Bond Formation Research Articles

Critical Sensing Modalities for Hydrogen: Technical Needs and Status of the Field to Support a Changing Energy Landscape.

Decarbonization of the energy system is a key aspect of the energy transition. Energy storage in the form of chemical bonds has long been viewed as an optimal scheme for energy conversion. With advances in systems engineering, hydrogen has the potential to become a low cost, low emission, energy carrier. However, hydrogen is difficult to contain, it exhibits a low flammability limit (>40000 ppm or 4%), low ignition energy (0.02 mJ), and it is a short-lived climate forcer. Beyond commercially available sensors to ensure safety through spot checks in enclosed environments, new sensors are necessary to support the development of low emission infrastructure for production, transmission, storage, and end use. Efficient scalable broad area hydrogen monitoring motivates lowering the detection limit below that (10 ppm) of best in class commercial technologies. In this perspective, we evaluate recent advances in hydrogen gas sensing to highlight technologies that may find broad utility in the hydrogen sector. It is clear in the near term that a sensor technology suite is required to meet the variable constraints (e.g., power, size/weight, connectivity, cost) that characterize the breadth of the application space, ranging from industrial complexes to remote pipelines. This perspective is not intended to be another standard hydrogen sensor review, but rather provide a critical evaluation of technologies with detection limits preferably below 1 ppm and low power requirements. Given projections for rapid market growth, promising techniques will also be amenable to rapid development in technical readiness for commercial deployment. As such, methods that do not meet these requirements will not be considered in depth.

Cisplatin-activated and hemoglobin-mediated injectable hydrogel system for antitumor chemodynamic and chemotherapy

Low specificity and hypoxia-induced drug resistance are significant challenges in traditional cancer treatment. To enhance the anticancer efficacy, an injectable hydrogel system is developed through the formation of dynamic covalent bonds in hyaluronic acid, allowing for localized controlled release of drugs. This system also utilizes double-stranded DNA sequences for the intercalation delivery of the chemotherapeutic drug, enabling a multifaceted approach to therapy. Cisplatin not only serves as a chemotherapy drug but also acts as a catalyst for chemodynamic therapy (CDT) to initiate CDT cascades by creating hydrogen peroxide for the Fenton reaction. Hemoglobin, enclosed in PLGA nanoparticles, provides ferrous ions that react with hydrogen peroxide in an acidic environment, yielding hydroxyl radicals that induce cancer cell death. Additionally, oxygen released from hemoglobin mitigates hypoxia-induced chemoresistance, bolstering overall anticancer efficacy. Results demonstrate the shear-thinning properties and injectability of the hydrogel. Cisplatin elevates intracellular hydrogen peroxide levels in tumor cells, while hemoglobin efficiently releases ferrous ions and generates reactive oxygen species (ROS) in the presence of hydrogen peroxide. In in vitro and in vivo study, the combinational use of chemo- and chemodynamic therapies achieves a synergistic anticancer effect on combating glioblastoma. In summary, our CDT-based hydrogel, activated by endogenous cues and mediated by chemo drugs, spontaneously produces ROS and ameliorates the adverse tumor microenvironment with rational and selective antitumor strategies.

Tris(pentafluorophenyl)borane‐catalyzed functionalization of benzylic C–F bonds

The activation of C(sp3)–F bonds by the commercially available catalyst B(C6F5)3 is reported and applied in reactions with arenes, allylic, vinylic and acetylenic silanes, and olefins to achieve a variety of C–C bond formations (45 examples).

Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis.

The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp3)-C(sp3) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.

Polymer containing Pd(II) chelates grafted from SBA-15 for C–C bond formation via the Mizoroki–Heck reaction

Polymer containing Pd(II) chelates grafted from SBA-15 for C–C bond formation via the Mizoroki–Heck reaction

Darobactin Substrate Engineering and Computation Show Radical Stability Governs Ether versus C-C Bond Formation.

The Gram-negative selective antibiotic darobactin A has attracted interest owing to its intriguing fused bicyclic structure and unique targeting of the outer membrane protein BamA. Darobactin, a ribosomally synthesized and post-translationally modified peptide (RiPP), is produced by a radical S-adenosyl methionine (rSAM)-dependent enzyme (DarE) and contains one ether and one C-C cross-link. Herein, we analyze the substrate tolerance of DarE and describe an underlying catalytic principle of the enzyme. These efforts produced 51 enzymatically modified darobactin variants, revealing that DarE can install the ether and C-C cross-links independently and in different locations on the substrate. Notable variants with fused bicyclic structures were characterized, including darobactin W3Y, with a non-Trp residue at the twice-modified central position, and darobactin K5F, which displays a fused diether ring pattern. While lacking antibiotic activity, quantum mechanical modeling of darobactins W3Y and K5F aided in the elucidation of the requisite features for high-affinity BamA engagement. We also provide experimental evidence for β-oxo modification, which adds support for a proposed DarE mechanism. Based on these results, ether and C-C cross-link formation was investigated computationally, and it was determined that more stable and longer-lived aromatic Cβ radicals correlated with ether formation. Further, molecular docking and transition state structures based on high-level quantum mechanical calculations support the different indole connectivity observed for ether (Trp-C7) and C-C (Trp-C6) cross-links. Finally, mutational analysis and protein structural predictions identified substrate residues that govern engagement to DarE. Our work informs on darobactin scaffold engineering and further unveils the underlying principles of rSAM catalysis.

Revealing the Roles of Guanidine Hydrochloride Ionic Liquid in Ion Inhibition and Defects Passivation for Efficient and Stable P erovskites Solar Cells.

As a result of full-scale ongoing global efforts, the power conversion efficiency (PCE) of the organic-inorganic metal halide perovskite has skyrocketed. Unfortunately, the long-term operational stability for commercialization standards is still lagging owing to intrinsic defects such as ion migration-induced degradation, undercoordinated Pb2+, and shallow defects initiated by disordered crystal growth. Herein, we employed multifunctional, non-volatile tetra-methyl guanidine hydrochloride [TMGHCL] ionic liquid (IL) as an additive to elucidate defects' passivation effects on organic-inorganic metal halide perovskite. More specifically, the formation of hydrogen bonds between H+ in GA+ and I- and coordinate bonding between Cl- and undercoordinated PbI2+could significantly passivate these defects. The hypothesis was confirmed by both experimental and DFT simulations displaying that the optimized ratio of IL integration restrains ion migration, improving grains' size, and significantly elongating the carrier lifetime. Remarkably, the modified cell achieved a peak efficiency of 22.00% with negligible hysteresis, compared to the control device's PCE of 20.12%. In addition, the TMGHCL-based device retains its 93.29% efficiency after 16 days of continuous exposure to air. This efficient approach of adding IL to perovskites absorber can produce high PCE and has strong commercialization potential.

Tuning structural and electronic properties of metal-organic framework 5 by metal substitution and linker functionalization.

The chemical flexibility of metal-organic frameworks (MOFs) offers an ideal platform to tune structure and composition for specific applications, from gas sensing to catalysis and from photoelectric conversion to energy storage. This variability gives rise to a large configurational space that can be efficiently explored using high-throughput computational methods. In this work, we investigate from first principles the structural and electronic properties of MOF-5 variants obtained by replacing Zn with Be, Mg, Cd, Ca, Sr, and Ba and by functionalizing the originally H-passivated linkers with CH3, NO2, Cl, Br, NH2, OH, and COOH groups. To build and analyze the resulting 56 structures, we employ density-functional theory calculations embedded in an in-house developed library for automatized calculations. Our findings reveal that structural properties are mainly defined by metal atoms and large functional groups, which distort the lattice and modify coordination. The formation energy is largely influenced by functionalization and enhanced by COOH and OH groups, which promote the formation of hydrogen bonds. The charge distribution within the linker is especially influenced by functional groups with electron-withdrawing properties, while the metal nodes play a minor role. Likewise, the bandgap size is crucially determined by ligand functionalization. The smallest gaps are found with NH2 and OH groups, which introduce localized orbitals at the top of the valence band. This characteristic makes these functionalizations particularly promising for the design of MOF-5 variants with enhanced gas uptake and sensing properties.

DEVELOPING NEXT-GENERATION INJECTABLE ADIPOSE TISSUE GRAFTS FOR SOFT-TISSUE RECONSTRUCTION

IntroductionAutologous fat grafting has favourable potential as a regenerative strategy and is the current gold-standard to repair large contour defects, as needed in breast reconstruction after mastectomy and traumatic soft tissue reconstruction. Clinically, there is a limit on the volume of lipoaspirate which can be utilised to repair a soft-tissue defect. Surgical complications are the result of poor structural fidelity of lipoaspirate and graft resorption as a filling material and are hindered further by poor graft vascularisation. This study aims to develop injectable lipoaspirate-derived adipose tissue grafts with enhanced biologically and clinically-admissible structural and functional properties adopting light photocrosslinking of unmodified lipoaspirate.MethodsPatient-derived lipoaspirate was harvested and crosslinked using novel photoinitiator and exposure to visible light (wavelength 450nm) in surgery, establishing bonds between extracellular matrix (ECM) proteins within the material. The degree of crosslinking was tuned (photoinitiator concentration, light exposure, light intensity) and covalent bond formation measured using mass spectrometry. To predict patient response, SWATH-MS was used to identify differences in patient ECM and crosslinked grafts were implanted in vivo using a subcutaneous mouse model. Functional vessel formation and resorption were quantified using micro-CT and tissue-remodelling was assessed via histology.ResultsThere was an increase in the relative abundance of covalent bonds present with increasing degree of crosslinking. When injected, crosslinked lipoaspirate had better shape fidelity compared with native lipoaspirate – demonstrated by a smaller fibre diameter. Crosslinked lipoaspirate remained viable over long term culture and resulted in more predictable resorption profiles when implanted in vivo.ConclusionsThe crosslinking approach described here is tunable and functional across different patient samples. Improving the structural properties of lipoaspirate through minimal manipulation has clinical utility for the delivery of grafts with higher shape fidelity and therefore increased graft survival when implanted.

Enhanced Surface Accessibility of SARS-CoV-2 Omicron Spike Protein Due to an Altered Glycosylation Profile.

SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding in proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including the ectodomain, receptor-binding domain, and N-terminal domain. Additionally, mutagenesis and pull-down assays reveal the role of glycosylation of a specific sequon (N149); furthermore, the correlation of MD simulation and HDX-MS identified several high-dynamic areas of the spike proteins. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies.

Synthesis of (Hetero)biaryls via Nickel Catalyzed Reductive Cross‐Electrophile Coupling Between (Hetero)aryl Iodides and Bromides

(Hetero)biaryls are fundamental building blocks in the pharmaceutical industry and rapid access to these scaffolds is imperative for the success of numerous medicinal chemistry campaigns. Herein, a highly general, mild, and chemoselective reductive cross‐electrophile coupling between (hetero)aryl iodides and heteroaryl bromides is reported. By employing more reactive (hetero)aryl halides, a broad range of successful substrates (45 examples) were identified. The reaction was also found to be chemoselective for C(sp2)–C(sp2) bond formation between (hetero)aryl iodides and bromides over (hetero)aryl chlorides, which were generally inert under the described reaction conditions. The efficiency of the procedure is also further demonstrated in parallel synthesis library format, on gram scale, as well as in the formal synthesis of Ruxolitinib, a potent JAK inhibitor. As such, we anticipate this method will find widespread utility in the assembly of (hetero)biaryls for medicinal chemistry efforts.

Palladium‐catalyzed domino reaction for the synthesis of benzo‐cyclohepta‐quinolinone analogues from Cedrus deodara oil

First‐time vinyl bromide‐substituted benzocycloheptene compound has been explored as a precursor for the synthesis of benzo‐cyclohepta‐quinolinone (BCQ) analogues following a domino reaction. The vinyl bromide‐substituted benzocycloheptene was synthesized from himachalenes, extracted from Cedrus deodara oil. The reaction proceeds through C‐C bond formation followed by palladium catalyzed C‐N cross‐coupling and dehydrogenative aromatization in a consecutive and atom‐economic approach for BCQ analogues synthesis. Moreover, the present methodology is applicable for various substituted β‐enaminones with good to moderate yield.

Deciphering Charge Transfer Processes in Transition Metal Complexes from the Perspective of Ultrafast Electronic and Nuclear Motions.

Chemical transformations in charge transfer states result from the interplay between electronic dynamics and nuclear reorganization along excited-state trajectories. Here, we investigate the ultrafast structural dynamics following photoinduced electron transfer from the metal-metal-to-ligand charge transfer state of an electron donor, a Pt dimer complex, to a covalently linked electron acceptor group using ultrafast time-resolved wide-angle X-ray scattering and optical transient absorption spectroscopy methods to disentangle the interdependence of the excited-state electronic and nuclear dynamics. Following photoexcitation, Pt-Pt bond formation and contraction takes up to 1 ps, much slower than the corresponding process in analogous complexes without electron acceptor groups. Because the Pt-Pt distance change is slow with respect to excited-state electron transfer, it can affect the rate of electron transfer. These results have potential impacts on controlling electron transfer rates via structural alterations to the electron donor group, tuning the charge transfer driving force.

Sustainable Synthesis through Catalyst-Free Photoinduced Cascaded Bond Formation.

The beginning of photochemical reactions revolutionized synthetic chemistry through sustainable practices. This review explores cutting-edge developments in leveraging light-induced processes for generating cascaded C-C and C-hetero bonds without catalysts. Significantly, catalyst-free photoinduced methodologies have garnered considerable attention, especially in the creation of varied heterocyclic frameworks for drug design and the synthesis of natural products. The article delves into underlying mechanisms, addresses limitations, and evaluates various methodologies, emphasizing the potential of photocatalyst and transition metal-free photochemical reactions to enhance sustainability. Divided into two sections, it covers recent strides in C-C and C-heteroatom and multiple C-heteroatom bond formation reactions.

Constructing interface chemical coupling S-scheme heterojunction MoO3-x@PPy for enhancing photocatalytic oxidative desulfurization performance: Adjusting LSPR effect via oxygen vacancy engineering

Construction of photocatalyst that combines excellent electron transfer and photoresponse capabilities to enhance photocatalytic performance remains a challenging task. In this work, interfacial Mo-N bonds and vacancy engineering collaborative modified MoO3-x@polypyrrole (MP) S-scheme heterojunction is rational designed for efficient photocatalytic oxidative desulfurization. The addition of polypyrrole introduces rich defects which inducing the localized surface plasmon resonance (LSPR) effect and enhancing light absorption. Furthermore, the combination facilitates the formation of Mo-N bonds. The modifications amplify the built-in electric field and conduct the efficacious separation of photogenerated carriers. With the synergism of LSPR effect and interfacial chemical Mo-N bonds, the optimal MP photocatalyst displays attractive desulfurization rate of 100% for dibenzothiophene (DBT) in 60 min under illumination, touching the objective of ultra-deep desulfurization. The study extends a novel understanding of the impact of LSPR effect and heterojunction interface charge transfer on the photocatalytic desulfurization ability.

Effects of electrical stimulation on carbon sequestration of photosynthetic bacteria: Response of the photosynthetic unit to electrical stimulation

Bioelectrochemical systems have been used to enhance the carbon sequestration of photosynthetic bacteria (PSB), but it is unclear whether the electrical stimulation affects the structure of membrane proteins involved in photochemical activity. In this study, the rate of CO2 fixation in the photosynthetic bacteria R. palustris increased with electrical stimulation, and the enhancement partly remained even after the power off. The CO2 fixation rate in electrical-stimulated PSB was 10% higher than in non-stimulated PSB, and the activity of the CO2 fixation enzyme Rubisco was 16% higher. This resulted from the improved light utilization efficiency of the photosynthetic units in R. palustris after electrical stimulation, particularly due to the enhancement of the primary reaction mediated by the light capture protein RC-LH1. The molar extinction coefficient of the light capture protein RC-LH1 increased from 3301 cm−1 mM−1 to 3733 cm−1 mM−1, and the maximum rate of the primary reaction increased from 6.88 × 10−3 e−RC−1s−1 to 8.66 × 10−3 e−RC−1s−1. Circular dichroism spectroscopy and Fourier transform infrared spectroscopy indicated that the electrical stimulation increased the dipole moment of the α-helix in RC-LH1 to facilitate the quinone transport in the primary reaction. Nuclear magnetic resonance spectroscopy revealed that the electrical stimulation increased the formation of hydrogen bonds in bacteriochlorophyll a for electron transition. This study investigated the response of photosynthetic bacteria to electrical stimulation, providing a distinct outlook on the electrochemical regulation of photosynthesis for carbon capture.

Molecular Hydrogen Acts as a Hydrogen Bond Proton Acceptor: From Protonated Betaine Tagging to the Weakest Hydrogen Bond.

In an attempt to gain further insights into the intermolecular interactions implied by Rizzo's group's cautionary tale related to molecular tagging in infrared multiple photon dissociation (IRMPD) spectroscopy with molecular messengers [Masson, A. . J. Chem. Phys. 2015, 143, 104313], in the present study, we provide an in-depth analysis of the noncovalent interaction between the molecular hydrogen and protonated betaine molecule in the gas phase. We aim to shed some new light on the fundamental issues concerning the wide diapason of hydrogen-bonding-type intermolecular interactions, with a wide variety of proton acceptors. We demonstrate that in the course of tagging the protonated betaine with molecular hydrogen from the OH group side, it is the σ bond of molecular hydrogen that plays the role of hydrogen-bonding proton acceptor. The tagging thus induces a small yet significant red shift of the protonated betaine O-H stretching mode. We investigate the performance of a wide range of density functional theory (DFT) functionals for the calculation of anharmonic vibrational frequency shifts of the studied system, which are essential for the correct interpretation of the experimental IRMPD data. For an accurate prediction of the OH stretching frequency shifts, specifically designed functionals such as Handy's group HCTH/407 should be applied. The empirical dispersion correction enhances the systematic overestimation of the anharmonic frequency shift, characteristic of the most widely used DFT functionals. Combining the full-wave function approach with the charge field perturbation and natural bond orbital (NBO) deletion analyses, we demonstrate that the frequency shift in the OH-tagged structure is governed by the σHH → σ*OH intermolecular charge transfer. This interaction stabilizes the OH-tagged dimer as well, in contrast to the dipole-quadrupole electrostatic interaction energy term. Topological analysis of the electron density reveals the presence of an intermolecular bond critical point with a positive value of the density Laplacian very close to the lower limit for hydrogen bonds. NCI analyses demonstrate that the OH···H2 interaction is weaker than the intramolecular CH···O one within the protonated betaine molecule, with the through of reduced density gradient appearing at less negative sign(λ2)·ρ values. Analyzing the O-H stretching vibrational potential with the second-generation absolutely localized molecular orbitals energy decomposition analysis (ALMO-EDA 2) revealed that in the case of betaineH(+) tagged from the OH group side, the permanent electrostatics (ΔEelec), polarization (ΔEpol), and charge-transfer (ΔEct) contributions to the total intermolecular interaction energy contribute favorably to the weak hydrogen bond formation and to the red shift of the fundamental O-H stretching frequency, the ΔEct contribution being the most significant in the last context. The Pauli repulsion term, on the other hand, favors an O-H stretching frequency blue shift as a consequence of the vibrational confinement effects.

Mechanical Interatomic Bond Formation in Ethanol and Methanol-Ethanol Mixture by Laser-Driven Shock Waves.

Molecules, which were predicted to be produced by C-C or C-O bond formation between ethanol molecules induced by a laser-driven shock wave, were identified by gas chromatography-mass spectrometry. Moreover, the laser irradiation of a methanol-ethanol mixture revealed the formation of C-C and C-O bonds between both components. Particularly, four hemiacetals (methoxymethanol, 1-methoxyethanol, ethoxymethanol, and 1-ethoxyethanol) were identified in the Ar-saturated alcohol samples, whereas acetalization dominated sufficiently in the CO2-saturated samples, significantly reducing the hemiacetals. It was verified that some molecules were produced by the dropout of an ethanol part during the C-C or C-O bond formation, supporting the contribution of laser-driven shock waves.

Shining bright: B@S-codoped graphitic carbon nitride nanorods illuminate enhanced catalytic C-N bond formation under visible-light

Graphitic carbon nitride as a photocatalyst seeking attention nowadays, due to its thermal stability, band structure, and chemical properties. Herein, we reported a boron sulfur co-doped graphitic carbon nitride (B@S-g-C3N4) photocatalyst synthesized by a one-pot thermal polycondensation mechanism. However, it was observed that due to co-doping in native carbon nitride structure the photocatalytic behavior and the band structure enhanced which was capable of fascinating the demand of organic transformations i.e. photocatalytic and charge transfer capability. The synthesized B@S-g-C3N4 photocatalyst was characterized by UV–vis DRS, FT-IR, XRD, SEM, EDX, HR-TEM, XPS and electrochemical properties. In addition, the synthesized B@S-g-C3N4 photocatalyst is a metal-free carbon nitride photocatalyst proven to be highly effective in performing organic transformations (conversion yield 98 %) like C-N bond formation under visible light source.

Rationally Designed Carbon‐Based Catalysts for Electrochemical C‐N Coupling

AbstractThe electrochemical C‐N coupling process, facilitating the production of organic nitrogen substances (such as urea, methylamine, formamide, and ethylamine) via the simultaneous reduction of carbon dioxide (CO2) and small nitrogen‐based substances, stands at the forefront of advancing carbon neutrality and the artificial nitrogen cycle. This method has garnered substantial interest due to its potential economic and environmental benefits. Although considerable progress has been achieved in this emerging field, it still faces challenges, including slow reactant adsorption, competing side reactions, and complex multi‐step pathways, resulting in low yields and selectivity. Strategically designing and developing low‐cost and exceptionally performant catalysts is crucial for cost‐effective and precise electrochemical C─N bonding. This article offers an in‐depth review of the electrosynthesis of valuable organic nitrogen compounds at ambient conditions from earth‐abundant resources/wastes, such as CO2 and small nitrogenous molecules (nitrogen: N2, nitrite: NO2−, nitrate: NO3−, ammonia: NH3, etc.), via electrochemical C─N bond formation reactions, especially using carbon‐based catalysts. The relevant electrochemical C─N bond formation mechanisms, the design principles of advanced carbon‐based electrocatalysts, and the impact of different electrolyser designs are discussed, along with the present obstacles and upcoming prospects in this dynamic field.