Two-state reactivity

The mechanism that has been developed for the conversion of methane to methanol by FeO+ is an excellent example of the synergy between experiment and theory. This mechanism includes two key concepts concerted reaction involving the critical [HO—Fe—CH3] insertion intermediate and two-state reactivity. The reaction proceeds as follows electrostatic interaction between FeO+ and methane produces the [OFe- GHJ entrance channel complex. 

Filatov, M., Shaik, S., 1998b, Theoretical Investigation of Two-State-Reactivity Pathways of H-H Activation by FeO+ Addition-Elimination, Rebound , and Oxene-Insertion Mechanisms , J. Phys. Chem. A, 102, 3835. 

Shaik, S., Danovich, D., Fiedler, A., Schroder, D., Schwarz, H., 1995, Two-State Reactivity in Organometallic Gas-Phase Ion Chemistry , Helv. Chim. Act., 78, 1393. 

Shaik, S., Filatov, M., Schroder, D. et al. (1998) Electronic structure makes a difference Cytochrome P-450 mediated hydroxylations of hydrocarbons as a two-state reactivity paradigm, Chem. Eur. J., 4, 193. 

Since the two-spin state forms can lead to different products, the products obtained will be a mixture that reflects the initial fractionation of the reaction between the two-spin states. The fractionation in turn is a reflection of the interplay and the probability of cross-over between the two-spin states (8). Thus, the two-state reactivity paradigm resolves the dilemma of whether a radical recombination or a direct insertion mechanism governs cytochrome P450-catalyzed hydroxylation actually they are both involved and the degree to which either is expressed depends upon the specific substrate hydroxylated and the specific enzyme. 

The detailed studies of this particular, rather simple reaction also formed the basis for the generaUzed concept of two-state reactivity [22], according to which thermal reactions are not necessarily confined to the spin... 

In subsequent research, it turned out that two-state reactivity can also provide a concept for the understanding of oxidation reactions way beyond the scope of gas-phase ion chemistry and can actually resolve a number of existing mechanistic puzzles. In enzymatic oxidations involving cytochrome P450, for example, changes in spin multiplicity appear to act as a kind of mechanistic distributor for product formation [27-29], and in the case of manganese-catalyzed epoxidation reactions, two-state scenarios have been put forward to account for the experimentally observed stereoselectivities [30-32], Two-state reactivity is not restricted to oxidation reactions, and similar scenarios have been proposed for a number of other experimentally studied reactions of 3d metal compounds [33-37]. Moreover, two-state scenarios have recently also been involved in the chemistry of main group elements [38]. The concept of two-state reactivity developed from the four-atomic system FeO /H2... 

Thus, the overall reaction starting from the high-spin state for the Co atom and ending with the formation of Co(II)P can presumably be described as a two-state reactivity process. 

This reaction profile also illustrates one of the other important challenges in the study of transition metal systems, namely that the metal-containing active site often has several accessible spin states. Specifically in the case of Fe(IV)=0, the triplet, quintet, and septet spin states. Consequently, the reaction can, in principle, proceed on different electronic potential energy surfaces and it is necessary to test all possibilities when exploring a reaction surface. This has been labeled two-state reactivity and has been elaborated by Shaik, Schwarz, Schroder, and co-workers (36—40). In the case of TauD, the results show that the reaction is only feasible on the quintet surface, in agreement with earlier DFT studies (11,41 —45). 

Detailed electronic structure studies, including insights gained from ligand field theory (46), can be especially useful in interpreting the reaction profiles and understanding the reactivity and selectivity of these systems. The exploration of two-state reactivity and the value of detailed electronic structure analysis are illustrated by our studies of the H atom abstraction step catalyzed by TauD (23,47), which are presented here for each spin-state surface the hypothetical septet, the quintet, and the triplet. 

Harris, N., Cohen, S., Filatov, M., Ogliaro, F., and Shaik, S. (2000) Two-state reactivity in the rebound step of alkane hydroxylation by cytochrome P-450 origins of free radicals with finite lifetimes. Angew. Chem., Int. Ed. 39, 2003-2007. 

Based on DFT calculations, Shaik and coworkers proposed a two-state reactivity process. The doublet and quartet states of P450 Compound I (see Figure 17) have virtually identical reactivity but follow very different pathways. The low-spin doublet state leads to a substrate radical transition state with no barrier to the rebound step, whereas the high-spin quartet state generates a radical with a significant barrier to rebound. In this model, predominance of the low-spin pathway explains the apparently short ( 100 fs) radical lifetimes in some radical clock experiments, while the high-spin pathway accounts for the finite radical lifetimes in others. The calculations further suggested that the doublet... 

The two-state reactivity concept developed by Schroder et al.136 contributed to emphasize the importance of spin crossover phenomena in organometallic reactions ... 

The exact mechanistic details of oxygen insertion into the C-H bond are still the subject of intense discussion. One of the most popular proposals appears to be that of the so-called rebound mechanism , which proceeds by an initial hydrogen abstraction from the alkane (RH) by the active oxygen intermediate to form a radical R and a hydroxo-iron species as intermediates. The radical then rebounds on the hydroxy group and generates the enzyme-product species[29). Alternative proposals involve cationic intermediates1301 or two-state reactivity with multiple electromer species for epoxidations131. ... 

As seen already, Cpd I is a triradicaloid with singly occupied -ir, -ir and aj orbitals and, hence, has a virtually degenerate pair of ground states ( Ajy). As such, it is expected that at least these electronic states will participate in the reactions, and will lead thereby to two-state reactivity (TSR) In TSR, each state may produce its specific set of products with different rate-constants, regio- and stereoselectivities and lead thereby to apparently controversial information when viewed through the perspective of singlestate reactivity (SSR). It is our contention that TSR resolves much of the controversy that has typified the P450 field of reaction mechanism in recent years , and opens new horizons for reactivity studies. 

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