High Level Theoretical Study of Benzene−Halide Adducts: The Importance of C−H−Anion Hydrogen Bonding

High level ab initio calculations were performed on the interaction of halide anions (F−, Cl−, Br−, and I−) to benzene. For these systems recent experimental and theoretical data are rather scarce, in spite of their growingly acknowledged importance for binding in complex biological systems. We have thus explored the complete basis set limit and the effect of counterpoise basis set superposition error corrections on the minimum geometries and energies of benzene−halide adducts in their possible interaction modes. The binding energy and enthalpy values (ranging from −15.3 kcal/mol for fluoride to −6.1 kcal/mol for iodide) show that the hydrogen bonding occurring in these complexes cannot be described as a weak interaction. We have furthermore investigated the topology of the minima and of other selected sections of the potential energy surface, so to gain further insight on the nature of the halide−benzene interaction. In particular, the geometry corresponding to the C6v symmetry, although being overall repulsive, has displayed the unprecedented presence of a small flex (a minimum in C6v symmetry) with interaction energy close to zero or slightly attractive

Metal Fragment Modulation of Metallacumulene Complexes: A Density Functional Study

Density functional calculations have been carried out on a series of metallacumulene complexes LmM(C)nH2 with several MLm metal fragments to study the electronic structure, the bonding, and the reactivity of these complexes and how they are affected by the metal termini. The considered metal fragments include [(Cp)2(PH3)Ti], [Cp(PH3)2Mo]+, [(CO)5Cr], [(CO)5Mo], [(CO)5W], [Cp(dppe)Fe]+, [trans-Cl(dppe)2Ru]+, [Cp(PMe3)2Ru]+, [BzCl(PH3)Ru]+, [trans-Cl(PH3)2Rh], and [trans-Cl(PH3)2Ir], which are quite common in the chemistry of metal vinylidene, allenylidene, and higher cumulenes and range from a d2 to a d8 configuration and from electron-poor to electron-rich character. The optimized geometries calculated for the considered complexes have been found to be in good agreement with the available X-ray data and show that the peculiar carbon−carbon bond alternation superimposed to an average cumulenic structure, which is typical of these systems, is slightly perturbed by the nature of the metal fragment with the exception of the d4 [Cp(PH3)2Mo]+. Bonding energies have been calculated for all considered systems, and their dependence on the nature of the metal termini has been discussed. In particular an increase of the electron richness within d6 metal fragments causes a slight decrease of metal−cumulene bond energy. On the other hand, bond energies for d8 and, to a lesser extent, d4−d2 complexes are larger than those for the d6 analogues. The charge distribution and the localization of the molecular orbitals have been employed to explain the known reactivity patterns of this class of complexes and to forecast their variation with the nature of the metal fragment for both even and odd chains

Density Functional Study of Butadiyne to Butatrienylidene Isomerization in [Ru(HCCCCH)(PMe₃)₂(Cp)]⁺

The butadiyne to butatrienylidene isomerization in [Ru(HCCCCH)(PMe3)2(Cp)]+ has been investigated by density functional calculations. Several possible minima have been identified on the potential energy surface for the coordinated C4H2 moiety, and a few plausible isomerization mechanisms have been analyzed by a DFT approach. The butatrienylidene complex has been found to be more stable than the butadiyne adduct by −13.1 kcal mol−1 in enthalpy and is the thermodynamically most stable species on the potential energy surface. The energetically most favorable isomerization pathway has been found to initially follow the same pathway experimentally and theoretically characterized for the simpler alkyne rearrangement on a d6 metal fragment, i.e. a 1,2-hydrogen shift passing through an agostic intermediate, and leading to a ethynyl vinyl intermediate, for which an activation enthalpy of 23.1 kcal mol−1 (activation free energy of 20.8 kcal mol−1) was found. The isomerization then proceeds through a proton migration from the Cβ to the terminal Cδ atom occurring through deprotonation of the ethynyl vinylidene, leading to a butadiynyl complex which is then reprotonated to the final butatrienylidene product, with an overall activation energy of 17.4 kcal mol−1 (activation free energy of 19.6 kcal mol−1)

Adsorption and Interfacial Chemistry of Pentacene on the Clean Si(100) Surface: A Density Functional Study

Density functional theory calculations have been performed on the main adsorption configurations of pentacene on the Si(100) surface and on the possible pathways for the following C−H bond cleavage. We considered possible candidates for all the orientations of pentacene experimentally observed with STM, i.e., on the top of silicon dimer rows, perpendicular to the dimer rows, diagonal to the dimer rows and between two adjacent dimer rows (“in between”). Our calculations indicate that the most stable adsorption configuration of pentacene on the Si(100) surface is the symmetric perpendicular structure with an adsorption energy of −128.3 kcal mol-1, with the in between structure 10.5 kcal mol-1 and the symmetric parallel structure 13.0 kcal mol-1 higher in energy. Transition states for the dissociation of C−H and formation of Si−H bonds from the main adsorption configurations of pentacene have been characterized and the corresponding energy barriers estimated. We identified two kinds of adsorbed configurations of pentacene from which the breaking of two C−H bonds can be accessible:  one on top of a silicon dimer row with one or both outer benzene rings di-σ−bonded through a [2 + 2] cycloaddition; one with one or more pentacene rings 1,4 di-σ-bonded across two dimer rows, such as the in between structure. The kinetically most favorable reactive channel is that from the in between configuration and involves the separate abstraction of two hydrogen atoms on the sp3 carbon atoms by the two silicon atoms of the two dimers bearing an unpaired electron, with an energy barrier of 29−30 kcal mol-1

An Insight on the Gold(I) Affinity of <i>golB</i> Protein via Multilevel Computational Approaches

Several bacterial species have evolutionary developed protein systems specialized in the control of intracellular gold ion concentration. In order to prevent the detrimental consequences that may be induced even at very low concentrations, bacteria such as Salmonella enterica and Cupriavidus metallidurans utilize Au-specific merR-type transcriptional regulators that detect these toxic ions and control the expression of specific resistance factors. Among these highly specialized proteins, golB has been investigated in depth, and X-ray structures of both apo and Au­(I)-bound golB have been recently reported. Here, the binding of Au­(I) at golB was investigated by means of multilevel computational approaches. Molecular dynamics simulations evidenced how conformations amenable for the Au­(I) chelation through the Cys-XX-Cys motif on helix 1 are extensively sampled in the phase space of apo-golB. Hybrid QM/MM calculations on metal-bound structures of golB also allowed to characterize the most probable protonation state for gold binding motif and to assess the structural features mostly influencing the Au­(I) coordination in this protein. Consistently with experimental evidence, we found that golB may control its Au­(I) affinity by conformational changes that affect the distance between Cys10 and Cys13, thus being able to switch between the Au­(I) sequestration/release-prone states in response to external stimuli. The protein structure enveloping the metal binding motif favors the thiol–thiolate protonation state of Au­(I)-golB, thus probably enhancing the binding selectivity for Au­(I) compared to other cations

Binding of Antitumor Ruthenium Complexes to DNA and Proteins: A Theoretical Approach

The thermodynamics of the binding of the antitumor ammine, amine, and immine complexes of ruthenium(II) and ruthenium(III) to DNA and peptides was studied computationally using model molecules. We performed density functional calculations on several monofunctional ruthenium complexes of the formula [Ru(NH3)5B]z+, where B is an adenine, guanine, or cytosine nucleobase or an 4-methylimidazole, a dimethylthioether, or a dimethylphosphate anion and z = 2 and 3. The pentammineruthenium fragment has been intensively studied and also constitutes a good model for a wide class of antitumor ammine, amine, and imine complexes of Ru(II) and Ru(III), while the considered bases/ligands have been chosen as models for the main binding sites of DNA, nucleobases, and phosphate backbone and proteins, histidyl, and sulfur-containing residue such as methionine or cysteine. Bond dissociation enthalpies and free energies have been calculated for all the considered metal binding sites both in the gas phase and in solution and allow building a binding affinity order for the considered nucleic acid or protein binding sites. The binding of guanine to some bifunctional complexes, [Ru(NH3)4Cl2], [cis-RuCl2(bpy)2], and [cis-RuCl2(azpy)2], has also been considered to evaluate the effect of a second labile chloro or aquo ligand and more realistic polypyridyl and arylazopyridine ligands

Activation and Reactivity of a Bispidine Analogue of Cisplatin: A Theoretical Investigation

The reactivity of a bispidine, 3,7-diazabicyclo[3.3.1]­nonane, analogue of cisplatin, a new anticancer drug with promising properties, is theoretically investigated to clarify the in vitro reactivity and in vivo mechanism of action of this compound. Thermodynamics and kinetics of the first and second aquation steps and of the reaction of the generated mono- and diaqua species with guanine, the main target of the platinum based antitumor compounds, have been studied. In agreement with the experimental evidence, the bispidine analogue is significantly less reactive than cisplatin toward aquation but the formed aquaspecies show a good reactivity with guanine, consistently with the promising anticancer properties of these new compounds

Aquation of the Ruthenium-Based Anticancer Drug NAMI-A: A Density Functional Study

We carried out density functional theory (DFT) calculations to investigate the thermodynamics and the kinetics of the double aquation reaction of the anticancer drug NAMI-A. Three explicit water molecules were included in the calculations to improve the PB solvation energies. Our calculations show that the chloride substitution reactions on the considered Ru(III) octahedral complex follow a dissociative interchange mechanism, Id, passing through a loose heptacoordinate transition state. We calculated an activation enthalpy and free energy for the first aquation step of 101.5 and 103.7 kJ mol-1, respectively, values that are in good agreement with the available experimental results. The activation enthalpy and free energy for the second aquation step were found significantly higher, 118.7 and 125.0 kJ mol-1, again in agreement with the experimental evidence indicating a slower rate for the second aquation