Solution phase association

The difference between gas phase and solution association can be best understood with the help of a thermodynamic cycle  

The free energy of association of A and B in aqueous solution at temperature T AGy(aq) is related to the solvation free energies of A(A(7t.so1v(A)), B(AGt-so1v(B)) and AB(4GySolv(AB)) and the gas phase free energy of association 4Gy(gas) by 

It is clear from Eqn. 4 how the solvent water dramatically changes the free energy of association of A with B from its value in the gas phase. For example, for A = Na and B = Cl, AGT(gas) is of the order of —400 to —600 kJ/mole. AGx(solv, A) and 

On the other hand, if A and B are non-polar molecules, their association is likely to be significantly more favorable in aqueous solution than in the gas phase, for reasons that are rather subtle. This hydrophobically driven association [14,15], which has stimulated much research, is due to the release of water molecules from A and B when the molecules associate and shows up mainly in the change in entropy upon association. This effect must be initially analyzed by examining thermodynamic data for the transfer of a hydrocarbon from a non-polar solvent or the gas phase to water. The dG(soln, A) for such a process is positive (unfavorable), despite the fact that for the process is either near zero or slightly negative (favorable). 

On the other hand 4S(soln, A) for such a process is very negative. Initially, one might expect d//(soln. A) to be positive because, by placing a hydrocarbon in water, one is replacing a strong attractive electrostatic water-water interaction with a less attractive (dispersion and polarization only) hydrocarbon-water interaction. They very negative d5 (soln. A) gives a clue. Computer simulations of such processes 

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Sections 27 15 through 27 17 describe the chemistry associated with the protection and deprotection of ammo and carboxyl functions along with methods for peptide bond formation The focus m those sections is on solution phase peptide synthesis Section 27 18 shows how these methods are adapted to solid phase synthesis... 

Since 1986, when the very first reports on the use of microwave heating to chemical transformations appeared [147,148], microwave-assisted synthesis has been shown to accelerate most solution-phase chemical reactions [24-27,32,35]. The first application of microwave irradiation for the acceleration of reaction rate of a substrate attached to a solid support (SPPS) was performed in 1992 [36]. Despite the promising results, microwave-assisted soHd-phase synthesis was not pursued following its initial appearance, most probably as a result of the lack of suitable instriunentation. Reproducing reaction conditions was nearly impossible because of the differences between domestic microwave ovens and the difficulties associated with temperature measurement. The technique became a Sleeping Beauty interest awoke almost a decade later with the publication of several microwave-assisted SPOS protocols [37,38,73,139,144]. There has been an extensive... 

While experiment and theory have made tremendous advances over the past few decades in elucidating the molecular processes and transformations that occur over ideal single-crystal surfaces, the application to aqueous phase catalytic systems has been quite limited owing to the challenges associated with following the stmcture and dynamics of the solution phase over metal substrates. Even in the case of a submersed ideal single-crystal surface, there are a number of important issues that have obscured our ability to elucidate the important surface intermediates and follow the elementary physicochemical surface processes. The ability to spectroscopically isolate and resolve reaction intermediates at the aqueous/metal interface has made it difficult to experimentally estabhsh the surface chemistry. In addition, theoretical advances and CPU limitations have restricted ab initio efforts to very small and idealized model systems. 

Furthermore, polymer-assisted solution-phase syntheses also show several advantages over Merrifield-type syntheses. Fxcept for some industrially employed heterogeneous catalysts the requirement of high loading capacities for the sohd supports is not necessarily of prime importance for immobilized catalysts. Because not every site needs to react, lower loadings are acceptable. The recovered catalyst is often available for immediate reuse. A discussion on immobilized catalysts should also include a brief listing of obstacles associated with their use, particular in comparison to their soluble analogs ... 

Solution-phase synthesis [5] often needs purification or clean-up procedures after each reaction step to remove excess reagent. These methods include scavenging, extractions and associated plate transfers. All these procedures cause the loss of the desired compound. Although the purity can be improved after treatment, the chemical yield is seriously compromised. In contrast, SPOS has a unique advantage in purifying bound compound without losing compound mass. However, if the reaction is not complete at each step, the side products will form on resin and they cannot be removed while bound to the resin. The final yield and purity wiU both suffer as a result. A 90% yield for a four-step synthesis wiU produce the final product in a disappointing 65% yield. 

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