Solvent effects theoretical studies

Solvent effects can significantly influence the function and reactivity of organic molecules.1 Because of the complexity and size of the molecular system, it presents a great challenge in theoretical chemistry to accurately calculate the rates for complex reactions in solution. Although continuum solvation models that treat the solvent as a structureless medium with a characteristic dielectric constant have been successfully used for studying solvent effects,2,3 these methods do not provide detailed information on specific intermolecular interactions. An alternative approach is to use statistical mechanical Monte Carlo and molecular dynamics simulation to model solute-solvent interactions explicitly.4 8 In this article, we review a combined quantum mechanical and molecular mechanical (QM/MM) method that couples molecular orbital and valence bond theories, called the MOVB method, to determine the free energy reaction profiles, or potentials of mean force (PMF), for chemical reactions in solution. We apply the combined QM-MOVB/MM method to... 

The initial attempts to account theoretically for solvent effects were made in the 1930s [1], but the suitability of these models for understanding chemical events in condensed phases was limited by their intrinsic simplicity. Thus, it was not until the 1970s, when continuum models were implemented within the quantum mechanical framework [2], that an accurate theoretical representation of solvent effects became possible. The last decade of this century has witnessed the spectacular growth of this new area of research [3]. It is expected that in the next century continuum methods will be the most used approach for the study of solvent effects in chemical systems. 

Monte Carlo simulation techniques have been extensively used to study solvent effects on molecular properties and equilibrium points. Jorgensen has summarized theoretical work of condensed-phase effects on conformational equilibria [63]. 

This explanation has been considered for sometime, but apparently the first published version is presented in a theoretical attack on solvation in proton transfers by Kurz and Kurz [38]. The problem has been extensively attacked by Caldin and Mateo [11] by studying solvent effects on reaction 9. 

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

A theoretical, comparative study of the tautomerism of 56 five-membered heterocyclic rings announced in (76AHC(Sl)l) has appeared (81MI40402). The stabilities of the three forms for 5-pyrazolones, 5-pyrazolethiones and 5-aminopyrazoles have been calculated by a simple Hiickel o) iterative method. The relative energies and the substituent and solvent effects are in agreement with the experimental results. 

Having considered how solvents can affect the reactivities of molecules in solution, let us consider some of the special features that arise in the gas phase, where solvation effects are totally eliminated. Although the majority of organic preparative reactions and mechanistic studies have been conducted in solution, some important reactions are carried out in the gas phase. Also, because most theoretical calculations do not treat solvent effects, experimental data from the gas phase are the most appropriate basis for comparison with theoretical results. Frequently, quite different trends in substituent effects are seen when systems in the gas phase are compared to similar systems in solution. 

Most of the chemical reactions presented in this book have been studied in homogeneous solutions. This chapter presents a conceptual and theoretical framework for these processes. Some of the matters involve principles, such as diffusion-controlled rates and applications of TST to questions of solvent effects on reactivity. Others have practical components as well, especially those dealing with salt effects and kinetic isotope effects. 

The second group of studies tries to explain the solvent effects on enantioselectivity by means of the contribution of substrate solvation to the energetics of the reaction [38], For instance, a theoretical model based on the thermodynamics of substrate solvation was developed [39]. However, this model, based on the determination of the desolvated portion of the substrate transition state by molecular modeling and on the calculation of the activity coefficient by UNIFAC, gave contradictory results. In fact, it was successful in predicting solvent effects on the enantio- and prochiral selectivity of y-chymotrypsin with racemic 3-hydroxy-2-phenylpropionate and 2-substituted 1,3-propanediols [39], whereas it failed in the case of subtilisin and racemic sec-phenetyl alcohol and traws-sobrerol [40]. That substrate solvation by the solvent can contribute to enzyme enantioselectivity was also claimed in the case of subtilisin-catalyzed resolution of secondary alcohols [41]. 

Theoretically, the problem has been attacked by various approaches and on different levels. Simple derivations are connected with the theory of extrathermodynamic relationships and consider a single and simple mechanism of interaction to be a sufficient condition (2, 120). Alternative simple derivations depend on a plurality of mechanisms (4, 121, 122) or a complex mechanism of so called cooperative processes (113), or a particular form of temperature dependence (123). Fundamental studies in the framework of statistical mechanics have been done by Riietschi (96), Ritchie and Sager (124), and Thorn (125). Theories of more limited range of application have been advanced for heterogeneous catalysis (4, 5, 46-48, 122) and for solution enthalpies and entropies (126). However, most theories are concerned with reactions in the condensed phase (6, 127) and assume the controlling factors to be solvent effects (13, 21, 56, 109, 116, 128-130), hydrogen bonding (131), steric (13, 116, 132) and electrostatic (37, 133) effects, and the tunnel effect (4,... 

In almost all theoretical studies of AGf , it is postulated or tacitly understood that when an ion is transferred across the 0/W interface, it strips off solvated molecules completely, and hence the crystal ionic radius is usually employed for the calculation of AGfr°. Although Abraham and Liszi [17], in considering the transfer between mutually saturated solvents, were aware of the effects of hydration of ions in organic solvents in which water is quite soluble (e.g., 1-octanol, 1-pentanol, and methylisobutyl ketone), they concluded that in solvents such as NB andl,2-DCE, the solubility of water is rather small and most ions in the water-saturated solvent exist as unhydrated entities. However, even a water-immiscible organic solvent such as NB dissolves a considerable amount of water (e.g., ca. 170mM H2O in NB). In such a medium, hydrophilic ions such as Li, Na, Ca, Ba, CH, and Br are selectively solvated by water. This phenomenon has become apparent since at least 1968 by solvent extraction studies with the Karl-Fischer method [35 5]. Rais et al. [35] and Iwachido and coworkers [36-39] determined hydration numbers, i.e., the number of coextracted water molecules, for alkali and alkaline earth metal... 

Cao X, Tolbert RW, McHale JL, Edwards WD (1998) Theoretical study of solvent effects on the intramolecular charge transfer of a hemicyanine dye. J Phys Chem A 102(17) 2739-2748... 

Another aspect that has been theoretically studied109,124,129 is experimental evidence that Diels-Alder reactions are quite sensitive to solvent effects in aqueous media. Several models have been developed to account for the solvent in quantum chemical calculations. They may be divided into two large classes discrete models, where solvent molecules are explicitly considered and continuum models, where the solvent is represented by its macroscopic magnitudes. Within the first group noteworthy is the Monte Carlo study... 

Further evidence for the Aa11 mechanism was obtained from a solvent kinetic isotope study. The theoretical kinetic isotope effects for intermediates in the three reaction pathways as derived from fractionation factors are indicated in parentheses in Scheme 6.143,144 For the Aa11 mechanism (pathway (iii)) a solvent KIE (/ch2o A d2o) between 0.48 and 0.33 is predicted while both bimolecular processes (pathways (i) and (ii)) would have greater values of between 0.48 and 0.69. Acid-catalysed hydrolysis of ethylene oxide derivatives and acetals, which follow an A1 mechanism, display KIEs in the region of 0.5 or less while normal acid-catalysed ester hydrolyses (AAc2 mechanism) have values between 0.6 and 0.7.145,146... 

A theoretical study at a HF/3-21G level of stationary structures in view of modeling the kinetic and thermodynamic controls by solvent effects was carried out by Andres and coworkers [294], The reaction mechanism for the addition of azide anion to methyl 2,3-dideaoxy-2,3-epimino-oeL-eiythrofuranoside, methyl 2,3-anhydro-a-L-ciythrofuranoside and methyl 2,3-anhydro-P-L-eiythrofuranoside were investigated. The reaction mechanism presents alternative pathways (with two saddle points of index 1) which act in a kinetically competitive way. The results indicate that the inclusion of solvent effects changes the order of stability of products and saddle points. From the structural point of view, the solvent affects the energy of the saddles but not their geometric parameters. Other stationary points geometries are also stable. 

Tortonda, F. R., Pascual-Ahuir, J. L., Silla, E. and Tunon, I. Solvent effects on the thermodynamics and kinetics of the proton transfer between hydronium ions and ammonia. A Theoretical study using the continuum and the discrete models, J. Phys. Chem., 99 (1995), 12525-12531... 

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