An Active Site Tyr Residue Guides the Regioselectivity of Lysine Hydroxylation by Nonheme Iron Lysine-4-hydroxylase Enzymes through Proton-Coupled Electron Transfer
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(17), С. 11726 - 11739
Опубликована: Апрель 18, 2024
Lysine
dioxygenase
(KDO)
is
an
important
enzyme
in
human
physiology
involved
bioprocesses
that
trigger
collagen
cross-linking
and
blood
pressure
control.
There
are
several
KDOs
nature;
however,
little
known
about
the
factors
govern
regio-
stereoselectivity
of
these
enzymes.
To
understand
how
can
selectively
hydroxylate
their
substrate,
we
did
a
comprehensive
computational
study
into
mechanisms
features
4-lysine
dioxygenase.
In
particular,
selected
snapshot
from
MD
simulation
on
KDO5
created
large
QM
cluster
models
(A,
B,
C)
containing
297,
312,
407
atoms,
respectively.
The
largest
model
predicts
regioselectivity
matches
experimental
observation
with
rate-determining
hydrogen
atom
abstraction
C4–H
position,
followed
by
fast
OH
rebound
to
form
4-hydroxylysine
products.
calculations
show
C,
dipole
moment
positioned
along
bond
substrate
and,
therefore,
electrostatic
electric
field
perturbations
protein
assist
creating
hydroxylation
selectivity.
Furthermore,
active
site
Tyr233
residue
identified
reacts
through
proton-coupled
electron
transfer
akin
axial
Trp
cytochrome
c
peroxidase.
Thus,
upon
formation
iron(IV)-oxo
species
catalytic
cycle,
phenol
loses
proton
nearby
Asp179
residue,
while
at
same
time,
transferred
iron
create
iron(III)-oxo
species.
This
charged
tyrosyl
directs
guides
selectivity
C4-hydroxylation
substrate.
Язык: Английский
Concerted Proton Electron Transfer or Hydrogen Atom Transfer? An Unequivocal Strategy to Discriminate these Mechanisms in Model Systems
Physical Chemistry Chemical Physics,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
The
combination
of
intrinsic
bond
orbital
and
activation
strain
analysis
allows
the
correct
identification
rationalization
operative
mechanism
between
HAT
CPET,
while
singly
occupied
molecular
does
not
fit
in
this
picture.
Язык: Английский
Cyclization Through Dual C(sp3)−H Functionalization
Advanced Synthesis & Catalysis,
Год журнала:
2024,
Номер
366(17), С. 3542 - 3563
Опубликована: Июль 11, 2024
Abstract
C(
sp
3
)−H
functionalization
methods
have
been
widely
employed
in
many
organic
transformations
such
as
cyclization
reactions,
heterocycle
synthesis,
cross‐coupling
protocols,
and
photochemical
transformations.
Among
these
transformations,
reaction
through
offers
a
direct
route
to
convert
simple
linear
substrates
complex
products.
There
are
three
common
modes
of
utilizing
bonds
reactions
including
single,
double,
dual
functionalization.
As
the
most
challenging
mode,
refers
converting
two
separate
one
molecule
into
desired
C−Z
which
can
be
reactions.
Cyclization
via
classified
based
on
C−H
reactivities.
Therefore,
categorized
classes
types
activated‐activated,
activated‐unactivated,
unactivated‐unactivated
bonds.
Most
published
reports
for
involve
activated‐activated
However,
number
reported
papers
other
has
growing.
This
review
focuses
protocols
used
categorizes
Язык: Английский
14‐Membered Macrocyclic β‐Diiminato Gold(II) – A New Member for the Gold(II) Complex Family?
Chemistry - A European Journal,
Год журнала:
2024,
Номер
30(34)
Опубликована: Апрель 16, 2024
The
chemistry
of
molecular
gold
compounds
is
dominated
by
the
oxidation
states
+I
and
+III.
For
intermediate
state
+II
with
5d
Язык: Английский
Proton-Coupled Electron Transfer and Hydrogen Tunneling in Olive Oil Phenol Reactions
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(12), С. 6341 - 6341
Опубликована: Июнь 7, 2024
Olive
oil
phenols
are
recognized
as
molecules
with
numerous
positive
health
effects,
many
of
which
rely
on
their
antioxidative
activity,
i.e.,
the
ability
to
transfer
hydrogen
radicals.
Proton-coupled
electron
reactions
and
tunneling
ubiquitous
in
biological
systems.
Reactions
olive
phenols,
hydroxytyrosol,
tyrosol,
oleuropein,
oleacein,
oleocanthal,
homovanillyl
alcohol,
vanillin,
a
few
phenolic
acids
DPPH•
(2,2-diphenyl-1-picrylhydrazyl)
radical
1,4-dioxane:water
=
95:5
or
99:1
v/v
solvent
mixture
were
studied
through
an
experimental
kinetic
analysis
computational
chemistry
calculations.
The
highest
rate
constants
corresponding
activity
obtained
for
ortho-diphenols
oleacein.
experimentally
determined
isotope
effects
(KIEs)
caffeic
acid
16.0,
15.4,
16.7,
respectively.
Based
these
KIEs,
thermodynamic
activation
parameters,
intrinsic
bond
orbital
(IBO)
along
IRC
path
calculations,
we
propose
proton-coupled
mechanism.
average
local
ionization
energy
donor
Fukui
function
compounds
show
that
most
reactive
electron-donating
sites
associated
π
electrons
above
below
aromatic
ring,
support
IBO
proposed
PCET
reaction
Large
KIEs
isotopic
values
Arrhenius
pre-exponential
factor
AH/AD
0.6,
1.3,
0.3,
respectively,
reveal
involvement
process.
Язык: Английский