Transition state mapping

When the solvent itself is the nucleophile X, then the transition state map has to be modified since there is now no diffusive encounter of the solvent and the species RY the solvent is already there. The diagram for a solvolysis reaction is shown in Fig. 3. The great difference between Fig. 1 and Fig. 3 is that in the former there can be no merging between the geometry of the SN1... 

Fig. 3 Transition state map for a solvolysis reaction, where the solvent, S, is already close to RY. The transition state for the SN1 route may be either in the breaking of the bond RY or at D, the diffusion away of Y. The latter case is the reverse of the Ritchie systems...

Fig. 4 Transition state map for the Sneen and Larsen mechanism showing both a solvolysis reaction (upper half) and a nucleophilic attack by X (lower half). At ordinary concentrations of X (< 1 m) transition states are unlikely to be found near (X, R+, Y). The transition state is so borderline that the extra nucleophilic assistance provided by X, compared to S, will not compensate for the free energy required for the association of X with RY. However, borderline transition states can be found for the solvolysis reaction since there is no association step...

Transition state mapping with multiple kinetie isotope elfeets has been carried out for a number of nucleoside hydrolases and phosphorylases. Intrinsic effects are given in Table 5.2 for structures of substrates, see Figures 3.14 and 5.31. 

As a final example, we compare potential maps of the reactants, transition state, and prodncts for an Sn2 reaction. Cl + CHsBr —> CICH3 + Br . The reactant and prodnct maps show negatively charged chloride and bromide ions, respectively therefore, this reaction canses electron density to shift from one atom to another. The transition state map is distinctive in that it shows partial negative charges on both Cl and Br, that is, the negative charge is delocalized over Cl and Br in the transition state. 

Two models for determining PEDs for dissociation along repulsive potentials are discussed here. The impulsive model is a very crude classical model whose major virtue is its simplicity. A more sophisticated model is the transition-state mapping model. Finally, we mention the use of classical trajectories in determining PEDs. 

HyperChem offers a Reaction Map facility under the Setup menu. This is needed for the synchronous transit method to match reactants and products, and depending on X (a parameter having values between 0 and 1, determining how far away from reactants structures a transition structure can be expected) will connect atoms in reactants and products and give an estimated or expected transition structure. This procedure can also be used if the eigenvector following method is later chosen for a transition state search method, i.e., if you just want to get an estimate of the transition state geometry. 

Examine atomic charges and the electrostatic potentit map for the lower-energy transition state. Which atom appear to be most electron rich in each Is the negativ charge concentrated on a single atom in the transition stat or delocalized Add this charge information (either or 5- ) to the molecular structure for the transition stat which you drew previously. 

Backside attack may be favored for electrostatic reasons. Examine electrostatic potential maps fox bromide + methyl bromide frontside attack and bromide + methyl bromide backside attack, transition states involving frontside and backside attack of Br (the nucleophile) onto CHsBr, respectively. Which atoms in the transition states are most electron-rich Which trajectory better minimizes electrostatic repulsion ... 

What other factors might be responsible for difference in activation energies Compare atomic charges anc electrostatic potential maps for the Sn2 transition states Does the increase in steric crowding lead to enhanced o diminished charge delocalization Explain. How, if at all would this be expected to affect the energy barrier Why ... 

Examine the transition state for the hydride shift. Calculate the barrier from the more stable initial carbocation. Is the process more facile than typical thermal rearrangements of neutral molecules (.05 to. 08 au or approximately 30-50 kcal/mol) Is the barrier so small (<.02 au or approximately 12 kcal/mol) that it would be impossible to stop the rearrangement even at very low temperature Where is the positive charge in the transition state Examine atomic charges and the electrostatic potential map to tell. Is the name hydride shift appropriate If not, propose a more appropriate name. 

Some derivatives of triafulvene undergo rotation about the carbon-carbon double bond even at room temperature. Given that cis-trans isomerization about double bonds is normally very difficult (see Chapter 7, Problem 1), how would you rationalize this Examine the electrostatic potential map for perpendicular hexaphenyltriafulvene (the rotational transition state).Would polar solvents tend to lower or raise the rotation barrier Explain. 

Electrostatic potential map for transition state for Sn2 reaction of trimethylamine and methyl iodide shows negatively-charged regions (in red) and positively-charged regions (in blue). 

Calculate activation energies for Sn2 reactions of ammonia and trimethylamine with methyl iodide via transition states ammonia+methyl iodide and trimethyl-amine+methyl iodide, respectively. Is attack by ammonia or trimethylamine more facile Rationalize your observation by comparing electrostatic potential maps for the two transition states. Which transition state requires more charge separation Is this also the higher-energy transition state ... 

Use geometries, electrostatic potential maps and spin densities to help you draw Lewis structures for butanal radical cation, the transition state and product. Where is the positive charge and the unpaired electron in each Is the positive charge (the unpaired electron) more or less delocalized in the transition state than in the reactant In the product ... 

Compare electrostatic potential maps for the following Diels-Alder transition states cyclopentadiene+ethene, cyclopentadiene+acrylonitrile and cyclopentadiene+ tetracyanoethylene, with those of reactants cyclopentadiene, ethene, acrylonitrile and tetracyanoethylene. Are electrons transferred from diene to dienophile in the transition states (relative to reactants) or vice versa For which reaction is the transfer the greatest The least Quantify your conclusion by measuring the total charge on the diene and dienophile components in the three transition states. 

Compare atomic charges and electrostatic potential maps between reactants and transition state. Is there charge transfer from one of the reactants to the other (count the migrating hydrogen as part of propene) If so, what is the direction of the transfer Why (See also Chapter 21, Problem 3.)... 

Figure 11.4 The transition state of an Sjvj2 reaction has a planar arrangement of the carbon atom and the remaining three groups. Electrostatic poten tial maps show that negative charge (red) is delocalized in the transition state.

Matouschek, A., Kellis,J. T., Serrano, L., and Fersht, A. R. (1989). Mapping the transition-state and pathway of protein folding by protein engineering. Nature 340, 122-126. 

Fig. 16. Three dimensional conformational map of cyclohexane. The representation is analogous to that of Fig. 15 the third (vertical) coordinate is the potential energy. The given calculated potential energy differences (kcal mole-1) of the minima and transition states are drawn to scale. The interconnecting curves are drawn qualitatively they are merely meant to indicate the absence of intermediate further minima and maxima. See ref. 106 for details of analytical representations of conformational maps of cyclohexane...

The intrazeolite cations necessary to balance the negative charge on the framework aluminum atoms are poorly shielded and as a result high electric (electrostatic) fields on the order of 1-10 V/nm are found in their vicinity. The magnitudes of the electric fields can be calculated from measured effects on the vibrational frequencies or intensities of IR bands of small diatomics such as CO or N2.24 They can also be determined from difference electron density maps determined by X-ray diffraction methods.25 These high electric fields can dramatically influence the stabilities of transition states with significant charge separations. 

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