7 research outputs found
QM/MM Study of the Formation of the Dioxetanone Ring in Fireflies through a Superoxide Ion
The
bioluminescence emission from fireflies is an astounding tool
to mark and view cells. However, the bioluminescent mechanism is not
completely deciphered, limiting the comprehension of key processes.
We use a theoretical approach to study for the first time the arrival
of a dioxygen molecule inside the fireflies protein and one path of
the formation of the dioxetanone ring, the high-energy intermediate
precursor of the bioluminescence. To describe this reaction step,
a joint approach combining classical molecular dynamics (MD) simulations
and hybrid quantum mechanics/molecular mechanics (QM/MM) calculations
is used. The formation of the dioxetanone ring has been studied for
both singlet and triplet states with the help of MS-CASPT2 calculations.
We also emphasize the role played by the proteinic environment in
the formation of the dioxetanone ring. The results obtained shed some
light on an important reaction step and give new insights concerning
the bioluminescence in fireflies
DataSheet1_Modeling Chemical Reactions by QM/MM Calculations: The Case of the Tautomerization in Fireflies Bioluminescent Systems.PDF
<p>In less than half a century, the hybrid QM/MM method has become one of the most used technique to model molecules embedded in a complex environment. A well-known application of the QM/MM method is for biological systems. Nowadays, one can understand how enzymatic reactions work or compute spectroscopic properties, like the wavelength of emission. Here, we have tackled the issue of modeling chemical reactions inside proteins. We have studied a bioluminescent system, fireflies, and deciphered if a keto-enol tautomerization is possible inside the protein. The two tautomers are candidates to be the emissive molecule of the bioluminescence but no outcome has been reached. One hypothesis is to consider a possible keto-enol tautomerization to treat this issue, as it has been already observed in water. A joint approach combining extensive MD simulations as well as computation of key intermediates like TS using QM/MM calculations is presented in this publication. We also emphasize the procedure and difficulties met during this approach in order to give a guide for this kind of chemical reactions using QM/MM methods.</p
Photostability Mechanisms in Human γB-Crystallin: Role of the Tyrosine Corner Unveiled by Quantum Mechanics and Hybrid Quantum Mechanics/Molecular Mechanics Methodologies
The tyrosine corner is proposed as a featured element
to enhance
photostability in human γB-crystallin when exposed to UV irradiation.
Different ultrafast processes were studied by multiconfigurational
quantum chemistry coupled to molecular mechanics: photoinduced singlet–singlet
energy, electron and proton transfer, as well as population and evolution
of triplet states. The minimum energy paths indicate two possible
UV photoinduced events: forward–backward proton-coupled electron transfer providing to the system a mechanism for ultrafast internal
conversion, and energy transfer, leading to fluorescence or phosphorescence.
The obtained results are in agreement with the available experimental
data, being in line with the proposed photoinduced processes for the
different tyrosine environments within γB-crystallin
Hybrid QM/MM Simulations of the Obelin Bioluminescence and Fluorescence Reveal an Unexpected Light Emitter
Obelia longissima, a tiny hydrozoan
living in temperate and cold seas, features the Obelin photoprotein,
which emits blue light. The Obelin bioluminescence and the Ca<sup>2+</sup>-discharged Obelin fluorescence spectra show multimodal characteristics
that
are currently interpreted by the concomitant participation of several
light emitters. Up to now, the coelenteramide luminophore is thought
to exist in different protonation states, one of them engaged in an
ion-pair with the nearby residue, His22. Using hybrid quantum mechanics/molecular
mechanics (QM/MM) calculations, we demonstrate that such an ion-pair
cannot exist as a stable light emitter. However, when His22 electric
neutrality is maintained by means of another proton transfer, the
phenolate state of coelenteramide exhibits emission properties in
agreement with experiment. Finally, an alternative nonradiative decay
pathway, involving the formation of a diradical excited state, is
postulated for the first time
Chemiluminescence of Coelenterazine and Fluorescence of Coelenteramide: A Systematic Theoretical Study
A systematic investigation of the structural and spectroscopic
properties of coelenteramide has been performed at the TD-CAM-B3LYP/6-31+G(d,p)
level of theory, including various fluorescence and chemiluminescence
states. The influence of geometric conformations, solvent polarity,
protonation state, and the covalent character of the O–H bond
of the hydroxyphenyl moiety were carefully studied. Striking differences
in geometries and electronic structures among the states responsible
for light emission were characterized. All fluorescence states can
be described as a limited charge transfer process for a planar amide
moiety. However, the chemiluminescence state is characterized by a
much larger charge transfer that takes place over a longer distance.
Moreover, the chemiluminescent coelenteramide structure exhibits an
amide moiety that is no longer planar, in agreement with recent, more
accurate <i>ab initio</i> results [Roca-Sanjuán et
al. <i>J. Chem. Theory Comput.</i> <b>2011</b>, <i>7</i>, 4060]. Because the chemiluminescence state appears to
be completely dark, a new mechanism is tentatively introduced for
this process
The Synthesis of a Corrole Analogue of Aquacobalamin (Vitamin B<sub>12a</sub>) and Its Ligand Substitution Reactions
The
synthesis of a Co(III) corrole, [10-(2-[[4-(1<i>H</i>-imidazol-1-ylmethyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]cobalt(III),
DPTC-Co, bearing a tail motif terminating in an imidazole ligand that
coordinates Co(III), is described. The corrole therefore places Co(III)
in a similar environment to that in aquacobalamin (vitamin B<sub>12a</sub>, H<sub>2</sub>OCbl<sup>+</sup>) but with a different equatorial
ligand. In coordinating solvents, DPTC-Co is a mixture of five- and
six-coordinate species, with a solvent molecule occupying the axial
coordination site trans to the proximal imidazole ligand. In an 80:20
MeOH/H<sub>2</sub>O solution, allowed to age for about 1 h, the predominant
species is the six-coordinate aqua species [H<sub>2</sub>O–DPTC-Co].
It is monomeric at least up to concentrations of 60 μM. The
coordinated H<sub>2</sub>O has a p<i>K</i><sub>a</sub> =
9.76(6). Under the same conditions H<sub>2</sub>OCbl<sup>+</sup> has
a p<i>K</i><sub>a</sub> = 7.40(2). Equilibrium constants
for the substitution of coordinated H<sub>2</sub>O by exogenous ligands
are reported as log <i>K</i> values for neutral N-, P-,
and S-donor ligands, and CN<sup>–</sup>, NO<sub>2</sub><sup>–</sup>, N<sub>3</sub><sup>–</sup>, SCN<sup>–</sup>, I<sup>–</sup>, and Cys in 80:20 MeOH/H<sub>2</sub>O solution
at low ionic strength. The log <i>K</i> values for [H<sub>2</sub>O–DPTC-Co] correlate reasonably well with those for
H<sub>2</sub>OCbl<sup>+</sup>; therefore, Co(III) displays a similar
behavior toward these ligands irrespective of whether the equatorial
ligand is a corrole or a corrin. Pyridine is an exception; it is poorly
coordinated by H<sub>2</sub>OCbl<sup>+</sup> because of the sterically
hindered coordination site of the corrin. With few exceptions, [H<sub>2</sub>O–DPTC-Co] has a higher affinity for neutral ligands
than H<sub>2</sub>OCbl<sup>+</sup>, but the converse is true for anionic
ligands. Density functional theory (DFT) models (BP86/TZVP) show that
the Co–ligand bonds tend to be longer in corrin than in corrole
complexes, explaining the higher affinity of the latter for neutral
ligands. It is argued that the residual charge at the metal center
(+2 in corrin, 0 in corrole) increases the affinity of H<sub>2</sub>OCbl<sup>+</sup> for anionic ligands through an electrostatic attraction.
The topological properties of the electron density in the DFT-modeled
compounds are used to explore the nature of the bonding between the
metal and the ligands
Simulation and Analysis of the Spectroscopic Properties of Oxyluciferin and Its Analogues in Water
Firefly
bioluminescence is a quite efficient process largely used
for numerous applications. However, some fundamental photochemical
properties of the light emitter are still to be analyzed. Indeed,
the light emitter, oxyluciferin, can be in six different forms due
to interexchange reactions. In this work, we present the simulation
of the absorption and emission spectra of the possible natural oxyluciferin
forms in water and some of their analogues considering both the solvent/oxyluciferin
interactions and the dynamical effects by using MD simulations and
QM/MM methods. On the one hand, the absorption band shapes have been
rationalized by analyzing the electronic nature of the transitions
involved. On the other hand, the simulated and experimental emission
spectra have been compared. In this case, an ultrafast excited state
proton transfer (ESPT) occurs in oxyluciferin and its analogues, which
impairs the detection of the emission from the protonated state by
steady-state fluorescence spectroscopy. Transient absorption spectroscopy
was used to evidence this ultrafast ESPT and rationalize the comparison
between simulated and experimental steady-state emission spectra.
Finally, this work shows the suitability of the studied oxyluciferin
analogues to mimic the corresponding natural forms in water solution,
as an elegant way to block the desired interexchange reactions allowing
the study of each oxyluciferin form separately