Solvation crown ethers

In this section, we review our first examinations of tryptophan probing sensitivity and water dynamics in a series of important model systems from simple to complex, which range from a tripeptide [70], to a prototype membrane protein melittin [70], to a common drug transporter human serum albumin [71], and to lipid interface of a nanochannel [86]. At the end, we also give a special case that using indole moiety of tryptophan probes supramolecule crown ether solvation, and we observed solvent-induced supramolecule folding [87]. The obtained solvation dynamics in these systems are linked to properties or functions of these biological-relevant macromolecules. 

Crown Ether Complexes In Chapter 6, we encountered the use of crown ethers, large cyclic polyethers that specifically solvate metal cations by complexing the metal in the center of the ring. Different crown ethers solvate different cations, depending on the relative sizes of the crown ether and the cation and the number of binding sites around the cation. The EPM of 18-crown-6 shows that the cavity in the center of the molecule is surrounded by electron-rich oxygen atoms that complex with the guest potassium cation. 

Bickelhaupt and coworicers have determined the crystal structures of a series of crown ether solvated magnesium compounds. A sequence of these compounds is illustrated as the internally coordinated 13-crown-4-xylylmagnesium chloride (134) and bromide (135), as well as the organometallic, rotaxane (136). Note the similarity between these structures and the corresponding aliphatic dialkylmagnesium rotaxane (83). 

Crown ethers, a class of macrocyclic polyethers,22,23) have the remarkable ability to solubilize alkali metal salts in solvents of low polarity. The crown ether solvates a metal cation by binding the ion to its oxygen atoms by means of ion-dipole interactions. The metal ion becomes located near or inside the cavity of the ether illus-... 

The solvent extraction of hydrophilic anions can be effected by the use of crown-ether solvated cations as in Equation 8.14. The order of extractability of potassium salts from aqueous solutions by 0.1 M DB-18-C-6 in m-cresol is according to Marcus et al. [45,46] ... 

In media such as water and alcohols fluoride ion is strongly solvated by hydro gen bonding and is neither very basic nor very nucleophilic On the other hand the poorly solvated or naked fluoride 10ns that are present when potassium fluoride dis solves m benzene m the presence of a crown ether are better able to express their anionic reactivity Thus alkyl halides react with potassium fluoride m benzene containing 18 crown 6 thereby providing a method for the preparation of otherwise difficultly acces sible alkyl fluorides... 

Phase transfer catalysis succeeds for two reasons First it provides a mechanism for introducing an anion into the medium that contains the reactive substrate More important the anion is introduced m a weakly solvated highly reactive state You ve already seen phase transfer catalysis m another form m Section 16 4 where the metal complexmg properties of crown ethers were described Crown ethers permit metal salts to dissolve m nonpolar solvents by surrounding the cation with a lipophilic cloak leav mg the anion free to react without the encumbrance of strong solvation forces... 

The crown ethers and cryptates are able to complex the alkaU metals very strongly (38). AppHcations of these agents depend on the appreciable solubihty of the chelates in a wide range of solvents and the increase in activity of the co-anion in nonaqueous systems. For example, potassium hydroxide or permanganate can be solubiHzed in benzene [71 -43-2] hy dicyclohexano-[18]-crown-6 [16069-36-6]. In nonpolar solvents the anions are neither extensively solvated nor strongly paired with the complexed cation, and they behave as naked or bare anions with enhanced activity. Small amounts of the macrocycHc compounds can serve as phase-transfer agents, and they may be more effective than tetrabutylammonium ion for the purpose. The cost of these macrocycHc agents limits industrial use. 

Particularly striking examples of the effect of specific solvation can be cited from among the crown ethers. These are maciocyclic polyethers that have the property of specifically solvating cations such as Na+ and K" ". 

Other measures of nucleophilicity have been proposed. Brauman et al. studied Sn2 reactions in the gas phase and applied Marcus theory to obtain the intrinsic barriers of identity reactions. These quantities were interpreted as intrinsic nucleo-philicities. Streitwieser has shown that the reactivity of anionic nucleophiles toward methyl iodide in dimethylformamide (DMF) is correlated with the overall heat of reaction in the gas phase he concludes that bond strength and electron affinity are the important factors controlling nucleophilicity. The dominant role of the solvent in controlling nucleophilicity was shown by Parker, who found solvent effects on nucleophilic reactivity of many orders of magnitude. For example, most anions are more nucleophilic in DMF than in methanol by factors as large as 10, because they are less effectively shielded by solvation in the aprotic solvent. Liotta et al. have measured rates of substitution by anionic nucleophiles in acetonitrile solution containing a crown ether, which forms an inclusion complex with the cation (K ) of the nucleophile. These rates correlate with gas phase rates of the same nucleophiles, which, in this crown ether-acetonitrile system, are considered to be naked anions. The solvation of anionic nucleophiles is treated in Section 8.3. 

Furthermore, the molecular size of the Li+ -solvating solvents may affect the tendency for solvent co-intercalation. Crown ethers [19, 152-154, 196, 197] and other bulky electrolyte additives [196] are assumed to coordinate Li+ ions in solution in such a way that solvent co-intercalation is suppressed. The electrochemical formation of binary lithiated graphites Li tC6 was also reported for the reduction... 

One of the most important factors affecting Qsei [76, 78, 87] is graphite-anode exfoliation, as a result of intercalation of solvated lithium ions. Factors that are reported to decrease (9lR are increasing the EC content in organic carbonates or di-oxolane solutions [98, 991 addition of C02 [31, 87, 99] or crown ethers [8, 71, 78] and increasing the current density [73] (this also lowers <2SE [14] as a result of decrease in (2s P ) ... 

Solvating additives (used in some instances in non-polar solvents) Crown-ethers (e.g. 15C5 or 18C6)... 

A possible explanation comes from X-ray analyses of the sulfonic acids [45]. All X-rayed crown ether crystals contained water and the sulfonic acid moiety was dissociated. Therefore in crystals of [45], macrocyclic ben-zenesulfonate anions and hydronium ions (sometimes hydrated) are present. The ions are bound to each other by hydrogen bonds. The size of the included water-hydronium ion cluster (varying by the number of solvating water molecules) depends on the ring size. In the 15-membered ring, HsO" was found, whereas in a 21-membered ring HsO and in the 27-membered ring were present. This means the sulfonic acid functions in [45] are... 

There are two other approaches to enhancing reactivity in nucleophilic substitutions by exploiting solvation effects on reactivity the use of crown ethers as catalysts and the utilization of phase transfer conditions. The crown ethers are a family of cyclic polyethers, three examples of which are shown below. 

Hindered lithium dialkylamides can generate aryl-substituted carbenes from benzyl halides.162 Reaction of a,a-dichlorotoluene or a,a-dibromotoluene with potassium r-butoxide in the presence of 18-crown-6 generates the corresponding a-halophenylcarbene.163 The relative reactivity data for carbenes generated under these latter conditions suggest that they are free. The potassium cation would be expected to be strongly solvated by the crown ether and it is evidently not involved in the carbene-generating step. 

An enormous variety of solvates associated with many different kinds of compounds is reported in the literature. In most cases this aspect of the structure deserved little attention as it had no effect on other properties of the compound under investigation. Suitable examples include a dihydrate of a diphosphabieyclo[3.3.1]nonane derivative 29), benzene and chloroform solvates of crown ether complexes with alkyl-ammonium ions 30 54>, and acetonitrile (Fig. 4) and toluene (Fig. 5) solvates of organo-metallic derivatives of cyclotetraphosphazene 31. In most of these structures the solvent entities are rather loosely held in the lattice (as is reflected in relatively high thermal parameters of the corresponding atoms), and are classified as solvent of crystallization or a space filler 31a). However, if the geometric definition set at the outset is used to describe clathrates as crystalline solids in which guest molecules... 

The stability constant is dependent, amongst other things, on the solvating medium. For example, for a simple crown ether kc is usually very large and kd also large, but in nonpolar solvents kd is much smaller than kc, so that Ks increases with decreasing polarity of the solvating medium. 

From the method of preparation of [BeCl(12-crown-4)]+ (179), it is known that the Cl ligand can be substituted by a solvent molecule. We applied our most common test solvents water and NH3 to a Be2+ cation, where most coordination sites are occupied by a chelating ligand, in this case the crown ether 12-crown-4. In contrast to the tetrahedral [Be(solvent)4]2+ solvated complexes, the precursor complexes [Be(solvent)(12-crown-4)]2+ are quadratic pyramidal, where four oxygen donor atoms of the crown ether form the quadratic basis, while Cl- or a coordinating solvent molecule occupies the apical position. Addition of one water or ammonia molecule to [Be(12-crown-4)]2+ is exothermic (see Table IX). 

Some caution is required when comparing the association constants obtained from extraction experiments with those measured under anhydrous, homogeneous conditions. Iwachido et al. (1976, 1977) have shown that the extracted cation retains part of its aqueous solvation shell on complexation. In particular, the small univalent cations (Li+, Na+) and bivalent cations give high hydration numbers for their crown-ether complexes. Water molecules completing the co-ordination sphere of the cation have frequently been encountered in the solid state of crown-ether complexes (Bush and Truter, 1970, 1971). The effect of small amounts of water on the equilibria (1) has not been studied yet for crown ethers. However, it has been found that the presence... 

The proportion of C-alkylation increases in the order OTs < Br < I, a sequence which is often associated with the balance of hardness between nucleophile and nucleofuge (Smith and Hanson, 1971). The work of Kurts et al. (1974) indicates that the overall reaction rate of the crown ether-assisted alkylation increases in the order Na+ < K+ < Rb+ < Cs+, which, according to these authors, reflects the increasing distance between cation and anion in the ion pairs. The high reactivity of the tetraphenylarsenate also fits in with this picture. The decrease of the kc/k0 ratio is only small in good cation-solvating solvents such as dimethyl sulfoxide (DMSO). Alkylation of the sodium derivative of [103] with ethyl iodide in DMSO gave kc/kQ = 15.7 addition of... 

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