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Z. Fu and J. Chen
molecules greatly expedited the rearrangement reaction in the physiological environment by lowering the barrier to 5.6 kcal/mol. By comparing the activation barriers
for the rate-limiting steps in the two pathways, it can be concluded that the phenolic
H-abstraction and hydroxyl rebound pathway were responsible for dihydroxylation
of PBDEs catalyzed by Compound I. These results support the absence of epoxide
hydrolase in in vitro observation [45]. For different HO-PBDE congeners (6-HOBDE-15, -47, -153), the rate-limiting hydroxyl rebound proceeds preferably on the
phenyl carbons ortho and para to the phenol, leading to the formation of catecholor hydroquinone-like di-HO-BDEs, which are in line with the identified structures
in the experiment.
PBDDs can have different sources in the environment, e.g., pyrolysis of PBDEs,
photochemical transformation of HO-PBDEs, free radical oxidation of HO-PBDEs
in the atmosphere, and biochemical oxidative coupling of bromophenols mediated
by marine organisms (e.g., sponge and red algae) [46]. Molecular mechanisms for
several cases, e.g., PBDD evolution from PBDEs pyrolysis and hydroxyl radical
(HO·)-initiated oxidation of HO-PBDEs, have been elucidated based on previous
DFT calculations [47, 48]. Though perceived as feasible, these mechanisms clearly
possess certain prerequisites; e.g., the direct dissociation of an ortho Br or H atom in
PBDE pyrolysis requires a tremendous amount of energy; the HO·-initiated oxidation
of HO-PBDEs involves the participation of multiple HO· species; the photolysis of
HO-PBDEs to yield PBDD is based on the existence of excited triplet states for
the reactants. It is therefore obvious that the inaccessibility of these prerequisites
precludes the viability of the aforementioned mechanisms for PBDD evolution in
P450 enzymatic reactions.
Structurally, only ortho-hydroxylated PBDEs can potentially be transformed into
PBDDs. Using 6-HO-BDE-47 as an example, two conventional pathways were proposed [42], including: (a) phenolic H-abstraction and successive O–C cyclization
of 6-HO-BDE-47 to form PBDD; (b) a secondary hydroxylation of 6-HO-BDE47 yields 6,6
-di-HO-BDE-47, which then dehydrates to PBDD. The calculated
results reveal that the O–C cyclization step has a high activation barrier and the
resultant PBDD radical requires multiple assisted water molecules to fulfill the Hrearrangement, which is tentatively inviable in the enzymatic environment. In pathway (b), hydroxylation of 6-HO-BDE-47 possesses a barrier approximate to PBDEs
hydroxylation, indicating that the dihydroxylation is viable if the substrate is properly orientated. However, the dehydration of 6,6
-di-HO-BDE-47 to PBDD is highly
energy-demanding; thus, this pathway can also be ruled out.
As indicated in the previous studies, bromophenols can be photo-transformed
into HO-PBDEs [49], following a scheme of aryl radical coupling. Specifically,
bromophenols are firstly converted to phenoxyl radicals that possess electronically
three resonance structures, i.e., one O-centered phenoxyl radical, two C-centered
radicals ortho and para to the phenoxyl. Coupling of the O-centered phenoxyl radical
with the C-centered radicals leads to the formation of HO-PBDEs products. Inspired
by the radical coupling scheme of the phenoxyl, it is anticipated that only heterocyclic
di-HO-BDEs with –OH substituted on phenyl carbons ortho and meta to the ether
bond can serve as precursors for PBDD.
Z. Fu and J. Chen
molecules greatly expedited the rearrangement reaction in the physiological environment by lowering the barrier to 5.6 kcal/mol. By comparing the activation barriers
for the rate-limiting steps in the two pathways, it can be concluded that the phenolic
H-abstraction and hydroxyl rebound pathway were responsible for dihydroxylation
of PBDEs catalyzed by Compound I. These results support the absence of epoxide
hydrolase in in vitro observation [45]. For different HO-PBDE congeners (6-HOBDE-15, -47, -153), the rate-limiting hydroxyl rebound proceeds preferably on the
phenyl carbons ortho and para to the phenol, leading to the formation of catecholor hydroquinone-like di-HO-BDEs, which are in line with the identified structures
in the experiment.
PBDDs can have different sources in the environment, e.g., pyrolysis of PBDEs,
photochemical transformation of HO-PBDEs, free radical oxidation of HO-PBDEs
in the atmosphere, and biochemical oxidative coupling of bromophenols mediated
by marine organisms (e.g., sponge and red algae) [46]. Molecular mechanisms for
several cases, e.g., PBDD evolution from PBDEs pyrolysis and hydroxyl radical
(HO·)-initiated oxidation of HO-PBDEs, have been elucidated based on previous
DFT calculations [47, 48]. Though perceived as feasible, these mechanisms clearly
possess certain prerequisites; e.g., the direct dissociation of an ortho Br or H atom in
PBDE pyrolysis requires a tremendous amount of energy; the HO·-initiated oxidation
of HO-PBDEs involves the participation of multiple HO· species; the photolysis of
HO-PBDEs to yield PBDD is based on the existence of excited triplet states for
the reactants. It is therefore obvious that the inaccessibility of these prerequisites
precludes the viability of the aforementioned mechanisms for PBDD evolution in
P450 enzymatic reactions.
Structurally, only ortho-hydroxylated PBDEs can potentially be transformed into
PBDDs. Using 6-HO-BDE-47 as an example, two conventional pathways were proposed [42], including: (a) phenolic H-abstraction and successive O–C cyclization
of 6-HO-BDE-47 to form PBDD; (b) a secondary hydroxylation of 6-HO-BDE47 yields 6,6
-di-HO-BDE-47, which then dehydrates to PBDD. The calculated
results reveal that the O–C cyclization step has a high activation barrier and the
resultant PBDD radical requires multiple assisted water molecules to fulfill the Hrearrangement, which is tentatively inviable in the enzymatic environment. In pathway (b), hydroxylation of 6-HO-BDE-47 possesses a barrier approximate to PBDEs
hydroxylation, indicating that the dihydroxylation is viable if the substrate is properly orientated. However, the dehydration of 6,6
-di-HO-BDE-47 to PBDD is highly
energy-demanding; thus, this pathway can also be ruled out.
As indicated in the previous studies, bromophenols can be photo-transformed
into HO-PBDEs [49], following a scheme of aryl radical coupling. Specifically,
bromophenols are firstly converted to phenoxyl radicals that possess electronically
three resonance structures, i.e., one O-centered phenoxyl radical, two C-centered
radicals ortho and para to the phenoxyl. Coupling of the O-centered phenoxyl radical
with the C-centered radicals leads to the formation of HO-PBDEs products. Inspired
by the radical coupling scheme of the phenoxyl, it is anticipated that only heterocyclic
di-HO-BDEs with –OH substituted on phenyl carbons ortho and meta to the ether
bond can serve as precursors for PBDD.