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A Detailed Reaction Mechanism for Thiosulfate Oxidation by Ozone in Aqueous Environments
No full textThe ozone oxidation, or ozonation, of thiosulfate is an important reaction for wastewater processing, where it is used for remediation of mining effluents, and for studying aerosol chemistry, where its fast reaction rate makes it an excellent model reaction. Although thiosulfate ozonation has been studied since the 1950’s, challenges remain in developing a realistic reaction mechanism that can satisfactorily account for all observed products with a sequence of elementary reaction steps. Here, we present novel measurements using trapped microdroplets to study the pH-dependent thiosulfate ozonation kinetics. We detect known products and intermediates, including SO32-, SO42-, S3O62-, and S4O62-, establishing agreement with the literature. However, we identify S2O42- as a new reaction intermediate, and find that the currently accepted mechanism does not directly explain observed pH effects. Thus, we develop a new mechanism, which incorporates S2O42- as an intermediate and uses elementary steps to explain the pH-dependence of thiosulfate ozonation. The proposed mechanism is tested using a kinetic model benchmarked to the experiments presented here, then compared to literature data. We demonstrate good agreement between the proposed thiosulfate ozonation mechanism and experiments, suggesting that the insights in this paper can be leveraged in wastewater treatment and in understanding potential climate impacts
Protocols for metallo- and serine-β-lactamase free energy predictions: insights from cross-class inhibitors
No full textWhile relative binding free energy (RBFE) calculations using alchemical methods are routinely carried out for many pharmaceutically relevant protein targets, challenges remain. For example, open-source tools do not support the easy setup and simulation of metalloproteins, particularly when ligands directly coordinate to the metal site. Here, we evaluate the performance of RBFE methods for KPC-2, a serine-β-lactamase (SBL), and two non-bonded metal parameter setups for VIM-2, a metallo-β-lactamase (MBL) with two active site zinc ions. We tested two different ways of modeling the ligand-zinc interactions. First, a restraint-based approach, in which FF14SB zinc parameters are combined with harmonic restraints between the zincs and their coordinating residues. The second approach uses an upgraded Amber force field (UAFF) for zinc-metalloproteins with adjusted partial charges and non-bonded terms of zinc-coordinating residues. Molecular mechanics (MM) and quantum mechanics/molecular mechanics (QM/MM) simulations show that the crystallographically observed zinc coordination is not retained in MM simulations with either zinc parameter set for a series of known phosphonic acid-based inhibitors bound to VIM-2. These phosphonic acid-based inhibitors exhibit known cross-class affinity for SBLs and MBLs and serve as a benchmark for RBFE calculations for VIM-2, after validation with KPC-2. The KPC-2 free energy of binding estimates are within expected literature accuracies for the lig- and series with a mean absolute error of 0.43 (0.25, 0.66) kcal/mol and a Pearson’s correlation coefficient of 0.93 (0.86, 0.98). For VIM-2, the UAFF approach has improved correlation from 0.48 (−0.02, 0.86) to 0.66 (−0.09, 0.94), compared to the restraint approach. The presented strategies for handling ligands coordinating to metal sites highlight that simple metal parameter models can provide some predictive free energy estimate for metalloprotein–ligand systems, but leave room for improvement in their ease of use, modeling of coordination sites, and as a result, their accuracy
Nano Trees: Nanopore signal processing and sublevel fitting using Decision Trees
No full textAs the complexity of solid-state nanopore experiments increases, analysis of the resulting electrical signals to determine biomolecular details becomes a challenge. State of the art techniques for this task perform poorly when transient signal characteristics approach the bandwidth limitations of the measurement electronics. In this work, we address this challenge through an algorithm, called Nano Trees, for fitting piecewise constant functions. Nano Trees leverages machine learning algorithms to provide accurate fits to the noisy piecewise constant data that is characteristic of nanopore ionic current signals, producing accurate fits on transients as short as twice the rise time of the measurement system. We demonstrate the performance of our algorithm on several real and synthetic datasets. These findings underscore the generalizability and accuracy of this approach in the regime of fast molecular translocations
Ultrafast Dynamics in Spatially Confined Photoisomerization: Accelerated Simulations through Machine Learning Models
No full textThis study sheds light on the exploration of photoresponsive host-guest systems, highlighting the intricate interplay between confined spaces and photosensitive guest molecules. Conducting nonadiabatic molecular dynamics (NAMD) simulations based on electronic structure calculations for such large systems remains a formidable challenge. Leveraging machine learning (ML) as an accelerator for NAMD simulations, we analytically constructed excited-state potential energy surfaces along relevant collective variables to investigate photoisomerization processes efficiently. Combining the quantum mechanics/molecular mechanics (QM/MM) methodology with ML-based NAMD simulations, we elucidated reaction pathways and identified key degrees of freedom as reaction coordinates leading to conical intersections. A machine learning-based nonadiabatic dynamics model has been developed to compare the excited-state dynamics of the guest molecule, benzopyran in both the gas phase against its behavior within the confined space of cucurbit[5]uril. This comparative analysis is designed to expose the influence of the environment on the photoisomerization rate of the guest molecule. The results underscore the effectiveness of ML models in simulating trajectory evolution cost-effectively. This research offers a practical approach to accelerate NAMD simulations in large-scale systems of photochemical reactions, with potential applications in other host-guest complex systems
On-chip Electrochemical Detection of Dissolved Oxygen: Eliminating the Requirement for Permeable Selective Membrane
No full textDissolved Oxygen (DO) quantification is an important measure of the overall health of a water system. Fluctuations from normal values can indicate the presence of contaminants, and predict further events, for example, fish deaths resulting from eutrophication. DO can vary due to a variety of environmental factors, including altitude, so regular monitoring is crucial to understanding the baseline water conditions. Electrochemical approaches offer good accuracy and ease of use but are currently limited by their requirement for an oxygen permeable membrane to remove interference. To this end, we propose the use of interdigitated electrode arrays to facilitate the quantification of DO, without the need for a membrane, by measuring the by-product of the oxygen reduction reaction: hydrogen peroxide. In this paper, we show the use of mixed metal electrode arrays to sufficiently produce, and subsequently quantify, hydrogen peroxide as a proxy measure of dissolved oxygen, with a detection limit of 0.36 ppm DO. We further show that this technique is adequate for the detection of DO in tidal river water, and can be reliably used in the presence of chlorine and iron, which have electrochemical activity in the same potential range
Flow-gel approach enables rapid extraction of pure magnesium phase from seawater
No full textCurrent methods for separating critical materials from feedstock solutions remain chemistry- and energy-intensive. We demonstrate the rapid extraction of a pure magnesium phase from seawater via precipitation with sodium hydroxide in a flow-gel device. Our approach is scalable, suitable for high-throughput extraction, and does not rely on specialty chemicals
Polymer of Intrinsic Microporosity as Light Absorber for Luminescent Solar Concentrators
No full textLuminescent solar concentrators (LSCs) hold the promise to make solar electricity more affordable by reducing the need for expensive photovoltaic cells and enabling less conventional forms of photovoltaics such as solar windows or roofs, and other architectural elements. Here we demonstrate the use of a polymer of intrinsic microporosity (PIM-1) as an efficient light absorber in an LSC, combined with a red-emitting dye. The prepared prototype LSC displays a good internal efficiency (25.3%) and external efficiency (11.4%), and performance metrics that show promise for the use of polymers of intrinsic microporosity as light harvesters. This work significantly broadens the potential applications of PIMs beyond their more traditional functions in molecular separations and other adsorption-based processes
Reaction Mechanism of 2-Amido-2-Aminoacetic Acid Formation From Iminoacetic Acid and Amide - A Comparative DFT Study
No full textA reaction mechanism for the reaction of iminoacetic acid with formamide, resulting in 2-amido-2-aminoacetic acid is proposed. The role of the Zn(II) - catalyst is elucidated. Two possible reaction pathways were calculated by means of DFT. Furthermore, a competing side reaction, yielding N-(1,1- dihodroxy-2-iminoethyl)amide was simulated. ETS-NOCV, IRI and CDA analysis was employed on various important molecular states. A reasonable mechanism for the main reaction was found, where the rate determining step is energetically more favorable than the rate determining step of the side reaction. Furthermore, this reaction mechanism explains the importance of the transition metal
Controlled Synthesis of Cluster Mimics of Nitrogenase FeMo-cofactor
No full textCatalytic conversion of atmosphere dinitrogen into ammonia by nitrogenase is one of the most important chemical processes in nature. FeMo-cofactor (FeMoco), the key active site of this conversion in the Mo-based nitrogenase, is one of the most complicated metalloenzyme molecules. The synthesis of FeMoco cluster holds the key to elucidating the mechanism of nitrogen fixation, but the complex framework with a unique sextuply-bridged carbide in FeMoco cluster dictates its synthesis to be an extreme challenge that remains unsolved for several decades. In this work, two cluster models have been synthesized as the first highly analogous mimics of FeMoco using a precisely-designed cluster-coupling strategy. A carbide ligand has been introduced into M-Fe-S (M = Mo or W) clusters and the characteristic triangular prismatic [Fe6(µ6-C)] moiety of FeMoco has been synthesized for the first time. The structural parameters of the two mimics match well with those of FeMoco identified in natural nitrogenase. Quantum chemical studies reveal that the electronic ground states of the mimics resemble those observed for FeMoco, with maximized antiferromagnetic coupling among the iron centers. The clusters synthesized in this work represent the only highly analogous synthetic mimics of FeMoco. The cluster-coupling reaction is a versatile strategy that allows the synthesis of more analogous mimics of FeMoco. These mimics and the cluster-coupling strategy provide an excellent platform for studying the function and behavior of FeMoco, and also pave the way for elucidating the mechanism of nitrogen fixation by nitrogenase
Concise Synthesis of 5α,6-Dihydroveragranine A and Veragranines A and B
No full text(-)-Veragranines A and B are two steroidal alkaloids that exhibit potent analgesic activity. Herein, we report a 5-step biomimetic synthesis of 5α,6-dihydroveragranine A from hecogenin acetate, and the first divergent approach that allows access to veragranines A and B in 10~12 steps from deoxycholic acid. The synthesis of 5α,6-dihydroveragranine A features a cascade EF ring-opening/bromination/aldol condensation and C20 epimerization in a single step, and a Raney Ni/H2 enabled C26-azide reduction, imine formation and C16-Br hydrodebromination cascade in one pot. Based on our synthesis, an alternative biosynthetic proposal of veragranines was proposed. The synthesis of veragranines A and B features a well-designed photoredox-catalyzed decarboxylative Minisci reaction, which not only has good regioselective control but also results in the inversion of the stereochemistry at C20 through a radical process. Besides, the selection of an A/B cis-fused starting material enabled late-stage introduction of the Δ5(6) double bond, which simplified the process to introduce such a bond, and would be valuable for the synthesis of related natural products