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L1 ligase (L1L) molecular switch is an in vitro optimized synthetic allosteric ribozyme that catalyzes the regioselective formation of a 5'-to-3' phosphodiester bond, a reaction for which there is no known naturally occurring RNA catalyst. L1L serves as a proof of principle that RNA can catalyze a critical reaction for prebiotic RNA self-replication according to the RNA world hypothesis. L1L crystal structure captures two distinct conformations that differ by a reorientation of one of the stems by around 80Å and are presumed to correspond to the active and inactive state, respectively. It is of great interest to understand the nature of these two states in solution and the pathway for their interconversion. In this study, we use explicit solvent molecular simulation together with a novel enhanced sampling method that utilizes concepts from network theory to map out the conformational transition between active and inactive states of L1L. We find that the overall switching mechanism can be described as a three-state/two-step process. The first step involves a large-amplitude swing that reorients stem C. The second step involves the allosteric activation of the catalytic site through distant contacts with stem C. Using a conformational space network representation of the L1L switch transition, it is shown that the connection between the three states follows different topographical patterns: the stem C swing step passes through a narrow region of the conformational space network, whereas the allosteric activation step covers a much wider region and a more diverse set of pathways through the network.

The relationship between formation of active in-line attack conformations and monovalent (Na(+)) and divalent (Mg(2+)) metal ion binding in hammerhead ribozyme (HHR) has been explored with molecular dynamics simulations. To stabilize repulsions between negatively charged groups, different requirements of the threshold occupancy of metal ions were observed in the reactant and activated precursor states both in the presence and in the absence of a Mg(2+) in the active site. Specific bridging coordination patterns of the ions are correlated with the formation of active in-line attack conformations and can be accommodated in both cases. Furthermore, simulation results suggest that the HHR folds to form an electronegative recruiting pocket that attracts high local concentrations of positive charge. The present simulations help to reconcile experiments that probe the metal ion sensitivity of HHR catalysis and support the supposition that Mg(2+), in addition to stabilizing active conformations, plays a specific chemical role in catalysis.

Although the hammerhead ribozyme is regarded as a prototype for understanding RNA catalysis, the mechanistic roles of associated metal ions and water molecules in the cleavage reaction remain controversial. We have investigated the catalytic potential of observed divalent metal ions and water molecules bound to a 2 A structure of the full-length hammerhead ribozyme by using X-ray crystallography in combination with molecular dynamics simulations. A single Mn(2+) is observed to bind directly to the A9 phosphate in the active site, accompanying a hydrogen-bond network involving a well-ordered water molecule spanning N1 of G12 (the general base) and 2'-O of G8 (previously implicated in general acid catalysis) that we propose, based on molecular dynamics calculations, facilitates proton transfer in the cleavage reaction. Phosphate-bridging metal interactions and other mechanistic hypotheses are also tested with this approach.

Molecular dynamics simulations have been performed to investigate the role of Mg2+ in the full-length hammerhead ribozyme cleavage reaction. In particular, the aim of this work is to characterize the binding mode and conformational events that give rise to catalytically active conformations and stabilization of the transition state. Toward this end, a series of eight 12 ns molecular dynamics simulations have been performed with different divalent metal binding occupations for the reactant, early and late transition state using recently developed force field parameters for metal ions and reactive intermediates in RNA catalysis. In addition, hybrid QM/MM calculations of the early and late transition state were performed to study the proton-transfer step in general acid catalysis that is facilitated by the catalytic Mg2+ ion. The simulations suggest that Mg2+ is profoundly involved in the hammerhead ribozyme mechanism both at structural and catalytic levels. Binding of Mg2+ in the active site plays a key structural role in the stabilization of stem I and II and to facilitate formation of near attack conformations and interactions between the nucleophile and G12, the implicated general base catalyst. In the transition state, Mg2+ binds in a bridging position where it stabilizes the accumulated charge of the leaving group while interacting with the 2'OH of G8, the implicated general acid catalyst. The QM/MM simulations provide support that, in the late transition state, the 2'OH of G8 can transfer a proton to the leaving group while directly coordinating the bridging Mg2+ ion. The present study provides evidence for the role of Mg2+ in hammerhead ribozyme catalysis. The proposed simulation model reconciles the interpretation of available experimental structural and biochemical data, and provides a starting point for more detailed investigation of the chemical reaction path with combined QM/MM methods.

The presented oxidative carbonylation of 2-arylphenols proceeds under acid-base free and mild conditions with a variety of substrates. [ABSTRACT FROM AUTHOR]

An efficient Pd-catalyzed oxidative carbonylation of N-sulfonyl-2-amino-biaryls is presented. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports the preparation of (AgIn) x Zn2(1− x )S2 solid solutions from acidic aqueous solutions consisting of silver nitrate, indium nitrate, zinc nitrate, and thioacetamide, without using toxic H2S gas. The reaction sequence of this multicomponent material was investigated, as well as the post thermal treatment conditions. The formation of quaternary semiconductor solid solutions after 800°C annealing were determined by X-ray diffraction. The peaks in the XRD patterns shifted to higher angles with an increase of [Zn]/[In] in the precursor solutions. Band gaps of the (AgIn) x Zn2(1− x )S2 solid solutions were estimated to be 2.11–2.45eV by diffuse reflection UV–Vis spectra. In addition, the band gap energy increased with [Zn]/[In] accordingly. The precipitates after heat treatment had a layered structure, as revealed by SEM; the compositions were analyzed by EDS. The photocatalytic H2 evolution rates in sacrificial reagents under a 300W Xe lamp of Pt-loaded (AgIn) x Zn2(1− x )S2 solid solutions were measured. A H2 evolution of 340μmol/h for 0.5g photocatalyst was obtained. The particles retained the photocatalytic activity for at least 100h. This study demonstrates that AgInS2–ZnS solid solution particles can be prepared from a completely aqueous route. [Copyright &y& Elsevier]

Abstract: Sb-doped AgIn5S8 polycrystalline films were grown on indium–tin–oxide coated glass substrates using solution growth technique. New procedures for growing Sb-doped Ag–In–S system photocatalyst films are presented. The influences of various deposition parameters on structural, optical, and photoelectrochemical properties of samples were investigated. The X-ray diffraction patterns of samples demonstrate the presence of polycrystalline AgIn5S8 phase in these films. The thicknesses and energy band gaps obtained from transmittance data are in the ranges of 538–1018nm and 1.72–1.73eV, respectively. The flat band potentials of these samples are in the range of −4.097 to −5.217V vs. an absolute electron potential; the potentials become more negative with an increase in Sb ion in reaction solution. With a molar ratio of Sb/Ag in precursor solution higher than 0.2, the conduction type of samples turns into p-type semiconductor. The maximum photocurrent density of samples with an external potential set at 3.5V was found to be −4.76mA/cm2 under illumination using a 300 Xe lamp system. [Copyright &y& Elsevier]

Rh-catalyzed reaction of N-hydroxybenzamidines with an excess of internal alkynes and an excess of Cu(OAc)2 as the oxidant is described to produce polyhetarenes in good yields. [ABSTRACT FROM AUTHOR]