Phenolic Dimers Research Articles

Guidelines for Identifying the Structure of Heavy Phenolics in Lignin Depolymerization by using High-Resolution Tandem Mass Spectrometry.

The efficient conversion of lignin contributes to reducing human reliance on fossil energy. As a complicated biopolymer, studies on the mechanism of lignin depolymerization is limited by inadequate structural identification of high molecular weight (MW) products like heavy phenolics. Up to now, no individual method can generate both MW and structural information in operando conditions. As a promising approach, tandem mass spectrometry (MS/MS) techniques can provide structural information via the dissociation of target ions. In this study, MS/MS technique was performed both in offline and in-situ mode during lignin depolymerization. The fundamental guidelines based on MS/MS dissociation principles for typical inter-unit linkages like β-O-4, 5-5, β-β, β-5, and β-1 were well established. Based on that, major phenolic dimers are successfully identified, including chemical formula and types of inter-unit linkages. More significantly, real-time monitoring of structural evolution was achieved by applying in-situ MS/MS analysis during lignin depolymerization. The results show the different evolution pathways of isomers with same chemical formula, confirming that structural changes during lignin depolymerization are common and obvious. Overall, this study develops an advanced strategy for the full-view analysis of lignin depolymerization, achieving the static analysis of composition and structure, both monitoring the dynamic evolution of structures.

Valence Electronic Structure of Interfacial Phenol in Water Droplets.

Biochemistry and a large part of atmospheric chemistry occur in aqueous environments or at aqueous interfaces, where (photo)chemical reaction rates can be increased by up to several orders of magnitude. The key to understanding the chemistry and photoresponse of molecules in and "on" water lies in their valence electronic structure, with a sensitive probe being photoelectron spectroscopy. This work reports velocity-map photoelectron imaging of submicrometer-sized aqueous phenol droplets in the valence region after nonresonant (288 nm) and resonance-enhanced (274 nm) two-photon ionization with femtosecond ultraviolet light, complementing previous liquid microjet studies. For nonresonant photoionization, our concentration-dependent study reveals a systematic decrease in the vertical binding energy (VBE) of aqueous phenol from 8.0 ± 0.1 eV at low concentration (0.01 M) to 7.6 ± 0.1 eV at high concentration (0.8 M). We attribute this shift to a systematic lowering of the energy of the lowest cationic state with increasing concentration caused by the phenol dimer and aggregate formation at the droplet surface. Contrary to nonresonant photoionization, no significant concentration dependence of the VBE was observed for resonance-enhanced photoionization. We explain the concentration-independent VBE of ∼8.1 eV observed upon resonant ionization by ultrafast intermediate state relaxation and changes in the accessible Franck-Condon region as a consequence of the lowering of the intermediate state potential energy due to the formation of phenol excimers and excited phenol aggregates. Correcting for the influence of electron transport scattering in the droplets reduced the measured VBEs by 0.1-0.2 eV.

Positive Impact of Late Harvest Date on Polyphenolic Composition of Plavac Mali (Vitis vinifera L.) Wine Depends on Location.

Asynchronous ripening is a significant challenge in winemaking. Green berries reduce alcohol and pH while increasing acidity. Green berries are rich in bitter and astringent compounds, with an unknown impact on wine quality. The aim of this study was to evaluate the impact of harvest date and vineyard location on the polyphenolic composition of Plavac Mali wines in Dalmatia, Croatia. Experiments were conducted in two locations, Split and Zadar, producing fifteen wines per location from four harvest dates (H1-H4), including green berry wines from H1. The first harvest date occurred 27 days after véraison (DAV) and the last at 69 DAV, corresponding to overripeness. Green berry wines of H1 had low alcohol content up to 4.4% (v/v) in Split. Epigallocatechin was the main flavonoid in those wines, followed by dimer B1 in Split and catechin in Zadar. Green wines from Split had a higher concentration of phenolic acids, flavan-3-ol monomers and dimers. Wines of H3 had the highest concentration of malvidin-3-O-glucoside. With a later harvest date, a dramatic decrease in catechin and dimers was observed in wines from Split, and a decrease in epicatechin, epigallocatechin and dimer B1 in those from Zadar. The final expression of the physiochemical and polyphenolic composition of Plavac Mali wine is determined by the dynamics of harvest date, location and their interactions.

Self-Association and Microhydration of Phenol: Identification of Large-Amplitude Hydrogen Bond Librational Modes.

The self-association mechanisms of phenol have represented long-standing challenges to quantum chemical methodologies owing to the competition between strongly directional intermolecular hydrogen bonding, weaker non-directional London dispersion forces and C-H⋯π interactions between the aromatic rings. The present work explores these subtle self-association mechanisms of relevance for biological molecular recognition processes via spectroscopic observations of large-amplitude hydrogen bond librational modes of phenol cluster molecules embedded in inert neon "quantum" matrices complemented by domain-based local pair natural orbital-coupled cluster DLPNO-CCSD(T) theory. The spectral signatures confirm a primarily intermolecular O-H⋯H hydrogen-bonded structure of the phenol dimer strengthened further by cooperative contributions from inter-ring London dispersion forces as supported by DLPNO-based local energy decomposition (LED) predictions. In the same way, the hydrogen bond librational bands observed for the trimeric cluster molecule confirm a pseudo-C3 symmetric cyclic cooperative hydrogen-bonded barrel-like potential energy minimum structure. This structure is vastly different from the sterically favored "chair" conformations observed for aliphatic alcohol cluster molecules of the same size owing to the additional stabilizing London dispersion forces and C-H⋯π interactions between the aromatic rings. The hydrogen bond librational transition observed for the phenol monohydrate finally confirms that phenol acts as a hydrogen bond donor to water in contrast to the hydrogen bond acceptor role observed for aliphatic alcohols.

Harnessing Atomically Dispersed Cobalt for the Reductive Catalytic Fractionation of Lignocellulose.

The reductive catalytic fractionation (RCF) of lignocellulose, considering lignin valorization at design time, has demonstrated the entire utilization of all lignocellulose components; however, such processes always require catalysts based on precious metals or high-loaded nonprecious metals. Herein, the study develops an ultra-low loaded, atomically dispersed cobalt catalyst, which displays an exceptional performance in the RCF of lignocellulose. An approximately theoretical maximum yield of phenolic monomers (48.3 wt.%) from lignin is realized, rivaling precious metal catalysts. High selectivity toward 4-propyl-substituted guaiacol/syringol facilitates their purification and follows syntheses of highly adhesive polyesters. Lignin nanoparticles (LNPs) are generated by simple treatment of the obtained phenolic dimers and oligomers. RCF-resulted carbohydrate pulp are more obedient to enzymatic hydrolysis. Experimental studies on lignin model compounds reveal the concerted cleavage of Cα-O and Cβ-O pathway for the rupture of β-O-4 structure. Overall, the approach involves valorizing products derived from lignin biopolymer, providing the opportunity for the comprehensive utilization of all components within lignocellulose.

An Engineered Laccase from Fomitiporia mediterranea Accelerates Lignocellulose Degradation.

Laccases from white-rot fungi catalyze lignin depolymerization, a critical first step to upgrading lignin to valuable biodiesel fuels and chemicals. In this study, a wildtype laccase from the basidiomycete Fomitiporia mediterranea (Fom_lac) and a variant engineered to have a carbohydrate-binding module (Fom_CBM) were studied for their ability to catalyze cleavage of β-O-4' ether and C-C bonds in phenolic and non-phenolic lignin dimers using a nanostructure-initiator mass spectrometry-based assay. Fom_lac and Fom_CBM catalyze β-O-4' ether and C-C bond breaking, with higher activity under acidic conditions (pH < 6). The potential of Fom_lac and Fom_CBM to enhance saccharification yields from untreated and ionic liquid pretreated pine was also investigated. Adding Fom_CBM to mixtures of cellulases and hemicellulases improved sugar yields by 140% on untreated pine and 32% on cholinium lysinate pretreated pine when compared to the inclusion of Fom_lac to the same mixtures. Adding either Fom_lac or Fom_CBM to mixtures of cellulases and hemicellulases effectively accelerates enzymatic hydrolysis, demonstrating its potential applications for lignocellulose valorization. We postulate that additional increases in sugar yields for the Fom_CBM enzyme mixtures were due to Fom_CBM being brought more proximal to lignin through binding to either cellulose or lignin itself.

Discovery, Identification, and Mode of Action of Phenolics from Marine-Derived Fungus Aspergillus ustus as Antibacterial Wilt Agents.

The bacterial wilt caused by Ralstonia solanacearum seriously affects crop yield and safety and is difficult to control. Biological activity-guided screening led to the isolation of 11 phenolic compounds including three undescribed compounds (carnemycin H-I and stromemycin B) from the secondary metabolites of a marine-derived Aspergillus ustus. One new compound is an unusual phenolic dimer. Their structures were elucidated by comprehensive spectroscopic data and J-based configurational analysis. The antibacterial activities of the isolated compounds against R. solanacearum were evaluated. Compound 3 exhibited excellent inhibitory activity with an MIC value of 3 μg/mL, which was comparable to that of streptomycin sulfate. Additionally, 3 significantly changed the morphology and inhibited the activity of succinate dehydrogenase (SDH) to interfere with the growth of R. solanacearum. Molecular docking was conducted to clarify the potential mechanisms of compound 3 with SDH. Further in vivo experiments demonstrated that 3 could remarkably inhibit the occurrence of bacterial wilt on tomatoes.

New monoterpene phenol dimers from the fruits of Psoralea corylifolia

Three new monoterpene phenol dimers, bisbakuchiols V-X (1-3), and two bakuchiol ethers (4 and 5), along with four known compounds (6-9) were isolated from the fruits of Psoralea corylifolia. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1, 2, 4, and 5 were specified by quantum chemical calculations of ECD spectra.

Effect of electronegative atoms on [formula omitted] – [formula omitted] stacking and hydrogen bonding behavior in simple aromatic molecules — An Ab initio MD study

Ab initio molecular dynamics studies have been performed on fluorobenzene, phenol, and aniline, which have the three most electronegative atoms, fluorine, oxygen, and nitrogen, respectively. Radial distribution functions show strong hydrogen bonding in the phenolic –OH group, whereas it is less prominent in the –NH2 group of aniline. Fluorobenzene does not show strong hydrogen bonds as no solvation shell is found between the fluorine atom and different aromatic hydrogens of the molecule. Spatial distribution functions show that the nitrogen atom of aniline interacts with the aromatic plane, the oxygen atom of phenol is concentrated near the –OH group and fluorobenzene’s fluorine atom interacts with the para hydrogen. Liquid phase dimer structures of these systems reveal that perpendicular orientation (Y-shaped) is preferred over parallel ones. Almost half of the total dimer population tends to prefer 90∘±30° angle. H-bond analyses show that fluorobenzene has the longest mean H-bond lifetime for the H-bond between the aromatic hydrogens and the fluorine atoms, whereas the aniline has the least. The mean lifetime between aromatic hydrogens and electronegative atoms increases steadily from aniline to fluorobenzene. Phenolic –OH and amino –NH2 groups show considerably longer mean H-bond lifetime than the aromatic hydrogens. Gas-phase binding energies obtained from quantum chemical calculations show that aniline and phenol dimers have higher binding energy values than the fluorobenzene dimer. Only the phenol dimer shows a perpendicular structure as a stable one, while aniline and fluorobenzene prefer the parallel orientation.

Mechanism insights into enol ether intermediate formation during β-O-4-type lignin pyrolysis

Enol ether (EE) is considered to be one of the important intermediates in lignin pyrolysis, but its formation process is still unclear. In this study, the generation of EE structure from the pyrolysis of β-O-4 linkages under vairous structural environments was studied systematically with simplified lignin models, covering phenyl dimers, phenolic dimers, and phenolic polymers, and its formation mechanism and inducing factors were summarily proposed. Results showed that EE intermediates were difficult to generate in β-O-4-type phenyl structures, but the activation of α/β-substituted side chains promoted the EE formation, confirming that elimination reactions in pyrolysis was the main driving force for EE generation. Free phenolic hydroxyl groups and corresponding phenoxy radicals were very effective EE formation activators, as they can both induce the production of quinone intermediates, which were easily converted to EE structure. These conclusions provided a new connotation for the pyrolysis of lignin β-aryl ether linkages.

The Role of Metal and Acid Sites in the Liquid‐phase Hydrodeoxygenation of Lignin‐derived Phenolic Dimers

AbstractBio‐oil obtained from the depolymerization of lignocellulosic biomass is a potential alternative source to replace fossil fuels. However, due to high oxygen content, the bio‐oil must be upgraded. In this direction, the hydrodeoxygenation reaction (HDO) is widely applied. Considering the complex chemical composition of the bio‐oil, a variety of model molecules have been used in the literature to study the mechanism of the HDO process. In this work, we discuss heterogeneous catalysts and reaction conditions (temperature, pressure, and solvent) generally used for the HDO of dimeric aryl ethers representative of the main ether linkages present in the lignin:α‐O‐4, β‐O‐4, and 4‐O‐5. The present work aims to shed light on the role of metal and acid sites and understand the influence of the reaction conditions on the reaction pathways.

Lignin Depolymerization to Guaiacol and Vanillin Derivatives via Catalytic Transfer Hydrogenolysis using Pd-Lewis Metal Oxide Supported on Activated Carbon Catalysts

Lignin valorization is the key to sustainability of second-generation bioethanol refineries. In this study, the catalytic activities of Pd-Lewis acid metal oxides (Mo, Zr) supported on commercial activated carbon (AC) and activated biochar (ABC) were evaluated for the selective production of monomeric phenols from alkali lignin through transfer hydrogenolysis. The catalysts were thoroughly characterized for phase, degree of graphitization, textural properties, and metal dispersion. The Pd crystallite size was 2.1-2.5 Å in the case of AC-supported catalysts, while it was smaller (1.4-1.5 Å) for ABC-supported catalysts. AC exhibited better degree of graphitization than ABC. 2%Pd-5%Mo supported on AC showed good catalytic activity for the production of guaiacol, alkyl guaiacols, alkene guaiacols, and vanillin derivatives, and their respective yields were 4.2, 10.3, 3.4, and 12 wt.%. Compared to other alcohols like methanol and ethanol, the use of isopropyl alcohol as solvent resulted in better yields of guaiacol, alkyl guaiacols and alkene guaiacols. Condensation reactions of the guaiacyl unit and syringyl unit were confirmed through Fourier transform infrared spectroscopic analysis of the residue. Dimerization of monomeric phenols was observed with Pd-metal oxide supported on ABC than with AC-based catalyst.

A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone

Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5-Seco-vibralactone (3) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans. Cyclization of 3 forms vibralactone (1) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3. The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate.

New Phenolic Dimers from Plant Paeonia suffruticosa and Their Cytotoxicity and NO Production Inhibition.

The Paeonia suffruticosa, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (1-5), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds 2, 4, and 5 showed cytotoxicity against three human cancer cell lines, with IC50 values ranging from 6.7 to 25.1 μM. Compounds 1 and 2 showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of P. suffruticosa are reported for the first time in this paper.

Fabrication and application of amphiphilic polyoxometalate catalyst (CTA)nH5-nPMo10V2O40 for transformation of lignin into aromatic chemicals

Conversion of renewable lignin into bio-aromatic chemicals offers a sustainable pathway to increase biorefinery profitability. However, the catalytic transformation of lignin into monomers remains a highly challenging task due to the complexity and stability of the lignin structure. In this study, a series of micellar molybdovanadophosphoric polyoxometalate (POM) catalysts, (CTA)nH5-nPMo10V2O40 (n = 1–5), were prepared by the ion exchange method and applied as oxidative catalysts for birch lignin depolymerization. These catalysts showed efficient cleavage of C-O/C-C bonds in lignin, and the introduction of an amphiphilic structure facilitated the generation of monomer products. The best catalytic activity was observed at 150 °C within 150 min under a 1.5 MPa oxygen atmosphere over (CTA)1H4PMo10V2O40, which yielded a maximum lignin oil yield of 48.7 % and lignin monomer yield of 13.5 %. We also employed phenolic and nonphenolic lignin dimer model compounds to explore the reaction pathway and demonstrated the selective cleavage of CC and/or CO lignin bonds. Moreover, these micellar catalysts have excellent recyclability and stability as heterogeneous catalysts, which can be used up to five times. The application of amphiphilic polyoxometalate catalysts facilitates the valorization of lignin, and we expect to develop a novel and practical strategy for harvesting aromatic compounds.

Tertiary Amines from RCF Lignin Mono- and Dimers: Catalytic N-Functionalized Antioxidants from Wood

Functionalization of bio-based aromatics offers an appealing opportunity toward a renewable way of fulfilling our current needs for chemicals and materials. Here, an atom-efficient Cu-catalyzed hydrogen borrowing strategy is presented, which successfully functionalizes aliphatic alcohols in aromatic monomers and dimers, derived from lignin by the reductive catalytic fraction (RCF), into tertiary dimethylamines. Kinetic experiments and ToF-SIMS analysis of the supported copper catalyst demonstrated a reduced catalytic activity for monomeric methoxyphenolics, such as guaiacol and syringols, relative to phenolic and nonphenolic model compounds. This is explained by the formation through demethylation and the adsorption of strong coordinating catechol species. The nature of the catalyst support proved to be key to cope with the catechol deactivation and keep high catalytic activity, with Cu supported on SiO2 outperforming earlier reported Cu-ZrO2. The hydrogen borrowing method was extended to real spruce wood-derived RCF lignin oil fractions, containing both phenolic mono- and oligomers. Special effort was done to identify the composition and molecular structure of the resulting phenolic dimer amines by GC × GC-TOF/MS and 1H-13C-NMR techniques. The stable lignin-derived tertiary amines displayed excellent antioxidant activity during an ABTS assay, highlighting the added value of the products obtained by the hydrogen borrowing upgrading strategy.

Thermodynamics of π-π Interactions of Benzene and Phenol in Water.

The π–π interaction is a major driving force that stabilizes protein assemblies during protein folding. Recent studies have additionally demonstrated its involvement in the liquid–liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs). As the participating residues in IDPs are exposed to water, π–π interactions for LLPS must be modeled in water, as opposed to the interactions that are often established at the hydrophobic domains of folded proteins. Thus, we investigated the association of free energies of benzene and phenol dimers in water by integrating van der Waals (vdW)-corrected density functional theory (DFT) and DFT in classical explicit solvents (DFT-CES). By comparing the vdW-corrected DFT and DFT-CES results with high-level wavefunction calculations and experimental solvation free energies, respectively, we established the quantitative credibility of these approaches, enabling a reliable prediction of the benzene and phenol dimer association free energies in water. We discovered that solvation influences dimer association free energies, but not significantly when no direct hydrogen-bond-type interaction exists between two monomeric units, which can be explained by the enthalpy–entropy compensation. Our comprehensive computational study of the solvation effect on π–π interactions in water could help us understand the molecular-level driving mechanism underlying the IDP phase behaviors.

Total chemocatalytic cascade conversion of lignocellulosic biomass into biochemicals

Because of its complexity, selective conversion of lignocellulosic biomass into platform chemicals presents significant challenges. Herein, we converted birch wood into high-yield lignin-derived phenolic monomers and dimers and holocellulose-derived polyols and monocarboxylic acids via a two-step cascade reaction using 0.1 wt% Pd on N-doped carbon (Pd0.1/CNx) and passivated alumina-coated Ni on activated carbon (Ni2 @Al2O3/AC) catalysts. The catalytic fractionation of birch sawdust using Pd0.1/CNx produced 11.1 wt% monomers, 5.6% dimers, and 63.4 wt% pulp-rich solid (PRS) based on feed weight. The subsequent conversion of PRS over passivated Ni2 @Al2O3/AC produced 21.6 wt% C2–C6 polyols and 7.9 wt% monocarboxylic acids. After the whole biomass conversion reaction, the Pd0.1/CNx and Ni2 @Al2O3/AC catalysts were separated using their different magnetic responses and reused three times without activity loss. The structure–performance relationships of the Pd0.1/CNx catalysts synthesized using different methods and effect of passivation on the performance of the Ni2 @Al2O3/AC catalyst were analyzed.

Lignin as a multifunctional photocatalyst for solar-powered biocatalytic oxyfunctionalization of C–H bonds

Each year, the pulp and paper industry produces approximately 50 million metric tons of lignin as waste, 95% of which is combusted or abandoned. Here, we report the use of lignin as a photocatalyst that forms H2O2 by O2 reduction and H2O oxidation under visible light. We investigated the photophysical and electronic properties of two lignin models, lignosulfonate and kraft lignin, by spectroscopic and photoelectrochemical analyses, and demonstrated the photoredox chemistry of lignin using these and other lignin models (for example, native-like cellulolytic enzyme lignin, artificial lignin dehydrogenation polymer and phenolic β-aryl ether-type lignin dimer). Furthermore, the integration of lignin and H2O2-dependent unspecific peroxygenases (UPOs) enabled the highly enantioselective oxyfunctionalization of various C–H bonds. The use of lignin photocatalysts solves a number of the challenges relating to the sustainable activation of UPOs, notably, eliminating the need for artificial electron donors and suppressing the HO·-mediated inactivation of UPOs. Thus, the lignin–UPO hybrid catalyst achieved a total turnover number of UPO of 81,000 for solar-powered biocatalytic oxyfunctionalization in photochemical platforms.

Bidysoxyphenols A–C, dimeric sesquiterpene phenols from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm

Three new sesquiterpene phenol dimers, bidysoxyphenols A–C (2–4), along with two known compounds, namely sesquiterpene phenol (1) and ionone derivatives (5), were isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm. The structures of these new compounds, including their absolute configurations, were elucidated by nuclear magnetic resonance spectroscopy, ultraviolet spectroscopy, infrared spectroscopy, high-resolution electrospray ionization time-of-flight mass spectrometry, and electronic circular dichroism. Compounds 1 and 2 showed cytotoxicity against human promyelocytic leukemia cells, with IC50 values of 18.25 ± 1.52 and 39.04 ± 3.12 μM, respectively.