Molecular modeling for physical property prediction

Multiscale modeling is becoming the standard approach for process study in a broader framework that promotes computer aided integrated product and process design. In addition to usual purity requirements, end products must meet new constraints in terms of environmental impact, safety of goods and people, specific properties. This chapter adresses the use of molecular modeling tools for the prediction of physical property usefull for chemical engineering practice

Non-empirical Force-Field Development for Weakly-Bound Organic Molecules

This thesis pioneers the development of non-empirical anisotropic atom-atom force-fields for organic molecules, and their use as state-of-the-art intermolecular potentials for modelling the solid-state. The long-range electrostatic, polarization and dispersion terms have been derived directly from the molecular charge density, while the short-range terms are obtained through fitting to the symmetry-adapted perturbation theory (SAPT(DFT)) intermolecular interaction energies of a large number of different dimer configurations. This study aims to establish how far this approach, previously used for small molecules, could be applied to specialty molecules, and whether these potentials improve on the current empirical force-fields FIT and WILLIAMS01. The scaling of the underlying electronic structure calculations with system size means many adaptions have been made. This project aims to generate force-fields suitable for use in Crystal Structure Prediction (CSP) and for modelling possible polymorphs, particularly high-pressure polymorphs. By accurately modelling the repulsive wall of the potential energy surface, the high pressure/temperature conditions typically sampled by explosive materials could be studied reliably, as shown in a CSP study of pyridine using a non-empirical potential. This thesis also investigates the transferability of these potentials from the gas to condensed-phase, as well as the transferability and importance of the intermolecular interactions of flexible functional groups, in particular NO2 groups. The charge distribution was found to be strongly influenced by variations in the observed NO2 torsion angle and the conformation of the rest of the molecule. This conformation dependence coupled with the novelty of the methods and size of the molecules has made developing non-empirical models for flexible nitro-energetic materials very challenging. The thesis culminates in the development of a bespoke non-empirical force-field for rigid trinitrobenzene and its use in a CSP study

Thermodynamics of Surface Defects at the Aspirin/Water Interface

We present a simulation scheme to calculate defect formation free energies at a molecular crystal/water interface based on force-field molecular dynamics (MD) simulations. To this end we adopt and modify existing approaches to calculate binding free energies of biological ligand/receptor complexes to be applicable to common surface defects, such as step edges and kink sites. We obtain statistically accurate and reliable free energy values for the aspirin/water interface, which can be applied to estimate the distribution of defects using well-established thermodynamic relations. As a show case we calculate the free energy upon dissolving molecules from kink sites at the interface. This free energy can be related to the solubility concentration and we obtain solubility values in excellent agreement with experimental results.Comment: 12 pages, 5 figure

Gas adsorption in active carbons and the slit-pore model 1 : pure gas adsorption

We describe procedures based on the polydisperse independent ideal slit-pore model, Monte Carlo simulation and density functional theory (a 'slab-DFT') for predicting gas adsorption and adsorption heats in active carbons.A novel feature of this work is the calibration of gas-surface interactions to a high surface area carbon, rather than to a low surface area carbon as in all previous work. Our models are used to predict the adsorption of carbon dioxide, methane, nitrogen, and hydrogen up to 50 bar in several active carbons at a range of near-ambient temperatures based on an analysis of a single 293 K carbon dioxide adsorption isotherm. The results demonstrate that these models are useful for relatively simple gases at near-critical or supercritical temperatures

Gas adsorption in active carbons and the slit-pore model 2 : mixture adsorption prediction with DFT and IAST

We use a fast density functional theory (a 'slab-DFT') and the polydisperse independent ideal slit-pore model to predict gas mixture adsorption in active carbons. The DFT is parametrized by fitting to pure gas isotherms generated by Monte Carlo simulation of adsorption in model graphitic slit-pores. Accurate gas molecular models are used in our Monte Carlo simulations with gas-surface interactions calibrated to a high surface area carbon, rather than a low surface area carbon as in all previous work of this type, as described in part 1 of this work (Sweatman, M. B.; Quirke, N. J. Phys. Chem. B 2005, 109, 10381). We predict the adsorption of binary mixtures of carbon dioxide, methane, and nitrogen on two active carbons up to about 30 bar at near-ambient temperatures. We compare two sets of results; one set obtained using only the pure carbon dioxide adsorption isotherm as input to our pore characterization process, and the other obtained using both pure gas isotherms as input. We also compare these results with ideal adsorbed solution theory (IAST). We find that our methods are at least as accurate as IAST for these relatively simple gas mixtures and have the advantage of much greater versatility. We expect similar results for other active carbons and further performance gains for less ideal mixtures

How Water's Properties Are Encoded in Its Molecular Structure and Energies.

How are water's material properties encoded within the structure of the water molecule? This is pertinent to understanding Earth's living systems, its materials, its geochemistry and geophysics, and a broad spectrum of its industrial chemistry. Water has distinctive liquid and solid properties: It is highly cohesive. It has volumetric anomalies-water's solid (ice) floats on its liquid; pressure can melt the solid rather than freezing the liquid; heating can shrink the liquid. It has more solid phases than other materials. Its supercooled liquid has divergent thermodynamic response functions. Its glassy state is neither fragile nor strong. Its component ions-hydroxide and protons-diffuse much faster than other ions. Aqueous solvation of ions or oils entails large entropies and heat capacities. We review how these properties are encoded within water's molecular structure and energies, as understood from theories, simulations, and experiments. Like simpler liquids, water molecules are nearly spherical and interact with each other through van der Waals forces. Unlike simpler liquids, water's orientation-dependent hydrogen bonding leads to open tetrahedral cage-like structuring that contributes to its remarkable volumetric and thermal properties

From dimers to the solid-state: Distributed intermolecular force-fields for pyridine

A.A. thanks A.W.E. financial support through the EngDoc studentship from M3S Centre for Doctoral Training (EPSRC Grant No. EP/G036675/1). General computational infrastructure used is developed under No. EPSRC EP/K039229/1

Competition of hydrophobic and Coulombic interactions between nano-sized solutes

The solvation of charged, nanometer-sized spherical solutes in water, and the effective, solvent-induced force between two such solutes are investigated by constant temperature and pressure Molecular Dynamics simulations of model solutes carrying various charge patterns. The results for neutral solutes agree well with earlier findings, and with predictions of simple macroscopic considerations: substantial hydrophobic attraction may be traced back to strong depletion (``drying'') of the solvent between the solutes. This hydrophobic attraction is strongly reduced when the solutes are uniformly charged, and the total force becomes repulsive at sufficiently high charge; there is a significant asymmetry between anionic and cationic solute pairs, the latter experiencing a lesser hydrophobic attraction. The situation becomes more complex when the solutes carry discrete (rather than uniform) charge patterns. Due to antagonistic effects of the resulting hydrophilic and hydrophobic ``patches'' on the solvent molecules, water is once more significantly depleted around the solutes, and the effective interaction reverts to being mainly attractive, despite the direct electrostatic repulsion between solutes. Examination of a highly coarse-grained configurational probability density shows that the relative orientation of the two solutes is very different in explicit solvent, compared to the prediction of the crude implicit solvent representation. The present study strongly suggests that a realistic modeling of the charge distribution on the surface of globular proteins, as well as the molecular treatment of water are essential prerequisites for any reliable study of protein aggregation.Comment: 20 pages, 25 figure

Molecular Force Fields with Gradient-Domain Machine Learning: Construction and Application to Dynamics of Small Molecules with Coupled Cluster Forces

We present the construction of molecular force fields for small molecules (less than 25 atoms) using the recently developed symmetrized gradient-domain machine learning (sGDML) approach [Chmiela et al., Nat. Commun. 9, 3887 (2018); Sci. Adv. 3, e1603015 (2017)]. This approach is able to accurately reconstruct complex high-dimensional potential-energy surfaces from just a few 100s of molecular conformations extracted from ab initio molecular dynamics trajectories. The data efficiency of the sGDML approach implies that atomic forces for these conformations can be computed with high-level wavefunction-based approaches, such as the "gold standard" CCSD(T) method. We demonstrate that the flexible nature of the sGDML model recovers local and non-local electronic interactions (e.g. H-bonding, proton transfer, lone pairs, changes in hybridization states, steric repulsion and $n\to\pi^*$ interactions) without imposing any restriction on the nature of interatomic potentials. The analysis of sGDML molecular dynamics trajectories yields new qualitative insights into dynamics and spectroscopy of small molecules close to spectroscopic accuracy