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>_a Values

The theoretical estimation of the dissociation constant, or p<i>K</i>_a, 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>_a 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>_a. We show for a series of organic acids that CPMD simulations in conjunction with metadynamics can provide reasonable estimates of p<i>K</i>_a 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>_a 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>_a values

Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating p<i>K</i>_a 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>_a 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>_a values with a mean relative error, with respect to experimental results, of 0.2 p<i>K</i>_a units

Ab Initio MD Simulations of the Brønsted Acidity of Glutathione in Aqueous Solutions: Predicting p<i>K</i>_a 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>_a 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>_a 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>_a 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>_a 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>_a values with a mean relative error, with respect to experimental results, of 0.2 p<i>K</i>_a units

Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating p<i>K</i>_a 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>_a 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>_a values with a mean relative error, with respect to experimental results, of 0.2 p<i>K</i>_a 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