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Inorganic Chemistry Aug 2023Characterization of reactive intermediates in C-H functionalization is challenging due to the fleeting lifetimes of these species. Synthetic photochemistry provides a...
Characterization of reactive intermediates in C-H functionalization is challenging due to the fleeting lifetimes of these species. Synthetic photochemistry provides a strategy to generate post-turnover-limiting-step intermediates in catalysis under cryogenic conditions that enable characterization. We have a long-standing interest in the structure and reactivity of Rh nitrene intermediates, which are implicated as transient intermediates in Rh-catalyzed C-H amination. Previously, we demonstrated that Rh complexes bearing organic azide ligands can serve as solid-state and photoprecursors in the synthesis of transient Rh nitrenoids. Complementary solution-phase experiments have not been available due to the weak binding of most organic azides to Rh complexes. Furthermore, the volatility of the N that is evolved during nitrene synthesis from these precursors has prevented the observation of C-H functionalization from lattice-confined nitrenes. Motivated by these challenges, here we describe the synthesis and photochemistry of nonclassical nitrene precursors based on sulfilimine ligands. Sulfilimines bind to Rh carboxylate complexes more tightly than the corresponding azides, which has enabled the full solid-state and solution-phase characterization of these new complexes. The higher binding affinity of sulfilimine ligands as compared with organic azides has enabled both solution-phase and solid-state nitrene photochemistry. Cryogenic photochemical studies of Rh sulfilimine complexes confined within polystyrene thin films demonstrate that sulfilimine photochemistry can be accomplished at low temperature but that C-H amination is rapid at temperatures compatible with N═S photoactivation. The potential of these structures to serve as platforms for multistep cascades is discussed.
PubMed: 37499228
DOI: 10.1021/acs.inorgchem.3c01820 -
Journal of the American Chemical Society Nov 2023Synthetic porous materials continue to garner attention as platforms for solid-state chemistry and as designer heterogeneous catalysts. Applications in photochemistry...
Synthetic porous materials continue to garner attention as platforms for solid-state chemistry and as designer heterogeneous catalysts. Applications in photochemistry and photocatalysis, however, are plagued by poor light harvesting efficiency due to light scattering resulting from sample microcrystallinity and poor optical penetration that arises from inner filter effects. Here we demonstrate the layer-by-layer growth of optically transparent, photochemically active thin films of porous salts. Films are grown by sequential deposition of cationic Zr-based porous coordination cages and anionic Mn porphyrins. Photolysis facilitates the efficient reduction of Mn(III) sites to Mn(II) sites, which can be observed in real-time by transmission UV-vis spectroscopy. Film porosity enables substrate access to the Mn(II) sites and facilitates reversible O activation in the solid state. These results establish optically transparent, porous salt thin films as versatile platforms for solid-state photochemistry and spectroscopy.
PubMed: 37939007
DOI: 10.1021/jacs.3c09188 -
Journal of Molecular Biology Dec 2023G protein-coupled receptors (GPCRs) form the largest superfamily of membrane proteins in the human genome, and represent one of the most important classes of drug...
G protein-coupled receptors (GPCRs) form the largest superfamily of membrane proteins in the human genome, and represent one of the most important classes of drug targets. Their structural studies facilitate rational drug discovery. However, atomic structures of only about 20% of human GPCRs have been solved to date. Recombinant production of GPCRs for structural studies at a large scale is challenging due to their low expression levels and stability. Therefore, in this study, we explored the efficacy of the eukaryotic system LEXSY (Leishmania tarentolae) for GPCR production. We selected the human A adenosine receptor (AAR), as a model protein, expressed it in LEXSY, purified it, and compared with the same receptor produced in insect cells, which is the most popular expression system for structural studies of GPCRs. The AAR purified from both expression systems showed similar purity, stability, ligand-induced conformational changes and structural dynamics, with a remarkably higher protein yield in the case of LEXSY expression. Overall, our results suggest that LEXSY is a promising platform for large-scale production of GPCRs for structural studies.
Topics: Humans; Drug Discovery; Receptors, G-Protein-Coupled; Recombinant Proteins; Leishmania; Receptor, Adenosine A2A; Protein Conformation; Ligands; Protein Stability
PubMed: 37806553
DOI: 10.1016/j.jmb.2023.168310 -
Chemical Record (New York, N.Y.) Mar 2024Cryptolepine, neocryptolepine, and isocryptolepine have remained popular synthetic targets ever since their isolation from the aqueous extracts of the West African... (Review)
Review
Cryptolepine, neocryptolepine, and isocryptolepine have remained popular synthetic targets ever since their isolation from the aqueous extracts of the West African climbing shrub Cryptolepis sanguinolenta. These natural alkaloids were found to contain significant antimalarial, antiproliferative and antimicrobial activities, making them ideal starting points for the development of novel drug candidates. As natural product synthesis is often plagued with step-heavy procedures and poor atom economy, the discovery of synthetic protocols addressing these concerns are sorely needed. In our laboratories, we have devoted our efforts into the development of regiodivergent synthesis whereby two of the indoloquinoline natural products, namely neocryptolepine and 11H-indolo[3,2-c]quinolines, could be assembled in only a few steps from a common and readily available starting material. Our synthetic endeavors to meet these goals include a cascade palladium-catalyzed Suzuki-Miyuara cross-coupling and intramolecular C-N bond formation and a photochemical nitrene insertion strategy. Furthermore, our methods also allowed for the construction of several diversely functionalized natural product derivatives which were subjected to biological evaluations.
Topics: Biological Products
PubMed: 38319822
DOI: 10.1002/tcr.202300362 -
Journal of the American Chemical Society May 2024We present a detailed study of the time-dependent photophysics and photochemistry of a known conformation of the two protonated pentapeptides Leu-enkephalin...
We present a detailed study of the time-dependent photophysics and photochemistry of a known conformation of the two protonated pentapeptides Leu-enkephalin (Tyrosine-Glycine-Glycine-Phenylalanine-Leucine, YGGFL) and its chromophore-swapped analogue FGGYL, carried out under cryo-cooled conditions in the gas phase. Using ultraviolet-infrared (UV-IR) double resonance, we record excited state IR spectra as a function of time delay between UV and IR pulses. We identify unique Tyr OH stretch transitions due to the S state and the vibrationally excited triplet state(s) formed by intersystem crossing, T(v). Photofragment mass spectra are recorded out of the S origin and following UV-IR double resonance. Several competing site-specific fragmentation pathways are discovered involving peptide backbone cleavage, Tyr side chain loss, and N-terminal NH loss mediated by electron transfer. In YGGFL, IR excitation in the S state promotes electron transfer (ET) from the aromatic ring to the N-terminal R-NH group leading to loss of neutral NH. This product channel is missing in FGGYL due to the larger distance for ET from Y(4) to NH. Selective loss of the Tyr side chain occurs out of an excited state process following UV excitation and is further enhanced by IR excitation in S and T(v) states of both YGGFL and FGGYL. Finally, IR excitation in the S or T(v) states fragments the peptide backbone exclusively at amide(4), producing the b cation. We postulate that this selective fragmentation results from intersystem crossing to produce vibrationally excited triplets with enough energy to launch the proton along a proton conduit present in the known starting structure.
Topics: Protons; Photochemical Processes; Spectrophotometry, Infrared; Peptides; Enkephalin, Leucine
PubMed: 38687970
DOI: 10.1021/jacs.4c01576 -
Angewandte Chemie (International Ed. in... Oct 2023Catalytic hydrogen atom transfer from metal-hydrides to alkenes allows feedstock olefins to be used as alkyl radical precursors. The chemoselectivity of this process... (Review)
Review
Catalytic hydrogen atom transfer from metal-hydrides to alkenes allows feedstock olefins to be used as alkyl radical precursors. The chemoselectivity of this process makes it an attractive synthetic tool and as such it has been regularly used in synthesis of complex molecules. However, onwards reactivity is limited by compatibility with the conditions which form the key metal-hydride species. Now, through the merger with photocatalysis or electrochemistry, milder methods are emerging which can unlock entirely new reactivity and offer perspectives on expanding these methods in unprecedented directions. This review outlines the most recent developments in electro- and photochemical cobalt catalysed methods and offers suggestions on the future outlook.
PubMed: 37184388
DOI: 10.1002/anie.202304882 -
Organic Letters Jan 2024Photooxygenation of flavonoids leads to the release of carbon monoxide (CO). Our structure-photoreactivity study, employing several structurally different flavonoids,...
Photooxygenation of flavonoids leads to the release of carbon monoxide (CO). Our structure-photoreactivity study, employing several structurally different flavonoids, including their C-labeled analogs, revealed that CO can be produced via two completely orthogonal pathways, depending on their hydroxy group substitution pattern and the reaction conditions. While photooxygenation of the enol 3-OH group has previously been established as the CO liberation channel, we show that the catechol-type hydroxy groups of ring B can predominantly participate in photodecarbonylation.
Topics: Carbon Monoxide; Flavonoids; Photochemistry
PubMed: 38227978
DOI: 10.1021/acs.orglett.3c04141 -
Small (Weinheim An Der Bergstrasse,... Jan 2024Cyano-rich g-C N materials are widely used in various fields of photochemistry due to the very powerful electron-absorbing ability and electron storage function of... (Review)
Review
Cyano-rich g-C N materials are widely used in various fields of photochemistry due to the very powerful electron-absorbing ability and electron storage function of cyano, as well as its advantages in improving light absorption, adjusting the energy band structure, increasing the polarization rate and electron density in the structure, active site concentration, and promoting oxygen activation ability. Notwithstanding, there is yet a huge knowledge break in the design, preparation, detection, application, and prospect of cyano-rich g-C N . Accordingly, an overall review is arranged to substantially comprehend the research progress and position of cyano-rich g-C N materials. An overall overview of the current research position in the synthesis, characterization (determination of their location and quantity), application, and reaction mechanism analysis of cyano-rich g-C N materials to provide a quantity of novel suggestions for cyano-modified carbon nitride materials' construction is provided. In view of the prevailing challenges and outlooks of cyano-rich g-C N materials, this paper will purify the growth direction of cyano-rich g-C N , to achieve a more in-depth exploration and broaden the applications of cyano-rich g-C N .
PubMed: 37670529
DOI: 10.1002/smll.202304404 -
The Journal of Physical Chemistry... Mar 2024Electron donor-acceptor (EDA) complex photochemistry has emerged as a vibrant area in visible-light-mediated synthetic radical chemistry. However, theoretical insights... (Review)
Review
Electron donor-acceptor (EDA) complex photochemistry has emerged as a vibrant area in visible-light-mediated synthetic radical chemistry. However, theoretical insights into the reaction mechanisms remain limited. Our study investigates the influence of solvent polarity and halogen atom types on radical reaction pathways in EDA complexes. We demonstrate that solvent polarity modulates the charge transfer and spatial arrangement within EDA complexes, thereby influencing their stability and reaction kinetics. Iodide ions play a crucial role in facilitating free radical generation and stabilizing reaction intermediates. Different halogen atom types exhibit distinct effects on radical reactions. Variations in radical concentration and solvent environment further affect the pathway selectivity. Additionally, light conditions influence the free radical generation and pathway selectivity. Our findings enhance the understanding of EDA complex photochemistry and radical reactions, offering insights for organic synthesis and photochemistry applications.
PubMed: 38502941
DOI: 10.1021/acs.jpclett.4c00455 -
Chemical Science Sep 2023Mn(diimine)(CO)X (X = halide) complexes are critical components of chromophores, photo- and electrocatalysts, and photoactive CO-releasing molecules (photoCORMs). While...
Mn(diimine)(CO)X (X = halide) complexes are critical components of chromophores, photo- and electrocatalysts, and photoactive CO-releasing molecules (photoCORMs). While these entities have been incorporated into metal-organic frameworks (MOFs), a detailed understanding of the photochemical and chemical processes that occur in a permanently porous support is lacking. Here we site-isolate and study the photochemistry of a Mn(diimine)(CO)Br moiety anchored within a permanently porous MOF support, allowing for not only the photo-liberation of CO from the metal but also its escape from the MOF crystals. In addition, the high crystallinity and structural flexibility of the MOF allows crystallographic snapshots of the photolysis products to be obtained. We report these photo-crystallographic studies in the presence of coordinating solvents, THF and acetonitrile, showing the changing coordination environment of the Mn species as CO loss proceeds. Using time resolved experiments, we report complementary spectroscopic studies of the photolysis chemistry and characterize the final photolysis product as a possible Mn(ii) entity. These studies inform the chemistry that occurs in MOF-based photoCORMs and where these moieties are employed as catalysts.
PubMed: 37712014
DOI: 10.1039/d3sc03553k