Hydrogen Atom Donor Research Articles

Chemical Synthesis of Monolignols: Traditional Methods, Recent Advances, and Future Challenges in Sustainable Processes.

Monolignols represent pivotal alcohol-based constituents in lignin synthesis, playing indispensable roles in plant growth and development with profound implications for industries reliant on wood and paper. Monolignols and their derivates have multiple applications in several industries. Monolignols exhibit antioxidant activity due to their ability to donate hydrogen atoms or electrons to neutralize free radicals, thus preventing oxidative stress and damage to cells. Characterized by their alcohol functionalities, monolignols present three main forms: p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol. In nature, particularly in plants, monolignols with geometry (E) predominate over their Z counterparts. The methods for obtaining the three canonical monolignols, two less-common monolignols, and a monolignol analogue are addressed to present an overview of these phenol-based compounds, particularly from a synthetic standpoint. A SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis is used to explain the advantages and disadvantages of synthesizing monolignols, key alcohol-containing raw materials with enormous significance in both plant biology and industrial applications, using bench chemical methods. The uniqueness of this work is that it provides an overview of the synthetic pathways of monolignols to assist researchers in pharmaceutical and biological fields in selecting an appropriate procedure for the preparation of their lignin models. Moreover, we aim to inspire scientists, particularly chemists, to develop more sustainable synthetic protocols for monolignols.

Spectroscopic Properties and Reactivity of a MnIII-Hydroperoxo Complex that is Stable at Room Temperature.

Manganese catalysts that activate hydrogen peroxide have seen increased use in organic transformations, such as olefin epoxidation and alkane C-H bond oxidation. Proposed mechanisms for these catalysts involve the formation and activation of MnIII-hydroperoxo intermediates. Examples of well-defined MnIII-hydroperoxo complexes are rare, and the properties of these species are often inferred from MnIII-alkylperoxo analogues. In this study, we show that the reaction of the MnIII-hydroxo complex [MnIII(OH)(6Medpaq)]+ (1) with hydrogen peroxide and acid results in the formation of a dark-green MnIII-hydroperoxo species [MnIII(OOH)(6Medpaq)]+ (2). The formulation of 2 is based on electronic absorption, 1H NMR, IR, and ESI-MS data. The thermal decay of 2 follows a first order process, and variable-temperature kinetic studies of the decay of 2 yielded activation parameters that could be compared with those of a MnIII-alkylperoxo analogue. Complex 2 reacts with the hydrogen-atom donor TEMPOH two-fold faster than the MnIII-hydroxo complex 1. Complex 2 also oxidizes PPh3, and this MnIII-hydroperoxo species is 600-fold more reactive with this substrate than its MnIII-alkylperoxo analogue [MnIII(OOtBu)(6Medpaq)]+. DFT and time-dependent (TD) DFT computations are used to compare the electronic structure of 2 with similar MnIII-hydroperoxo and MnIII-alkylperoxo complexes.

Photoinduced Radical Approach for Desulfurative Alkylation of Cysteine Derivatives to Make Unnatural Amino Acids.

Unnatural amino acids (UAAs) are highly valuable molecules in organic synthesis, pharmaceutical sciences, and material science. Herein, we present a photocatalytic radical approach for desulfurative alkylation of cysteine derivatives with arenethiol as the hydrogen atom transfer catalyst for making UAAs and peptides. The formate salt, acting as the hydrogen atom donor, in situ generates the highly reductive CO2 radical anion species, which is the key to unlocking the C-S bond cleavage process with a simple benzoyl protecting group. No photocatalyst is required for the radical initiation and propagation, which makes such a visible-light-induced process mild, efficient, and sustainable.

Cu‐Catalyzed Formal Addition of Aliphatic C(sp3)−H Bonds to Alkenes via Phenyl Radical Involved Intermolecular HAT

AbstractA copper catalyzed aerobic formal addition of aliphatic C(sp3)−H bonds to alkenes via a phenyl radical mediated intermolecular HAT process is reported herein, in which the phenylhydrazine not only acts as a HAT reagent precursor, but also as a hydrogen atom donor. This reaction affords an alternative method for the direct formal addition of aliphatic C(sp3)−H bonds to alkenes utilizing air as the radical initiator without additional reductants at ambient temperature. A variety of alkanes and electron‐deficient alkenes are successfully incorporated, furnishing a series of aliphatic C(sp3)−H formal addition products in 20–93% yield. Preliminary mechanistic studies show that the 2‐tetrahydrofuranyl and phenyl radical are formed in this reaction.

Visible‐Light‐Induced Synthesis of γ‐Amino Sulfones from Vinyl Sulfones and Amino Acids

AbstractA method for the synthesis of γ‐amino sulfones through visible light‐induced oxidative decarboxylation and radical reductive addition is described. Various readily available N‐protected natural amino acids react with aromatic/aliphatic vinyl sulfones to directly produce γ‐amino sulfone derivatives. This reaction is also applicable to α‐N(O)‐acids and other aliphatic carboxylic acids, resulting in the corresponding sulfone derivatives. The method operates without the need for sacrificial reducing agents or additional hydrogen atom donors. The sole by‐product is CO2 released from decarboxylation, rendering the process both atom‐ and step‐economical.

Photoinduced Remote Selective C(sp3)−H Alkylation Mediated by Cesium Formate

AbstractHerein, we developed a photoinduced remote selective C(sp3)−H alkylation of protected amines in the presence of cesium formate. The protected amines were synthesized from commercially available inexpensive 2‐iodo benzoyl chloride. Under mild reaction conditions, the in situ generated aryl radical is converted to α‐amidoalkyl radical via [1,5]‐HAT process, which combines with different Michael acceptors and affords corresponding alkylation products in good yields. Preliminary mechanistic studies revealed that formate anion acts as a source of carbon dioxide radical anion (CO2⋅−) and hydrogen atom donor was directly confirmed by isotope‐labeling studies.

Visible-Light-Induced Hydrodifluoromethylation of Unactivated Alkenes with Difluoroacetic Anhydride.

We herein described a practical and efficient protocol for hydrodifluoromethylation of unactivated alkenes using readily available difluoroacetic anhydride as a difluoromethyl source by merging photocatalysis and N-hydroxyphthalimide activation. This method features a wide substrate scope and excellent compatibility with various functional groups, as demonstrated by more than 50 examples, including bioactive molecules and pharmaceutical derivatives. Mechanism investigation indicated that N-hydroxyphthalimide may also serve as the hydrogen atom donor.

Catalyst-Free Visible Light-Driven Hydrosulfonylation of Alkenes and Alkynes with Sulfonyl Chlorides in Water.

A convenient and sustainable method for synthesizing sulfonyl-containing compounds through a catalyst-free aqueous-phase hydrosulfonylation of alkenes and alkynes with sulfonyl chlorides under visible light irradiation is presented. Unactivated alkenes, electron-deficient alkenes, alkyl and aryl alkynes can be hydrosulfonylated with various sulfonyl chlorides at room temperature with excellent yields and geometric selectivities by using tris(trimethylsilyl)silane as a hydrogen atom donor and silyl radical precursor to activate sulfonyl chlorides. Mechanistic studies revealed that the photolysis of tris(trimethylsilyl)silane in aqueous solution to produce silyl radical is crucial for the success of this reaction.

Highly Efficient Photoinitiation Systems Based on Dibenzo[a,c]phenazine Sensitivity to Visible Light for Dentistry.

In this work, photoinitiation systems based on dibenzo[a,c]phenazine sensitivity to visible light were designed for their potential application in dentistry. Modification of the structure of dibenzo[a,c]phenazine consisted of introducing electron-donating and electron-withdrawing substituents and heavy atoms into position 11. The synthesized compounds are able to absorb radiation emitted by dental lamps during photoinitiation of the polymerization process. In the presence of acrylates, dibenzo[a,c]phenazines show excellent photoinitiating abilities in systems containing an electron donor or a hydrogen-atom donor as a second component. The developed systems initiate the polymerization process comparable to a commercial photoinitiator, i.e., camphorquinone. Moreover, the performed studies showed a significant shortening of the polymerization time and a reduction in the amount of light absorber. This indicates that polymeric materials are obtained at a similar rate despite a significant reduction in the concentration of the newly developed two-component photoinitiating systems.

Design of Dyes Based on the Quinoline or Quinoxaline Skeleton towards Visible Light Photoinitiators.

Dyes based on quinoline and quinoxaline skeletons were designed for application as visible light photoinitiators. The obtained compounds absorb electromagnetic radiation on the border between ultraviolet and visible light, which allows the use of dental lamps as light sources during the initiation of the photopolymerization reaction. Their another desirable feature is the ability to create a long-lived excited state, which enables the chain reaction to proceed through the mechanism of intermolecular electron transfer. In two-component photoinitiating systems, in the presence of an electron donor or a hydrogen atom donor, the synthesized compounds show excellent abilities to photoinitiate the polymerization of acrylates. In control tests, the efficiency of photopolymerization using modified quinoline and quinoxaline derivatives is comparable to that obtained using a typical, commercial photoinitiator for dentistry, camphorquinone. Moreover, the use of the tested compounds requires a small amount of photoinitiator (only 0.04% by weight) to initiate the reaction. The research also showed a significant acceleration of the photopolymerization process and shortening of the reaction time. In practice, this means that the new two-component initiating systems can be used in much lower concentrations without slowing down the speed of obtaining polymer materials. It is worth emphasizing that these two features of the new initiating system allow for cost reduction by reducing financial outlays on both materials (photoinitiators) and electricity.

Potential of Polyphenolic Compounds in Rosella Flowers on Reducing Oxidative Stress and Inflammation After Exercise: A Systematic Review

Study purpose. This study aims to analyze and highlight the potential of rosella flowers in reducing oxidative stress and inflammation after physical activity. Materials and methods. The study used a systematic review method by searching various journal databases such as Scopus, Web of Science, Pubmed and Embase. The inclusion criteria in this study were articles published in the last 5 years and articles discussing Rosella Flowers, Oxidative Stress, Free Radicals, Inflammation, and Exercise. The exclusion criteria in this research were articles published in disreputable journals. A total of 357 articles from the Scopus, Web of Science Pubmed and Embase databases were identified. A total of 8 articles that met the inclusion criteria were selected and analyzed for this systematic review. For standard operations, this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) assessment. Results. The results of this systematic review research report that the flavonoid content found in rosella flowers has anti-oxidant and anti-inflammatory properties which have the potential to reduce oxidative stress and uncontrolled inflammation caused by physical activity and intense exercise. Conclusions. Rosella flowers show their ability as an anti-oxidative by donating hydrogen atoms to free radicals through phenolic compounds, thus breaking the cycle of ROS formation. The natural active ingredients in rosella flowers are able to reduce MDA and increase GSH which contributes to reducing oxidative stress and decreasing TNF-α which provides an anti-inflammatory effect in athletes after exercise.

Enhancement of Vitamin C's Protective Effect against Thimerosal-Induced Neurotoxicity in the Cerebral Cortex of Wistar Albino Rats: An In Vivo and Computational Study.

Vitamin C was examined to ameliorate the neurotoxicity of thimerosal (THIM) in an animal model (Wistar albino rats). In our work, oxidative and antioxidative biomarkers such as SOD, LPO, and GSH were investigated at various doses of THIM with or without concurrent vitamin C administration. Furthermore, the adverse effects of THIM on hepatic tissue and cerebral cortex morphology were examined in the absence or presence of associated vitamin C administration. Also, we studied the effect of vitamin C on the metallothionein isoforms (MT-1, MT-2, and MT-3) in silico and in vivo using the RT-PCR assay. The results showed that the antioxidant biomarker was reduced as the THIM dose was raised and vice versa. THIM-associated vitamin C reduced the adverse effects of the THIM dose. The computation studies demonstrated that vitamin C has a lower ΔG of -4.9 kcal/mol compared to -4.1 kcal/mol for THIM to bind to the MT-2 protein, which demonstrated that vitamin C has a greater ability to bind with MT-2 than THIM. This is due to multiple hydrogen bonds that exist between vitamin C and MT-2 residues Lys31, Gln23, Cys24, and Cys29, and the sodium ion represents key stabilizing interactions. Hydrogen bonds involve electrostatic interactions between hydrogen atom donors (e.g., hydroxyl groups) and acceptors (e.g., carbonyl oxygens). The distances between heavy atoms are typically 2.5-3.5 Å. H-bonds provide directed, high-affinity interactions to anchor the ligand to the binding site. The five H-bonds formed by vitamin C allow it to form a stable complex with MT, while THIM can form two H-bonds with Gln23 and Cys24. This provides less stabilization in the binding pocket, contributing to the lower affinity compared to vitamin C. The histopathological morphologies in hepatic tissue displayed an expansion in the portal tract and the hepatocytes surrounding the portal tract, including apoptosis, binucleation, and karyomegaly. The histopathological morphologies in the brain tissue revealed a significant decrease in the number of Purkinje cells due to THIM toxicity. Interestingly, THIM toxicity was associated with hemorrhage and astrogliosis. Both intracellular and vasogenic edema appeared as the concentrations of THIM rose. Finally, vitamin C ameliorated the adverse effect on the cerebral cortex in Wistar albino rats.

Antioxidant and Nitric Oxide Inhibitory Activity of the Six Most Popular Instant Thai Curries.

All living organisms undergo molecular damage by free radical products. Disrupting the balance between antioxidants and free radicals leads to greater risks of diabetes, hypertension, stroke, and cancer. Consumption of curries containing various herbs and spices provides antioxidant and anti-inflammatory benefits which promote health. The antioxidant and nitric oxide (NO) inhibitory properties of six popular Thai curries, including green curry (G), Panang curry (P), Massaman curry (M), spicy basil leaf curry (SB), southern sour curry (SS), and southern spicy yellow curry (SY) were determined. All six curries contained phenolic and flavonoid compounds and provided antioxidant activity based on electron transfer and hydrogen atom donor properties, as well as having the ability to reduce oxidized metal. The highest antioxidant value was found in SB, followed by M, SS, and SY. The replacement of sugar with dried stevia powder at 50% (Re) improved antioxidant activity. The ORAC assay provided five times higher results than DPPH, ABTS, and FRAP. Extracts of all curries at 1 mg/mL on the macrophage cell line RAW 264.7 showed no cytotoxicity. The highest NO inhibition was found in SB (p < 0.05). All curry extracts contained quercetin, kaempferol, luteolin, and apigenin. The six selected popular Thai curries had antioxidant and anti-inflammatory health benefits. Nutraceuticals, functional foods, and the ingredients of each raw material and curry powder should be further investigated.

Visible Light-Induced Hydroacylation of Benzylidenemalononitriles with Aroyl Chlorides Using Silane as a Hydrogen Donor.

A novel photoredox-catalyzed direct hydroacylation of benzylidenemalononitriles is described. In this method, aroyl chlorides are employed as a readily available and affordable source of acyl groups, while commercially available tris(trimethylsilyl)silane acts as both the hydrogen atom donor and electron donor. By eliminating the requirement for complex synthesis of acyl precursors and hydrogen atom-transfer (HAT) reagents, this approach offers a convenient and efficient strategy for the hydroacylation of benzylidenemalononitriles.

Triethyl amine as an effective reducing agent for sulfoxide deoxygenation.

Enabled by triethyl amine (Et3N) and thionyl chloride (SOCl2), an efficient and practical protocol for deoxygenation of sulfoxide to sulfide was developed. This new method features a wide range of substrate scope, including diaryl, dialkyl and aryl alkyl substituted sulfoxides. Detailed mechanistic investigations reveal the crucial role played by Et3N as an electron-donating reductant rather than a hydrogen-atom donor.

Square-planar imido complexes of cobalt: synthesis, reactivity and computational study.

Treatment of [Co(N2)(tBuPNP)] (tBuPNP = anion of 2,5-bis(di-tert-butylphosphinomethyl)pyrrole) with one equivalent of an aryl azide generates the four-coordinate imido complexes [Co(NAr)(tBuPNP)] (Ar = mesityl, phenyl, or 4-tBu-phenyl). X-ray crystallographic analysis of the compounds shows an unusual square-planar geometry about cobalt with nearly linear imido units. In the presence of the hydrogen atom donor, TEMPOH, [Co(NPh)(tBuPNP)] undergoes addition of the H atom to the imido nitrogen to generate the corresponding amido complex, [Co(NHPh)(tBuPNP)], whose structure and composition were verified by independent synthesis. Despite the observation of H atom transfer reactivity with TEMPOH, the imido complexes do not show catalytic activity for C-H amination or aziridination for several substrates examined. In the case of [Co(NPh)(tBuPNP)], addition of excess azide produced the tetrazido complex, [Co(N4Ph2)(tBuPNP)], whose bond metrics were most consistent with an anionic Ph2N4 ligand. Density Functional Theory (DFT) investigations of the imido and tetrazido species suggest that they adopt a ground state best described as possessing a low-spin cobalt(II) ion ferromagnetically coupled to an iminyl radical.

Coupling Titanium and Chromium Catalysis in a Reaction Network for the Reprogramming of [BH4 ]- as Electron Transfer and Hydrogen Atom Transfer Reagent for Radical Chemistry.

We describe a unique catalytic system with an efficient coupling of Ti- and Cr-catalysis in a reaction network that allows the use of [BH4 ]- as stoichiometric hydrogen atom and electron donor in catalytic radical chemistry. The key feature is a relay hydrogen atom transfer from [BH4 ]- to Cr generating the active catalysts under mild conditions. This enables epoxide reductions, regiodivergent epoxide opening and radical cyclizations that are not possible with cooperative catalysis with radicals or by epoxide reductions via Meinwald rearrangement and ensuing carbonyl reduction. No typical SN 2-type reactivity of [BH4 ]- salts is observed.

Coupling Titanium and Chromium Catalysis in a Reaction Network for the Reprogramming of [BH4]− as Electron Transfer and Hydrogen Atom Transfer Reagent for Radical Chemistry

AbstractWe describe a unique catalytic system with an efficient coupling of Ti‐ and Cr‐catalysis in a reaction network that allows the use of [BH4]− as stoichiometric hydrogen atom and electron donor in catalytic radical chemistry. The key feature is a relay hydrogen atom transfer from [BH4]− to Cr generating the active catalysts under mild conditions. This enables epoxide reductions, regiodivergent epoxide opening and radical cyclizations that are not possible with cooperative catalysis with radicals or by epoxide reductions via Meinwald rearrangement and ensuing carbonyl reduction. No typical SN2‐type reactivity of [BH4]− salts is observed.

Synthetic iron-sulfur clusters as hydrogen atom donors

Synthetic iron-sulfur clusters as hydrogen atom donors

Visible‐Light‐Promoted Aliphatic C−H Chlorination and Bromination Using Haloform as the Halogen Donor and Azidobenziodoxole as the Mediator

AbstractAn azidobenziodoxole (BIN3)‐mediated tunable radical reaction system for selective chlorination and bromination of tertiary and secondary C(sp3)−H bonds of alkyl substrates using haloform as the halogen donor was developed. Reactions of various substrates with BIN3 under visible light irradiation without any photo or metal catalysts gave C−H chlorinated or brominated products. These reactions are selective, and compatible with many functional groups. Mechanistic studies suggest that haloform serves as the halogen atom donor and HN3 generated in situ from the reaction of BIN3 and water relays the radical chain reaction as the hydrogen atom donor. HN3 reacts with CHX2⋅ to form CH2X2 and N3⋅, which propagates a radical chain by abstracting a hydrogen atom of the alkane substrate.