Non-aqueous solvation

Non-aqueous Solvation.—Structural radii and electron-cloud radii, together with lattice enthalpies and enthalpies of solvation of ionic crystals, have been reviewed.84 The free energies of transfer, AGtr(K+), of potassium ions from water to 14 non-aqueous solvents have been reported, and they were derived from measurements in an electrochemical cell assumed to have a negligible liquid-junction potential. The essentially electrostatic nature of its solvation allows K+ to be used as a model for non-specific solvent-ion interactions. A 

Erdey-Gruz, E. Kugler, K. Vasse-Balthazer, and I. Nagy-Czako, Magyar Kem. Folyoirat, 

Mitsuji and Y. Tsujii, Nara Kyoiku Daigaku Kiyo Shizert Kagaku, 1973, 22, 19. 

Csl-Cdl2 7CsBr,3CdBr2 CsBr,CdBr2 3CsI,CdI2 80 

CsCl-AgCl-MeOH 2CsI,CdI2 CsI,CdI2,H20 CsAgCl2 81 

Villermaux, V. Baudot, and J. J. Delpuech, Bull. Soc. chim. France, 1972, 1781. 

Turgunbekova, K. Nogoev, and K. Sulaimankulov, Zhur. neorg. Khim., 1973, 18, 1119. 

K2SO4—CSNH2 K2SO4—CSNH2—MnS04 KjSO —(NH4)2S04—ZnS04 

8H20 Kj0,2B203,4H20 K2O, BaOa)2HaO 

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We report the results from a molecular dynamics simulation of the serine protease y-chymotrypsin (y-CT) in hexane. The active site of chymotrypsin contains the "catalytic triad" which consists of Ser-His-Asp. y-CT suspended in nearly anhydrous solvents has been found to be catalytically active. In order for proteins to retain their activity in anhydrous solvents some water molecules are required to be present. These "essential waters" have been suggested to function as a molecular lubricant for the protein. Hexane, having a dielectric constant of 1.89, is a suitable non-aqueous solvent for enzymatic reactions. The low dielectric constant of hexane allows it to not compete with the protein for the essential water and allows enzymes to retain their catalytic activity. y-CT in hexane is thus an ideal system to further explore the effect of non-aqueous solvation on protein structure, function and dynamics. 

Compounds of pharmaceutical interest can exist in different solid forms. Broadly, they can be classified as being in the amorphous or in the crystalline state. In crystalline pharmaceuticals, solvates are formed when the solvent molecule is incorporated, either stoichiometrically or non-stoichiometrically, in the crystalline lattice. Hydrates are a subclass of solvates, wherein the incorporated solvent is water. Because of regulatory considerations, non-aqueous solvates find limited use as pharmaceuticals. Our dis-cu.ssions will, therefore, be restricted to hydrates. If the solvent is non-volatile, co-crystals are obtained, and this is an emerging field in solid-state pharmaceutics. In case of weakly acidic and basic compounds, salt forms are prepared with the goal of obtaining the desired biopharmaceutical properties. Figure 3 is a schematic representation of the various types of solid forms of interest in pharmaceuticals (6). 

Evaluation of the interaction of the API with water is an important and essential pre-formulation activity. For the purposes of our discussion, we will assume (/) the API of interest is a non-porous solid, (//) the API does not form a non-stoichiometric hydrate, and ( 7/) non-aqueous solvates of the API will not be considered for development. If these issues are of interest, they are addressed in the literature (35). 

Acids can also exist in non-aqueous solvents. Since ammonia can also solvate a proton to give the ammonium ion. substances... 

HyperChem allows solvation of arbitrary solutes (including no solute) in water, to simulate aqueous systems. HyperChem uses only rectangular boxes and applies periodic boundary conditions to the central box to simulate a constant-density large system. The solvent water molecules come from a pre-equilibrated box of water. The solute is properly immersed and aligned in the box and then water molecules closer than some prescribed distance are omitted. You can also put a group of non-aqueous molecules into a periodic box. 

Finally, we want to describe two examples of those isolated polymer chains in a sea of solvent molecules. Polymer chains relax considerably faster in a low-molecular-weight solvent than in melts or glasses. Yet it is still almost impossible to study the conformational relaxation of a polymer chain in solvent using atomistic simulations. However, in many cases it is not the polymer dynamics that is of interest but the structure and dynamics of the solvent around the chain. Often, the first and maybe second solvation shells dominate the solvation. Two recent examples of aqueous and non-aqueous polymer solutions should illustrate this poly(ethylene oxide) (PEO) [31]... 

The solvation of inorganic substances and complex formation in non-aqueous solutions. A. M. Golub, Russ. Chem. Rev. (Engl. Transl.), 1976,45, 479-500 (358). 

K. Burger, Solvation, Ionic and Complex Formation Reactions in Non-Aqueous Solvents Experimental Methods for Their Investigation, Akademiai Kiado, Budapest, 1983. 

Electrodes of the first kind have only limited application to titration in non-aqueous media a well-known example is the use of a silver electrode in the determination of sulphides and/or mercaptans in petroleum products by titration in methanol-benzene (1 1) with methanolic silver nitrate as titrant. As an indicator electrode of the second kind the antimony pH electrode (or antimony/antimony trioxide electrode) may be mentioned its standard potential value depends on proton solvation in the titration medium chosen cf., the equilibrium reaction on p. 46). 

K. Burger, Solvation, Ionic and Complex Formation Reactions in Non-Aqueous Solvents (Experimental Methods for their Investigation), Studies in Analytical Chemistry, Vol. 6, Elsevier, Amsterdam, 1983, Ch. 2 and 3 and Ch. 9, pp. 256-257. 

Remarkable data on primary hydration shells are obtained in non-aqueous solvents containing a definite amount of water. Thus, nitrobenzene saturated with water contains about 0.2 m H20. Because of much higher dipole moment of water than of nitrobenzene, the ions will be preferentially solvated by water. Under these conditions the following values of hydration numbers were obtained Li+ 6.5, H+ 5.5, Ag+ 4.4, Na+ 3.9, K+ 1.5, Tl+ 1.0, Rb+ 0.8, Cs+0.5, tetraethylammonium ion 0.0, CIO4 0.4, NO3 1.4 and tetraphenylborate anion 0.0 (assumption). 

A review of preparative methods for metal sols (colloidal metal particles) suspended in solution is given. The problems involved with the preparation and stabilization of non-aqueous metal colloidal particles are noted. A new method is described for preparing non-aqueous metal sols based on the clustering of solvated metal atoms (from metal vaporization) in cold organic solvents. Gold-acetone colloidal solutions are discussed in detail, especially their preparation, control of particle size (2-9 nm), electrophoresis measurements, electron microscopy, GC-MS, resistivity, and related studies. Particle stabilization involves both electrostatic and steric mechanisms and these are discussed in comparison with aqueous systems. 

In addition to pure water, we extended our investigation on solvated Li+ to NH3 (90), NH3-H20 mixtures (91), dimethylsulf-oxide (DMSO) (92), DMS0-H20 mixtures (92), HCN and CH3CN, and their mixtures with water (93). For NH3 as a water-like solvent, all published X-ray structures are tetrahedrally coordinated, [Li(NH3)4] + (94-97). Therefore, we expect to have [Li(NH3)4]+ in solution. The validity of this assumption is also supported by the exchange mechanism. In the case of DMSO, a variety of theoretical and experimental studies on liquid DMSO (98-104), DMSO-water mixtures (105-110), DMSO-non-aqueous... 

D. J. Giesen, G. D. Hawkins, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, A universal solvation model for the quantum mechanical calculation of free energies of solvation in non-aqueous solvents, Theoret. Chem. Acc. 98 85-109 (1997) erratum 101 309 (1999). 

Notice how we generally infer the solvated proton, H30+, each time we write a concentration as [H+], which helps explain why the concept of pH is rarely useful when considering acids dissolved in non-aqueous solvents. When comparing the battery acid with the bench acid, we say that the battery acid has a lower pH than does the bench acid, because the number of solvated protons is greater and, therefore, it is more acidic. Figure 6.1 shows the relationship between the concentration of the solvated protons and pH. We now appreciate why the pH increases as the concentration decreases. 

The recent introduction of non-aqueous media extends the applicability of CE. Different selectivity, enhanced efficiency, reduced analysis time, lower Joule heating, and better solubility or stability of some compounds in organic solvent than in water are the main reasons for the success of non-aqueous capillary electrophoresis (NACE). Several solvent properties must be considered in selecting the appropriate separation medium (see Chapter 2) dielectric constant, viscosity, dissociation constant, polarity, autoprotolysis constant, electrical conductivity, volatility, and solvation ability. Commonly used solvents in NACE separations include acetonitrile (ACN) short-chain alcohols such as methanol (MeOH), ethanol (EtOH), isopropanol (i-PrOH) amides [formamide (FA), N-methylformamide (NMF), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA)] and dimethylsulfoxide (DMSO). Since NACE—UV may present a lack of sensitivity due to the strong UV absorbance of some solvents at low wavelengths (e.g., formamides), the on-line coupling of NACE... 

Cobalt(II) R-dtp complexes have been the subject of several studies js3,34i) Co(ethyl-dtp)2 occurs in a tetrahedral non-solvated form in carbon tetrachloride but undergoes solvation in other non-aqueous solvents 3 9. The spectrochemical series for tetrahedral Co(S2PX2)2 (where X = F,... 

Both in acetonitrile and in other non-aqueous solvents, a major problem arises in terms of the manner in which the potential values are reported by various investigators. Koepp, Wendt, and Strehlow [6] noted that hydrogen ion is the poorest reference material on which to base nonaqueous potentials because of the extreme differences in its solvation in various solvents. On the basis of an investigation of the solvent dependence of 18 redox couples, these investigators concluded that ferrocene/ferrocenium ion (i.e. bis(cyclopentadienyl)iron(III/II), abbreviated as Fc+ /Fc°) and/or cobal-tocene/cobalticenium ion represented optimal potential reference materials for nonaqueous studies. On the basis of their minimal charge (+1, 0) and their symmetry (treated as though they were roughly spherical), the potentials of these two redox couples are presumed to be relatively independent of solvent properties. 

A similar linear relationship between Cu(II/I) potential values and logarithmic Cu" L stabiKty constants may exist in non-aqueous solvents, but such a relationship has not been adequately established. Measurements conducted in our laboratories on a variety of polythioether complexes have shown that the Cu"L stability constants tend to increase by approximately 10 on going from water to acetonitrile, whereas the Cu L stability constants tend to decrease by a similar order of magnitude [54]. These values obviously reflect the preference of Cu (I I) to be solvated by water and the corresponding preference of Cu(I) to be coordinated to acetonitrile [111]. 

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