Reaction pathway bifurcated

Fig. 20 Reaction pathways in the reduction of methyl (a) and /-butyl chloride (b) by NO". , reactant and products , transition states. In (a) and (b), the full line is the mass-weighted IRC path from the reactant to the product states the dashed line is a ridge separating the Sn2 and ET valleys and the dotted-dashed line is the mass-weighted IRC path from the Sn2 product state to the ET product state (homolytic dissociation). The dotted line in (a) represents the col separating the reactant and the SN2 product valleys. The dotted line in (b) represents the steepest descent path from the bifurcation point, B, to the Sn2 product. In (a), B is the point of the col separating the reactant and the SN2 product valleys where the ridge separating the SN2 and ET valleys starts.

Dynamics effects, which were described in previous sections, on reaction pathways, concerted-stepwise mechanistic switching, and path bifurcation have in most cases been examined for isolate systems without medium effects. Since energy distribution among vibrational and rotational modes and moment of inertia of reacting subfragment are likely to be modified by environment, it is intriguing to carry out simulations in solution. The difference or similarity in the effect of dynamics in the gas phase and in solution may be clarified in the near future by using QM/MM-MD method. Such study would provide information that is comparable with solution experiment and help us to understand reaction mechanisms in solution. 

In reactions of mechanistic borderline, the reaction pathway may not follow the minimum energy path, but the reaction proceeds via unstable species on the PES. In other cases, the reacting system remains on the IRC but does not become trapped in the potential energy minimum. In some cases, intermediates are formed in reactions that should be concerted, whereas in other reactions a concerted TS gives an intermediate. Thus, the question of concerted versus stepwise appears too simple and the definition of concerted and stepwise reactions becomes unclear. In some reactions, the post-TS dynamics do not follow IRCs, and path bifurcation gives two types of products through a common TS. 

The saddle-node bifurcations discussed in Section 111. A play a crucial role in the dynamics of the molecules investigated, because the stable PO bom at the bifurcation follows the reaction pathway over a large energy range. Consequently, the quantum states that are scarred by this PO stretch further and further along the reaction pathway and can be considered as the precursors of the... 

Itoh, S. Yoshimura, N. Sato, M. Yamataka, H. Computational study on the reaction pathway of a-bromoacetophenones with hydroxide ion Possible path bifurcation in the addition/substitution mechanism, 7. Org. Chem. 2011, 76, 8294-8299. 

The pathway bifurcates at chorismate. Let us first follow the prephenate branch (Figure 24,17). A mutase converts chorismate into prephenate, the immediate precursor of the aromatic ring of phenylalanine and tyrosine. This fascinating conversion is a rare example of an electrocyclic reaction in biochemistry, mechanistically similar to the well-known Diels-Alder reaction from organic chemistry. Dehydration and decarboxylation yield phenylpyruvate. Alternatively, prephenate can be oxidatively decarboxylated to p-hydroxyphenylpyruvate. These a-ketoacids are then transaminated to form phenylalanine and tyrosine. 

Dubreuil, D., Cleophax, J., De Almeida, M. V., Verre-Sebrie, C., Liaigre, J., Vass, G., Gero, S. D. Stereoselective synthesis of 6-deoxy and 3,6-dideoxy-D-myoinositol precursors of deoxy myoinositol phosphate analogs from D-galactose. Tetrahedron 1997, 53,16747-16766. Paquette, L. A., Kinney, M. J., Dullweber, U. Practical Synthesis of Spirocyclic Bis-C,C-glycosides. Mechanistic Models in Explanation of Rearrangement Stereoselectivity and the Bifurcation of Reaction Pathways. J. Org. Chem. 1997, 62,1713-1722. 

In foods, we often have what may be called reaction cascades, i.e., a whole series of reactions, partly consecutive, partly parallel, with bifurcations and with more than one reaction pathway leading to the same product. Examples are nonenzymatic browning or Maillard reactions, as well as several changes occurring during heat treatment. Chain reactions may be involved as well, as in the formation of hydroperoxides during the autoxidation of fats ... 

From all these deductions the connectivities of chemical species and a reaction pathway can be inferred (fig. 6.7). G6P is transformed into F6P, with some reversibility in that step. F6P in turn is transformed irreversibly into F1,6BP, which subsequently produces two molecules of DHAP in a fast reaction that is close to equilibrium. At this point in the reaction pathway a bifurcation occurs into two branches, one leading to G3P the other to 3PG. NADH is involved as effector or substrate on the branch producing G3P, and as an inhibitor or substrate on the branch producing 3PG. From the... 

We discussed some aspects of the responses of chemical systems, linear or nonlinear, to perturbations on several earlier occasions. The first was the responses of the chemical species in a reaction mechanism (a network) in a nonequilibrium stable stationary state to a pulse in concentration of one species. We referred to this approach as the pulse method (see chapter 5 for theory and chapter 6 for experiments). Second, we studied the time series of the responses of concentrations to repeated random perturbations, the formulation of correlation functions from such measurements, and the construction of the correlation metric (see chapter 7 for theory and chapter 8 for experiments). Third, in the investigation of oscillatory chemical reactions we showed that the responses of a chemical system in a stable stationary state close to a Hopf bifurcation are related to the category of the oscillatory reaction and to the role of the essential species in the system (see chapter 11 for theory and experiments). In each of these cases the responses yield important information about the reaction pathway and the reaction mechanism. 

Adam and coworkers have characterized [Mn (salen)] complexes by ESI-MS/ MS [80]. The group proposed that cis and trans epoxide formation followed separate pathways, and the possibility that the reaction mixture had multiple, rapidly equilibrating oxidizing species, each of which preferentially followed one of the reaction pathways, could not be excluded. Herein, they suggested a bifurcation step in the catalytic cycle to account for the dependence of the diastereoselectivities on the oxygen source as depicted in Scheme 5.21 [80bj. 

Catalytic reactions involve a series of chemical transformations resulting from substrate-catalyst interactions, which taken together are referred to as the mechanism of the catalytic reaction. Frequently mentioned in textbooks and research papers alike as catalytic cycles, they should be more appropriately referred to as catalytic reaction networks comprising multiple bifurcation points and parallel reaction pathways. Detailed knowledge of the mechanism is a prerequisite for a rational approach in catalyst development, and a great deal of effort goes into their systematic investigation. 

Katori T, Itoh S, Sato M, Yamataka H (2010) Reaction pathways and possible path bifurcation for the Schmidt reaction. J Am Chem Soc 132(10) 3413-3422. doi 10.1021/ja908899u... 

The bifurcation of the electron pathways is aided by the mobility of the catalytic domain of the Rieske protein. Three positional states of the catalytic domain of the Rieske protein have been observed in different crystal forms of the 6ci complex (Fig. 8b see Section III,B,5) (41, 42). In each single positional state, the Rieske protein is unable to perform all electron transfer reactions occuring during turnover ... 

In the ethyl and isopropyl cases, the steepest descent pathway still connects the Sn2-TS to the SN2 products but the formation of ET products along the bifurcation in the indirect ET pathway is expected to increase. These trends are likely to be at the origin of the stereochemistry of the reaction of the anion radical of anthracene with optically active 2-octyl halides recalled at the beginning of this section. 

Besides the two most well-known cases, the local bifurcations of the saddle-node and Hopf type, biochemical systems may show a variety of transitions between qualitatively different dynamic behavior [13, 17, 293, 294, 297 301]. Transitions between different regimes, induced by variation of kinetic parameters, are usually depicted in a bifurcation diagram. Within the chemical literature, a substantial number of articles seek to identify the possible bifurcation of a chemical system. Two prominent frameworks are Chemical Reaction Network Theory (CRNT), developed mainly by M. Feinberg [79, 80], and Stoichiometric Network Analysis (SNA), developed by B. L. Clarke [81 83]. An analysis of the (local) bifurcations of metabolic networks, as determinants of the dynamic behavior of metabolic states, constitutes the main topic of Section VIII. In addition to the scenarios discussed above, more complicated quasiperiodic or chaotic dynamics is sometimes reported for models of metabolic pathways [302 304]. However, apart from few special cases, the possible relevance of such complicated dynamics is, at best, unclear. Quite on the contrary, at least for central metabolism, we observe a striking absence of complicated dynamic phenomena. To what extent this might be an inherent feature of (bio)chemical systems, or brought about by evolutionary adaption, will be briefly discussed in Section IX. 

Building on the bifurcated pathway, developed to enable the selective synthesis of thiazoles or imidazoles (Scheme 73), Baxendale et al. (2005) subsequently demonstrated the synthesis of a HIV-1 RTI analog 255 using the same reaction methodology. 

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