Steric and Electrostatic Effects

The Lewis-type (L) contribution is considered the easy part of chemical wavefunction analysis, because it corresponds closely to the elementary Lewis structure model of freshman chemistry. Nevertheless, controversy often arises over the magnitude of steric or electrostatic effects that are associated with the Lewis model itself [i.e., distinct from the resonance-type effects contained in (NL)]. The NBO program offers useful tools for quantifying both steric and electrostatic interactions in terms of the space-filling (size and shape) and dielectric properties (charge, dipole moment, etc.) of the electron pair bonds and lone pairs that comprise the Lewis structure model. This chapter discusses the physical nature and numerical quantitation of these important chemical effects, which are often invoked in a hand-waving manner that reflects (and promotes) significant misconceptions. 

In principle, we are attempting to dissect classical-like steric exchange and electrostatic contributions to (L) firom an idealized uncrowded and 

Such dissection assumes, somewhat superficially, that steric and electrostatic (polarity) contributions belong exclusively to the dominant Lewis structure component E(L) in (5.8) [i.e., with no coupling terms to (NL)], consistent with the hoped-for interpretation for each contribution as a classical-like correction to an apolar ball and stick image of the starting Lewis structure. 

Discovering Chemistry With Natural Bond Orbitals, First Edition. Frank Weinhold and Clark R. Landis. 2012 John Wiley Sons, Inc. Published 2012 by John Wiley Sons, Inc. 

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Figure 3.51 also contains a dissection of the total energy ( totai) into Lewis (ii(L)) and non-Lewis (ElSL>) components. The localized Lewis component E" corresponds to more than 99.3% of the full electron density, and so incorporates steric and classical electrostatic effects in nearly exact fashion. Yet, as shown in Fig. 3.51, this component predicts local minima (at 70° and 180°) and maxima (at = 0° and 130 ) that are opposite to those of the full potential. In contrast, the non-Lewis component E (NL) exhibits a stronger torsional dependence that is able to cancel out the unphysical behavior predicted by (L), leading to minima correctly located near 0° and 120°. Thus, the hyperconjugative interactions incorporated in E(SL> clearly provide the surprising stabilization of 0° and 120° conformers that counter the expected steric and electrostatic effects contained in ElL>. 

In this way, efficient and consistent QM/MM Car-Parinello simulations of complex extended systems of several tens of thousands to several hundred thousand atoms can be performed in which the steric and electrostatic effects of the surrounding are taken explicitly into account. 

Reactions of nitrile oxides with 1,1-disubstituted alkenes afford products in which the oxygen atom of the nitrile oxide gets attached to the most crowded carbon atom of the dipolarophile. This high regioselectivity does not seem to depend on the type of substituent present on the alkene (142-152). Some of the results cannot be satisfactorily interpreted on the basis of FMO theory (149,151). Both steric and electrostatic effects often counteract each other and contribute to the regioselectivity actually observed. With trisubstituted alkenes, the orientation of cycloaddition is apparently dominated by this phenomenon. The preference is for the more substituted carbon atom to end up at the 5-position of the heterocyclic product (153,154). However, cases of opposite regiodifferentiation are also found, in particular with donor-substituted alkenes (42,155-157) (Scheme 6.21). 

The significance of these results for differences in reactivities of nucleophiles is that, despite the unfavorable relative equilibrium constants, Me2S is more reactive toward the quinone methide than chloride ion by a factor of nearly 3000. This mismatch of rate and equilibrium effects is summarized in Scheme 35. It must imply (a) that there is a relatively long partial bond between sulfur and carbon in the transition state so that the unfavorable steric and electrostatic effects are not developed and (b) that the favorable carbon-sulfur bonding interaction is well developed despite the long bonding distance. 

This so-called stereoelectronic factor operates to maximize or minimize orbital overlap, as the case requires, to obtain the most favorable energy. This was evident from the three- and four-center systems we have discussed by the VB and HMO methods. It was also implicit in favored anti-1,2-additions, 1,3-cyclizations (Fig. 23), fragmentations (e.g. (174)), etc. Here we have selected several reaction types to illustrate the principle. In this and other sections, we show that the tendency for reaction centers to be collinear or coplanar stems largely from orbital symmetry (bonding), but may also derive from steric and electrostatic effects, as well as PLM. 

The kinetics of such reactions are controlled by steric and electrostatic effects as well as by the pKas of all thiol groups involved, since the actual nucleophilic... 

The presence of a substituent at the adjacent position tends to alter the conformation due to hydrogen-bonding, steric, and electrostatic effects. Thus a C-3 substituent in thiophene-2-carbaldehyde 135 increases the stability of the 3, 0-fM-form. 

On the basis of the origin of molecular descriptors used in calculations, QSAR methods can be divided into three groups. One group is based on a relatively small number (usually many times smaller than the number of compounds in a data set) of physicochemical properties and parameters describing,for example, hydrophobic, steric, and electrostatic effects. Usually, these descriptors are used as independent variables in multiple regression approaches (18) Jn the literature, these methods are typically referred to as Hansch analysis (8).These types of descriptors and corresponding linear optimization methods used in traditional QSAR analyses are discussed extensively in the chapter by Celassie (7) and therefore is not reviewed here. 

One of the important differences between molecules in zeolite cages and species isolated in other matrices such as cyclodextrins [22], micelles [23], vesicles [24] and polymers [25] arises from the fact that the zeolite can be an active host and influence the structure and reactivity of the encapsulated molecules. The nature of the intra-zeolitic environment has been extensively studied and the influence of polarity, steric and electrostatic effects on encapsulated molecules is beginning to be well understood. 

In summary, it is dear that the zeolite is a novel host for the entrapment of molecules and the rigidity and the charged nature of the framework allow for steric and electrostatic effects on the encapsulated molecules. Isolation of entrapped molecules can also influence their reactivity. The interest in zeolites as hosts for electron-transfer reactions stems from a combination of properties, including... 

Azido-groups at C(3) influence the position of equilibrium at C(5) in 6-oxo steroids by a combination of steric and electrostatic effects.The electrostatic interaction between the polar groups at C(3) and C(6) tends to stabilize the axial relative to the equatorial azido-isomers. 

Finally, electronic, eventually steric, and electrostatic effects in the case of halogenobenzenes. The ESE° values of those compounds are always negative and may be very large for perhalogeno derivatives (ESE° of C6CU = -25.83 kcal mol1). 

On the other hand, sodium decyl sulfate, sodium dodecyl sulfate, and a sodium hexadecyl-octadecyl sulfate mixture result in equal PLMA MW for equal surfactant concentrations. These anionic surfactant concentrations are at or above their CMCs. That there is little or no influence on the aggregation number of the mixed micelles as the anionic surfactant tail varies from decyl to octadecyl is an indication of the importance of steric and electrostatic effects in the head-group region in these mixed micelles, at least for the 60 40 nonionic-anionic composition investigated here (34, 35). 

The cyclopropane ring in both epimers occupies the same position with respect to the departing group both epimers form a stable bisected cyclopropylcarbinyl cation. The exo endo rate ratio can reflect the contribution ratio of steric factors on the formation of the unsubstituted 2-benzonorbomenyl cation out of the two epimers. The hydrolysis of compounds 269 and 270 has resulted in an exo endo rate ratio of 12 and agrees fairly well with the previous value. A comparison of these data with the value of 15000 for the unsubstituted compounds clearly shows the steric and electrostatic effects to have a low value for secondary systems and in the absence of the ring 7i-participation the exo-isomer solvolyzes faster than its endo epimer only 2- to 10-fold. 

In a recent article Bingham questioned the existence of long range attractive interactions and cited the Kollman work and certain experimental cases as evidence against our proposal The experimental data which Bingham cites are consistent with our ideas. Thus, the geometries of the isomeric 1,2-difluoroethylenes and the conformational preference exhibited by diaminomaleonitrile have already been discussed in previous sections. The stmctural features of these molecules are understandable in terms of our concepts. The preferred conformation of the pentadienyl anion and that of cis-hexacyanobutadiene anion are probably dictated by conventional steric and electrostatic effects. On the other hand, acetylacetonate adopts a conformation where nonbonded attraction between the methyl groups can occur. 

Andersson and coworkers investigated the role of solvation, dispersion, and steric effects on the enantioselectivity. The authors results agree with the fact that gas-phase B3LYP calculations describe the drop in enantioselectivity of 2,3,4,5,6-pentafluoroacetophenone compared to acetophenone where steric and electrostatic effects are the only major effects, but the approximation is too crude to reproduce quantitatively the extent of enantioselection observed experimentally. In order to extract the isolated contributions of steric effects, the authors correlated the same energetic parameter with respect to an empirical steric parameter called STERIMOL B1 [132]. Their results showed that bulkier alkyl groups tend to decrease the enantioselectivity, which correlates well with the B1 parameter. Based on this observation, it seems that an intrinsic steric factor enhances or depresses the enantioselectivity in the reduction of acetophenone and other n-alkyl aryl ketones. However, a generalized rationalization of this effect is not trivial, and investigation of similar catalysts reveals only a small role for steric effects [105, 109]. 

A large series of purine analogues has been assayed to determine the mechanism for discrimination between right and wrong dNTP by the high fidelity polymerase Pol I from B.stearothermophilus has been reported, " " " whilst purine analogues have been used to probe the steric and electrostatic effects of incorporation by the translesion DNA polymerase Pol IV from S.solfataricus and human DNA Pol... 

The rule is not without exceptions, especially when several effects work in opposite directions. Furthermore, the underlying stereoelectronic bias can be masked or overruled by steric and electrostatic effects but it remains an important component in the overall picture. When (or if) the stereoelectronic component is amplified by bond stretching or breaking in the process of chemical reaction, the previously invisible stereoelectronic effect may come to the fore and define selectivity or reactivity in a chemical system. The richness and diversity of stereoelectronic interactions makes such situations not uncommon, leaving many opportunities for surprising and educational discoveries in the future. 

Steric and electrostatic effects on photoisomerization dynamics using QM/MM ab initio multiple spawning... 

Interactions of a chromophore with its local environment can be broadly decomposed into two categories steric and electrostatic effects. The precise interplay of these effects in biological systems has been the subject of a great deal of research and some controversy. Over the past 30 years, for instance, many broad mechanisms of protein activity have been ascribed to steric strain [15-17]. However, later theoretical studies have disputed many of these conclusions, finding that electrostatic interactions, in particular, play a more important role [6-14, 18-20]. Electrostatic interactions are increasingly recognized as an important factor in many realms of biochemistry [20-22]. 

The acid or base catalyzed hydrolysis of polyacrylamide (PAM) or Its partially hydrolyzed counterpart (HPAM) In aqueous solutions has been the subject of numerous studies. In part because this system provides an opportunity for evaluating the influence of polymer composition, and steric and electrostatic effects on the course of a simple organic reaction In a convenient solvent medium. 

Fig. 6 Mechanism for Coenzyme A attack on acylcarnitine. The carboxylate (triangle with negative charge) is folded back to allow the thiol to approach the carbonyl. We propose the CoA attacks from this side rather than the opposite (shown as dotted lines) because of steric and electrostatic effects (see text).

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