pi-Bonding versus oligomerisation in the aromatic anions [C(6)H(4)N(2)E](-): formation of the cyclic tetrameric tetraanion [C(6)H(4)N(2)Sb](4)(4-)

The reaction of 1,2-(NH(2))(2)C(6)H(4) with Sb(NMe(2))(3)/(n)BuLi gives the formally-aromatic heterocyclic anion [C(6)H(4)N(2)Sb](-) which oligomerises into a cyclic tetrameric arrangement in the complex [C(6)H(4)N(2)SbLi.PMDETA](4) () (PMDETA = {Me(2)NCH(2)CH(2)}(2)NMe) using a donor-acceptor bonding mode that is unique in related main group heterocyclic anions.     

Automated molecular simulation based binding affinity calculator for ligand-bound HIV-1 proteases

The successful application of high throughput molecular simulations to determine biochemical properties would be of great importance to the biomedical community if such simulations could be turned around in a clinically relevant timescale. An important example is the determination of antiretroviral inhibitor efficacy against varying strains of HIV through calculation of drug-protein binding affinities. We describe the Binding Affinity Calculator (BAC), a tool for the automated calculation of HIV-1 protease-ligand binding affinities. The tool employs fully atomistic molecular simulations alongside the well established molecular mechanics Poisson-Boltzmann solvent accessible surface area (MMPBSA) free energy methodology to enable the calculation of the binding free energy of several ligand-protease complexes, including all nine FDA approved inhibitors of HIV-1 protease and seven of the natural substrates cleaved by the protease. This enables the efficacy of these inhibitors to be ranked across several mutant strains of the protease relative to the wildtype. BAC is a tool that utilizes the power provided by a computational grid to automate all of the stages required to compute free energies of binding: model preparation, equilibration, simulation, postprocessing, and data-marshaling around the generally widely distributed compute resources utilized. Such automation enables the molecular dynamics methodology to be used in a high throughput manner not achievable by manual methods. This paper describes the architecture and workflow management of BAC and the function of each of its components. Given adequate compute resources, BAC can yield quantitative information regarding drug resistance at the molecular level within 96 h. Such a timescale is of direct clinical relevance and can assist in decision support for the assessment of patient-specific optimal drug treatment and the subsequent response to therapy for any given genotype.     

Early transition metal complexes bearing a C-capped tris(phenolate) ligand incorporating a pendant imine arm: synthesis, structure, and ethylene polymerization behavior

The ligand 3-[2,2'-methylenebis(4,6-di- tert-butylphenol)-5- tert-butylsalicylidene-(2,6-diisopropyl)phenylimine] (L(1)H 3) was reacted with MCl 4 (M = Ti, Zr) or MCl 5 (M = Nb, Ta) to give complexes of the type [MCl 2(L(1)H 2) 2] (M = Ti (1); Zr (2)), [NbCl 3( L (1)H)] (3), or [TaCl 4(L(1)H 2)] (4), respectively. Single crystal X-ray diffraction of 1- 4 revealed common "iminium" species resulting in zwitterionic complexes. Reaction of [V(N p-tol)(O n-Pr) 3] with L (1)H3 afforded [{(VN p-tol)(L(1)H)} 2(mu-O n-Pr)2] (5), and a second complex [(VO) 2(mu-O)(L(3)H) 2] (6)(L(3)H being derived from 3-[2,2'-methylenebis(4,6-di-tert-butylphenol)-5-tert-butylsalicylidene- p-tolylimine]). The condensation reaction between 3-[2,2'-methylenebis(4,6-di-tert-butylphenol)-5-tert-butyl-2-hydroxybenzaldehyde] (L(0)H 3) and o-phenylenediamine (1,2-diaminobenzene) afforded two products: a pseudo-16-membered hydrogen bonded macrocyclic structure {1,2-bis-3-[2,2'-methylenebis(4,6-di-tert-butylphenol)-5-tert-butylsalicylidene-benzyldiimine]} (L(5)H6), or the benzimidazolyl bearing ligand (L(6)H 3). The reaction of L (5)H6 or L(6)H 3 with [VO(O n-Pr) 3] under varying conditions produced the complexes [(VO)(L(5)H 4)] (7), [(VO) 2(L(5)H)] (8), or [VO(L(6)H 2) 2] (9). L (0)H 3 was reacted with a number of anilines to give the proligands {3-[2,2'-methylenebis(4,6-di- tert-butylphenol)-5-tert-butylsalicylidene-R-imine]}, where R = NC 6H 5 (L(2)H3), NC 6H 4-Me (L(3)H 3), and NC 6H 2-Me 3 (L(4)H 3). Reactions of these ligands with [VO(O n-Pr) 3] formed bischelating complexes of the form [(VO)(L(2-4)H 2)2] (10, 11, and 12, respectively). The reaction of L (1)H 3 with trimethylaluminum led to a bis-aluminum complex {(AlMe 2)[AlMe(NCMe)] L (1)} (13). The ability of complexes 1-12 to polymerize ethylene in the presence of an organoaluminum cocatalyst was investigated. Procatalysts 1 and 2 were found to produce negligible activities in the presence of dimethylaluminum chloride (DMAC) and the reactivator ethyltrichloroacetate (ETA), whereas 3 and 4 were found to be completely inactive for polymerization using a variety of different organoaluminum cocatalysts. Using the combination of DMAC and ETA, complexes 5-12 were found to be highly active catalysts; in all cases, the polymer formed was of high molecular weight linear polyethylene.     

Structure of (NH4)3GaF6 investigated by multinuclear magic-angle spinning NMR spectroscopy in comparison with rietveld refinement

The structure of ammonium gallium cryolite (NH(4))(3)GaF(6) was investigated by (19)F and (69,71)Ga magic-angle spinning (MAS) NMR in comparison with X-ray powder diffraction followed by Rietveld refinement. In agreement with previous thermodynamic measurements, NMR experiments on (NH(4))(3)GaF(6) support the model of rigid GaF(6) octahedra. At high spinning speeds (30 kHz), the scalar coupling between the six equivalent (19)F nuclei and (69,71)Ga can be directly observed in the powder spectra. The coupling constants are J(19)F(69)Ga = 197 Hz and J(19)F(71)Ga = 264 Hz. To explain the (71)Ga spectra recorded at 3 kHz a small distribution of quadrupolar frequencies has to be included. The spread of the spinning sidebands hints to a largest nu(Q) value of 28 kHz for (71)Ga. This can be explained by the occurrence of highly symmetric GaF(6) octahedra, which are tilted against the surrounding atoms. In addition, the incomplete motional excitation does not average out the quadrupolar effects. NMR findings are in discrepancy to those of Rietveld refinement. As result it appears that X-ray diffraction is not sensitive enough to deliver proper results.     

Synthesis and structures of new binuclear zinc alkyl,aryl and aryloxo complexes

The synthesis of a series of binuclear zinc complexes with Cl, N and O bridges is reported. The reaction of EtZnCl with B(C₆F₅)₃ in the presence of hexamethylbenzene affords the arene complex [Zn(μ-Cl)(C₆F₅)(η-C₆Me₆)]₂ in which the C₆Me₆ ligand may be regarded as η³-bonded. The comproportionation of Zn[N(SiMe₃)₂]₂ with ZnBu^t₂ or Zn(C₆F₅)₂ · toluene gave [Bu^tZn{μ-N(SiMe₃)₂}]₂ and [C₆F₅Zn{μ-N(SiMe₃)₂}]₂, respectively, with three-coordinate zinc. The reaction of ZnEt₂ with C₆F₅OH in the presence of pyridine gave [EtZn(μ-OC₆F₅)(py)]₂, while ZnMe₂ and C₆F₅OH followed by recrystallisation from THF gave [Zn(OC₆F₅)(μ-OC₆F₅)(THF)₂]₂ with five-coordinate zinc in a trigonal-bipyramidal geometry. The structures of these compounds have been determined.     

Compliance signaling games: toward modeling the deterrence of insider threats

In a typical workplace, organizational policies and their compliance requirements set the stage upon which the behavioral patterns of individual agents evolve. The agents’ personal utilities, access to information, and strategic deceptions shape the signaling systems of an intricate information-asymmetric game, thus mystifying assessment and management of organizational risks, which are primarily due to unintentional insider threats. Compliance games, as discussed here, model a rudimentary version of this signaling game between a sender (employee) and a receiver (organization). The analysis of these games’ equilibria as well as their dynamics in repeated game settings illuminate the effectiveness or risks of an organizational policy. These questions are explored via a repeated and agent-based simulation of compliance signaling games, leading to the following: (1) a simple but broadly applicable model for interactions between sender agents (employees) and receiver agents (principals in the organization), (2) an investigation of how the game theoretic approach yields the plausible dynamics of compliance, and (3) design of experiments to estimate parameters of the systems: evolutionary learning rates of agents, the efficacy of auditing using a trembling hand strategy, effects of non-stationary and multiple principal agents, and ultimately, the robustness of the system under perturbation of various related parameters (costs, penalties, benefits, etc.). The paper concludes with a number of empirical studies, illustrating a battery of compliance games under varying environments designed to investigate agent based learning, system control, and optimization. The studies indicate how agents through limited interactions described by behavior traces may learn and optimize responses to a stationary defense, expose sensitive parameters and emergent properties and indicate the possibility of controlling interventions which actuate game parameters. We believe that the work is of practical importance—for example, in constraining the vulnerability surfaces arising from compliance games.