Revisiting HO Nucleation around Au and Hg: The Peculiar "Pseudo-Soft" Character of the Gold Cation.

In this contribution, we propose a deeper understanding of the electronic effects affecting the nucleation of water around the Au and Hg metal cations using quantum chemistry. To do so, and in order to go beyond usual energetical studies, we make extensive use of state of the art quantum interpretative techniques combining ELF/NCI/QTAIM/EDA computations to capture all ranges of interactions stabilizing the well characterized microhydrated structures. The Electron Localization Function (ELF) topological analysis reveals the peculiar role of the Au+ outer-shell core electrons (subvalence) that appear already spatially preorganized once the addition of the first water molecule occurs.

Investigation of the hydroxylation mechanism of noncoupled copper oxygenases by ab initio molecular dynamics simulations.

In Nature, the family of copper monooxygenases comprised of peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM) is known to perform dioxygen-dependent hydroxylation of aliphatic C-H bonds by using two uncoupled metal sites. In spite of many investigations, including biochemical, chemical, and computational, details of the C-H bond oxygenation mechanism remain elusive. Herein we report an investigation of the mechanism of hydroxylation by PHM by using hybrid quantum/classical potentials (i.

Understanding the Chemistry of Lead at a Molecular Level: The Pb(II) 6s6p Lone Pair Can Be Bisdirected in Proteins.

Pb(2+) complexes can attain several different topologies, depending of the shape of the Pb 6s6p lone pair. In this paper, we study structures with a bisdirected Pb lone pair with quantum mechanics (DFT) and QM/MM calculations. We study small symmetric Pb(2+) models to see what factors are needed to get a bisdirected lone pair.

Revisiting the holo- and hemidirected structural transition within the [Pb(CO)n]2+ model series using first-principles molecular dynamics.

In this article, we resort to first-principles molecular dynamic simulations to examine the thermal effects on the structure of [Pb(CO)(n)](2+) complexes. Values of n are chosen to sample structures where hemidirected (n = 2, 4 and 6) or holodirected (n = 7 and 8) structures are found when using static approaches. In all cases, highly flexible structures are observed.

Many-body exchange-repulsion in polarizable molecular mechanics. I. Orbital-based approximations and applications to hydrated metal cation complexes.

We have quantified the extent of the nonadditivity of the short-range exchange-repulsion energy, E(exch-rep), in several polycoordinated complexes of alkali, alkaline-earth, transition, and metal cations. This was done by performing ab initio energy decomposition analyses of interaction energies in these complexes. The magnitude of E(exch-rep(n-body, n > 2)) was found to be strongly cation-dependent, ranging from close to zero for some alkali metal complexes to about 6 kcal/mol for the hexahydrated Zn(2+) complex.

Spin-driven activation of dioxygen in various metalloenzymes and their inspired models.

Although potentially powerful, molecular oxygen is an inert oxidant due to the triplet nature of its ground state. Therefore, many enzymesse various metal cations (M) to produce singlet active species M(n) O(2) . In this communication we investigate the topology of the Electron Localization Function (ELF) within five biomimetic complexes which are representative of the strategies followed by metalloenzymes to activate O(2) .

Role of Cation Polarization in holo- and hemi-Directed [Pb(H2O)n](2+) Complexes and Development of a Pb(2+) Polarizable Force Field.

Reduced Variational Space (RVS) calculations are reported that afford insight into the energetic origins of the hemi- and holo-directing behavior of [Pb(H2O)n](2+) complexes. It is shown that the distribution of ligands around the Pb(2+) center arises from a delicate balance between the first-order Coulomb plus exchange-repulsion energy that favors holo-directionality, and the second-order charge transfer plus polarization term that favors hemi-directionality. It is additionally demonstrated that the pseudopotential/basis set combination used to study such complexes should be carefully selected, as artifacts can arise when using large-core pseudopotentials.

Importance of backdonation in [M-(CO)]p+ complexes isoelectronic to [Au-(CO)]+.

In this contribution, we study several monocarbonyl-metal complexes in order to unravel the contribution of relativistic effects to the metal-ligand bond length and complexation energy. Using scalar density functional theory (DFT) constrained space orbital variation (CSOV) energy decomposition analysis supplemented by all-electron four-component DFT computations, we describe the dependency of relativistic effects on the orbitals involved in the complexation for the Au(+) isoelectronic series, namely, the fully occupied 5d orbitals and the empty 6s orbitals. We retrieve the well-known sensitivity of gold toward relativity.

Gas-phase folding of a two-residue model peptide chain: on the importance of an interplay between experiment and theory.

In order to assess the ability of theory to describe properly the dispersive interactions that are ubiquitous in peptide and protein systems, an isolated short peptide chain has been studied using both gas-phase laser spectroscopy and quantum chemistry. The experimentally observed coexistence of an extended form and a folded form in the supersonic expansion was found to result from comparable Gibbs free energies for the two species under the high-temperature conditions (< or = 320 K) resulting from the laser desorption technique used to vaporize the molecules. These data have been compared to results obtained using a series of quantum chemistry methods, including DFT, DFT-D, and post-Hartree-Fock methods, which give rise to a wide range of relative stabilities predicted for these two forms.

Understanding selectivity of hard and soft metal cations within biological systems using the subvalence concept. I. Application to blood coagulation: direct cation-protein electronic effects vs. indirect interactions through water networks.

Following a previous study by de Courcy et al. ((2009) Interdiscip. Sci.

Study of the docking of competitive inhibitors at a model of tyrosinase active site: insights from joint broken-symmetry/Spin-Flip DFT computations and ELF topological analysis.

Following our previous study (Piquemal et al., New J. Chem.

Lead substitution in synaptotagmin: a case study.

Quantum chemistry computations have been used to investigate the possibility of a Pb(2+)/Ca(2+) substitution in the three calcium sites of the synaptotagmin enzyme. Provided explicit cation solvation is taken into account, it is shown that the substitution is energetically feasible and induces a strong reorganization of the Ca(2+)-coordinating sites, which may preclude the enzyme for any efficient role when lead poisoning occurs.

Directional control and supramolecular protection allowing the chemo- and regioselective transformation of a triamine.

A Zn(II)-funnel complex based on a calix[6]arene ligand decorated with three tris(imidazolyl) arms at one end of the cone and three NH(2) substituents at the other end, acts as a multipoint recognition host for polyfunctionalized guests. The selectivity is ensured by coordination to Zn(II), CH-pi interaction within the calix cone, and H-bonding at both rims of the cavity. As a result of these multiple interactions, the host can wrap and orient an unsymmetrical triamine guest with a high selectivity.

Dioxygen activation by mononuclear copper enzymes: insights from a tripodal ligand mimicking their Cu(M) coordination sphere.

A mononuclear cuprous complex is proposed as a novel in silico model for the Cu(M) active site of noncoupled copper monooxygenases. To the best of our knowledge, it is one of the first biomimicking models that allows one to recover the intimate structural features of the enzymatic oxygenated adducts and to gain clear-cut insights relevant to dioxygen activation by these enzymes.

Replacement of a nitrogen by a phosphorus donor in biomimetic copper complexes: a surprising and informative case study with calix[6]arene-based cryptands.

The aim of the paper is to characterize Cu complexes in the P(Ar)N(3) environment provided by ligands derived from triphenylphosphine P(C(6)H(4)CH(2)NHR)(3) and compare their coordination behavior and reactivity with those obtained with all-nitrogen ligands such as tren. It is shown that coordination of the PN(3) ligand (R = iPr) to Cu(I) and Cu(II) leads to complexes whose coordination sphere is hardly controlled as they readily undergo decoordination of either one N or the P donor together with oxidation of the latter. In strong contrast, when grafted on the small rim of a calix[6]arene, the P(Ar)N(3) is geometrically constrained into a tripod that enforces the metal center to remain in the same environment with a P-Cu bond for both oxidation states.

Application of the topological analysis of the electronic localization function to archetypical [Pb(II)Ln]p complexes: the bonding of Pb2+ revisited.

The coordination of neutral ligands (L = OC, HCN, NH3, PH3, SH2, HNCO and H2O) to Pb2+ is investigated and analyzed by means of the topological analysis of the Electronic Localization Function (ELF). It is shown that the mean charge density of the V(Pb) basin ((V(Pb))) can reach a ligand-independent limiting value from n = 6, a coordination number from which the [PbL(n)]2+ complexes adopt holodirected structures. The investigations performed on anionic series (L = HS-, OH-, CN-, F-, Cl-, and Br-) lead to optimized stable structures in which the coordination number does not exceed n = 4, even in the presence of a model aqueous solvent.

Molecular recognition and self-assembly special feature: Multipoint molecular recognition within a calix[6]arene funnel complex.

A multipoint recognition system based on a calix[6]arene is described. The calixarene core is decorated on alternating aromatic subunits by 3 imidazole arms at the small rim and 3 aniline groups at the large rim. This substitution pattern projects the aniline nitrogens toward each other when Zn(II) binds at the Tris-imidazole site or when a proton binds at an aniline.

Shuffling lithiated mixed aggregates: NMR and Car-Parrinello molecular dynamics reveal an unexpected associative pathway.

The exchange of Me(6)Li aggregated to a lithium amide by (7)LiCl leads to a specific isotope distribution whose microscopic origin is assigned to an edge-to-edge interaction between the R(2)NLi-MeLi aggregate and (LiCl)(2) by NMR and Car-Parrinello molecular dynamics.

Theoretical exploration of the oxidative properties of a [(tren Me1)CuO2]+ adduct relevant to copper monooxygenase enzymes: insights into competitive dehydrogenation versus hydroxylation reaction pathways.

Singlet and triplet H-transfer reaction paths from C-H and N-H bonds were examined by means of DFT and spin-flip TD-DFT computations on the [(tren Me1)CuO2]+ adduct. The singlet energy surfaces allow its evolution towards H2O2 and an imine species. Whereas N-H cleavage appears to be a radical process, C-H rupture results in a carbocation intermediate stabilized by an adjacent N atom and an electrostatic interaction with the [CuIOOH] metal core.

Understanding lead chemistry from topological insights: the transition between holo- and hemidirected structures within the [Pb(CO)n]2+ model series.

In this contribution, we focus to the currently unknown [Pb(CO)(n)](2+) model series (n=1 to 10), a set of compounds which allows us to investigate in-depth the holo- and hemidirectional character that lead complexes can exhibit. By means of DFT computations performed using either relativistic four-component formalisms coupled to all-electron basis sets for [Pb(CO)](2+), [Pb(OC)](2+) and [Pb(CO)(2)](2+), or scalar relativistic pseudopotentials for higher n values, the structure and the energetics of these species are investigated. The results are complemented by Constrained Space Orbital Variations (CSOV) and Electron Localization Function (ELF) comprehensive analyses in order to get better insights into the poorly documented chemical fundamentals of the Pb(2+) cation.

Simple Formulas for Improved Point-Charge Electrostatics in Classical Force Fields and Hybrid Quantum Mechanical/Molecular Mechanical Embedding.

We present a simple damping scheme for point-charge electrostatics that could be used directly in classical force fields. The approach acts at the charge (or monopole) level only and allows the inclusion of short-range electrostatic penetration effects at a very low cost. Results are compared with density functional theory Coulomb intermolecular interaction energies and with several other methods such as distributed multipoles, damped distributed multipoles, and transferable Hermite-Gaussian densities.

Long distance electron-transfer mechanism in peptidylglycine alpha-hydroxylating monooxygenase: a perfect fitting for a water bridge.

The active sites of copper enzymes have been the subject of many theoretical and experimental investigations from a number of years. Such studies have embraced topics devoted to the modeling of the first coordination sphere at the metallic cations up to the development of biomimetic, or bioinspired, catalytic systems. At least from the theoretical viewpoint, fewer efforts have been dedicated to elucidate how the two copper cations act concertedly in noncoupled dicopper enzymes such as peptidylglycine alpha-hydroxylating monooxygenase (PHM) and dopamine beta-monooxygenase (DbetaM).

Singlet-triplet gaps in large multireference systems: spin-flip-driven alternatives for bioinorganic modeling.

The proper description of low-spin states of open-shell systems, which are commonly encountered in the field of bioinorganic chemistry, rigorously requires using multireference ab initio methodologies. Such approaches are unfortunately very CPU-time consuming as dynamic correlation effects also have to be taken into account. The broken-symmetry unrestricted (spin-polarized) density functional theory (DFT) technique has been widely employed up to now to bypass that drawback, but despite a number of relative successes in the determination of singlet-triplet gaps, this framework cannot be considered as entirely satisfactory.

First-principles molecular dynamics evaluation of thermal effects on the NMR (1)J(Li,C) spin-spin coupling.

Car-Parrinello (CP) molecular dynamics were applied to sample conformations of various models of organolithium aggregates which are chosen to estimate (1)J(Li,C) NMR coupling constants. The results show that the deviations from the values computed using static (optimized) geometries are small provided no large-amplitude motions occur within the timescale of the simulations. In the case of the vinyllithium dimer, for which rotation of the vinyl chain is observed, this approach allows analysis of the various contributions to the experimentally measured constants.