MECHANISMS OF CHOSEN ENZYME REACTIONS - New Trends in Enzyme Catalysis and Biomimetic Chemical Reactions - page 106

Shaik and coworkers (Filatov et al., 1999; Ogliaro et al., 2000; Visser et al., 2001) the
ferryl-hydroxo species in the enzyme may also exist in two electromeric forms, FeIII
centered with a cation radical porphyrin and Fe V centered with a neutral porphyrin. The

spin state of the complex may be low (S= 1), intermediate (S = 2) and high (S = 3).
When porphyrin orbitals are involved in the substrate oxidizing process, closely lying
states and with different symmetry may be taken into consideration (Fig. 3.11). A
two-state reactivity (TSR) situation, which involves high-spin (HS) and low-spin (LS)
states, has been suggested. Orbital diagrams showing the HS and LS rebound processes
are presented in Fig. 3.11.
As one can see from the Figure 3.11, the “high-spin” pathway retains the values of
the system spin constant (S = 3/2) and is accompanied by an electron transfer from the
binding orbital to the orbital of iron involved in the formation of the with
the oxygen atom. Simultaneously, orbitals are filled. The excitation causes
the elongation of the Fe-S and Fe-O bond lengths and is manifested in the increase of the
energy barrier for the recombination process. In contrast, in the “low-spin” pathway, the
transition does not occur.
Along this pathway, two additional effects are expected: 1) an electron transfer from
the antibonding orbital to the porphyrin “hole” in the orbital, which
strengthens the C-O linkage in the three-electron transition state and 2) strengthening the
Fe-S bond as a result of interaction of the orbital with the ps(S) orbital and
stronger p-back bonding of thiolate to iron. As a result of all these effects, the
recombination between carbon-centered radicals and • OH radicals connected with iron
can run practically barrierlessly. The aforementioned model predicted the high kinetic
isotope effect for both TSR pathways and the dependence of the “radical clock” results
on the donor ability of substrates. The two-state reactivity suggesting multiple
electromer species has been also applied to the reaction of epoxidation of ethane in the
chytochrome P450 active site (de Visser et al., 2001b). Two reaction pathways were
considered: 1) addition of the Compound I- and Compound II-like species to the ethane
double bond with formation of a radical intermediate and 2) concerted addition of the
species oxygen atoms to the double bond.
Theoretical calculation of the kinetic isotope effect showed that for three systems in
which methoxyl and tertiary butoxyl radicals and porphyirin-Fe

I

) are involved
in the reaction of a hydrogen abstraction from methane and toluene (Ogliaro et al.,
2000). The approximate tunneling corrections were done. The calculation indicates large
(8-15) for the reactions of alkoxy radicals and less

0 (Por-Fe 0

(6-9) for the high- and

low-spin pathways of Por-Fe . It is significant that the values were found to be

similar for the high-spin patway implicating formation of a long-living substrate radical
and for the low-spin pathway with a short-living radical.

0