Comparison of Conventional and Nonconventional Hydrogen Bond Donors in Au^- Complexes

Although gold has become a well-known nonconventional hydrogen bond acceptor, interactions with nonconventional hydrogen bond donors have been largely overlooked. In order to provide a better understanding of these interactions, two conventional hydrogen bonding molecules (3-hydroxytetrahydrofuran and alaninol) and two nonconventional hydrogen bonding molecules (fenchone and menthone) were selected to form gas-phase complexes with Au-. The Au-[M] complexes were investigated using anion photoelectron spectroscopy and density functional theory. Au-[fenchone], Au-[menthone], Au-[3-hydroxyTHF], and Au-[alaninol] were found to have vertical detachment energies of 2.71 ± 0.05, 2.76 ± 0.05, 3.01 ± 0.03, and 3.02 ± 0.03 eV, respectively, which agree well with theory. The photoelectron spectra of the complexes resemble the spectrum of Au- but are blueshifted due to the electron transfer from Au- to M. With density functional theory, natural bond orbital analysis, and atoms-in-molecules analysis, we were able to extend our comparison of conventional and nonconventional hydrogen bonding to include geometric and electronic similarities. In Au-[3-hydroxyTHF] and Au-[alaninol], the hydrogen bonding comprised of Au-···HO as a strong, primary hydrogen bond, with secondary stabilization by weaker Au-···HN or Au-···HC hydrogen bonds. Interestingly, the Au-···HC bonds in Au-[fenchone] and Au-[menthone] can be characterized as hydrogen bonds, despite their classification as nonconventional hydrogen bond donors

Quantum Mechanical Study of Weak Molecular Interactions

Noncovalent interactions have a long history and have received huge attention since their discovery almost a century ago. The prevalence of noncovalent interactions can be seen in the formation of simple dimers to structural and functional modification of large biomolecules. Even though plenty of experimental and theoretical studies are performed to understand various noncovalent interactions, the nature and variety of those interactions are still subject of study. And still they are receiving tremendous attention due to their significant role in the stability and conformation of biomolecules, catalysis of organic and inorganic reactions, crystal packing and material design. This dissertation explores various new sorts of noncovalent interactions, compares them with existing ones, and extensively studies the relevance of noncovalent interactions to various biological systems of interest by applying quantum mechanical tools. A new sort of noncovalent interaction has been identified where two electronegative atoms interact directly with each other with no intervening hydrogen or halogen atoms. These interactions are found to be surprisingly strong, even stronger than regular OH···O and NH···O hydrogen bonds in some cases, and are stabilized by the charge transfer from electron donor to electron acceptor. The major portion of this dissertation deals with the rigorous investigation of new sorts of interactions like P···N, S···N, Cl···N and several other charge transfer types of interactions with side by side comparison with hydrogen and halogen bonds. Similarly, a new carbonyl-carbonyl stacking geometry in peptide-peptide interactions is explored. These stacking geometries are energetically close to stronger NH···O hydrogen bonds, and get some assistance from CH···O hydrogen bonds. Carbon is considered one of the potent H-bond donors, albeit weaker, due to its ubiquitous presence in biomolecules. So, another portion of this dissertation is focused on the study of neutral and charged CH hydrogen bonds simulating various interpeptide interactions and enzyme catalysis. And the last part of this dissertation deals with the putative H-bonds that might be present in tip functionalized carbon nanotubes

A Computational Study of Small Gold Clusters with H2S, Thiols, H2O, and Alcohols

Alkane thiols, RSH, are commonly used in aqueous solution to stabilize and prevent aggregation of gold clusters, Aun. Initially a RSH-Aun complex is formed and, subsequently, there is hydrogen atom transfer to form a RSAunH complex. We examine the rate of this reaction for small neutral gold clusters, with n=1-2 and short-chain thiols with R = H, CH3, and CH3CH2, using transition state theory. The comparison of DFT (with the functionals, BP86 and M06-2X), and MP2 was performed. A pseudopotential was employed to account for the large relativisitic effects exhibited by gold. Equilibrium geometries and vibrational frequencies of the RSH-Aun and RSAunH complexes were obtained, as well as thermo-chemical values for the transfer of a hydrogen atom from sulphur to gold. The activation energy and rate of hydrogen atom transfer was also determined

Assessment of W1 and W2 theories for the computation of electron affinities, ionization potentials, heats of formation, and proton affinities

The performance of two recent {\em ab initio} computational thermochemistry schemes, W1 and W2 theory [J.M.L. Martin and G. de Oliveira, J. Chem. Phys. 111, 1843 (1999}], is assessed for an enlarged sample of thermochemical data consisting of the ionization potentials and electron affinities in the G2-1 and G2-2 sets, as well as the heats of formation in the G2-1 and a subset of the G2-2 set. We find W1 theory to be several times more accurate for ionization potentials and electron affinities than commonly used (and less expensive) computational thermochemistry schemes such as G2, G3, and CBS-QB3: W2 theory represents a slight improvement for electron affinities but no significant one for ionization potentials. The use of a two-point $A+B/L^5$ rather than a three-point $A+B/C^L$ extrapolation for the SCF component greatly enhances the numerical stability of the W1 method for systems with slow basis set convergence. Inclusion of first-order spin-orbit coupling is essential for accurate ionization potentials and electron affinities involving degenerate electronic states: inner-shell correlation is somewhat more important for ionization potentials than for electron affinities, while scalar relativistic effects are required for the highest accuracy. The mean deviation from experiment for the G2-1 heats of formation is within the average experimental uncertainty. W1 theory appears to be a valuable tool for obtaining benchmark quality proton affinities.Comment: Journal of Chemical Physics, in press (303115JCP). 2 RevTeX files, first is text and tables, second is E-PAPS tables S-1 through S-5. Additional supplementary material (total energies, basis function exponents) available at http://theochem.weizmann.ac.il/web/papers/w1w2.htm

Simulations of Chemical Catalysis

This dissertation contains simulations of chemical catalysis in both biological and heterogeneous contexts. A mixture of classical, quantum, and hybrid techniques are applied to explore the energy profiles and compare possible chemical mechanisms both within the context of human and bacterial enzymes, as well as exploring surface reactions on a metal catalyst. A brief summary of each project follows. Project 1 — Bacterial Enzyme SpvC The newly discovered SpvC effector protein from Salmonella typhimurium interferes with the host immune response by dephosphorylating mitogen-activated protein kinases (MAPKs) with a -elimination mechanism. The dynamics of the enzyme substrate complex of the SpvC effector is investigated with a 3.2 ns molecular dynamics simulation, which reveals that the phosphorylated peptide substrate is tightly held in the active site by a hydrogen bond network and the lysine general base is positioned for the abstraction of the alpha hydrogen. The catalysis is further modeled with density functional theory (DFT) in a truncated active-site model at the B3LYP/6-31 G(d,p) level of theory. The truncated model suggested the reaction proceeds via a single transition state. After including the enzyme environment in ab initio QM/MM studies, it was found to proceed via an E1cB-like pathway, in which the carbanion intermediate is stabilized by an enzyme oxyanion hole provided by Lys104 and Tyr158 of SpvC. Project 2 — Human Enzyme CDK2 Phosphorylation reactions catalyzed by kinases and phosphatases play an indispensable role in cellular signaling, and their malfunctioning is implicated in many diseases. Ab initio quantum mechanical/molecular mechanical studies are reported for the phosphoryl transfer reaction catalyzed by a cyclin-dependent kinase, CDK2. Our results suggest that an active-site Asp residue, rather than ATP as previously proposed, serves as the general base to activate the Ser nucleophile. The corresponding transition state features a dissociative, metaphosphate-like structure, stabilized by the Mg(II) ion and several hydrogen bonds. The calculated free-energy barrier is consistent with experimental values. Project 3 — Bacterial Enzyme Anthrax Lethal Factor In this dissertation, we report a hybrid quantum mechanical and molecular mechanical study of the catalysis of anthrax lethal factor, an important first step in designing inhibitors to help treat this powerful bacterial toxin. The calculations suggest that the zinc peptidase uses the same general base-general acid mechanism as in thermolysin and carboxypeptidase A, in which a zinc-bound water is activated by Glu687 to nucleophilically attack the scissile carbonyl carbon in the substrate. The catalysis is aided by an oxyanion hole formed by the zinc ion and the side chain of Tyr728, which provide stabilization for the fractionally charged carbonyl oxygen. Project 4 — Methanol Steam Reforming on PdZn alloy Recent experiments suggested that PdZn alloy on ZnO support is a very active and selective catalyst for methanol steam reforming (MSR). Plane-wave density functional theory calculations were carried out on the initial steps of MSR on both PdZn and ZnO surfaces. Our calculations indicate that the dissociation of both methanol and water is highly activated on \ufb02at surfaces of PdZn such as (111) and (100), while the dissociation barriers can be lowered significantly by surface defects, represented here by the (221), (110), and (321) faces of PdZn. The corresponding processes on the polar Zn-terminated ZnO(0001) surfaces are found to have low or null barriers. Implications of these results for both MSR and low temperature mechanisms are discussed

Reactivity and Thermochemistry of Gaseous Iron Compounds of Different Valency

In der vorliegenden Arbeit werden Untersuchungen zur Reaktivität und Thermochemie von Übergangsmetallverbindungen des Eisens, sowie der Aktivierung von organischen Substraten durch "nackte" Eisen- und Cobalt-Kationen durchgeführt. Dabei werden theoretische Ansätze sowie massenspektrometrische Methoden verwendet. Die verschiedenen experimentellen Techniken ergänzen sich hierbei, so daß die untersuchten Systeme unter unterschiedlichen Gesichtspunkten betrachtet werden können. Kapitel 3 beschäftigt sich mit den Reaktionen und der Thermochemie von Eisen-Oxo und Eisen-Hydroxo Verbindungen. Dabei stehen (i) die Untersuchung des Sauerstoffaustausches von FeO+ und FeOH+ mit 18O-markiertem Wasser, (ii) die Untersuchung der drei [Fe,O2,H2]+-Isomere sowie der entsprechenden Dikationenspezies und (iii) die Bestimmung der vertikalen und adiabatischen Ionisierungsenergien der betrachteten FeOmHn+-Teilchen im Mittelpunkt. In Kapitel 4 werden die adiabatischen und vertikalen Elektronentransferprozesse in Eisenchloriden untersucht. Die Bestimmung der vertikalen Redoxeigenschaften der FeClmn-Teilchen (m = 1 - 4, n = -1, 0, 1, 2) erfolgt mittels charge-stripping, charge-reversal, charge-exchange und neutralization-reionization Massenspektrometrie. Die korrespondierenden adiabatischen Redoxeigenschaften werden durch die Kombination von experimentellen Daten und quantenchemischen Rechnungen bestimmt. In Kapitel 5 wird die Aktivierung von Wasserstoff und Methan durch Eisensulfid-Kationen, FeS+, beschrieben. Beide Reaktionen werden im Guided-Ion-Beam- und Fourier-Transform-Ionen-Cyclotron-Resonanz-Massenspektrometer sowie durch quantenchemische Rechnungen untersucht. Die Aktivierung beider Substrate erfolgt über eine 1,2-Insertion des FeS+ in eine sigma-Bindung des Substrates unter Spin-Inversion von der Sextett- zur Quartett-Potentialfläche wobei als Hauptprodukt die Bildung von Fe+ unter Einbau des Schwefelatoms in die aktivierte Bindung des Substrates beobachtet wird. Den letzten thematischen Schwerpunkt stellt in Kapitel 6 die Aktivierung von organischen Substraten durch verschiedene Übergangsmetalle am Beispiel von Ethylsilan dar. Es zeigt sich experimentell, daß die im Periodensystem "benachbarten" Übergangsmetalle Cobalt und Eisen bei der Aktivierung von Ethylsilan deutlich unterschiedliche Produkte bilden, während die Reaktionen aber nach ähnlichen Mechanismen ablaufen.This Thesis presents investigations on the reactivity and thermochemistry of different iron complexes, as well as a study of the activation behavior of "bare" iron and cobalt cations towards small organic substrates. The applied techniques comprise several mass-spectrometric approaches and quantum chemical calculations using density-functional theory. In the first part, reactions and thermochemistry of iron-oxo and iron-hydroxy species are investigated. In particular, three main focuses exist, i.e. (i) the oxygen exchange reaction of FeO+ and FeOH+ with 18O labelled water, (ii) the existence of several [Fe,O2,H2] isomers on the monocationic and the dicationic potential energy surface, and (iii) the determination of vertical and adiabatic ionization energies of the FeOmHn+ species under consideration. The next chapter comprises a study of the vertical and adiabatic electron transfer processes of iron chlorides. The experimental methods for the determination of vertical redox properties include charge-stripping, charge-reversal, charge-exchange, and neutralization-reionization mass spectrometry. The adiabatic redox properties are obtained from combining experimental data and quantum chemical calculations. The reactivity of the iron sulfide cation FeS+ is the main focus of the next chapter. The activation of molecular hydrogen and methane is investigated by Guided-Ion Beam and FT-ICR mass spectrometry as well as density-functional theory.Reaction mechanisms for the activation of both substrates are proposed, both starting with a 1,2-insertion of the FeS+ into a sigma-bond of the substrate. Both mechanisms are also shown to occur under spin-inversion, thus providing examples for the two-state reactivity concept. The last chapter deals with the activation behavior of "bare" iron- and cobalt cations. Experimental investigations on the substrate ethylsilane showed, that even "neighboring" metals can exhibit quite different product selectivities. The following B3LYP density-functional theory study, however, provides indications that these different product selectivities are not due to different reactions mechanisms but rather due to kinetic effects along the potential-energy surface

Molecular Modeling of Ions in Biological Systems

Ions are ubiquitous in biological systems. Metal ions contribute to biological function as counter ions, as triggers to cellular response, and as catalytic cofactors. They play structural roles and are part of the catalytic active site of metalloenzymes. NH4+ ions provide a source of nitrogen for amino acid synthesis in plants and bacteria and help maintaining the acid-base balance in mammals. The cationic side chains of amino acids Lys and Arg contribute to the stability of proteins and protein-DNA complexes through cation–π interactions with the π electrons of aromatic amino acids. Developing molecular models for ion-protein interactions is required to investigate and understand the various biological functions of ions and to complement and interpret experimental data. In this regard, the aims of this thesis are to: 1- Investigate the selectivity of alkali ions toward N, O, and S-containing ligands (a step toward understanding protein selectivity to metal ions). 2- Optimize new semiempirical quantum mechanical models for calcium and magnesium metalloproteins. 3- Study the strength and directionality of cation–π interactions involving inorganic and organic cations interacting with model compounds of aromatic amino acid side chains in both gas phase and aqueous solution. 4- Investigate the selectivity and binding affinity of AmtB and RhCG ammonium transport proteins toward various ions and study the function of amino acids that line the transport pathway of these proteins. Proteins bind metal ions through N, O, and S atoms from the side chains of the amino acids His, Asp, Glu, Ser, Tyr, Asn, Gln, Cys, and Met and from main chain carbonyl and amino groups. NH3, H2O, and H2S are used as minimal models for N, O, and S ligands to investigate the selectivity of alkali metal ions. Polarizable potential models for NH3 and H2S that accurately reproduce the experimental properties of the pure and aqueous liquids are developed. The models are used, together with a previously developed model for water, to study the solvation structures and solvation free energies of the ions in the pure liquids and to investigate the selectivity of alkali ions toward the three ligands. The models yield solvation structures and solvation free energies in good agreement with experiments and show a selectivity of alkali ions toward the three ligands that follows the order H2O > NH3 > H2S. Magnesium and Calcium are two of the most bioavailable metals and are known to play roles in signal transduction and in muscular contraction and are cofactors in many enzymes. Semiempirical models are optimized for the two metals based on the ab initio structures and binding energies of complexes formed between Mg2+ and Ca2+ with ligands that model binding groups in biological and chemical systems. Optimized models are tested on the ab initio properties of ~170 ion-ligand binary and ion-water-ligand ternary complexes. Optimized models of Mg underestimate the binding energies of S-containing complexes but give structures and binding energies of other complexes in agreement with ab initio data. Models for Ca reproduce the ab initio properties of all complexes, including S complexes. Cation–π interactions are common among protein structures and are believed to play key roles in stabilizing proteins and protein complexes with ligands and DNA. Polarizable potential models for the interaction of Rb+, Cs+, Tl+, ammonium, tetramethylammonium, and tetraethylammonium with aromatic amino acid side chains are calibrated based on the ab initio properties of the different cation–π complexes. The models are used to study the binding affinity and complexation geometry of the different pairs in water. Results are showing that cation–π interactions persist in aqueous solutions and are stronger than charge-dipole interactions (such as interactions of Rb+, Cs+, Tl+ with ethanol and acetamide). It is also found that cation–π complexes have geometries in aqueous solution similar to gas phase. In addition, results suggest that cation–π interactions influence the solubility of aromatic compounds in aqueous solutions. Proteins of the Amt/Mep/Rh family —ammonium transporters (Amt) in plants and bacteria, methylamine permease (Mep) in yeast, and rhesus (Rh) blood-group associated glycoproteins in animals— facilitate the permeation of ammonium across cell membranes. Crystal structures of AmtB and RhCG proteins reveal structural differences along the transport pathways. Amt proteins are selective toward NH4+ over Na+ and K+, yet their activity can be inhibited by ions such as Cs+ and Tl+. Polarizable potential models for NH3, NH4+, Na+, K+, Rb+, Cs+, and Tl+ interacting with model compounds to side chains of amino acids that line the transport pathway are optimized. The models are used to calculate the binding affinity of both proteins toward the various ligands and to study the functional roles of amino acids along the transport pathway. Results show that among the various ligands, only Cs+ and Tl+ can compete with NH4+ for binding the two proteins and hence inhibit the protein activity. Results also show that the large hydrophobicity of the pore lumen in RhCG protein destabilizes NH4+ and water molecules in the pore which suggests a net NH3 transport mechanism of the protein

Computational Studies in Molecular Geochemistry and Biogeochemistry

The ability to predict the transport and transformations of contaminants within the subsurface is critical for decisions on virtually every waste disposal option facing the Department of Energy (DOE), from remediation technologies such as in situ bioremediation to evaluations of the safety of nuclear waste repositories. With this fact in mind, the DOE has recently sponsored a series of workshops on the development of a Strategic Simulation Plan on applications of high perform-ance computing to national problems of significance to the DOE. One of the areas selected for application was in the area of subsurface transport and environmental chemistry. Within the SSP on subsurface transport and environmental chemistry several areas were identified where applications of high performance computing could potentially significantly advance our knowledge of contaminant fate and transport. Within each of these areas molecular level simulations were specifically identified as a key capability necessary for the development of a fundamental mechanistic understanding of complex biogeochemical processes. This effort consists of a series of specific molecular level simulations and program development in four key areas of geochemistry/biogeochemistry (i.e., aqueous hydrolysis, redox chemistry, mineral surface interactions, and microbial surface properties). By addressing these four differ-ent, but computationally related, areas it becomes possible to assemble a team of investigators with the necessary expertise in high performance computing, molecular simulation, and geochemistry/biogeochemistry to make significant progress in each area. The specific targeted geochemical/biogeochemical issues include: Microbial surface mediated processes: the effects of lipopolysacchardies present on gram-negative bacteria. Environmental redox chemistry: Dechlorination pathways of carbon tetrachloride and other polychlorinated compounds in the subsurface. Mineral surface interactions: Describing surfaces at multiple scales with realistic surface functional groups Aqueous Hydrolysis Reactions and Solvation of Highly Charged Species: Understanding the formation of polymerized species and ore formation under extreme (Hanford Vadose Zone and geothermo) conditions. By understanding on a fundamental basis these key issues, it is anticipated that the impacts of this research will be extendable to a wide range of biogeochemical issues. Taken in total such an effort truly represents a “Grand Challenge” in molecular geochemistry and biogeochemistry

The Magnitude and Mechanism of Charge Enhancement of CH∙∙O H-bonds

Quantum calculations find that neutral methylamines and thioethers form complexes, with N-methylacetamide (NMA) as proton acceptor, with binding energies of 2–5 kcal/mol. This interaction is magnified by a factor of 4–9, bringing the binding energy up to as much as 20 kcal/mol, when a CH3+ group is added to the proton donor. Complexes prefer trifurcated arrangements, wherein three separate methyl groups donate a proton to the O acceptor. Binding energies lessen when the systems are immersed in solvents of increasing polarity, but the ionic complexes retain their favored status even in water. The binding energy is reduced when the methyl groups are replaced by longer alkyl chains. The proton acceptor prefers to associate with those CH groups that are as close as possible to the S/N center of the formal positive charge. A single linear CH··O hydrogen bond (H-bond) is less favorable than is trifurcation with three separate methyl groups. A trifurcated arrangement with three H atoms of the same methyl group is even less favorable. Various means of analysis, including NBO, SAPT, NMR, and electron density shifts, all identify the +CH··O interaction as a true H-bond