The
utilization of CO2 to generate chemical fuels, such
as formic acid, is a potentially beneficial route to balance carbon
emissions and reduce dependence on fossil fuels. The development of
efficient catalysts for CO2 hydrogenation is needed to
implement this fuel generation. In the molecular catalyst design presented
here, we covalently attached a rhodium complex, ([RhI(PNglyP)2]−, where PNglyP is defined as PEt2
–CH2–N(CH2CO2
–)–CH2–PEt2
) to a protein scaffold, (lactococcal multidrug resistant regulator
from Lactococcus lactis) to use the protein environment
around the metal center to control substrate delivery and therefore
enable and improve catalytic activity. The reactivities of the rhodium
complex and the synthetic metalloenzyme were characterized by high-pressure
operando NMR techniques. In solution, the rhodium complex alone is
not a catalyst for CO2 hydrogenation. Incorporation of
the rhodium complex into the protein scaffold resulted in a gain of
function, turning on CO2 hydrogenation activity. The metalloenzyme
displayed a turnover frequency of 0.38 ± 0.03 h–1 at 58 atm and 298 K and achieved an average turnover number of 14
± 3. Proposed catalytic intermediates generated and characterized
suggest that the protein scaffold enables catalysis by facilitating
the interaction between CO2 and the hydride donor intermediate.
A facile surface-amide coupling method was examined to attach dye and catalyst molecules to silatrane-decorated NiO electrodes. Using this method, electrodes with a push-pull dye were assembled, and characterized by photoelectrochemistry and transient absorption spectroscopy. The dye-sensitized electrodes exhibited hole injection into NiO and good photoelectrochemical stability in water, highlighting the stability of the silatrane anchoring group and the amide linkage. The amide coupling protocol was further applied to electrodes that contain additional proton reduction nickel catalysts for use in photocathode architectures. Evidence for catalyst reduction was observed during photoelectrochemical measurements and via fs-transient absorption spectroscopy demonstrating the possibility for application in photocathodes.
A virtual reality (VR) session was
introduced to an advanced inorganic
chemistry class, a class available to junior and senior undergraduate
students at the University of California, Los Angeles. The VR session
helped the students to learn complicated aspects of metal coordination
chemistry and molecular orbitals via an immersive three-dimensional
experience.
Virtual reality is a powerful tool with the ability to immerse a user within a completely external environment. This immersion is particularly useful when visualizing and analyzing interactions between small organic molecules, molecular inorganic complexes, and biomolecular systems such as redox proteins and enzymes. A common tool used in the biomedical community to analyze such interactions is the Adaptive Poisson-Boltzmann Solver (APBS) software, which was developed to solve the equations of continuum electrostatics for large biomolecular assemblages. Numerous applications exist for using APBS in the biomedical community including analysis of protein ligand interactions and APBS has enjoyed widespread adoption throughout the biomedical community. Currently, typical use of the full APBS toolset is completed via the command line followed by visualization using a variety of two-dimensional external molecular visualization software. This process has inherent limitations: visualization of three-dimensional objects using a two-dimensional interface masks important information within the depth component. Herein, we have developed a single application, UnityMol-APBS, that provides a dual experience where users can utilize the full range of the APBS toolset, without the use of a command line interface, by use of a simple graphical user interface (GUI) for either a standard desktop or immersive virtual reality experience.
The protein scaffold around the active site of enzymes is known to influence catalytic activity, but specific scaffold features responsible for favorable influences are often not known. This study focuses on using an artificial metalloenzyme to probe one specific feature of the scaffold, the position of a positive charge in the outer coordination sphere around the active site. Previous work showed that a small molecular complex, [Rh(P Et 2 N glycine P Et 2)2 ] − , immobilized covalently within a protein scaffold was activated for CO 2 hydrogenation. Here, using an iterative design where the effect of arginine, histidine, or lysine residues placed in the outer coordination sphere of the catalytic active site were evaluated, we tested the hypothesis that positively charged groups facilitate CO 2 hydrogenation with seven unique constructs. Single-, double-, and triple-point mutations were introduced to directly compare catalytic activity, as monitored by turnover frequencies (TOFs) measured in real time with 1 H NMR spectroscopy, and evaluate related structural and electronic properties. Two of the seven constructs showed a 2-and 3-fold increase relative to the wild type, with overall rates ranging from 0.2 to 0.7 h −1 , and a crystal structure of the fastest of these shows the positive charge positioned next to the active site. A crystal structure of the arginine-containing complex shows that the arginines are positioned near the metal. Molecular dynamics (MD) studies also suggest that the positive charge is oriented next to the active site in the two constructs with faster rates but not in the others and that the positive charge near the active site holds the CO 2 near the metal, all consistent with a positive charge appropriately positioned in the scaffold benefiting catalysis. The MD studies also suggest that changes in the water distribution around the active site may contribute to catalytic activity, while modest structural changes and movement of the complex within the scaffold do not.
Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound’s cellular activity. A fraction derived from the plant Polyalthia sp. showed activity against Mycobacterium tuberculosis at 62.5 μge/μL. A known compound, altholactone, was identified from this fraction that showed activity towards M. tuberculosis at an minimum inhibitory concentration (MIC) of 64 μM. Retrospective analysis of a target-based screen against a TB proteome panel using native mass spectrometry established that the active fraction was bound to the mycobacterial protein Rv1466 with an estimated pseudo-Kd of 42.0 ± 6.1 µM. Our findings established Rv1466 as the potential molecular target of altholactone, which is responsible for the observed in vivo toxicity towards M. tuberculosis.
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