Phenolic Function Research Articles

Synthesis and evaluation of KX-01 analogs with an exploration of linker attachment points for antibody-drug conjugates.

KX-01 (tirbanibulin, Klisyri®) is a recently FDA-approved drug for treating actinic keratosis, with a distinct dual mechanism of action combining microtubule disruption and non-ATP-competitive Src inhibition. This unique mechanism and novel chemotype highlight KX-01's potential as a payload for antibody-drug conjugates. In this study, we synthesized and evaluated KX-01 derivatives to enhance anticancer potency and explore functional groups suitable for antibody conjugation. Notably, replacing the morpholine group with an N-benzoylpiperazine scaffold resulted in an analog with significantly improved in vitro antiproliferative activity, attributed to enhanced microtubule disruption and Src inhibition. Furthermore, introducing a phenol or aniline functionality as a common linker attachment point preserved substantial cytotoxicity. These results suggest the potential of KX-01 derivatives for future use as ADC payloads.

Development of a Novel Mixed-Metal-Organic Framework: An Innovative Photocatalyst for Simultaneous Cr(VI) Reduction and Phenol Degradation.

The direct use of sunlight as an infinite source of energy for wastewater treatment is an overwhelming idea. For this aim, the development of novel and practical photocatalysts has been the main challenge of researchers. Among the different methodologies used, the introduction of multifunctional MOFs as photocatalysts shows a great deal of potential. Here, a simple and useful approach for the synthesis of rare mixed-valence, mixed-metal organic frameworks (MM-MOF) [Fe2CoO(TPBTM6)(H2O)3]n (Fe2CoMOF) [H6TPBTM: N,N',N″-Tris(isophthalyl)-1,3,5-benzenetricarboxamide] was investigated using a one-step hydrothermal approach. Applying mixed-metal clusters as preformed SBUs introduces multifunctionality into the MOF structure, leading to high performance in wastewater treatment. The coexistence of Fe3+ and Co2+ leads to super photocatalytic ability of the structure. Therefore, the catalytic activity of Fe2CoMOF was explored for concurrent photocatalytic Cr(VI) reduction and phenol degradation. For a better understanding of the cooperative reaction among Cr(VI) reduction and phenol oxidation, methodical tests were conducted to disclose the Cr(VI), phenol, and MOF functions in the photocatalytic procedures. The influence of the primary substrate concentration and pH on the reduction procedure was also examined empirically.

Decarboxylative Alkylation of Carboxylic Acids with Easily Oxidizable Functional Groups Catalyzed by an Imidazole-Coordinated Fe3 Cluster under Visible Light Irradiation.

Decarboxylative alkylation of carboxylic acids with easily oxidizable functional groups such as phenol and indole functionalities was achieved using a catalytic amount of basic iron(III) acetate, Fe(OAc)2(OH), in the presence of benzimidazole under 427 nm LED irradiation. Kinetic analyses of this catalytic reaction revealed that the reaction rate is first-order in alkenes and is linearly correlated with the light intensity; the faster reaction rate for the benzimidazole-ligated species was consistent with the increased absorbance in the visible light region. Wide functional group tolerance for the easily oxidizable groups is ascribed to the weak oxidation ability of the in situ-generated oxo-bridged iron clusters compared with other iron(III) species.

Introducing Hydrogen Bond Networks in the Self‐Assembly of Chitin Nanocrystals: Strong and Flexible Bioactive Films Containing Natural Polyphenols

AbstractFree‐standing, highly transparent and flexible films are obtained from solvent casting of aqueous colloidal dispersions of surface‐deacetylated chitin nanocrystals. The Young's modulus and the water absorption of the films is further modulated by the addition of three natural polyphenols, i.e., epigallocatechingallate, tannic acid and one lignosulfonate, which differ one another in terms of molecular weight, and overall amount of hydroxy, phenolic and catecholic functionalities. The polyphenolic molecules create an extensive network of hydrogen bonds with the nanocrystals, thus controlling interfacial interactions. Therefore, they act as crosslinkers exerting a reinforcing and structuring action and hampering water absorption. The films do not show dissolution in water upon 7 days of incubation at room temperature, and the release profiles of the polyphenols in aqueous media evidence hindered Fickian diffusion kinetics confirming the presence of interactions with the nanostructured matrix. Lastly, the developed films possess bioactive properties, as they show both radical scavenging and antimicrobial activity. These characteristics are enhanced by the phenolic and, most importantly, catecholic moieties present in tannins (and to a lesser extent in lignins), allowing to reach bactericidal effects as high as 99.99% against both Gram‐positive and Gram‐negative strains.

Synthesis and Spectroscopic Characterization of Selected Water-Soluble Ligands Based on 1,10-Phenanthroline Core.

Water-soluble ligands based on a 1,10-phenanthroline core are relatively poorly studied compounds. Developing efficient and convenient syntheses of them would result in new interesting applications because of the importance of 1,10-phenanthrolines. In this manuscript, we describe novel and practical ways to introduce a carboxyl and, for the first time, a phenol and dithiocarboxyl group under mild reaction conditions. This strategy enables highly efficient and practical synthesis of suitable organosulfur compounds with high added value, high chemoselectivity, and a broad substrate range. We present the selective conversion of a hydroxydialdehyde in the form of 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde into its derivative, unique hydroxydicarboxylic acid, by an oxidation procedure, giving 10-hydroxybenzo[h]quinoline-7,9-dicarboxylic acid. A similar procedure resulted in the formation of 9-methyl-1,10-phenanthroline-2-carboxylic acid by oxidation of commercially available neocuproine. An alternative method of obtaining 1,10-phenanthroline derivatives possessing carboxylic acid group can be based on the hydrolysis of ester or nitrile groups; however, this synthesis leads to unexpected products. Moreover, we apply Perkin condensation to synthesize a vinyl (or styryl) analog of 1,10-phenanthroline derivatives with phenol function. This reaction also demonstrates a new, simple, and efficient strategy for converting methyl derivatives of 1,10-phenanthroline. We anticipate that the new way of converting methyl will find wide application in chemical synthesis.

Determination of Polyphenolic Compounds Present in Guduchyadi Kashaya Using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

The utilization of various contemporary analytical methods has become indispensable when it comes to assessing polyherbal Ayurvedic formulations, aiming to ensure their quality, safety, and effectiveness. Quality control of herbal medicines involve analytical evaluation using instrumental techniques such as TLC, HPTLC, HPLC, GC-MS, LC-MS and spectrophotometer etc. Among them Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) is a powerful hyphenated analytical technique that combines the separating power of liquid chromatography with the mass analysis capabilities of mass spectrometry. Generally, its application is oriented towards the specific detection and potential identification of chemicals in a complex mixture. Polyphenolic compounds are usually referred to as a diverse group of naturally occurring compounds containing multiple phenolic functionalities. The anti-inflammatory, anti-aging, antiproliferative, and antioxidant like biological properties of phenolic compounds have been described in several studies. This research study was taken to analyse polyphenolic compounds in Guduchyadi kashaya by LC-MS/MS. Phenolic compounds are abundant in the ingredients of Guduchyadi kashaya, as evidenced by previous studies. So, to determine the polyphenolic contents of Guduchyadi kashaya, this study was conducted. The quantification of the polyphenols was carried out on Shimadzu Shim Pack GISS C18 column with .1%formic acid as mobile phase. A total of 28 polyphenolic compounds were analysed, and 24 of these compounds were found to be present in Guduchyadi kashaya. The results showed that the phenolic compounds present in the ingredients were also present in the formulation in high abundance.

Advancements and Perspectives toward Lignin Valorization via O‐Demethylation

AbstractLignin represents the largest aromatic carbon resource in plants, holding significant promise as a renewable feedstock for bioaromatics and other cyclic hydrocarbons in the context of the circular bioeconomy. However, the methoxy groups of aryl methyl ethers, abundantly found in technical lignins and lignin‐derived chemicals, limit their pertinent chemical reactivity and broader applicability. Unlocking the phenolic hydroxyl functionality through O‐demethylation (ODM) has emerged as a valuable approach to mitigate this need and enables further applications. In this review, we provide a comprehensive summary of the progress in the valorization of technical lignin and lignin‐derived chemicals via ODM, both catalytic and non‐catalytic reactions. Furthermore, a detailed analysis of the properties and potential applications of the O‐demethylated products is presented, accompanied by a systematic overview of available ODM reactions. This review primarily focuses on enhancing the phenolic hydroxyl content in lignin‐derived species through ODM, showcasing its potential in the catalytic funneling of lignin and value‐added applications. A comprehensive synopsis and future outlook are included in the concluding section of this review.

Advancements and Perspectives toward Lignin Valorization via O-Demethylation.

Lignin represents the largest aromatic carbon resource in plants, holding significant promise as a renewable feedstock for bioaromatics and other cyclic hydrocarbons in the context of the circular bioeconomy. However, the methoxy groups of aryl methyl ethers, abundantly found in technical lignins and lignin-derived chemicals, limit their pertinent chemical reactivity and broader applicability. Unlocking the phenolic hydroxyl functionality through O-demethylation (ODM) has emerged as a valuable approach to mitigate this need and enables further applications. In this review, we provide a comprehensive summary of the progress in the valorization of technical lignin and lignin-derived chemicals via ODM, both catalytic and non-catalytic reactions. Furthermore, a detailed analysis of the properties and potential applications of the O-demethylated products is presented, accompanied by a systematic overview of available ODM reactions. This review primarily focuses on enhancing the phenolic hydroxyl content in lignin-derived species through ODM, showcasing its potential in the catalytic funneling of lignin and value-added applications. A comprehensive synopsis and future outlook are included in the concluding section of this review.

Silicon distyryl-BODIPY hybrid photodiode: moving a step ahead from organic interface layer to type II band alignment

Organic-inorganic heterojunctions are becoming an attractive topic of research for their applications in hybrid photodetectors, solar cells, resistive switching memory devices etc. The easy chemical synthesis and low-cost fabrication for organic thin films come with the benefit of high light absorptivity, high fluorescence quantum yield and band gap tunability along with high charge carrier lifetime that could be combined with the existing silicon-based technology. In this aspect, various organic dyes utilised as an interfacial layer with silicon Schottky junction are reported earlier. However, the photo responses are quite limited. Here, in this report, a Type II Silicon/Distyryl-BODIPY p-n junction has been proposed as an organic-inorganic hybrid photodetector which has not been explored extensively yet. The transformation from a mere organic interfacial layer to band aligned junction enhances the charge carrier separation providing higher photo-responsive behaviour. With the simple spin-coating technique, the Distyryl-BODIPY derivative with phenolic functionalities is coated to fabricate the p-n junction diode. To further improve the performance, pyramidal surface texturization on silicon is deployed using wet chemical etching that supplements the light absorption with internal reflections. Both the devices have been investigated for their photo-response characteristic where a high photo-responsivity of 4353 A W−1 is attained for the textured device as compared to 118 A W−1 for the planar silicon device at a − 3 V bias with an ultra-high specific detectivity of 1012 Jones and 1010 Jones respectively. The behaviours of interfacial states have been demonstrated using the capacitance (C), conductance (G) and series resistance (RS) vs voltage (V) curves at different frequencies. Further calculations of interfacial state density revealed the existence of 1000 times higher interfacial states in planar device leading to lower performance as compared to pyramidal device. The findings in this report suggest that dye-based organic-inorganic heterostructures find potential applications in photodetectors and other optoelectronic devices.

C–H Functionalization of Arenes and Phenols with Alkynes Catalyzed by Palladium Nanoparticles

C–H Functionalization of Arenes and Phenols with Alkynes Catalyzed by Palladium Nanoparticles

Mask and Release Strategy-Enabled Diversity-Oriented Synthesis for DNA-Encoded Library.

An ideal DNA-encoded library (DEL) selection requires the library to consist of diverse core skeletons and cover chemical space as much as possible. However, the lack of efficient on-DNA synthetic approaches toward core skeletons has greatly restricted the diversity of DEL. To mitigate this issue, this work disclosed a "Mask & Release" strategy to streamline the challenging on-DNA core skeleton synthesis. N-phenoxyacetamide is used as a masked phenol and versatile directing group to mediate diversified DNA-compatible C-H functionalization, introducing the 1st-dimensional diversity at a defined site, and simultaneously releasing the phenol functionality, which can facilitate the introduction of the 2nd diversity. This work not only provides a set of efficient syntheses toward DNA-conjugated drug-like core skeletons such as ortho-alkenyl/sulfiliminyl/cyclopropyl phenol, benzofuran, dihydrobenzofuran but also provides a paradigm for on-DNA core skeleton synthetic method development.

Photodegradation of Triclosan on the Kaolinite Surface: Kinetic, Mechanistic, and Molecular Modeling Approach.

The photodegradation of triclosan (TCS) was investigated on the kaolinite surface. The quantum yield was evaluated, and the photoproducts were identified by HPLC/MS (LC/Q-TOF), showing that the phototransformation is completely different from that reported in aqueous solutions. In particular, the formation of dioxin derivatives was fostered and occurred with a higher efficiency when compared to aqueous solutions. This suggests that TCS has specific interactions with the clay that clearly modifies its photochemical behavior. Moreover, it has also been shown that higher concentrations of TCS, namely, higher than 1.0 μmol g-1 of kaolinite, lead to a significant decrease of the photodegradation rate constant and enhance the formation yield of dimer-type photoproducts. This suggests that the distribution of TCS is clearly not homogeneous at the clay surface and the formation of aggregates is more likely occurring. To get a better insight into this specific interaction, a molecular dynamic modeling of TCS adsorption at the surface of kaolinite was carried out. This clearly shows that when equilibrium is reached, TCS binds to the kaolinite surface by hydrogen bonds involving the phenol function of TCS and the hydroxyl groups of the kaolinite surface. Such behavior confers a particular conformation to the adsorbed TCS that is different from that obtained in water and which could be a key step to partially explain the specific photochemical reactivity in both media. In addition, several TCS molecules appear to interact with each other through the π-stacking (aromatic stacking) process while retaining this hydrogen bond with the kaolinite surface. This is clearly in favor of cluster formation on the clay surface and promotes dimer-type photoproducts.

Ustilago maydis PR-1-like protein has evolved two distinct domains for dual virulence activities

The diversification of effector function, driven by a co-evolutionary arms race, enables pathogens to establish compatible interactions with hosts. Structurally conserved plant pathogenesis-related PR-1 and PR-1-like (PR-1L) proteins are involved in plant defense and fungal virulence, respectively. It is unclear how fungal PR-1L counters plant defense. Here, we show that Ustilago maydis UmPR-1La and yeast ScPRY1, with conserved phenolic resistance functions, are Ser/Thr-rich region mediated cell-surface localization proteins. However, UmPR-1La has gained specialized activity in sensing phenolics and eliciting hyphal-like formation to guide fungal growth in plants. Additionally, U. maydis hijacks maize cathepsin B-like 3 (CatB3) to release functional CAPE-like peptides by cleaving UmPR-1La’s conserved CNYD motif, subverting plant CAPE-primed immunity and promoting fungal virulence. Surprisingly, CatB3 avoids cleavage of plant PR-1s, despite the presence of the same conserved CNYD motif. Our work highlights that UmPR-1La has acquired additional dual roles to suppress plant defense and sustain the infection process of fungal pathogens.

Nanomolar detection of hypochlorite in ground water samples by a norbornene-based polymeric sensor via unusual fluorescence turn-on response

Hypochlorite anion has been widely used as a bleaching and disinfecting agent in daily life. Selective and sensitive identification ofOCl-ions from water is very important for researchers. For this purpose, monomeric (NPh), and polymeric (PNPh-Peg) novel fluorescent sensors have been established for the specific and excellently unique sensors that exhibit selective characteristics like excellent resistance to bleaching and a high fluorescence brightness. A multi-functional random polymer (PNPh-Peg) with ICT (intramolecular charge transfer) active para–amino phenol functionality and reactive oxygen species (ROS) responsive, PEG attached are readily prepared via ROMP (ring-opening metathesis polymerization).: An ICT-active random polymer (PNPh-Peg) exhibited an unexpectedly strong cyan blue emission in a water medium compared to that in other common organic solvents, which was dramatically increased by adding a trace amount of NaOCl.: Incorporating PEG moiety in the polymeric backbone increases the water solubility of a copolymer, and the ROS-responsive groups make the polymer a good ROS scavenger. Upon oxidation of the phenol group into carbonyl, both the monomeric (NPh) and polymeric (Norp-PEG oh) sensors showed a selective, noticeable, unusual fluorescence turn-on response towardsanalyteOCl-ions with a very fast response (within three minutes). The detection limit (59.14 nM) and (126.93 nM) were calculated for monomeric and polymeric sensors, respectively. This was a selective, specific oxidation reaction of the completely water-soluble random polymeric sensor (PNPh-Peg) for hypochlorite anions and can be applicable for quantitative measurement of aqueous OCl-. This ICT-active random polymeric molecule (PNPh-Peg) can also be used as a fluorescent sensor for unique OCl- detection from contaminated water by preparing a sensor-coated paper strip. Thus, these multi-functional monomeric (NPh) and polymeric (PNPh-Peg) sensors are anticipated to apply to the environment.

An upconversion nanosensor with phenolic-like functionality for accurate identification of chlorpyrifos in grapes

The inappropriate use of the organophosphorus pesticide chlorpyrifos (CPF) in agricultural production could be harmful to the environment and non-target organisms. Here, we prepared a nano-fluorescent probe with phenolic function based on covalently coupled rhodamine derivatives (RDP) of upconverted nano-particles (UCNPs) for trace detection of chlorpyrifos. Due to the fluorescence resonance energy transfer (FRET) effect in the system, the fluorescence of UCNPs is quenched by RDP. The phenolic-functional RDP is converted to the spironolactone form when it captures chlorpyrifos. This structural shift prevents the FRET effect in the system and allows the fluorescence of UCNPs to be restored. In addition, the 980nm excitement conditions of UCNPs will also avoid interference from non-target fluorescent backgrounds. This work has obvious advantages in terms of selectivity and sensitivity, which can be widely applied to the rapid analysis of chlorpyrifos residues in food samples.

Polybenzoxazine bearing phosphonium and phenol functions catalyzed the cycloaddition of CO2 into epoxide reactions

Polybenzoxazine bearing phosphonium and phenol functions was firstly designed, synthesized, and evaluated for the cycloaddition of CO2 into epoxide (CCE) reactions. Benzoxazine monomers intrinsically installed with phosphonium halide moiety were thermally polymerized to obtain phenolic-type polybenzoxazines. The bifunctional polybenzoxazine catalyst promoted CCE reactions at 120 °C within 2 h to afford high yields up to 96% under atmospheric pressure. The catalyst was recycled four times and maintained 92% yield. A possible bifunctional catalytic mechanism composed of hydrogen-bonding activation by phenol and co-catalysis by halide was proposed and validated. The easy preparation of the benzoxazine monomers with variety of catalytic moieties, and one-step fabrication of the polybenzoxazines suggest untapped potential of manifold polymeric catalyst design and applications.

Recent Advances in Regioselective C-H Bond Functionalization of Free Phenols.

Phenols are important readily available synthetic building blocks and starting materials for organic synthetic transformations, which are widely found in agrochemicals, pharmaceuticals, and functional materials. The C-H functionalization of free phenols has proven to be an extremely useful tool in organic synthesis, which provides efficient increases in phenol molecular complexity. Therefore, approaches to functionalizing existing C-H bonds of free phenols have continuously attracted the attention of organic chemists. In this review, we summarize the current knowledge and recent advances in ortho-, meta-, and para-selective C-H functionalization of free phenols in the last five years.

Screening for Bisphenol Chemicals: A Strategy Based on Dansyl Chloride Derivatizatio n Coupled with In-Source Fragmentation by High-Resolution Mass Spectrometry.

Bisphenol chemicals (BPs) represent a complexity of halogenated and nonhalogenated substances sharing a common structure of two phenol functionalities, some of which exhibit ubiquitous environmental distributions and endocrine-disrupting activities. However, environmental monitoring of complex BP-like chemicals has faced analytical challenges arising from the lack of commercially available reference standards and efficient screening strategies. In the present study, we developed a strategy based on dansyl chloride (DnsCl) derivatization in combination with in-source fragmentation (D-ISF) during high-resolution mass spectrometry analysis to screen for bisphenol chemicals in complex environmental samples. The strategy contains three steps, including DnsCl derivatization to enhance the detection sensitivity by one to more than four orders of magnitude, in-source fragmentation to produce characteristic loss of 234.0589, 63.9619, and 298.0208 Da for the identification of DnsCl-derivatized compounds, and data processing and annotation. The D-ISF strategy was further validated and then applied to identify BPs in six types of particular matters as representative environmental samples, including settled dust from an electronic waste dismantling site, homes, offices, and vehicles, and airborne particles from indoor and outdoor environments. A total of six halogenated and fourteen nonhalogenated BPs were identified in the particles, including several chemicals that had rarely or never been identified in environmental samples. Our strategy offers a powerful tool for the environmental monitoring of bisphenol chemicals and assessment of human exposure risks.

Protein Fractions from Flaxseed: The Effect of Subsequent Extractions on Composition and Antioxidant Capacity.

Flaxseed proteins exhibit functionalities interesting for the food industry, including antioxidant capacity. Antioxidant activity depends on the protein composition and the presence of phenolic compounds extracted with them from the matrix. The research focused on the effect of subsequent protein extractions (water, salt and alkaline) of flaxseed meals (of three cultivars) on the protein fraction composition and its relations to antioxidant capacity. The protein and phenolic profiles and antioxidant functionalities (in antiradical ORAC and emulsion assays) were analysed. Spectroscopic characteristics of the fractions (fluorometric and FT-IR analysis) were also included. Our study has shown the effect of fractionation on the share of proteins at MW from 56-38 kDa (globulin-like) and <15 kDa (albumin-like) in the protein profiles. The highest globulin share was in the alkaline-extracted fractions (AEF) and albumin in the salt-extracted (SEF) ones. SDG (secoisolariciresinol diglucosides) and phenolic acids (p-coumaric and ferulic) were extracted with flaxseed proteins. Their contents were fraction-dependent and the highest in AEF. The concentration of phenolics in AEF corresponded with the highest antiradical capacity (ORAC) compared with the other fractions. However, the SEF showed a higher ability to inhibit oxidation in emulsions than AEF, which could be associated with the higher content of the low MW proteins.

Synthesis of Phenol-Tagged Ruthenium Alkylidene Olefin Metathesis Catalysts for Robust Immobilisation Inside Metal–Organic Framework Support

Two new unsymmetrical N-heterocyclic carbene ligand (uNHC)-based ruthenium complexes featuring phenolic OH function were obtained and fully characterised. The more active one was then immobilised on the metal–organic framework (MOF) solid support (Al)MIL-101-NH2. The catalytic activity of such a heterogeneous system was tested, showing that, while the heterogeneous catalyst is less active than the corresponding homogeneous catalyst in solution, it can catalyse selected olefin metathesis reactions, serving as the proof-of-concept for the immobilisation of catalytically active complexes in MOFs using a phenolic tag.