CMC, the rates cannot be measured because of insolubility of the ligands. Although unmeasured, the rates of the 29 and 32 complexes must be greatly enhanced in the presence of CTAB micelles up to CMC, but further increase of the micelle concentration above CMC cause a rate decrease. This type of micellar effect can be seen in many micellar reactions 27). Hence, it should be noted that the rate constants in Table 3 would be several times larger if they are measured by using a lower concentration of CTAB than 5 x 10-3 M. 

Figure 5a indicates the effect of the CTAB concentration on the rate constants of the complexes of 38b and 38c. In the case of the water soluble 38b ligand, the rate increases with increasing CTAB concentration up to a saturation level. This type of saturation kinetics is usually interpreted to show the incorporation of a ligand-metal ion complex into a micellar phase from a bulk aqueous phase, and the catalytic activity of the complex is higher in the micellar phase than in the aqueous phase. In the case of lipophilic 38c, a very similar curve as in Fig. 4 is obtained. At a first glance, there appears to be a big difference between these two curves. However, they are rather common in micellar reactions and obey the same reaction mechanism 27). 

Another features of the ligand lipophilicity and the- stability of the complex on the rates are shown in Fig. 6 Rate saturation corresponds to the formation of a 1 1 or 2 1 ligand-metal ion complex. Non-micellar reactions of curves b and c indicate that the N-butyl ligand 38b forms a more active complex than N-methyl ligand 38a does. It may be interesting to note that in the micellar reaction of 38b, a flat... 

In the foregoing micellar reactions, it is likely that the reaction proceeds through the acylation of the hydroxyl group of the ligands, and the results indicate that the acylation step is greatly enhanced by complexation with Zn2 + ions under micellar... 

In contrast to 1, isomeric p-nitrophenyl nicotinate shows almost no catalysis. Thus, it is clear that substrate coordination to the metal ion complex plays the critical role for an enormous rate enhancement. The lipophilic ester (R = C5Hn) also undergoes a large rate enhancement indicating the importance of substrate binding into the micellar phase by hydrophobic interaction. A large rate enhancement can also be seen in lipophilic esters which lack the metal coordination site as given below with the enantioselective micellar reactions (Table 9, 10). 

Enantioselective deacylation of esters in micellar reactions has been extensively studied in order to understand enzyme stereospedficity, and some micellar systems... 

Table 9 indicates that the rate enhancement (kL/ko) is relatively small when Zn2 + ions or a ligand is used separately for both 50 and 52 substrates. A large rate enhancement is obtained only when a ligand and the metal ion are used together as in the previous examples (Table 1, 3, 4, 7). Ligands L-45 and L-46 are relatively inactive as compared to other ligands having the imidazole moiety. The ligand activation by metal ion is the order of Zn2+ > Co2+ > Ni2+ in all the cases, the same as in non-micellar reactions (Table 1). Rate-enhancing effects (kL/ko) of L-47-Zn2 +, L-48-Zn2 +, and L,L-49-Zn2+ ion complexes are remarkably large in view of the consideration...

The uncatalyzed rates in the Triton X-100 micelle are much smaller than those of the CTAB micelle as expected in ionic micellar reactions. However, in the catalyzed reactions much larger rate enhancements occur in the former micelle than in the latter micelle, similarly as in achiral systems (Table 4, 5). In Table 10, ester 50 shows... 

The study on micellar models is still at the beginning. An amphiphilic ligand which can form micelles by itself has not yet been prepared. It is necessary to obtain complexes of higher stability in order to activate the hydroxyl group strong enough in the reactions of inactive esters or amides. Enantioselectivity must reach higher specifity. Nevertheless it seems to be clear that many features or some important clues have already been disclosed for further refinements of this micellar systems. More details about the present micellar reactions will be reported elsewhere in near future. 

Mechanisms of micellar reactions have been studied by a kinetic study of the state of the proton at the surface of dodecyl sulfate micelles [191]. Surface diffusion constants of Ni(II) on a sodium dodecyl sulfate micelle were studied by electron spin resonance (ESR). The lateral diffusion constant of Ni(II) was found to be three orders of magnitude less than that in ordinary aqueous solutions [192]. Migration and self-diffusion coefficients of divalent counterions in micellar solutions containing monovalent counterions were studied for solutions of Be2+ in lithium dodecyl sulfate and for solutions of Ca2+ in sodium dodecyl sulfate [193]. The structural disposition of the porphyrin complex and the conformation of the surfactant molecules inside the micellar cavity was studied by NMR on aqueous sodium dodecyl sulfate micelles [194]. 

Micellar reaction (H2O, CTAB, 30 °C, 3h). Thermal reaction (PhMe110°C, 10-12h). 

Schilling, M., F. Patett et al. (2007). Influence of solubility-enhancing fusion proteins and organic solvents on the in vitro biocatalytic performance of the carotenoid cleavage dioxygenase AtCCDl in a micellar reaction system. Appl. Microbiol. Biotechnol. 75(4) 829-836. 

Specific-ion electrodes are expensive, temperamental and seem to have a depressingly short life when exposed to aqueous surfactants. They are also not sensitive to some mechanistically interesting ions. Other methods do not have these shortcomings, but they too are not applicable to all ions. Most workers have followed the approach developed by Romsted who noted that counterions bind specifically to ionic micelles, and that qualitatively the binding parallels that to ion exchange resins (Romsted 1977, 1984). In considering the development of Romsted s ideas it will be useful to note that many micellar reactions involving hydrophilic ions are carried out in solutions which contain a mixture of anions for example, there will be the chemically inert counterion of the surfactant plus the added reactive ion. Competition between these ions for the micelle is of key importance and merits detailed consideration. In some cases the solution also contains buffers and the effect of buffer ions has to be considered (Quina et al., 1980). 

It seems possible that a very hydrophilic anion such as OH- might not in fact penetrate the micellar surface (Scheme 1) so that its interaction with a cationic micelle would be non-specific, and it would exist in the diffuse, Gouy-Chapman layer adjacent to the micelle. In other words, OH" would not be bound in the Stem layer, although other less hydrophilic anions such as Br, CN or N 3 probably would bind specifically in this layer. In fact the distinction between micellar and aqueous pseudophases is partially lost for reactions of very hydrophilic anions. The distinction is, however, appropriate for micellar reactions of less hydrophilic ions. 

It is more difficult to interpret micellar effects upon reactions of azide ion. The behavior is normal , in the sense that k /kw 1, for deacylation, an Sn2 reaction, and addition to a carbocation (Table 4) (Cuenca, 1985). But the micellar reaction is much faster for nucleophilic aromatic substitution. Values of k /kw depend upon the substrate and are slightly larger when both N 3 and an inert counterion are present, but the trends are the same. We have no explanation for these results, although there seems to be a relation between the anomalous behavior of the azide ion in micellar reactions of aromatic substrates and its nucleophilicity in water and similar polar, hydroxylic solvents. Azide is a very powerful nucleophile towards carboca-tions, based on Ritchie s N+ scale, but in water it is much less reactive towards 2,4-dinitrohalobenzenes than predicted, whereas the reactivity of other nucleophiles fits the N+ scale (Ritchie and Sawada, 1977). Therefore the large values of k /kw may reflect the fact that azide ion is unusually unreactive in aromatic nucleophilic substitution in water, rather than that it is abnormally reactive in micelles. 

Several workers have attempted to draw analogies between reactions in functional micelles and in enzymes, but in general this seems to be unjustified because there is generally little substrate- or stereo-specificity in the micellar reactions and usually limited turnover rates. 

First, micelles have very loose, mobile, structures and there are considerable entropy costs in a concerted reaction. These costs are much less serious in enzymic systems where conformation at the active site is tailor-made to fit the transition state. Secondly, the sites of micellar reactions are very wet and omnipresent water molecules are available to transfer protons. 

The degree of stereoselectivity is usually not large in these reactions and appears to be due to transition-state rather than initial-state interactions. In other words the diastereomeric transition states derived from the enantiomeric substrates have different free energies in the micelle. To this extent the situation is essentially no different to the stereoselectivity which is often observed in non-micellar reactions involving reactions of enantiomeric substrates with a chiral reagent. In some cases it is possible to identify the noncovalent interactions which are responsible for the stereoselectivity (Brown et al., 1981). 

N-Alkylhydroxamic acid hydrolysis Methyl Violet + OH" Cl C12H25S03Na + H30+, CTABr + OH". An attempt made to separate electronic and hydrophobic effects on the micellar reaction Anionic and cationic micelles. Effect of surfactant structure examined Berndt el at., 1984 Malaviya and Katiyar, 1984... 

Acetylation rates have also been studied by Centola37 who treated natural and mercerized ramie fibers for varying times with acetic anhydride and sodium acetate and examined the reaction products chemically and by X-ray diffraction. The reagent was considered to penetrate into the interior of fibers. A heterogeneous micellar reaction was believed to occur that converted a semi-permeable elastic membrane around the micelles into the triacetate. The rate of acetylation of mercerized ramie was observed to be faster than that of unmercerized fiber. Centola concluded that about 40 % of the cellulose in native ramie is amorphous and acetylates rapidly. 

Turner MS, Cates ME. Linear viscoelasticity of wormlike micelles—a comparison of micellar reaction-kinetics. J Phys II 1992 2 503-519. 

Use these values to criticize or defend the following proposition The smaller endothermic value for AH% in CTABr means the product molecules must be more readily expelled from these micelles, making the enthalpy contribution more favorable to the reaction in this case. The solubilized substrate has a higher entropy, so the decrease in entropy for the micellar reaction is larger. The last problem shows that the reaction occurs about twice as fast in water as in 0.01 M NaLS. The rate in water determines the kinetic parameters in the last case. 

The highly flexible nature of the micellar reaction cavities has been... 

The selectivity of the trap towards hydroxyl radicals was demonstrated by several control experiments using different radicals, showing that the formation of the respective hydroxylation product, 5-hydroxy-6-0-zso-propyl-y-tocopherol (57), was caused exclusively by hydroxyl radicals, but not by hydroperoxyl, alkylperoxyl, alkoxyl, nitroxyl, or superoxide anion radicals. These radicals caused the formation of spin adducts from standard nitrone-and pyrroline-based spin traps, whereas a chemical change of spin trap 56 was only observed in the case of hydroxyl radicals. This result was independent of the use of monophasic, biphasic, or micellar reaction systems in all OH radical generating test systems, the trapping product 57 was found. For quantitation, compound 57 was extracted with petrol ether, separated by adsorption onto basic alumina and subsequently oxidized in a quantitative reaction to a-tocored, the deeply red-colored 5,6-tocopheryldione, which was subsequently determined by UV spectrophotometry (Scheme 23). 

Robinson, 1969a). It is probable that the hydrophobic nature of the phenyl groups of p-nitrophenyl diphenyl phosphate results in deep penetration of the neutral ester in the Stern layer, thus shielding the phosphoryl group from nucleophilic attack. Unlike other reactions between nucleophiles and neutral substrates catalyzed by cationic micelles (Bunton and Robinson, 1968, 1969a) and the hydrolysis of dinitrophenyl phosphate dianions in the presence of cationic micelles (Bunton et al., 1968), the catalysis of the hydrolysis of -nitrophenyl diphenyl phosphate by CTAB arises from an increase in the activation entropy rather than from a decrease in the enthalpy of activation. The Arrhenius parameters for the micelle-catalyzed and inhibited reactions are most probably manifestations of the extensive solubilization of this substrate. However, these parameters can be composites of those for the micellar and non-micellar reactions and the eifects of temperature on the micelles themselves are not known. Interpretation of the factors which affect these parameters must therefore be carried out with caution. In addition, the inhibition of the micelle-catalyzed reactions by added electrolytes has been observed (Bunton and Robinson, 1969a Bunton et al., 1969, 1970) and, as in the cases of other anion-molecule reactions and the heterolysis of dinitrophenyl phosphate dianions, can be reasonably attributed to the exclusion of the nucleophile by the anion of the added salt. 

The products are the same as those in the homogeneous reactions (Table 1). Sodium undec-10-enoate and sodium dodecyl sulfate were used as detergents at concentrations exceeding the critical micelle concentration. The differences in the cisjtrans ratios of both the hydroformyl-ation and hydrogenation products in the homogeneous and micellar reactions have been discussed. Performed in supercritical carbon dioxide, 10 and 11 are obtained in similar distribution from 9 and HMn(CO)5. ... 

---