Microsolvation

Clearly, one must truncate the number of solvation shells to limit the number of water molecules to some reasonable value. But just how many water molecules are necessary to obtain bulk liquid water Certainly a calculation of the solute and just the first solvation shell does not capture the effect of bulk water. Without the next solvation shell, the water molecules in the first shell do not have these neighboring water molecules to interact with via hydrogen bonding. Instead, the water molecules might seek out additional favorable interactions with the solute or be forced to have some dangling O-H bonds and lone pairs. 

The microsolvation computations °° ° are excellent models of, for example, small hydrated clusters that can be observed in the gas phase. ° ° Still under intense computational study is how informative microsolvation computations are for understanding true solution phase chemistry. 

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The rate acceleration imposed by 0-cyclodextrin was explained in terms of a microsolvent effect 6> The inclusion of the substrate within the hydrophobic cavity of cyclodextrin simulates the changes in solvation which accompany the transfer of the substrate from water to an organic solvent. Uekama et al.109) have analyzed the substituent effect on the alkaline hydrolysis of 7-substituted coumarins (4) in the... 

In contrast to the reactions of the cycloamyloses with esters of carboxylic acids and organophosphorus compounds, the rate of an organic reaction may, in some cases, be modified simply by inclusion of the reactant within the cycloamylose cavity. Noncovalent catalysis may be attributed to either (1) a microsolvent effect derived from the relatively apolar properties of the microscopic cycloamylose cavity or (2) a conformational effect derived from the geometrical requirements of the inclusion process. Kinetically, noncovalent catalysis may be characterized in the same way as covalent catalysis that is, /c2 once again represents the rate of all productive processes that occur within the inclusion complex, and Kd represents the equilibrium constant for dissociation of the complex. 

The manifestation of noncovalent catalysis as a microsolvent effect is illustrated by cycloamylose-catalyzed decarboxylations of activated carboxylic acid anions. Anionic decarboxylations, as illustrated in scheme VII, are generally assumed to proceed by a rate-determining heterolytic... 

Cramer and Kampe (1965), in fact, proposed a specific interaction between the included substrate and the cycloamylose hydroxyl groups to explain accelerated rates of decarboxylation. In view of the more recent results, particularly the insensitivity of the rate accelerations to the structure of the substrate and the pH independence, a nonspecific microsolvent effect now seems more likely. 

An additional example of cycloamylose-induced catalysis which can probably be attributed to a microsolvent effect is the oxidation of a-hy-droxyketones to a-diketones (Scheme VIII). The rate of this oxidation is accelerated by factors ranging from 2.1 to 8.3 as the structure of the substrate is varied. As noted by Cramer (1953), these accelerations may be attributed to a cycloamylose-induced shift of the keto-enol equilibrium to the more reactive enol form. 

Hydrolyses of p-nitrophenyl and 2,4-dinitrophenyl sulfate are accelerated fourfold and eightfold, respectively, by cycloheptaamylose at pH 9.98 and 50.3° (Congdon and Bender, 1972). These accelerations have been attributed to stabilization of the transition state by delocalization of charge in the activated complex and have been interpreted as evidence for the induction of strain into the substrates upon inclusion within the cycloheptaamylose cavity. Alternatively, accelerated rates of hydrolysis of aryl sulfates may be derived from a microsolvent effect. A comparison of the effect of cycloheptaamylose with the effect of mixed 2-propanol-water solvents may be of considerable value in distinguishing between these possibilities. 

Recently, an example of cycloamylose-induced catalysis has been presented which may be attributed, in part, to a favorable conformational effect. The rates of decarboxylation of several unionized /3-keto acids are accelerated approximately six-fold by cycloheptaamylose (Table XV) (Straub and Bender, 1972). Unlike anionic decarboxylations, the rates of acidic decarboxylations are not highly solvent dependent. Relative to water, for example, the rate of decarboxylation of benzoylacetic acid is accelerated by a maximum of 2.5-fold in mixed 2-propanol-water solutions.6 Thus, if it is assumed that 2-propanol-water solutions accurately simulate the properties of the cycloamylose cavity, the observed rate accelerations cannot be attributed solely to a microsolvent effect. Since decarboxylations of unionized /3-keto acids proceed through a cyclic transition state (Scheme X), Straub and Bender suggested that an additional rate acceleration may be derived from preferential inclusion of the cyclic ground state conformer. This process effectively freezes the substrate in a reactive conformation and, in this case, complements the microsolvent effect. 

An additional example of a cycloamylose-induced rate acceleration which may be reasonably attributed to a conformational effect is the facilitation of the transfer of the trimethylacetyl group from the phenolic oxygen of 9 to the aliphatic oxygen of the adjacent hydroxymethyl group to form 10. This intramolecular transesterification is remarkably enhanced relative to a comparable intermolecular reaction,6 and occurs, at pH 7.0 and 25.5°, with a rate constant of 0.0352 sec-1 (Griffiths and Bender, 1972). An even larger rate enhancement is achieved upon inclusion of this material within the cyclohexaamylose cavity—fc2 = 0.16 sec-1. This fivefold acceleration cannot be satisfactorily explained either by a microsolvent effect which would be expected to depress the rate of the reaction or, at this pH, by covalent... 

Hu and Truhlar have recently reported a modeling transition state solvation at a single-water representation [295]. Recent experimental advances leading to the study of SN2 reactions of gas-phase microsolvated clusters which can advantageously been studied with ab initio electronic theory. These experiments and theoretical studies are quite relevant to chemical reactions in supercritical water. 

Microsolvation approaches have also been considered toward understanding the role of the primary solvation shell of a carbonium ion (18,90,91,97,98). These ions tend to become transition states whenever strong solvation is taking place (Figure 27). 

I. Dauster, M. A. Suhm, U. Buck, and T. Zeuch, Experimental and theoretical study of the microsolvation of sodium atoms in methanol clusters Differences and similarities to sodium water and sodium ammonia. Phys. Chem. Chem. Phys. 10, 83 95 (2008). 

B. Brutschy, The structure of microsolvated benzene derivatives and the role of aromatic... 

The rate of decarboxylation of activated carboxylate anions [e.g. (10)], shows strong solvent dependence. It is not surprising, therefore, that these reactions have been used to probe the microsolvent effects of micelles and CDs (Fendler and Fendler, 1975). In particular, it was anticipated that complexation with a CD might result in catalysis by providing an environment for the reaction that is less polar than water. 

Bierbaum, V. M. et al. Deuterium kinetic isotope effects in microsolvated gas-phase E2 reactions. J. Am. Soc. Mass. Spectrom. 18, 1046 (2007) Deuterium kinetic isotope effects in gas-phase SN2 and E2 reactions comparison of experiment and theory. J. Am. Chem. Soc. 128, 736 (2006). 

At high pressures, a non-covalent ionic complex can be regarded as a microsolvated ion. It represents the simplest model for ions generated in a dynamic environment, such as in a solvent cage in solution. The main difference is that the behavior of a microsolvated ion is not perturbed by those environmental factors (solvation, ion pairing, etc.) which normally affect the fate of intimate ion-dipole pairs in solution. Hence, a detailed study of the dynamics and the reactivity of microsolvated ions may provide valuable information on the intrinsic factors governing the reaction and how these factors may be influenced by the solvent cage in solution.4 493... 

The arenium ion/(R)-(— )-2-chlorobutane adducts. A crucial question concerns the chemical identity and the relative spatial arrangement of the components of a microsolvated system, two features of paramount importance to assess the kinetic and the mechanistic role of the corresponding ion-dipole pairs in solution. In the example reported in this section, Cacace and coworkers consider the ion-molecule complexes involved in the classical Friedel-Crafts alkylation of arenes." " At 300 K and under FT-ICR conditions, the benzenium ion CeH reacts with 2-chlorobutane C4H9CI to give the CloHj5 ion with a rate constant of 5 X 10 cm molecule corresponding to a collision efficiency of 2.5% (equations (33) or (34)). ... 

Solvent KIEs for MeCl + CP in the presence of 1-4 molecules of water were examined by ab initio calculations.70 The ratio /q /kV) was <1 for the monohydrated system and > 1 for the dihydrated system it increased with the number of microsolvating water molecules, owing to breakage of hydrogen bonds in attaining the transition state. 

The stabilization of a substratS)(as the result of inclusion complex formation occurs noncova-lently and may be the result of either a microsolvent effect ora conformational effect (Szejtli, 1982). The kinetic method utilizes this reduction in rate of the reactioiScrfhen ligand is present to obtain information about the nature of the complex. The basic assumption is that the decreased reactivity is the sole result of complexation, the compleSdsfeing less reactive than frtafeThe kinetic scheme can be represented as Scheme 8.1 ... 

Recent experimental developments in coupling IR spectroscopy techniques with mass spectrometry, which allow the structural characterization of isolated and microsolvated protonated aromatic molecules in the gas phase have been summarized.64 Hydrogen-deuterium exchange has been observed at Ha in (59) and some closely related substrates when this ligand is complexed to Cu1 in [2Hg]acetone.65 The process is finely controlled by the precise coordination distance required to form agostic interaction between Cu(I) and the C-H bond and is believed to involve the enol form of [2H6]acetone and a reversible Cu(I) to Cu(III) interconversion. 

Other theoretical studies discussed above include investigations of the potential energy profiles of 18 gas-phase identity S 2 reactions of methyl substrates using G2 quantum-chemical calculations," the transition structures, and secondary a-deuterium and solvent KIEs for the S 2 reaction between microsolvated fluoride ion and methyl halides,66 the S 2 reaction between ethylene oxide and guanine,37 the complexes formed between BF3 and MeOH, HOAc, dimethyl ether, diethyl ether, and ethylene oxide,38 the testing of a new nucleophilicity scale,98 the potential energy surfaces for the Sn2 reactions at carbon, silicon, and phosphorus,74 and a natural bond orbital-based CI/MP through-space/bond interaction analysis of the S 2 reaction between allyl bromide and ammonia.17... 

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