7 research outputs found
Dissociation Constants of Weak Acids from ab Initio Molecular Dynamics Using Metadynamics: Influence of the Inductive Effect and Hydrogen Bonding on p<i>K</i><sub>a</sub> Values
The theoretical estimation of the
dissociation constant, or p<i>K</i><sub>a</sub>, of weak
acids continues to be a challenging
field. Here, we show that ab initio Car–Parrinello molecular
dynamics simulations in conjunction with metadynamics calculations
of the free-energy profile of the dissociation reaction provide reasonable
estimates of the p<i>K</i><sub>a</sub> value. Water molecules,
sufficient to complete the three hydration shells surrounding the
acid molecule, were included explicitly in the computation procedure.
The free-energy profiles exhibit two distinct minima corresponding
to the dissociated and neutral states of the acid, and the difference
in their values provides the estimate for p<i>K</i><sub>a</sub>. We show for a series of organic acids that CPMD simulations
in conjunction with metadynamics can provide reasonable estimates
of p<i>K</i><sub>a</sub> values. The acids investigated
were aliphatic carboxylic acids, chlorine-substituted carboxylic acids, <i>cis-</i> and <i>trans-</i>butenedioic acid, and the
isomers of hydroxybenzoic acid. These systems were chosen to highlight
that the procedure could correctly account for the influence of the
inductive effect as well as hydrogen bonding on p<i>K</i><sub>a</sub> values of weak organic acids. In both situations, the
CPMD metadynamics procedure faithfully reproduces the experimentally
observed trend and the magnitudes of the p<i>K</i><sub>a</sub> values
Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating p<i>K</i><sub>a</sub> Values from Metadynamics Sampling
Changes in the protonation and deprotonation
of amino acid residues
in proteins play a key role in many biological processes and pathways.
Here, we report calculations of the free-energy profile for the protonation–deprotonation
reaction of the 20 canonical α amino acids in aqueous solutions
using ab initio Car–Parrinello molecular dynamics simulations
coupled with metadynamics sampling. We show here that the calculated
change in free energy of the dissociation reaction provides estimates
of the multiple p<i>K</i><sub>a</sub> values of the amino
acids that are in good agreement with experiment. We use the bond-length-dependent
number of the protons coordinated to the hydroxyl oxygen of the carboxylic
and the amine groups as the collective variables to explore the free-energy
profiles of the Bronsted acid–base chemistry of amino acids
in aqueous solutions. We ensure that the amino acid undergoing dissociation
is solvated by at least three hydrations shells with all water molecules
included in the simulations. The method works equally well for amino
acids with neutral, acidic and basic side chains and provides estimates
of the multiple p<i>K</i><sub>a</sub> values with a mean
relative error, with respect to experimental results, of 0.2 p<i>K</i><sub>a</sub> units
Ab Initio MD Simulations of the Brønsted Acidity of Glutathione in Aqueous Solutions: Predicting p<i>K</i><sub>a</sub> Shifts of the Cysteine Residue
The tripeptide glutathione (GSH)
is one of the most abundant peptides
and the major repository for nonprotein sulfur in both animal and
plant cells. It plays a critical role in intracellular oxidative stress
management by the reversible formation of glutathione disulfide with
the thiol–disulfide pair acting as a redox buffer. The state
of charge of the ionizable groups of GSH can influence the redox couple,
and hence the p<i>K</i><sub>a</sub> value of the cysteine
residue of GSH is critical to its functioning. Here we report ab initio
Car–Parrinello molecular dynamics simulations of glutathione
solvated by 200 water molecules, all of which are considered in the
simulation. We show that the free-energy landscape for the protonation–deprotonation
reaction of the cysteine residue of GSH computed using metadynamics
sampling provides accurate estimates of the p<i>K</i><sub>a</sub> and correctly predicts the shift in the dissociation constant
values as compared with the isolated cysteine amino acid
Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating p<i>K</i><sub>a</sub> Values from Metadynamics Sampling
Changes in the protonation and deprotonation
of amino acid residues
in proteins play a key role in many biological processes and pathways.
Here, we report calculations of the free-energy profile for the protonation–deprotonation
reaction of the 20 canonical α amino acids in aqueous solutions
using ab initio Car–Parrinello molecular dynamics simulations
coupled with metadynamics sampling. We show here that the calculated
change in free energy of the dissociation reaction provides estimates
of the multiple p<i>K</i><sub>a</sub> values of the amino
acids that are in good agreement with experiment. We use the bond-length-dependent
number of the protons coordinated to the hydroxyl oxygen of the carboxylic
and the amine groups as the collective variables to explore the free-energy
profiles of the Bronsted acid–base chemistry of amino acids
in aqueous solutions. We ensure that the amino acid undergoing dissociation
is solvated by at least three hydrations shells with all water molecules
included in the simulations. The method works equally well for amino
acids with neutral, acidic and basic side chains and provides estimates
of the multiple p<i>K</i><sub>a</sub> values with a mean
relative error, with respect to experimental results, of 0.2 p<i>K</i><sub>a</sub> units
Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating p<i>K</i><sub>a</sub> Values from Metadynamics Sampling
Changes in the protonation and deprotonation
of amino acid residues
in proteins play a key role in many biological processes and pathways.
Here, we report calculations of the free-energy profile for the protonation–deprotonation
reaction of the 20 canonical α amino acids in aqueous solutions
using ab initio Car–Parrinello molecular dynamics simulations
coupled with metadynamics sampling. We show here that the calculated
change in free energy of the dissociation reaction provides estimates
of the multiple p<i>K</i><sub>a</sub> values of the amino
acids that are in good agreement with experiment. We use the bond-length-dependent
number of the protons coordinated to the hydroxyl oxygen of the carboxylic
and the amine groups as the collective variables to explore the free-energy
profiles of the Bronsted acid–base chemistry of amino acids
in aqueous solutions. We ensure that the amino acid undergoing dissociation
is solvated by at least three hydrations shells with all water molecules
included in the simulations. The method works equally well for amino
acids with neutral, acidic and basic side chains and provides estimates
of the multiple p<i>K</i><sub>a</sub> values with a mean
relative error, with respect to experimental results, of 0.2 p<i>K</i><sub>a</sub> units
Charge-Transfer-Driven Inclusion of Neutral TCNQ Molecules in the Galleries of a Layered Double Hydroxide: An Experimental and Computational Study
The layered double hydroxides (LDH) or anionic clays
are an important
class of ion-exchange materials. They consist of positively charged
brucite-like inorganic sheets with charge-compensating exchangeable
anions in the interlamellar space. Here we show how neutral TCNQ (7,7,8,8-tetracyanoquinodimethane)
molecules can be included within the galleries of an LDH. To do so,
we exploit the fact that TCNQ is a good electron acceptor that forms
donor–acceptor complexes with a variety of donors. The electron
donor aniline was intercalated into a Mg–Al LDH as <i>p</i>-aminobenzoate (AB) ions by a conventional ion-exchange
reaction. We show here that neutral TCNQ molecules may be driven into
the galleries of the layered solid by charge-transfer complex formation
with the intercalated <i>p</i>-aminobenzoate anions. We
use diffraction and spectroscopic measurements in combination with
molecular dynamics simulations and quantum chemical calculations to
establish the nature of interactions and arrangement of the charge-transfer
complex within the galleries of the layered double hydroxide. Electrostatic
interactions between the TCNQ molecules and the anchored AB ions,
subsequent to charge transfer, are the driving force for the inclusion
of TCNQ molecules in the galleries of the LDH
Fluorescent Porous Organic Frameworks Containing Molecular Rotors for Size-Selective Recognition
Fluorescent porous materials have
been under intensive investigation
recently, because of their wide applications in molecular recognition
and chemical sensing. However, it is a great challenge to achieve
size selectivity and sensing linearity for molecular recognition.
Herein, we report a series of porous organic frameworks (POFs) containing
flexible tetraphenylethylene (TPE) moieties as molecular rotors with
responsive fluorescent behavior. These fluorescent POFs exhibit size-selective
turn-on fluorescence for the effective chemical sensing of volatile
organic compounds (VOCs), which can be attributed to the different
degrees of motion restriction of flexible TPE rotors by various VOCs,
leading to the partially freezing of rotors in more fluorescent conformations.
Significantly, a linear aggregation-induced emission (AIE) relationship
is observed between the fluorescent POFs and the VOCs over a wide
range of concentrations, which is highly beneficial for quantitative
sensing applications. The gas-phase detection of arene vapors using
POFs is also proven with unprecedentedly high sensitivity, selectively,
and recyclability. The mechanism of responsive fluorescence in POFs
is further investigated using molecular simulations and density functional
theory (DFT) calculations