Enrico Riccardi

Rational Surface Design for Molecular Dynamics Simulations of Porous Polymer Adsorbent Media

The construction and use of nonflat agarose surfaces in a simulation box, together with the employment of criteria for the immobilization of a set of dextran polymer chains on the nonflat agarose surfaces whose mathematical physics is compatible with that of the criteria used for the immobilization of the same set of dextran polymer chains on flat agarose surfaces, are shown to generate, through the use of molecular dynamics simulations whose simulation box has linear dimensions along the lateral directions that are the same when flat and nonflat agarose surfaces are used, dextran porous polymer structures whose pore sizes at the outermost surface and in the vicinity of the outermost surface of the porous medium can be controlled by an indirect manner through the variation of the parameters that characterize the nonflat surface. The use of a nonflat surface for the generation of desired large pores requires only a small or modest increase in the number of solvent molecules in the simulation box, while the use of a flat surface for the construction of the same desired large pores requires significant increases in the size of the linear dimensions of the flat surface. This increases so substantially the number of solvent molecules that the computational loads become intractable. The results in this work show that through the use of nonflat surfaces porous dextran polymer layers having pores of desired sizes can be effectively constructed, and this approach could be used for the design and construction of polymer-based porous adsorbent media that could effectively facilitate the transport and adsorption of an adsorbate biomolecule of interest that must be separated from a mixture of components. A useful definition about the properties that a porous polymer structure must have in order to become, for an adsorbate biomolecule of interest of known molecular size, a useful adsorbent medium, is presented and is used to (1) evaluate the porous polymer structures generated through the employment of different nonflat surface models and (2) determine and select the nonflat surface model from a set of nonflat surface models that is effective in producing promising porous structures. Then a procedure is presented by which a set of porous polymer media is generated through the use of the selected nonflat surface model, and the desired porous structure from this set is determined and could be considered to be used for the transport and immobilization of the selected affinity groups/ligands and the subsequent transport and adsorption of the desired to be separated adsorbate.

Porous Polymer Adsorbent Media Constructed by Molecular Dynamics Modeling and Simulations: the Immobilization of Charged Ligands and Their Effect on Pore Structure and Local Nonelectroneutrality

A molecular dynamics modeling and simulation approach is presented and employed to construct porous dextran polymer ion-exchange adsorbent media. Both the activation step of the surface of the pores of the dextran polymer layer grafted on an agarose surface and the immobilization of charged ligands on the activated surface of the porous dextran polymer layer are considered. For the systems studied in this work, the activation step modifies slightly the pore structure of the base, nonactivated porous dextran polymer, while the immobilization of the ligands on the activated pore surface of the dextran layer changes significantly the pore structure of the activated dextran layer. The density distributions of the counterions and immobilized charged ligands along the direction of net transport in the adsorbent media constructed in this study are found to be nonuniform. The variables that affect the shape and magnitude of the density distributions of the counterions and immobilized charged ligands as well as the total number of charged ligands that can be immobilized on the activated porous dextran layer are identified and presented in this work. Furthermore, the data clearly show that there is local nonelectroneutrality in the porous dextran polymer ion-exchange adsorbent media, and this result has very important practical implications for the operation and performance of separation systems involving ion-exchange adsorbent media (e.g., ion-exchange chromatography systems). Also, the results of this work suggest approaches for (1) controlling the immobilization process of charged ligands and (2) constructing and studying the behavior of chromatographic polymeric monoliths and packed bed columns having a gradient of density of functionalities along the axis of the chromatographic polymeric monolith or packed bed column.

Ab Initio Molecular Dynamics Study on the Interactions between Carboxylate Ions and Metal Ions in Water.

The interaction between a carboxylate anion (deprotonated propanoic acid) and the divalent Mg(2+), Ca(2+), Sr(2+), Ba(2+) metal ions is studied via ab initio molecular dynamics. The main focus of the study is the selectivity of the carboxylate-metal ion interaction in aqueous solution. The interaction is modeled by explicitly accounting for the solvent molecules on a DFT level. The hydration energies of the metal ions along with their diffusion and mobility coefficients are determined and a trend correlated with their ionic radius is found. Subsequently, a series of 16 constrained molecular dynamics simulations for every ion is performed, and the interaction free energy is obtained from thermodynamic integration of the forces between the metal ion and the carboxylate ion. The results indicate that the magnesium ion interacts most strongly with the carboxylate, followed by calcium, strontium, and barium. Because the interaction free energy is not enough to explain the selectivity of the reaction observed experimentally, more detailed analysis is performed on the simulation trajectories to understand the steric changes in the reaction complex during dissociation. The solvent dynamics appear to play an important role during the dissociation of the complex and also in the observed selectivity behavior of the divalent ions.

Density Functional Theory Study on the Interactions of Metal Ions with Long Chain Deprotonated Carboxylic Acids.

In this work, interactions between carboxylate ions and calcium or sodium ions are investigated via density functional theory (DFT). Despite the ubiquitous presence of these interactions in natural and industrial chemical processes, few DFT studies on these systems exist in the literature. Special focus has been placed on determining the influence of the multibody interactions (with up to 4 carboxylates and one metal ion) on an effective pair-interaction potential, such as those used in molecular mechanics (MM). Specifically, DFT calculations are employed to quantify an effective pair-potential that implicitly includes multibody interactions to construct potential energy curves for carboxylate-metal ion pairs. The DFT calculated potential curves are compared to a widely used molecular mechanics force field (OPLS-AA). The calculations indicate that multibody effects do influence the energetic behavior of these ionic pairs and the extent of this influence is determined by a balance between (a) charge transfer from the carboxylate to the metal ions which stabilizes the complex and (b) repulsion between carboxylates, which destabilizes the complex. Additionally, the potential curves of the complexes with 1 and 2 carboxylates and one counterion have been examined to higher separation distance (20 Å) by the use of relaxed scan optimization and constrained density functional theory (CDFT). The results from the relaxed scan optimization indicate that near the equilibrium distance, the charge transfer between the metal ion and the deprotonated carboxylic acid group is significant and leads to non-negligible differences between the DFT and MM potential curves, especially for calcium. However, at longer separation distances the MM calculated interaction potential functions converge to those calculated with CDFT, effectively indicating the approximate domain of the separation distance coordinate where charge transfer between the ions is occurring.

A test on reactive force fields for the study of silica dimerization reactions.

We studied silica dimerization reactions in the gas and aqueous phase by density functional theory (DFT) and reactive force fields based on two parameterizations of ReaxFF. For each method (both ReaxFF force fields and DFT), we performed constrained geometry optimizations, which were subsequently evaluated in single point energy calculations using the other two methods. Standard fitting procedures typically compare the force field energies and geometries with those from quantum mechanical data after a geometry optimization. The initial configurations for the force field optimization are usually the minimum energy structures of the ab initio database. Hence, the ab initio method dictates which structures are being examined and force field parameters are being adjusted in order to minimize the differences with the ab initio data. As a result, this approach will not exclude the possibility that the force field predicts stable geometries or low transition states which are realistically very high in energy and, therefore, never considered by the ab initio method. Our analysis reveals the existence of such unphysical geometries even at unreactive conditions where the distance between the reactants is large. To test the effect of these discrepancies, we launched molecular dynamics simulations using DFT and ReaxFF and observed spurious reactions for both ReaxFF force fields. Our results suggest that the standard procedures for parameter fitting need to be improved by a mutual comparative method.

Modeling the construction of polymeric adsorbent media: Effects of counter-ions on ligand immobilization and pore structure

Molecular dynamics modeling and simulations are employed to study the effects of counter-ions on the dynamic spatial density distribution and total loading of immobilized ligands as well as on the pore structure of the resultant ion exchange chromatography adsorbent media. The results show that the porous adsorbent media formed by polymeric chain molecules involve transport mechanisms and steric resistances which cause the charged ligands and counter-ions not to follow stoichiometric distributions so that (i) a gradient in the local nonelectroneutrality occurs, (ii) non-uniform spatial density distributions of immobilized ligands and counter-ions are formed, and (iii) clouds of counter-ions outside the porous structure could be formed. The magnitude of these counter-ion effects depends on several characteristics associated with the size, structure, and valence of the counter-ions. Small spherical counter-ions with large valence encounter the least resistance to enter a porous structure and their effects result in the formation of small gradients in the local nonelectroneutrality, higher ligand loadings, and more uniform spatial density distributions of immobilized ligands, while the formation of exterior counter-ion clouds by these types of counter-ions is minimized. Counter-ions with lower valence charges, significantly larger sizes, and elongated shapes, encounter substantially greater steric resistances in entering a porous structure and lead to the formation of larger gradients in the local nonelectroneutrality, lower ligand loadings, and less uniform spatial density distributions of immobilized ligands, as well as substantial in size exterior counter-ion clouds. The effects of lower counter-ion valence on pore structure, local nonelectroneutrality, spatial ligand density distribution, and exterior counter-ion cloud formation are further enhanced by the increased size and structure of the counter-ion. Thus, the design, construction, and functionality of polymeric porous adsorbent media will significantly depend, for a given desirable ligand to be immobilized and represent the adsorption active sites, on the type of counter-ion that is used during the ligand immobilization process. Therefore, the molecular dynamics modeling and simulation approach presented in this work could contribute positively by representing an engineering science methodology to the design and construction of polymeric porous adsorbent media which could provide high intraparticle mass transfer and adsorption rates for the adsorbate biomolecules of interest which are desired to be separated by an adsorption process.

Structure and Orientation of Tetracarboxylic Acids at Oil–Water Interfaces

Fouling caused by tetracarboxylic acids in transport and separation process chains involving petroemulsions occurs when the interfacial concentration of tetraacids becomes large enough for calcium ions in the water phase to “crosslink” the adsorbed tetraacid molecules and form a precipitate. At present, the structure and orientation of tetraacid molecules at oil–water interfaces, which influences the precipitation behavior, has not been studied in detail. In this work, molecular dynamics simulations of indigenous and synthetic tetracarboxylic acid compounds are presented to describe the structure and spatial orientation of tetraacid molecules at oil–water interfaces. Molecular distributions relative to the oil–water dividing surface along with the length and orientation angle distributions of the acidic arm groups are presented. The probability distributions determined here that describe the tetraacids at an oil–water interface can be employed to reconstruct the density of carboxylic acid groups at the oil–water interface. The interfacial carboxylic acid density can be employed to determine the fraction of adsorbed tetraacid molecules that are “crosslinked” with calcium ions based on the distances between carboxylic acid groups. The simulations presented also form a basis to calculate interfacial molecular areas and virial coefficients to employ in molecular mixed monolayer adsorption isotherms.

Fast Decorrelating Monte Carlo Moves for Efficient Path Sampling

Many relevant processes in chemistry, physics, and biology are rare events from a computational perspective as they take place beyond the accessible time scale of molecular dynamics (MD). Examples are chemical reactions, nucleation, and conformational changes of biomolecules. Path sampling is an approach to break this time scale limit via a Monte Carlo (MC) sampling of MD trajectories. Still, many trajectories are needed for accurately predicting rate constants. To improve the speed of convergence, we propose two new MC moves, stone skipping and web throwing. In these moves, trajectories are constructed via a sequence of subpaths obeying superdetailed balance. By a reweighting procedure, almost all paths can be accepted. Whereas the generation of a single trajectory becomes more expensive, the reduced correlation results in a significant speedup. For a study on DNA denaturation, the increase was found to be a factor 12.

PyRETIS: A well-done, medium-sized python library for rare events

Transition path sampling techniques are becoming common approaches in the study of rare events at the molecular scale. More efficient methods, such as transition interface sampling (TIS) and replica exchange transition interface sampling (RETIS), allow the investigation of rare events, for example, chemical reactions and structural/morphological transitions, in a reasonable computational time. Here, we present PyRETIS, a Python library for performing TIS and RETIS simulations. PyRETIS directs molecular dynamics (MD) simulations in order to sample rare events with unbiased dynamics. PyRETIS is designed to be easily interfaced with any molecular simulation package and in the present release, it has been interfaced with GROMACS and CP2K, for classical and ab initio MD simulations, respectively.

Aggregates of poly-functional amphiphilic molecules in water and oil phases

The solvation and aggregate formation of complex amphiphilic molecules such as tetra-acids in polar and nonpolar phases are studied via Molecular Dynamics simulations. The nonpolar core of tetra-acid molecules is found to be effectively impermeable for water molecules resulting in a low solubility in the polar solvent, while nonpolar solvent molecules sufficiently solvate the amphiphilic molecules considered, enabling an open conformation of their molecular structure. The rigidity of the core region of the tetra-acid molecules has been found to play a crucial role in their behavior in both polar and nonpolar phases. In the polar phase, simulations have shown that tetra-acids form micelle-like structures with a small aggregation number, confirming previous experimental work. The identification of a case of study in which micelle-like structures can form only with a small aggregation number enables the study via Molecular Dynamics of micelle-micelle interactions. Micelle stability and dispersion in the polar phase under different conditions can be therefore investigated. In the nonpolar phase, the preferential interactions between carboxyl groups, the affinity of the tetra-acids with the solvent molecules, and the structural characteristics of the central core moiety of the tetra-acids have been found to possibly induce a web like array, or network.