Global solvent effect

Studies on the reactions of small model radicals with monomers provide indirect support but do not prove the bootstrap effect.111 Krstina et ahL i showed that the reactivities of MMA and MAN model radicals towards MMA, S and VAc were independent of solvent. However, small but significant solvent effects on reactivity ratios are reported for MMA/VAc111 and MMA S 7 copolymerizations. For the model systems, where there is no polymer coil to solvate, there should be no bootstrap effect and reactivities are determined by the global monomer ratio [Ma0]/[Mb0].1j1... 

Despite the fact that solvent effects on enzyme enantioselectivity appear to resist our efforts to rationalize their outcome using commonly accepted solvent descriptors, the effects are certainly there. An impressive example is provided in a report on the successful resolution of ds/trans-( 1 R,5 R)-bicyclo[3.2.0]hept-6-ylidene-acetate ethyl esters, intermediates in the synthesis of GABA (y-aminobutyric acid) analogs, by the Pfizer Bio transformations and Global R D groups (Scheme 2.2) [136]. From a screening protocol, CaLB was identified as a reactive catalyst for the hydrolysis of the racemic mixture of / //-os lor enantiomers with approximately equal activity for the ds- and tmns-isomers and a rather modest (E = 2.7) preference for the /Z-(lR,5R)-enantiomers. Application of medium engineering resulted in a phenomenal increase in the enantioselectivity (addition of 40% acetone, E > 200), while the ds- and trans-isomers were still converted at an almost equal rate. 

Because of the ease with which molecular mechanics calculations may be obtained, there was early recognition that inclusion of solvation effects, particularly for biological molecules associated with water, was essential to describe experimentally observed structures and phenomena [32]. The solvent, usually an aqueous phase, has a fundamental influence on the structure, thermodynamics, and dynamics of proteins at both a global and local level [3/]. Inclusion of solvent effects in a simulation of bovine pancreatic trypsin inhibitor produced a time-averaged structure much more like that observed in high-resolution X-ray studies with smaller atomic amplitudes of vibration and a fewer number of incorrect hydrogen bonds [33], High-resolution proton NMR studies of protein hydration in aqueous... 

One of the main goals in physical organic chemistry is the systematic description of the influence of chemical substitution in the reactivity pattern of molecules.124 The major difficulty to achieve this objective is that substituent effects are experimentally assessed as global responses, and therefore steric and solvent effects may mask the intrinsic electronic contributions. Many detailed linear relationships between substituent groups and chemical properties have been developed to date.71014125 In many cases, such relationships can be expressed quantitatively, thereby providing useful clues for interpreting reaction mechanisms and to predict reaction rates and equilibria. 

To illustrate the solvent effect on the average structure of a protein, we describe results obtained from conventional molecular dynamics simulations with periodic boundary conditions.92,193 This method is well suited for a study of the global features of the structure for which other approaches, such as stochastic boundary simulation methods, would not be appropriate. We consider the bovine pancreatic trypsin inhibitor (BPTI) in solution and in a crystalline environment. A simulation was carried out for a period of 25 ps in the presence of a bath of about 2500 van der Waals particles with a radius and well depth corresponding to that of the oxygen atom in ST2 water.193 The crystal simulation made use of a static crystal environment arising from the surrounding protein molecules in the absence of solvent. These studies, which were the first application of simulation methods to determine the effect of the environment on a protein, used simplified representations of the surround-... 

In this chapter, we present different global and local reactivity descriptors vis-a-vis the associated electronic structure principles for analyzing structures, properties, reactivity, bonding, interactions, and dynamics in the contexts of various physicochemical processes such as molecular vibrations, internal rotations, chemical reactions, aromaticity, stability of isomers, ion-atom collisions, atom-filled interactions, solvent effect, etc. Global reactivity descriptors are presented in Section 2, whereas Section 3 provides their theoretical basis. Section 4 delineates the local reactivity descriptors. Electronic structure principles associated with electronegativity and hardness are given in Sections 5 and 6, respectively. Section 7 presents the reactivity... 

R. Balawender, B. Safi, P. Geerlings, Solvent Effects on the Global and Atomic DET-Based Reactivity Descriptors Using the Effective fragment Potential Model. Solvation of Ammonia,/. Phys. Chem. A, 2001, 105, 6703-6710. 

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