Energy-entropy prediction of octanol–water logP of SAMPL7 N-acyl sulfonamide bioisosters

From Springer Nature via Jisc Publications RouterHistory: received 2021-03-04, accepted 2021-06-17, registration 2021-06-18, pub-print 2021-07, pub-electronic 2021-07-10, online 2021-07-10Publication status: PublishedFunder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266; Grant(s): EP/L015218/1, EP/N025105/1Abstract: Partition coefficients quantify a molecule’s distribution between two immiscible liquid phases. While there are many methods to compute them, there is not yet a method based on the free energy of each system in terms of energy and entropy, where entropy depends on the probability distribution of all quantum states of the system. Here we test a method in this class called Energy Entropy Multiscale Cell Correlation (EE-MCC) for the calculation of octanol–water logP values for 22 N-acyl sulfonamides in the SAMPL7 Physical Properties Challenge (Statistical Assessment of the Modelling of Proteins and Ligands). EE-MCC logP values have a mean error of 1.8 logP units versus experiment and a standard error of the mean of 1.0 logP units for three separate calculations. These errors are primarily due to getting sufficiently converged energies to give accurate differences of large numbers, particularly for the large-molecule solvent octanol. However, this is also an issue for entropy, and approximations in the force field and MCC theory also contribute to the error. Unique to MCC is that it explains the entropy contributions over all the degrees of freedom of all molecules in the system. A gain in orientational entropy of water is the main favourable entropic contribution, supported by small gains in solute vibrational and orientational entropy but offset by unfavourable changes in the orientational entropy of octanol, the vibrational entropy of both solvents, and the positional and conformational entropy of the solute

Exploring kinetics and thermodynamics in fast-ion conductors and hydrogen-storage materials using ab-initio molecular dynamics

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2007.Includes bibliographical references (p. 173-190).We investigate the interplay between various kinetic processes and thermodynamic factors in three materials--silver iodide (AgI), cesium hydrogen sulfate (CsHSO4), and sodium alanate (NaAlH4)-using ab-initio molecular dynamics simulations. The time-averaged and instantaneous silver substructure in the fast-ion conductor AgI is analyzed, resulting in a set of ordering rules that govern the distribution of the mobile silvers in the first coordination shell surrounding an iodine. We find evidence of an independent phase transition of the silver ions which drives the structural transformation to the high-mobility phase. A thermodynamic motivation for the existence of fast-ion conduction is suggested in terms of an entropic stabilization associated with the decrease in silver mobility upon melting. We also find a unique chemical signature for the fourth nearest-neighbor silver to an iodine. This fourth silver is weakly bound and relatively unconstrained, and we isolate it as the predominant agent in the diffusion process. Next, a detailed statistical analysis is performed on simulations of the fuel-cell electrolyte CsHSO4 to isolate the interplay between the dynamics of the O-H chemical bonds, the ... H hydrogen bonds, and the SO4 tetrahedra in promoting proton conduction. A high reversal rate limits the apparent success rate of the otherwise rapid chemical-bond dynamics, which are dominated by the Grotthuss mechanism of proton transfer. Rapid angular hops in concert with small reorientations of the SO4 tetrahedra constitute a new dominant mechanism for hydrogen-bond network reorganization. The SO4 dynamics are found to control the attempt rate of chemical-bond dynamical events and the success rate of hydrogen-bond dynamical events; this enables a novel interpretation of the diminished CsHSO4/CsDSO4 isotope effect.(cont.) Two distinct timescales for SO4 reorientation events are linked to different diffusion mechanisms along different crystal directions. Finally, a graph-theoretic analysis of the hydrogen-bond network topology demonstrates an increased likelihood for diffusion in connectivity configurations favoring linear network chains over closed rings. We have discovered and characterized a new phase (-y) of the hydrogen-storage material NaAlH4 that is energetically close to the known ground state. The manifestation of this phase is kinetically inhibited in the bulk but is favored in a (001) surface slab above 225 K. The transition involves first activating the surface AlH4 rotational modes. This is followed by a lattice expansion perpendicular to the slab and a shear of successive lattice planes. A possible connection between 7-NaAlH4 and the dehydrogenation product Na3aAH6 is suggested. We also show that hydrogen transport in NaAlH4 can be treated independently from the observed phase transition, and that the presence of certain point defects can enable transport of hydrogen via a structural diffusion mechanism. A link between long-range hydrogen migration and the rotational mobility of A1Hz groups is demonstrated.by Brandon C. Wood.Ph.D

NOVEL APPROACHES TOWARDS THE OPTIMISATION OF METAL NANOPARTICLE BASED CATALYSTS

The main goal of my Ph.D. project has been the development of novel approaches for the optimisation of supported noble metal nanoparticles, which are well-established catalysts for liquid phase oxidation reactions. The partial oxidation of oxygen-containing compounds (alcohols, aldehydes, carbohydrates) is a profitable process, the corresponding products (aldehydes, ketones, epoxides, carboxylic acids, esters and lactones) being key intermediates in the synthesis of fine chemicals and commodity. In the perspective of biomass valorisation these processes are recently assuming an increasing relevance. Indeed, many biomass-derived platform molecules contain oxidizable functional groups and therefore can be easily converted in value-added compounds by oxidation. The oxidation of organic compounds can be carried out in the gas phase through continuous-flow reactors using air or oxygen as oxidant. Nevertheless, these processes require high temperatures and their application is restricted to volatile and thermally stable reactants and products. From this point of view working in the liquid phase seems to be more suitable for energy saving, since milder conditions can be adopted, compared to gas phase. The main drawback of the current industrial technologies for liquid phase oxidation processes is the use of stoichiometric inorganic oxidants, such as dichromate and permanganate, which are toxic and corrosive. The employment of these reactants therefore entails environmental issues (production of high volumes of toxic wastes), handling difficulties and reactor maintenance problems (corrosion, plating out on reactor walls). According to green chemistry principles, the replacement of toxic stoichiometric processes with catalytic and environmentally benign routes is then heartily recommended. Noble metal unsupported and supported nanoparticles have been extensively explored as heterogeneous catalysts for the liquid phase oxidation of oxygen-containing organic compounds in the presence of molecular oxygen, air or hydrogen peroxide as sole oxidants. In particular platinum group metals (Pt, Pd, Ru, Rh) have shown to be able to oxidize alcohols to the corresponding carbonyl or carboxylic compounds under mild conditions (close to ambient conditions) . However, these systems rapidly undergo deactivation by over-oxidation or metal dissolution into solution (leaching). Otherwise, nano-sized gold exhibits a remarkable activity and it possesses unexpected advantages over platinum group metals in terms of selectivity control and resistance to deactivation. The strongest limitation in using gold NPs as catalysts is the compulsory use of a basic environment . Recent studies showed that alloying gold with a second metal (platinum or palladium) is possible to obtain effective catalytic systems in terms of activity, durability and selectivity even in the absence of a base. Besides the use of bi- or multimetallic systems (e.g. AuPt or AuPd), the catalytic performances are strongly affected by many factors, including the addition of promoters (e.g. Bi), the influence of support and the preparation route. A simultaneous fine tuning of all these parameters is not a straightforward task, therefore the design of catalysts is a still challenging research target. A multidisciplinary approach seems to be the better strategy for facing this challenge. In this view, the development of a catalyst should be the result of the combination of three main aspects (preparation, characterization, testing), which can be investigated on different levels (from atomic to macroscopic level) and with several tools (from in situ characterization to computational modelling). During my Ph.D. project a similar approach has been adopted. In the first section (Chapter 2) my research focused on the possible strategies for tuning the selectivity in base-free glycerol oxidation, a reaction of industrial interest, which has attracted significant attention in the last decades, due to the need for the valorisation of this bio-platform molecule. The reaction pathway of glycerol oxidation is complex and leads to a large number of valuable organic compounds (glyceric acid, tartronic acid, dihydroxyacetone, lactic acid, etc.). Therefore directing the reaction to the desired target product represents a key-point. Two main features were investigated in the detail: the role of support and the addition of promoters. It has been observed that the support greatly affected the selectivity of AuPt based catalysts in base-free glycerol oxidation. In particular, using an acidic support, H-Mordenite, an enhancement in the selectivity to C3 products (glyceric and tartronic acid) has been obtained.4a Also basic supports such as hydroxyapatite and MgO have been shown to be useful supports.4b In order to investigate more in the detail the effect of support acidity, I extended these studies to a series of supports with different acid-base properties, namely H-Mordenite, SiO2, MCM-41, sulfated ZrO2, Activated Carbon (AC X40S) as representative of acidic supports, and MgO and NiO as references for basic supports. Acidic surface properties of these materials have been full characterised by means of Infrared Spectroscopy and microcalorimetry, and their influence on the catalytic behaviour of alloyed AuPt nanoparticles was highlighted. An high selectivity to C3 compounds was observed, using acidic supports, glyceric acid and glyceraldehyde being the main products. Both these compounds are obtained by the oxidation of the primary hydroxyl function, on the other hand the main product of secondary hydroxyl group oxidation, dihydroxyacetone (DHA), is economically the most interesting oxidation product due to its use as tanning agent in cosmetic industries. In the literature it has been reported that the addition of Bi as promoter for Pt catalysts enhances the yield of DHA. On the other hand Bi-Pt catalysts suffer from heavy deactivation during reaction, due to the leaching of metals. On the basis of these considerations, we decided to modify AuPt and AuPd alloyed catalysts with Bi to investigate the effect of the addiction of this promoter, not only in terms of selectivity to DHA, but also for the durability of the catalyst. In the second part (Chapter 3) Operando Attenuated Total Reflectance Infrared (ATR-IR) spectroscopy and catalytic batch reactor experiments were performed in parallel to elucidate the different catalytic performance of Au, Pd, and AuPd supported on TiO2 and Al2O3 in the liquid-phase oxidation of benzyl alcohol. In particular the development of different surface species and the role of the protective agent (polyvinyl alcohol, PVA) in catalysts prepared by a sol immobilization route were examined. Finally, in the last part of the thesis (Chapter 4) a periodic Density Functional Theory (DFT) study of the adsorption and activation of ethanol on different surfaces (13 atom Au cluster, oxygenated 13 atom Au cluster, TiO2 rutile surface and Au ribbon on TiO2 surface) is proposed, in order to unravel the presence of preferential sites for the adsorption of alcohol on catalyst surfaces. Simulations were carried out using the plane wave basis set code VASP and the Perdew, Burke and Ernzerhof (PBE) functional

Understanding the Structure of Materials at the Intersection of Rationalisation, Prediction and Big Data

Theoretical materials science has a large and growing role to play in modern society thanks to its ability to deliver materials with new and interesting properties. The properties of any material are, on some level, a function of its internal structure. In this work we combine three important tools spanning the last 100 years of materials research, rationalisation, prediction and big data in an attempt to understand the factors that underpin the stability of ordered structures and to build an understanding of structure that is agnostic of a particular element or building block. We apply rationalisation to data mining of the Inorganic Crystal Structure Database, using various proposed structure descriptors to probe the factors affecting structure stability. Extensive prediction is performed on the Fe-Ni-Si system at inner earth core pressures to determine the phases most likely to be present, yielding a new, stable, Ni-Si structure. A new prediction technique for 2D grain boundaries is presented that doubles the size of system that can reasonably be studied at the ab initio level of theory. The structurally rich phosphorus and arsenic systems are investigated using structure prediction, producing new metastable structures. Finally, we use a simple model for particles that attract at long range and repel at short to probe all the possible binary structures over a wide range of stoichiometries. By carrying out prediction over a wide range of potential parameters we build a database of almost 20M entries. Contained within are a number of unreported structures including many in parts of parameter space that go beyond the periodic table in terms of size and bond energy ratios. Our work provides hints that these hypothetical structures could be realised in self assembling systems made up from constituents with tunable interactions opening the door to the possibility of new properties

Two decades of Martini:Better beads, broader scope

The Martini model, a coarse-grained force field for molecular dynamics simulations, has been around for nearly two decades. Originally developed for lipid-based systems by the groups of Marrink and Tieleman, the Martini model has over the years been extended as a community effort to the current level of a general-purpose force field. Apart from the obvious benefit of a reduction in computational cost, the popularity of the model is largely due to the systematic yet intuitive building-block approach that underlies the model, as well as the open nature of the development and its continuous validation. The easy implementation in the widely used Gromacs software suite has also been instrumental. Since its conception in 2002, the Martini model underwent a gradual refinement of the bead interactions and a widening scope of applications. In this review, we look back at this development, culminating with the release of the Martini 3 version in 2021. The power of the model is illustrated with key examples of recent important findings in biological and material sciences enabled with Martini, as well as examples from areas where coarse-grained resolution is essential, namely high-throughput applications, systems with large complexity, and simulations approaching the scale of whole cells. This article is categorized under: Software > Molecular Modeling Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods Structure and Mechanism > Computational Materials Science Structure and Mechanism > Computational Biochemistry and Biophysics

A computational atomistic study of lithium transport in graphitic anode materials

In this dissertation, atomistic simulations of Lithium transport into and through graphite grain boundaries are studied. Graphite is a commonly used negative electrode (anode) material in Lithium-ion batteries yet Li diffusion shows high levels of variability in a material that has been in use for the last 25 years. Researchers have used both experiments and computations to prove such variable diffusion and have proposed numerous hypotheses toward explaining the differences. It is known that intralayer transport is most rapid; the purpose of this study is to address secondary mechanisms for diffusion and therefore, cell charging. Although clues have led to the importance of defects such as grain boundaries in battery anodes, there has not yet been an exhaustive study, either experimentally or computationally, that addresses their role. Grain boundaries have widely been studied in metallic systems, but the covalent nature of graphite creates a two-fold motivation for this study. Not only is transport addressed, but also the underlying GB structure that abets and impedes such motion. The aforementioned studies are performed using Molecular Dynamics with both as-written and modified interatomic potentials. Potential optimizations and modifications were performed on existing models to fit the needs of this work. Carbon-Carbon interactions are well described, but Lithium-Carbon and Lithium-Lithium potentials were optimized using ab initio and experimental data of the lithium-graphite and lithium-graphene systems. From this, the modified potentials better represent the equilibrium structures of LixC6 albeit with limitations.Li diffusion from a free surface and into a graphite grain boundary fosters discussions on how surface structure influences transport rates. While no electrolyte or solid-electrolyte interface (SEI) are modeled here, it is thought that all grain boundaries would be subject to approximately the same level of SEI formation and therefore diffusive flux at the GBs will be similar. Therefore, any differences in intercalation rates that manifest provide additional reasoning to diffusional variability in graphite. While the results may not be absolute, the relativity is what is important here.Lastly, grain boundary diffusion is studied for the systems analyzed during intercalation simulations. While one boundary may have faster surface intercalation than another, there are underlying questions as to whether surface behavior correlates with or against internal behavior. Data is presented addressing collective mechanisms for diffusion as well as the role of inherent GB structure on mass transport. Finally, recommendations are made to connect this dissertation with continuum models in addition to advance into new material systems for energy storage applications