Inner-sphere water ligands

In the course of our investigations to develop new chiral catalysts and catalytic asymmetric reactions in water, we focused on several elements whose salts are stable and behave as Lewis acids in water. In addition to the findings of the stability and activity of Lewis adds in water related to hydration constants and exchange rate constants for substitution of inner-sphere water ligands of elements (cations) (see above), it was expected that undesired achiral side reactions would be suppressed in aqueous media and that desired enanti-oselective reactions would be accelerated in the presence of water. Moreover, besides metal chelations, other factors such as hydrogen bonds, specific solvation, and hydrophobic interactions are anticipated to increase enantioselectivities in such media. 

S. Kobayashi, S. Nagayama, T. Busujima, Lewis Acid Catalysts Stable in Water. Correlation between Catalytic Activity in Water and Hydrolysis Constants and Exchange Rate Constants for Substitution of Inner-Sphere Water Ligands J. Am. Chern. Soc 1998, 120, 8287-8288. 

Table 1 Hydrolysis constants and exchange rate constants for substitution of inner-sphere water ligands...

Another approach is to design homogeneous Lewis acids which are water-compatible. For example, triflates of Sc, Y and lanthanides can be prepared in water and are resistant to hydrolysis. Their use as Lewis acid catalysts in aqueous media was pioneered by Kobayashi and coworkers [144-146]. The catalytic activity is dependent on the hydrolysis constant (Kh) and water exchange rate constant (WERC) for substitution of inner sphere water ligands of the metal cation [145]. Active catalysts were found to have pKh values in the range 4-10. Cations having a pKh of less than 4 are easily hydrolyzed while those with a pKh greater than 10 display only weak Lewis acidity. 

Now some remarks should be made about the chemical and mechanistical realization of this specialized reaction sequence. The formation of a crypto-hydroxyl radical has been discussed already implicitly in Ref.95). It can be accomplished in two ways a) If the central manganese ion of a storage place is coordinated directly with a water molecule, then a univalent oxidative valence change of the manganese by electron transfer to Chl-an can lead to an electronic redistribution between the central ion and the inner sphere water ligand in the form ... 

Figure 2. Schematic drawing of the active site of staphylococcal nuclease. Protein side chains are shown by light bonds, while the PdTp molecule is in dark. The Ca ion is shown as the large sphere below the inhibitor molecule. Also shown are the three inner sphere water ligands of the calcium ion and the water molecule bridging Glu-43 and the 5 -phosphate of the inhibitor (this bridging water is the putative nucleophile in the hydrolysis of phosphoesters) (from ref. 1).

FIGURE 15.1 (See color insert following page 40). Hydrolysis constants (fli) and water exchange rate constants for substitution of inner-sphere water ligands for metal cations. 

Three papers have dealt with manganese(n) systems. Gale and co-workers proposed a simple method to estimate the inner-sphere hydration state of the Mn(ii) ion in coordination complexes and metal-loproteins. The method makes use of the 0 linewidth measurements for bulk water in the presence and in the absence of Mn(n), which allows the determination of transverse 0 relaxivity. Doing this as a function of temperature and finding the maximum yields a quantity which is directly proportional to the number of inner-sphere water ligands. Molnar et... 

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