Proximal disruptor aided ligation (ProDAL) of kilobase-long RNAs

<p>RNA with site-specific modification is a useful tool for RNA biology studies. However, generating kilobase (kb) -long RNA with internal modification at a site distant from RNA termini remains challenging. Here we report an enhanced splint ligation technique, proximal disruptor aided ligation (ProDAL), which allows adequate efficiency toward this purpose. The key to our approach is using multiple DNA oligonucleotides, ‘proximal disruptors’, to target the RNA substrate sequence next to the ligation site. The binding of disruptors helps to free the ligation site from intramolecular RNA basepairing, and consequently promotes more efficient formation of the pre-ligation complex and a higher overall ligation yield. We used naturally occurring 1.0 kb renilla and 1.9 kb firefly luciferase mRNA sequences to test the efficacy of our approach. ProDAL yielded 9–14% efficiency for the ligation between two RNA substrates, both of which were between 414 and 1313 nucleotides (nt) long. ProDAL also allowed similarly high efficiency for generating kb-long RNA with site-specific internal modification by a simple three-part ligation between two long RNA substrates and a modification-carrying RNA oligonucleotide. In comparison, classical splint ligation yielded a significantly lower efficiency of 0–2% in all cases. We expect that ProDAL will benefit studies involving kb-long RNAs, including translation, long non-coding RNAs, RNA splicing and modification, and large ribonucleoprotein complexes.</p

Atom Condensed Fukui Functions Calculated for 2973 Organic Molecules

<p>Data set Fukui_2973</p> <p>==================</p> <p>Atomic NBO charges for non-hydrogen atoms in 2973 small organic molecules at the B3LYP/6-31G*//DFTB level of theory.</p> <p> </p> <p> </p> <p>Related publication:</p> <p>* Qingyou Zhang, Fangfang Zheng, Tanfeng Zhao, Xiaohui Qu, João Aires-de-Sousa:</p> <p>Machine Learning Estimation of Atom Condensed Fukui Functions.</p> <p>Molecular Informatics (2015)</p> <p>DOI: 10.1002/minf.201500113</p> <p> </p> <p>This data set is publicly available at</p> <p>http://dx.doi.org/10.6084/m9.figshare.1400514</p> <p> </p> <p>Files</p> <p>-----</p> <p>Fukui_2973_sdf.tar.gz - 2973 molecules in the MDL SDFile format</p> <p>charges_Fukui_2973.xlsx - NBO atomic charges for the non-hydrogen atoms in neutral and charged species</p> <p> </p> <p>Molecules</p> <p>---------</p> <p>For a subset of the fragment-like ZINC database [1] consisting of 2973 neutral organic molecules composed from elements H,C,N,O,S, molecular geometries were relaxed by DFTB+ [2] and atomic charges were calculated by the NBO 5.9 program [3] from a natural population analysis on the B3LYP/6-31G* wavefunction. Charged species (+1:cation and -1:anion) were calculated with the geometry obtained for the corresponding neutral species.</p> <p> </p> <p>Format</p> <p>------</p> <p>Each molecule is stored in its own file, ending in ".sdf".</p> <p>The format is the standard MDL SDFile generated with the Marvin/JChem 5.8.2, 2012, software [5].</p> <p>Atomic charges are stored in the charges_Fukui_2973.xlsx file. Three different sheets are used for the neutral, cation and anion species respectively.</p> <p> </p> <p>Column Content</p> <p>------ -------</p> <p>1 Molecule ID (as appears in the corresponding .sdf file name and in the ZINC database)</p> <p>2,... Atomic charge (in elementary charge units) for atoms in the same sequence as in the corresponding .sdf file</p> <p> </p> <p>References</p> <p>----------</p> <p>[1] Irwin JJ, Sterling T, Mysinger MM, Bolstad ES, Coleman RG: ZINC: a free tool to discover chemistry for biology. J Chem Inf Model 2012, 52: 1757-1768.</p> <p>[2] Aradi B, Hourahine B, Frauenheim T: DFTB+, a sparse matrix-based implementation of the DFTB method. J Phys Chem A 2007, 111:2678-5684.</p> <p>[3] NBO 5.9. Glendening ED, Badenhoop JK, Reed AE, JCarpenter JE, Bohmann JA, Morales CM, Weinhold F: Theoretical Chemistry Institute, University of Wisconsin, Madison, WI, 2011; [http://www.chem.wisc.edu/~nbo5].</p> <p>[4] Schmidt MW, Baldridge KK, Boatz JA, Elbert ST, Gordon MS, Jensen JJ, Koseki S, Matsunaga N, Nguyen KA, Su S, Windus TL, Dupuis M, Montgomery JA: General atomic and molecular electronic structure system. J Comput Chem 1993, 14:1347-1363. GAMESS Version 11 Aug 2011 (R1)</p> <p>[5] ChemAxon [http://www.chemaxon.com/]</p

Accurate, Uncertainty-Aware Classification of Molecular Chemical Motifs from Multimodal X‑ray Absorption Spectroscopy

Accurate classification of molecular chemical motifs from experimental measurement is an important problem in molecular physics, chemistry, and biology. In this work, we present neural network ensemble classifiers for predicting the presence (or lack thereof) of 41 different chemical motifs on small molecules from simulated C, N, and O K-edge X-ray absorption near-edge structure (XANES) spectra. Our classifiers not only achieve class-balanced accuracies of more than 0.95 but also accurately quantify uncertainty. We also show that including multiple XANES modalities improves predictions notably on average, demonstrating a “multimodal advantage” over any single modality. In addition to structure refinement, our approach can be generalized to broad applications with molecular design pipelines

The Coupling between Stability and Ion Pair Formation in Magnesium Electrolytes from First-Principles Quantum Mechanics and Classical Molecular Dynamics

In this work we uncover a novel effect between concentration dependent ion pair formation and anion stability at reducing potentials, e.g., at the metal anode. Through comprehensive calculations using both first-principles as well as well-benchmarked classical molecular dynamics over a matrix of electrolytes, covering solvents and salt anions with a broad range in chemistry, we elucidate systematic correlations between molecular level interactions and composite electrolyte properties, such as electrochemical stability, solvation structure, and dynamics. We find that Mg electrolytes are highly prone to ion pair formation, even at modest concentrations, for a wide range of solvents with different dielectric constants, which have implications for dynamics as well as charge transfer. Specifically, we observe that, at Mg metal potentials, the ion pair undergoes partial reduction at the Mg cation center (Mg²⁺ → Mg⁺), which competes with the charge transfer mechanism and can activate the anion to render it susceptible to decomposition. Specifically, TFSI^– exhibits a significant bond weakening while paired with the transient, partially reduced Mg⁺. In contrast, BH₄^– and BF₄^– are shown to be chemically stable in a reduced ion pair configuration. Furthermore, we observe that higher order glymes as well as DMSO improve the solubility of Mg salts, but only the longer glyme chains reduce the dynamics of the ions in solution. This information provides critical design metrics for future electrolytes as it elucidates a close connection between bulk solvation and cathodic stability as well as the dynamics of the salt

Computational Design of New Magnesium Electrolytes with Improved Properties

In this work, we use computational design to examine 15 new electrolyte salt anions by performing chemical variations and mutations on the bis­(trifluoromethane)­sulfonamide (TFSI) anion. On the basis of our calculations, we propose two new anions as potential candidates for magnesium energy-storage systems, which are evolved from TFSI with the substitution of sulfur atoms in TFSI and the modification of functional groups. The applicability of these new anion salts is examined through comprehensive calculations using both first-principles as well as benchmarked classical molecular dynamics. We elucidate the important properties of these anions, including the electrochemical stability window, chemical decomposition, preferred solvation structure, diffusion coefficient, and other dynamical properties for 15 rationally designed molecules. Two of the designed anions are found to successfully avoid the vulnerability of TFSI during ion-pair charge-transfer reactions while retaining comparable or better performance of other properties. As such, our work provides, to our knowledge, the first theoretically designed electrolyte salt for contemporary multivalent batteries and provides guidance for the synthesis and testing of novel liquid electrochemical systems

Materials Genomics Screens for Adaptive Ion Transport Behavior by Redox-Switchable Microporous Polymer Membranes in Lithium–Sulfur Batteries

Selective ion transport across membranes is critical to the performance of many electrochemical energy storage devices. While design strategies enabling ion-selective transport are well-established, enhancements in membrane selectivity are made at the expense of ionic conductivity. To design membranes with both high selectivity and high ionic conductivity, there are cues to follow from biological systems, where regulated transport of ions across membranes is achieved by transmembrane proteins. The transport functions of these proteins are sensitive to their environment: physical or chemical perturbations to that environment are met with an adaptive response. Here we advance an analogous strategy for achieving adaptive ion transport in microporous polymer membranes. Along the polymer backbone are placed redox-active switches that are activated in situ, at a prescribed electrochemical potential, by the device’s active materials when they enter the membrane’s pore. This transformation has little influence on the membrane’s ionic conductivity; however, the active-material blocking ability of the membrane is enhanced. We show that when used in lithium–sulfur batteries, these membranes offer markedly improved capacity, efficiency, and cycle-life by sequestering polysulfides in the cathode. The origins and implications of this behavior are explored in detail and point to new opportunities for responsive membranes in battery technology development

Accelerating Electrolyte Discovery for Energy Storage with High-Throughput Screening

Computational screening techniques have been found to be an effective alternative to the trial and error of experimentation for discovery of new materials. With increased interest in development of advanced electrical energy storage systems, it is essential to find new electrolytes that function effectively. This Perspective reviews various methods for screening electrolytes and then describes a hierarchical computational scheme to screen multiple properties of advanced electrical energy storage electrolytes using high-throughput quantum chemical calculations. The approach effectively down-selects a large pool of candidates based on successive property evaluation. As an example, results of screening are presented for redox potentials, solvation energies, and structural changes of ∼1400 organic molecules for nonaqueous redox flow batteries. Importantly, on the basis of high-throughput screening, <i>in silico</i> design of suitable candidate molecules for synthesis and electrochemical testing can be achieved. We anticipate that the computational approach described in this Perspective coupled with experimentation will have a significant role to play in the discovery of materials for future energy needs

Origin of Electrochemical, Structural, and Transport Properties in Nonaqueous Zinc Electrolytes

Through coupled experimental analysis and computational techniques, we uncover the origin of anodic stability for a range of nonaqueous zinc electrolytes. By examination of electrochemical, structural, and transport properties of nonaqueous zinc electrolytes with varying concentrations, it is demonstrated that the acetonitrile–Zn­(TFSI)₂, acetonitrile–Zn­(CF₃SO₃)₂, and propylene carbonate–Zn­(TFSI)₂ electrolytes can not only support highly reversible Zn deposition behavior on a Zn metal anode (≥99% of Coulombic efficiency) but also provide high anodic stability (up to ∼3.8 V vs Zn/Zn²⁺). The predicted anodic stability from DFT calculations is well in accordance with experimental results, and elucidates that the solvents play an important role in anodic stability of most electrolytes. Molecular dynamics (MD) simulations were used to understand the solvation structure (e.g., ion solvation and ionic association) and its effect on dynamics and transport properties (e.g., diffusion coefficient and ionic conductivity) of the electrolytes. The combination of these techniques provides unprecedented insight into the origin of the electrochemical, structural, and transport properties in nonaqueous zinc electrolytes

Three-Dimensional Growth of Li₂S in Lithium–Sulfur Batteries Promoted by a Redox Mediator

During the discharge of a lithium–sulfur (Li–S) battery, an electronically insulating 2D layer of Li₂S is electrodeposited onto the current collector. Once the current collector is enveloped, the overpotential of the cell increases, and its discharge is arrested, often before reaching the full capacity of the active material. Guided by a new computational platform known as the Electrolyte Genome, we advance and apply benzo­[<i>ghi</i>]­peryleneimide (BPI) as a redox mediator for the reduction of dissolved polysulfides to Li₂S. With BPI present, we show that it is now possible to electrodeposit Li₂S as porous, 3D deposits onto carbon current collectors during cell discharge. As a result, sulfur utilization improved 220% due to a 6-fold increase in Li₂S formation. To understand the growth mechanism, electrodeposition of Li₂S was carried out under both galvanostatic and potentiostatic control. The observed kinetics under potentiostatic control were modeled using modified Avrami phase transformation kinetics, which showed that BPI slows the impingement of insulating Li₂S islands on carbon. Conceptually, the pairing of conductive carbons with BPI can be viewed as a vascular approach to the design of current collectors for energy storage devices: here, conductive carbon “arteries” dominate long-range electron transport, while BPI “capillaries” mediate short-range transport and electron transfer between the storage materials and the carbon electrode

Supramolecular Perylene Bisimide-Polysulfide Gel Networks as Nanostructured Redox Mediators in Dissolved Polysulfide Lithium–Sulfur Batteries

Here we report a new redox-active perylene bisimide (PBI)-polysulfide (PS) gel that overcomes electronic charge-transport bottlenecks common to lithium–sulfur (Li–S) hybrid redox flow batteries designed for long-duration grid-scale energy storage applications. PBI was identified as a supramolecular redox mediator for soluble lithium polysulfides from a library of 85 polycyclic aromatic hydrocarbons by using a high-throughput computational platform; furthermore, these theoretical predictions were validated electrochemically. Challenging conventional wisdom, we found that π-stacked PBI assemblies were stable even in their reduced state through secondary interactions between PBI nanofibers and Li₂S_<i>n</i>, which resulted in a redox-active, flowable 3-D gel network. The influence of supramolecular charge-transporting PBI-PS gel networks on Li–S battery performance was investigated in depth and revealed enhanced sulfur utilization and rate performance (C/4 and C/8) at a sulfur loading of 4 mg cm^–2 and energy density of 44 Wh L^–1 in the absence of conductive carbon additives