Mapping Enzymatic Catalysis using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be $18.3\pm 3.5$ kcal mol$^{-1}$ for MP2/cc-pVDZ and $19.3\pm 3.6$ for MP2/cc-pVTZ in an ONIOM approach using EFMO-RHF/6-31G(d) for the high and low layers, respectively.Comment: SI not attache

Kinematically complete experiments for electron induced break-up of small molecules and clusters

The electron collision induced ionization and fragmentation dynamics is studied for tetrafluoromethane (CF4), carbondioxide (CO2) and small water clusters (H2O)n (n ≤ 6). With a multi-particle imaging spectrometer for each collision two electrons and one ion were recorded in triple-coincidence. The dissociation dynamics of CF4 was analyzed as a function of the ionized orbitals. For the CO2 target the angular emission pattern of the ejected electron was studied as function of the projectile scattering kinematics. Fully differential cross sections were recorded to test a recently developed theoretical method. In addition ionization experiments for small water clusters revealed details on their stability, ionization energies and proton transfer reactions. Specific states of the stable dimers ions where observed for the first time

Characterization Of Charge Accommodation In Biologically Important Hydrogen-Bonded Clusters

The underlying motivation of chemical physics and physical chemistry is to understand naturally occurring chemical and physical processes from the nanoscopic molecular level to the macroscopic condensed phase. Over the past half-century, experimentalists have developed a number of laser-based analytical techniques to bridge the gap between the bulk phase and the single molecule. Here, we look at bulk phase and gas phase clusters to compare the local hydrogen-bonded network. To better understand the role noncovalent interactions have on biologically relevant building blocks in a natural environment, we compare the microhydration of gas phase cluster ions to condensed phase spectra. The accommodation of excess charge plays an essential character in a number of biochemical processes involving peptides, nucleobases, aerosols, etc. A time-of-flight mass spectrometer was constructed to isolate discrete numbers of solute and solvent molecules for spectroscopic interrogation via light-matter interactions. We also employed high-resolution Raman spectroscopy for vibrational interrogation of temperature dependence in crystalline lattice modes as well as effects of surface-enhanced Plasresonances. Electronic structure methods were employed for accurate spectral assignment and identification of structural motifs

Proton Transfer in Hydrated Molecular Ions

In this work I employ quantum and mixed quantum mechanical/molecular mechanical techniques to describe proton transfer in solvated molecular ions. I explore the role of solvation in facilitating proton-coupled electron transfer in pyridine∙(H2O) n –. The underlying physics which accounts for the differences observed in the N-H region of the infrared spectra of pyridine ∙ (H2O)n=3– when compared to the n≥4 clusters, is also explored. Theoretical challenges encountered when calculating one-dimensional potential energy surfaces are examined. The merits of mapping the potential energy surface of H+(H2O)21 by employing the multistate empirical valence-bond model are evaluated by calculating isomerization pathways

A PHYSICAL CHEMIST'S GUIDE TO APPLIED COMPUTATIONAL CHEMISTRY: PRACTICAL CALCULATION OF POLYPROTIC ACID PKA VALUES, MERCURY HALIDES, THIOLS, AND METHYLMERCURY ANALOGUES' STABILITIES AND STRUCTURES, AND RAMAN SPECTRA OF MYO-INOSITOL HEXAKIS PHOSPHATE.

In this thesis, we present both ab-initio investigation of the series of compounds HgClxy and the charges of each system running x=(0,1,2,3,4) and y=(+2,+1,0,-1,-2). We investigate the energies of formation using Gaussian 03 (G03), a quantum chemistry package. In our calculations, HgCl3-1 was most stable in the gas phase, and HgCl20 the most stable in the polarizable continuum model water-solvated phase. The addition of a solvent layer of H2O molecules did not significantly affect the results. DFT calculations on the series running between HgCl+, through HgCl20, and HgCl3-1 compounds done with the Amsterdam Density Functional (ADF) program from Scientific Computing and Modeling (SCM) yielded absolute Hg NMR shieldings with a Δ of approximately -1000 ppm for each additional atom of Chlorine bonding to the Mercury for the first two additions. We also investigate H3PO4, H3AsO4, and the HClOx acid series with x=(1,2,3,4). We have succeeded in determining pKas with theoretical quality results within 2 kcal/mol of experimental measurement for the majority of the systems examined by use of a discovered linear correlation between experimental and calculated pKa values. Finally, we present our contribution to a joint project involving myo-inositol hexakis phosphate with an experimental group, confirming the observed experimental trends seen in the Raman spectra

How molybdenum species cleave the phosphoester bond.

217 p.Metal species have a great impact on the biochemistry of living systems. It has been reported that polyoxomolybdates exhibit anti-tumor activity similar to that of commercial drugs. However, the mechanism by which these species are effective against cancer has been an elusive topic. It is believed that their activity is related to their interaction with phosphoester' containing biomolecules.Experimental studies have demonstrated that molybdenum species can cause cleavage in different model phosphoester molecules.However, the complex chemistry of molybdates has made these experimental studies difficult to interpret. We used computational methodologies to shed light on the phosphoesterase activity of molybdenum species in different reaction models. The study employed density functional theory to explore the mechanistic details of hydrolysis reactions of phosphate monoesters and diestersin the presence of different molybdenum species.The study results on the speciation of MoO2Cl2(DMF)2 supported the experimental findings that reported DMF release and Mo¿Clbond breakage. Two different NPP hydrolysis pathways were proposed depending on the complex concentration. Lower concentrations disfavoured the formation of polynuclear species, and the hydrolysis proceeded through less favourable mononuclear intermediates. With enough complex concentration, a nucleation process was favoured over the phosphate interaction. After theformation of dinuclear species, the incorporation of NPP and its consequent hydrolysis showed lower energetic barriers than theuncatalysed reaction. We also examined heptamolybdate as it was reported to hydrolyse NPP while its nuclearity decreased.Pentanuclear active species proposed by experimentals showed a higher activation barrier for its hydrolysis and cannot beconsidered as a catalyst. The study proposed a dinuclear compound resulting from heptamolybdate fragmentation as the catalytic species, which decreased the energetic barrier compared to the non¿catalysed reaction. With DNA and RNA models BNPP andHPNP, the calculations supported the experimental findings that heptamolybdate can hydrolyse phosphodiester molecules without fragmentation. With phosphate diesters, the hydrolysis proceeded through more compact mechanisms than with phosphatemonoesters, in which phosphorane structures are formed.The study revealed that the dinuclear species and the heptamolybdate cluster provide a structural motif that catalyses the hydrolysisof these phosphates. The molybdate structure generally augments the electrophilia of the phosphorous atom and can deprotonateand activate the nucleophile, favouring associative mechanisms. This information can aid in designing effective and non¿toxicphosphoesterases.DIP

An Electron Force Field for Simulating Large Scale Excited Electron Dynamics

We introduce an electron force field (eFF) that makes simulation of large scale excited electron dynamics possible and practical. The forces acting on thousands of electrons and nuclei can be computed in less than a second on a single modern processor. Just as conventional force fields parameterize the ground state potential between nuclei, with electrons implicitly included, electron force fields parameterize the potential between nuclei and simplified electrons, with more detailed degrees of freedom implicitly included. The electrons in an electron force field are Gaussian wave packets whose only parameters are its position and its size. Using a simple version of the electron force field, we compute the dissociation and ionization behavior of dense hydrogen, and obtain equations of state and shock Hugoniot curves that are in agreement with results obtained from vastly more expensive path integral Monte Carlo methods. We also compute the Auger dissociation of hydrocarbons, and observe core hole decays, valence electron ionizations, and nuclear fragmentation patterns consistent with experiment. We show we can describe p-like valence electrons using spherical Gaussian functions, enabling us to compute accurate ionization potentials and polarizabilities for first row atoms, and accurate dissociation energies and geometries of atom hydrides and hydrocarbons. We show also that we can describe delocalized electrons in a uniform electron gas using localized eFF orbitals. We reproduce the energy of a uniform electron gas, including correlation effects; and following the historical development of density functional theory, we develop a preliminary eFF that can compute accurate exchange and correlation energies of atoms and simple molecules.</p

Attosecond spectroscopy of bio-chemically relevant molecules

Understanding the role of the electron dynamics in the photochemistry of bio-chemically relevant molecules is key to getting access to the fundamental physical processes leading to damage, mutation and, more generally, to the alteration of the final biological functions. Sudden ionization of a large molecule has been proven to activate a sub-femtosecond charge flow throughout the molecular backbone, purely guided by electronic coherences, which could ultimately affect the photochemical response of the molecule at later times. We can follow this ultrafast charge flow in real time by exploiting the extreme time resolution provided by attosecond light sources. In this work recent advances in attosecond molecular physics are presented with particular focus on the investigation of bio-relevant molecules

Toward atomic-based understanding of some reactive and non-reactive surfaces

The thesis is composed of two broad themed sections with the underlying aim of understanding on a precise atomic basis, the electronic and structural factors governing the reactive and non-reactive surfaces of two metal oxides belonging to the same group in the periodic table; boron (B) and aluminium (Al). Using accurate density functional theory (DFT) computations, we first elucidate the initial reaction steps of the surface oxidation of elemental boron into its respective oxide; boron trioxide (B₂O₃). The highly exoergic reaction obtained for the dissociative adsorption of molecular oxygen over the boron surface coincides with the widely used boron oxidation reaction as secondary energy source in rockets. The relatively large activation energy for the O-O dissociation step marks the non-spontaneity of elemental boron oxidation at room temperature. Having established routes for the formation of B₂O₃-like precursors, we then investigate the relative stability of four low-index surfaces of the low-pressure B₂O₃ phase; namely the B₂O₃-I configuration. We demonstrate that none of the investigated low-index surfaces have dangling bonds, which reasonably relates to the experimentally observed low reactivity of this compound. The most stable surface terminations of B₂O₃ orientations entail tetrahedral BO₄ units. Such termination incurs a lower surface energy than orientations that consist of only triangular BO₃ units. Electronic and structural factors provide atomic-base elucidation of the observed inertness of B₂O₃. Combined experimental techniques (i.e. diffuse reflectance infrared spectroscopy) and DFT simulation are used to answer some of the most intriguing questions pertinent to factors underpinning the well-documented catalytic inhibition by B₂O₃ and its hygroscopic behaviour. We investigate the adsorption and dissociation mechanisms of two hydrogen chalcogenides, namely water (H₂O) and hydrogen sulfide (H₂S) molecules over B₂O₃-I (101) surfaces. We show that the diboron trioxide surface exhibits high physiochemical reactivity towards water molecules. The Lewis acid properties of B₂O₃-I lead to the formation of a molecular adsorption state (rather than dissociative adsorption) of the H₂S molecule via the acceptance of an electron pair into the low-energy orbital of the boron valence shell. While acting as water scavenger to generate dissociated radicals, B₂O₃ exhibits an inhibitor characteristic towards the dissociation of H₂S molecules, representing an ideal reactor wall coating in such systems. Alumina have been widely utilised as independent catalysts or as support materials for other catalysts. From an environmental perspective, alumina nanoclusters dispersed on surfaces of particulate matter PM₁₂ generate from various combustion processes play a critical role in the synthesis of environmental persistent free radicals (EPFR). Of particular importance are phenoxy-type EPFR that often acts as building blocks for the formation of notorious pollutants. Herein, we provide a comprehensive thermo-mechanistic account of alumina-surface mediated formation of phenoxy-type EPFR on different structural alumina models encompassing the following surfaces: dehydrated alumina surface, fully hydrate alumina surface, surfaces with different hydration coverage, and silicon-alumina doped surface. We show that fission of the phenol’s hydroxyl bond over dehydrated alumina systematically incurs lower energy barriers in reference to the hydrate surfaces. The catalytic activity of the alumina surface in producing the phenoxy/phenolate species reversibly correlates with the degree of hydroxyl coverage. Furthermore, we clarify the effect doping on the catalytic activity of alumina. The activation energy barrier required to form phenoxy moiety on Si-substituted Al₂O₃(0001) surface is ~40% lower than that of analogous barriers encountered over undoped dehydrate alumina surface. Overall, all considered models of alumina configurations are shown to produce adsorbed phenolate; however, desorption of the latter into the gas phase requires a rather sizable energy. Thus, the fate of absorbed phenolate is most likely to be dictated by decomposition affording carboneous layer of self-decomposition into other stable molecules