Metallomicelles

For effective catalytic hydrolysis of lipophilic phosphate esters in aqueous solution, metallomicelles such as 3 [21], 4 [22], 5 [23], 6 [24], 7 [25], and 8 [26] have been designed (Scheme 3). These complexes are essentially metal ions chelated with ligands that are attached with lipophilic long alkyl chains. Some of these were used together with surfactants to make water-miscible solutions. 

The common problems with those metallomicelles may be summarized as follows (1) Most of these complexes were prepared in situ and often were not isolated. Hence, the intended structures of the metallomicelles in solution or in the solid state were not verified. (2) The metal complexes in solution were not identified or characterized in rigorous thermodynamic senses by potentiometric pH titration, etc. The complexation constants and possible species distribution at various pH s were totally unknown. (3) Possible catalytically active species L-Mn+—OH were not identified by means of the thermodynamic pvalues. Those described were all obtained merely in kinetics. (4) The product (phosphate anion) inhibition was not determined. Accordingly, it often was not clear whether it was catalytic or not. (5) Often, the substrates studied were limited. (6) The kinetics was complex, probably as a result of the existence of various species in solution. Thus, in most of the cases only pseudo-first-order rates (e.g., with excess metal complexes) were given. No solid kinetic studies combined with thermodynamic studies have been presented. It is thus impossible to compare the catalytic efficiency of these metallomicelles with that of the natural system. Besides, different... 

Figure 3 Proposed difunctional or push-pull mechanism for diphenyl 4-nitrophenyl phosphate by Breslow s metallomicelle 5.

Tagaki et al. [24] and Fomasier et al. [25] reported another type of metallomicelle attached with a metal-bound alkoxide nucleophile. Tagaki s zinc(II) and copper(II) complexes (with possible structures 6a and b) promoted the hydrolysis of 4-nitrophenyl picolinate in a comicellar system with hexadecyl trimethy-lammonium bromide. However, no detailed mechanistic study was reported. Scrimin s zinc(II) and copper(II) complexes (proposed structures 7a and b) also promoted the hydrolysis of 4-nitrophenyl picolinate. A postulated mechanism for the catalytic activity of 7 is shown in Figure 4. An aggregate of 7 more effectively... 

Figure 4 Proposed intramolecular reaction mechanism for 4-nitrophenyl picolinate hydrolysis by Scrimin s metallomicelle 7. See text for details.

Very recently, a new type of metallomicelle with a zinc(II) cyclen attached to a hexadecyl group, 11, has been synthesized (Scheme 6). An unprecedented clear picture of its catalytic behavior in a comicellar solution with Triton X-100 has been disclosed [28], Since the parent Zn2+—cyclen complex 2 showed discrete behavior in aqueous solution (i.e., no dissociation of the zinc(II) ion stable, discrete monomeric species) [7,13,14], 11 was anticipated to behave in an orderly way, and that turned out to be the case. 

The lipophilic zinc(II) complex 11 (0.25-1.0 mM) with 10 mM Triton X-100 also showed phosphodiesterase activity in BNP (5-10 mM) hydrolysis at 35°C with similar kinetic behavior to that exhibited in the NA and TNP hydrolysis. The rate-pH profile curve disclosed an inflection point at pH 8.3 with 1.0 mM 11, indicating that the kinetically active species was again the zinc(II)-bound OH- complex lib (Scheme 9). The second-order rate constant BNP (see Eq. [9]) for the hydrolysis of BNP promoted by lib was 4.3 X 10-4 M-1 sec-1 at 35°C and pH 10.2 (20 mM CAPS buffer) with I = 0.10 (NaN03). The fcBNP value for lib with 10 mM Triton X-100 is only approximately 20 times larger than the reported kBNP value for 2b (2.1 X 10-5 M-1 sec-1) [9] under the same conditions. The rate enhancement (i.e., 20 times) by the metallomicelles is not as dramatic as that for the more lipophilic TNP (290 times) and NA (50 times), because the less lipophilic nature of BNP relative to that of TNP and NA would result in smaller partition into the metallomicelles. 

Scrimin and co-workers have extensively studied the ester-cleavage abilities of various Cu(II)-chelating bidentate ligand [(2-hydroxymethyl)pyridine] amphi-phile, 9, and related bolaphile, 10, in micellar media [32], The corresponding metallomicelles are powerful catalysts for the cleavage of substrates, e.g. p-nitrophenyl alkanoates, that do not coordinate with the metal-complex core. Subsequent studies demonstrated that tridentate ligand amphiphiles such as 9,... 

Fomasier et al.13 utilized metallomicelles formed with either bolaphiles 58 or simple surfactants 57 as catalysts in the hydrolysis of... 

This tendency of metalloaggregates to modulate the coordination to transition metal ions appears quite general. For instance, very recently we have observed [49] that copper(II) metallomicelles made of the ligand shown in Figure 11 shift the coordination equilibrium toward the five-coordinate complex even at very low pH, while the water-soluble ligand is only tetracoordinated with the second imidazole in its protonated form. Clearly, the cationic metalloaggregate drives the deprotonation of the second... 

The modulation of the coordination to the transition metal has not necessarily positive implications on the reactivity. For instance, we observed [50] that the copper(II) complex (8) of tetramethyl-l,2-diaminoethane catalyzes the hydrolysis of the phosphoric acid triester PNPDPP via an electrophilic mechanism which involves the pseudointramolecular attack of deprotonated water, as illustrated in (9). The electrophilic mechanism contribution to the hydrolytic process totally disappears in micellar aggregates made of the amphiphilic complex (10). Clearly, micellization does not allow the P O group of the substrate to interact with the metal ion. This could be a result of steric constraint of the substrate when bound to the micelle and/or the formation of binuclear dihydroxy complexes, like (11), in the aggregate. So, in spite of the quite large rate accelerations observed [51] in the cleavage of PNPDPP in metallomicelles made of the amphiphilic complex (10), the second-order rate constant [allowing for the difference in pXa of the H2O molecules bound to copper(II) in micelles and monomers] is higher for (8) than for (10) (k > 250). 

It is noteworthy that metallomicelles of Ni(II) complexes with long-chain N-al-kylated ethylenediamine ligands catalyze the epimerization of aldoses in an aqueous dispersion [24]. A reexamination of the effect of metallomicelles on the hydrolysis of phosphate and carboxylate esters was given by Scrimin et al. [25], Acceleration in second-order reactions are often to interpret as a local concentration increase of the reactants. The catalytic effect of metallosurfactants in enzyme-related reactions has been investigated by Nolte s working group [26], also carefully considering the assembly structure [27]. The wide field of artificial enzymes was recently reviewed by Murakami et al. [28]. 

Fomasier et al. used metallomicelles formed from bolaphiles and surfactants with only one head group as catalysts for the cleavage for para-nitrophenyl picolinate. [9]... 

Metallomicelles made up of ligand surfactants and bound metal ions have been studied extensively as artificial hydrolytic metallo-enzymes. Many such systems have become large and complex, but a study of a simple (1 1) Co(II) complex with triethanolamine showed that in the presence of CTAB or Triton X-100, it could catalyse PNPP (67) hydrolysis at pH 7 with a rate enhancement factor of 1000-fold. " ... 

In this section, the effect of aggregates such as metallomicelles comprised of nickel and hydrophobic diamines on the epimerization of aldoses is outhned. A homologous series of nickel/ethylenediamine complexes of various N,N-dime-thyl-N -alkylethylenediamines (l,l,n -en) was prepared and examined [64], The influence of the hydrophobicity of the Hgand on the epimerization in aqueous media was assessed. The objective of this work was to clarify why differences in hydrophobicity affect the outcome of the epimerization and to characterize the nature of the aggregative metallomicelle. 

It has been suggested that significant enhancement of the epimerization was due to the formation of metallomicelles in the reaction system. To confirm the existence of the micelles, the surface tension of the reaction system was measured. It was confirmed that hydrophobic Ni/diamine complexes containing alkyl chains longer than decyl form micelles, whereas Ni/diamine complexes containing alkyl chains shorter than nonyl do not. It should be emphasized that such formation of micelles was in accordance with the occurrence of epimerization. The fact that a nickel complex that can aggregate to form metallomicelles shows excellent epimerizing ability is the most noteworthy point. 

Comparison of these results may not be straightforward, since the surface tension and epimerization were measured at different temperatures (the former at 25 °C and the latter at 80 C). However, it is interesting that the findings are consistent with the interpretation that aggregates were formed, giving additional evidence for metallomicelles. 

Previous studies on the Ni(ll)- and Ca(II)-complex-catalysed C-2 epimerizations of aldoses by use of C-enriched substrates have been reviewed (19 refs.). Anq)hiphilic ctxnplexes between Ni(U) and long-chain V-alkyl ethylenediamines gave rise to "metallomicelles" which coordinated with aldoses which then underwent epimerization (see Vol. 25, Chapter 2, Ref. SI) short-chain complexes had little activity. The epimerization of aldoses by Ca in basic aqueous or alcoholic solution, which proceeds by molecular rearrangement (see Vol. 24, Chapter 2, Ref. 47), has now been developed into a preparative method for converting glucose and xylose to mannose and lyxose, respectively. ... 

Figure 6 Some compounds used to generate metallomicelles.

Almost all the kinetic studies on metaUomiceUar-mediated reactions have been carried out in the presence of either nonfunctional metallomicelles in which micellar head groups are incapable of acting as ligands for metal-ligand complex formation or induced functional metaUomiceUes in which micellar head groups act as effective ligands for metal-Ugand complex formation. 

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