Phenolic Substituents Research Articles

Utilizing pyrolysis cleavage products from softwood kraft lignin as a substitute for phenol in phenol-formaldehyde resins for modifying different wood species

Phenol-formaldehyde resins can be used for wood modification through an impregnation process and subsequent curing within the wood cell wall. Phenol is gained from non-renewable resources, and its substitution by renewable chemicals has been a research goal. A promising example for renewable phenol substituents are lignin-derived organic chemicals. Phenol-formaldehyde resins with such substitutions have been studied, however, knowledge of their application for wood modification is deficient. While there are attempts to modify pine and beech wood with this method, studies on other wood species are scarce. Considering the increasing use of different wood species in wood industry, determining the influence of the wood species on the modification quality is an important research goal. Therefore, in this study, vacuum-pressure impregnation of five wood species – Scots pine sapwood (Pinus sylvestris), Norway spruce (Picea abies), European beech (Fagus sylvatica), Silver birch (Betula pendula), and European aspen sapwood (Populus tremula) – with phenol-formaldehyde resins is described. Here, up to 45% of the phenol in the synthetic resin is substituted by vacuum low-temperature microwave-assisted pyrolysis cleavage products from commercial softwood kraft lignin. The solution uptake, weight% gain, leaching, and anti-swelling efficiency of the modified wood are analyzed and compared. The results indicate that up to 30% of the phenol can be substituted without significant decreases in the performance of the modification. The method gives comparable results for most of the wood species described herein, with exception of beech wood, for which the modification had a lower quality. The results could help to develop more environmentally friendly wood modification methods for several common European wood species.

Organoplatinum Chemistry Related to Alkane Oxidation: The Effect of a Nitro Substituent in Ligands Having an Appended Phenol Group

The organoplatinum chemistry of the ligands 2-C5H4N-CH2-NH-C6H3-2-OH-5-X (L1, X = H; L3, X = NO2) and 2-C5H4N-CH=N-C6H3-2-OH-5-X (L2, X = H; L4, X = NO2), which contain an appended phenol substituent, is described. Comparisons are made between the ligands with amine or imine groups (L1, L3 vs. L2, L4) and ligands with X = H or NO2 (L1, L2 vs. L3, L4), and major differences are observed. Thus, on reaction with the cycloneophylplatinum(II) complex [{Pt(CH2CMe2C6H4)(μ-SMe2)}2], ligands L1, L2 and L4 give the corresponding platinum(II) complexes [Pt(CH2CMe2C6H4)(κ2-N,N′-L)], containing a Pt··HO hydrogen bond, whereas L3 gives a mixture of isomeric platinum(IV) hydride complexes [PtH(CH2CMe2C6H4)(κ3-N,N′,O-L3-H)], which are formed by oxidative addition of the phenol O-H bond and which react further with oxygen to give [Pt(OH)(CH2CMe2C6H4)(κ3-N,N′,O-L3-H)]. The differences in reactivity are proposed to be due to the greater acidity of the nitro-substituted phenol groups in L3 and L4 and to the greater ability of the deprotonated amine ligand L3 over L4 to stabilize platinum(IV) by adopting the fac-κ3-N,N′,O-L3-H coordination mode.

Synthesis and Antioxidant Activity of Novel Thiazole and Thiazolidinone Derivatives with Phenolic Fragments

In this work, a series of thiosemicarbazones with phenol fragments were used as starting compounds for the synthesis of new effective antioxidants containing both a phenol substituent and a heterocyclic fragment: thiazole and thiazolidinone. To determine the most stable conformation of thiosemicarbazone, a potential energy scan was used, along with NOESY NMR spectroscopy data. A number of thiazole derivatives were obtained due the interaction of thiosemicarbazones with several bromoketones: bromoacetophenone, bromodimedone, and bromoacetylcoumarin. The product yields varied from 71 to 94%. Thiazolidinone derivatives were obtained through the reaction between thiosemicarbazones and chloroacetic acid or maleic anhydride with good yields of 82–95%. The antioxidant activities of all the products were determined in vitro: the radical cation scavenging activity was estimated using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate), while the ferric reducing capacity was determined using the ferricyanide/Prussian blue method. It was found that the antioxidant activity of most synthesized substances in both tests exceeds the activity of 4-methyl-2,6-di-tert-butylphenol, while derivatives with a fragment of 2,6-di-tert-butylphenol have the highest activity.

Two-Photon Absorption Response of Functionalized BODIPY Dyes in Near-IR Region by Tuning Conjugation Length and Meso-Substituents.

BODIPY dyes substituted by phenol or -COOMe units at the meso-position (C8) with and without a distyryl group including a methoxy moiety at the -C3 and -C5 positions of the BODIPY have been synthesized to analyze the photophysical properties. To clarify the ground-state interaction, absorption and emission features were investigated in the THF environment. Extending the π-conjugation with the methoxy moiety at -C3 and -C5 positions of BODIPY leads to a spectral shifting of the absorption maxima toward red by 120 nm. In addition, attaching the -COOMe unit at the meso-position of the BODIPY structure increases nonradiative molecular relaxation as compared to compounds possessing phenol substituents at the same position. We have investigated the effect of phenol and a -COOMe group and π-extended conjugation length with a methoxy moiety on the properties of two-photon absorption (TPA) and electron transfer dynamics by performing open-aperture (OA) Z-scan and femtosecond transient absorption spectroscopy measurements, respectively. The synthesized BODIPY compounds with the distyryl group including the methoxy unit show TPA character due to the longer conjugation length and therefore intramolecular charge transfer ability. Based on the OA Z-scan experiments upon photoexcitation with 800 nm pulsed laser light, TPA cross-section values were obtained as 74 and 81 GM for the compounds possessing phenol and -COOMe units at the meso-position of BODIPY treated by distyryl group with methoxy moieties, respectively. Additionally, optical and electronic properties were calculated theoretically by using the DFT method.

Antiproliferative activity of meso-substituted BODIPY photocages: Effect of electrophiles vs singlet oxygen

A series of BODIPY compounds with a methylphenol substituent at the meso-position and halogen atoms on the BODIPY core, or OCH3 or OAc substituents at the phenolic moiety was synthesized. Their spectral and photophysical properties and the photochemical reactivity upon irradiation in CH3OH were investigated. The molecules with the phenolic substituent at the meso-position undergo more efficient photo-methanolysis at the boron atom, while the introduction of the OCH3 group at the phenolic moiety changes the reaction selectivity towards the cleavage at the meso-position. The introduction of the halogen atoms into the BODIPY increases the photo-cleavage reaction efficiency, as well as the ability of the molecules to sensitize oxygen and form reactive oxygen species (ROS). The efficiency of the ROS formation was measured in comparison with that of tetraphenylporphyrin. The antiproliferative effect of BODIPY molecules was investigated against three human cancer cell lines MCF-7 (breast carcinoma), H460 (lung carcinoma), HCT116 (colon carcinoma), and two non-cancer cell lines, HEK293T (embryonic kindey) and HaCaT (keratinocytes), with the cells kept in the dark or irradiated with visible light. For most of the compounds a modest or no antiproliferative activity was observed for cells in the dark. However, when cells were irradiated, a dramatic increase in cytotoxicity was observed (more than 100-fold), with IC50 values in the submicromolar concentration range. The enhancement of the cytotoxic effect was explained by the formation of ROS, which was studied for cells in vitro. However, for some BODIPY compounds, the effects due to the formation of electrophilic species (carbocations and quinone methides, which react with biomolecules) cannot be disregarded. Confocal fluorescence microscopy images of H460 cells and HEK293T show that the compounds enter the cells and are retained in the cytoplasm and membranes of the various organelles. When the cells treated with the compounds are irradiated, photo-processes lead to cell death by apoptosis. The study performed is important because it provides bases for the development of novel photo-therapeutics capable of exerting photo-cytotoxic effects in both oxygenated and hypoxic cells.

Manganese(III) complexes stabilized with N-heterocyclic carbene ligands for alcohol oxidation catalysis.

The chemistry of N-heterocyclic carbenes with Earth-abundant manganese has largely focused on low-valent systems for reductive catalysis. Here, we have decorated imidazole- and triazole-derived carbenes with phenol substituents to access higher-valent Mn(III) complexes [Mn(O,C,O)(acac)], where acac = acetylacetonato, and O,C,O = bis(phenolate)imidazolylidene (1) or bis(phenolate)triazolylidene (2). Both complexes catalyze the oxidation of alcohols in the presence of tBuOOH as terminal oxidant. Complex 2 is slightly more active than 1 (TOF up to 540 h-1vs. 500 h-1), yet significantly more robust towards deactivation. Secondary and primary alcohols are oxidized, the latter with high selectivity and essentially no overoxidation of the aldehyde product to carboxylic acids unless the reaction time is substantially extended. Mechanistic investigations using Hammett parameters, IR spectroscopy, isotope labelling experiments, and specific substrates and oxidants as probes support the formation of a manganese(V) oxo system as the active species and subsequent turnover-limiting hydrogen atom abstraction.

New reactions of 2,3-diaminonaphthaline with carbonyl electrophiles

The reaction of 2,3-diaminonaphthalene with dimedone gave 3-[(3-amino-2-naphthyl)amino]-5,5-dimethylcyclohex-2-en-1-one that reacts with alloxan to afford a product of addition at the enamine moiety. The latter is converted to a spiro derivative on heating in CF3COOH, or undergoes condensation with 2,6-di-tert-butyl-p-benzoquinone to give a benzophenazinone derivative with a sterically hindered phenol substituent.

Ethylated analogue of Zingerone: A new and eco-respectful preservative in cosmetics.

This article describes the eco-design of a new preservative in cosmetics based on bio-inspiration of natural extracts from traditional medicines. In order to reach the multiple specification targets, various structures have been synthesized and evaluated to select the one demonstrating broad antimicrobial spectrum with favorable environmental profile and application potential to a wide variety of formulas. In order to evaluate the antimicrobial activity of the synthesized structures, the method of the challenge test consisting in an artificial contamination of the sample with collection microbial strains and evaluation of the number of revivable microorganisms was used to select the most promising candidate. Validation of its antimicrobial potential was later confirmed on Gram positive and Gram negative bacteria, yeast and mold with measurement of its Minimum Inhibitory Concentration (MIC) in comparison with known preservatives. Environmental impact assessment of the selected candidate was achieved with the help of ready biodegradability and aquatic ecotoxicity tests performed according to appropriate Organization tes a strfor Economic Co-operation and Development (OECD) and European Union (EU) guidelinesy. Bio-inspired from turmeric and ginger extracts, an ethylated analog of Zingerone (EZ) with the chemical name 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one demonstrates the strongest activity on Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans. Moreover, EZ shows a solubility in water two times higher than that of Zingerone thus increasing its interest as a potential preservative. Finally, its assessment of ready biodegradability and aquatic ecotoxicity in OECD-EU tests with a favorable environmental profile confirms its unique interest and fully justifies its use in cosmetic formulas as an eco-respectful preservative. Bio-inspiration based on technologies without noteworthy side effects but also on eco-design, particularly through the use of measures of potential environmental impact very upstream of a development, are two fundamental elements for the launching of new eco-friendly cosmetic ingredients. This approach has thus validated the strong potential of EZ as a preservative of eco-respectful formulas. The selection of EZ is also a very good example of the achievement of two key objectives targeted by cosmetic companies for the development of a novel active ingredient: environmental performance and technical performance.

Dynamic Hydroxyl-Yne Reaction with Phenols.

Dynamic Covalent Chemistry (DCvC) has gained increasing importance in supramolecular chemistry and materials science. Herein we prove the dynamic nature of the exchange between phenols and vinyl ethers. Exchange is fast at room temperature and under mild conditions. The equilibrium constants and the electronic effect of the phenol substituents were calculated. This novel incorporation to the DCvC toolbox could be quite useful, and as a proof it was used for the synthesis of a responsive molecular cage.

Phenyliodine(III) diacetate-mediated dearomatization of 2-(2-hydroxyaryl)benzoxazoles and 2-(2-hydroxyaryl)benzothiazoles: Regio- and stereoselective synthesis of tetramethoxycyclohexenones and bicyclo[2.2.2]octenones

A range of stereochemically defined oxidative dearomatization products formed by treating 2-(2-hydroxyaryl)benzoxazoles and 2-(2-hydroxyaryl)benzothiazoles with phenyliodine(III) diacetate have been described, demonstrating remarkable regiochemical and stereochemical dictated by the nature of the phenol substituents. Benzoxazole-substituted phenols undergo dearomatization leading to the regio- and stereoselective synthesis of tetramethoxy-substituted cyclohexenones (4,4,5,6-tetramethoxycyclohex-2-en-1-ones). However, benzothiazole-substituted phenols readily undergo regio- and stereoselective [4+2] dimerization to bicyclo[2.2.2]octenone. Further, halogenated 2-(2-hydroxyaryl)benzoxazoles lead to formation of a different tetramethoxy-substituted cyclohexenones (2,4,5,6-tetramethoxycyclohex-2-en-1-ones) whereas halogenated 2-(2-hydroxyaryl)benzothiazoles afforded 4-methoxycyclohexa-2,5-dien-1-ones. The structure of all the compounds were established using NMR, FT-IR and HRMS techniques, and the structure of two compounds were confirmed by X-ray crystallography.

Insightful characterization of sesamol-based polybenzoxazines: Effect of phenol and amine chain type on physical and nanomechanical properties

We report the synthesis of sesamol-based polyethyleneimine (PEI) polybenzoxazines. Their physico-chemical features have been compared with other aliphatic diamine chains and the influence on thermo-mechanical properties of the phenol substituent was investigated. Their molecular structures were checked through Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectrometry. Differential scanning calorimetry (DSC) revealed that the curing process takes place in two stages indicating the first polymerization exotherm <180 °C which is lower than for other similar PEI-based benzoxazines reported before. Thermogravimetric (TGA) and Dynamic mechanical analyses (DMA) showed good thermal stability, high glass transition (Tg) values (>120 °C) and elevated char yield suggesting that not only primary amines are involved in the benzoxazine rings formation, but also secondary or tertiary amines may participate influencing the crosslinking process. The limiting oxygen index (LOI) was determined by using van Krevelen equation showing that sesamol-based polybenzoxazines exhibit flame retardancy capability. Contact angle tests (CA) showed that sesamol-based thermosets display more hydrophilic character caused by the inherent hydrophilicity of the nitrogen enriched PEI oligomer. However, consistent differences between sesamol and phenol-PEI based polybenzoxazines were observed for the micromechanical properties, the latter showing overall increased micro-elastic and hardness modulus due to higher content of benzoxazine moieties.

Effect of Phenolic Substituent Position in Boron Complexes of Imidazo[1,5‐a]pyridine

AbstractWe have synthesized two boron complexes of 3‐(o‐hydroxyphenyl)imidazo[1,5‐a]pyridine exhibiting blue emission in solution. The transient absorption and theoretical studies of the complexes and their 1‐(o‐hydroxyphenyl) substituted isomers revealed that the phenolic substituent position in boron complex of imidazo[1,5‐a]pyridine affected the excites state dynamics involved in photoluminescence (PL). Although the introduction of phenolic substituent at 1‐position of the boron complex is effective to achieve the strong emission, the introduction of phenolic substituent at 3‐position results in the decreasing PL quantum yield due to intersystem crossing from the singlet excited state to the triplet excited state.

Chemoselective Preparation of New Families of Phenolic-Organoselenium Hybrids-A Biological Assessment.

Being aware of the enormous biological potential of organoselenium and polyphenolic compounds, we have accomplished the preparation of novel hybrids, combining both pharmacophores in order to obtain new antioxidant and antiproliferative agents. Three different families have been accessed in a straightforward and chemoselective fashion: carbohydrate-containing N-acylisoselenoureas, N-arylisoselenocarbamates and N-arylselenocarbamates. The nature of the organoselenium framework, number and position of phenolic hydroxyl groups and substituents on the aromatic scaffolds afforded valuable structure–activity relationships for the biological assays accomplished: antioxidant properties (antiradical activity, DNA-protective effects, Glutathione peroxidase (GPx) mimicry) and antiproliferative activity. Regarding the antioxidant activity, selenocarbamates 24–27 behaved as excellent mimetics of GPx in the substoichiometric elimination of H2O2 as a Reactive Oxygen Species (ROS) model. Isoselenocarbamates and particularly their selenocarbamate isomers exhibited potent antiproliferative activity against non-small lung cell lines (A549, SW1573) in the low micromolar range, with similar potency to that shown by the chemotherapeutic agent cisplatin (cis-diaminodichloroplatin, CDDP) and occasionally with more potency than etoposide (VP-16).

Isatin-3-acylhydrazones with Enhanced Lipophilicity: Synthesis, Antimicrobial Activity Evaluation and the Influence on Hemostasis System.

Water-soluble trialkylammonium isatin-3-hydrazone derivatives bearing phenolic substituent were easily synthesized with high yields. XRD studies confirmed the presence of these compounds as trans-(Z)-isomers in a crystal. It was shown that an increase in the lipophilicity of the cationic center leads to an increase in activity against Gram-positive bacteria Staphylococcus aureus and Bacillus cereus, including methicillin-resistant Staphylococcus aureus (MRSA) strains. The MIC values of all compounds turned out to be 2-100 times higher than the MIC of norfloxacin against the MRSA strains in the absence of hemo- and cytotoxicity. Antiaggregation and anticoagulation properties were in vitro better than for acetylsalicylic acid and sodium heparin drugs. It has been shown by UV spectroscopy and fluorescence microscopy that the mechanism of antimicrobial action of new acylhydrazones is associated with their ability to destroy the bacterial cell membrane.

Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(3H)-ones.

Quinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3H)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TEACCUPRAC, to obtain key information about the structure–antioxidant activity relationships of a diverse set of substituents at position 2 of the main quinazolinone scaffold. Regarding the antioxidant activity, ABTS and TEACCUPRAC assays were more sensitive and gave more reliable results than the DPPH assay. To obtain antioxidant activity of 2-phenylquinazolin-4(3H)-one, the presence of at least one hydroxyl group in addition to the methoxy substituent or the second hydroxyl on the phenyl ring in the ortho or para positions is required. An additional ethylene linker between quinazolinone ring and phenolic substituent, present in the second series (compounds 25a and 25b), leads to increased antioxidant activity. Furthermore, in addition to antioxidant activity, the derivatives with two hydroxyl groups in the ortho position on the phenyl ring exhibited metal-chelating properties. Our study represents a successful use of three different antioxidant activity evaluation methods to define 2-(2,3-dihydroxyphenyl)quinazolin-4(3H)-one 21e as a potent antioxidant with promising metal-chelating properties.

Inverse gas chromatographic evaluation of polysiloxanes containing phenolic and fluorophenolic functional groups for use in gas sensors

The paper presents the results of inverse gas chromatographic (IGC) research on two novel polysiloxanes: poly{dimethylsiloxane-co -[4-(2,3-difluoro-4-hydroxyphenoxy)butyl]methylsiloxane} and poly{dimethylsiloxane-co -[4-(4-hydroxyphenoxy)butyl]methylsiloxane}, dubbed PMFOS and PMOS respectively, designed for use as chemosensitive coatings for acoustoelectronic sensors. These materials contain phenolic functional substituents that differ by the presence of fluorine atoms. The materials’ solvation properties were identified by IGC with application of an LSER solvation model at temperatures ranging from 40 to 120 °C. In the case of both polysiloxanes, the research revealed that the dominant type of intermolecular interaction was the formation of acidic hydrogen bonds. The material with fluorine-activated hydroxyl groups, PMFOS, is much more acidic and less basic than the other one and thus more interesting. According to LSER, PMFOS exhibits high affinity and selectivity to hydrogen bond bases. In addition, the material retains its properties even at a temperature of 120 °C.

Solution-processed small-molecule organic solar cells based on non-aggregated zinc phthalocyanine derivatives: A comparative experimental and theoretical study

A series of non-aggregated zinc phthalocyanine derivatives containing either bulky thiophenol or phenol substituents were synthesized as a novel donor component for bulk heterojunction (BHJ) solar cell applications. The molecular structure and photophysical properties of ZnPc derivatives were investigated by combined experimental and theoretical studies using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. In order to evaluate the physical properties of ZnPcs in the solvent environment, we applied the conductor-like polarizable continuum model (CPCM). Within this scope, light-harvesting efficiency (LHE), excited-state lifetime (τ), maximum absorption wavelengths (λmax), oscillator strength (f) and hyperpolarizability (β tensors) were calculated both in vacuum and chloroform (ε = 4.9) medium. Furthermore, divergent types of global descriptors such as EHOMO, ELUMO, and bandgap (Egap) energies, ionization potential (I), electron affinity (A), hardness (η), and electrophilicity index (ω) were also calculated. Our computational findings revealed that the linker heteroatoms [sulfur for the ZnPc (1–2); oxygen for the ZnPc (3–4) including the substituent type (isopropyl for the ZnPc (2–4), and phenyl for the ZnPc (1–3] severely affected the photophysical properties of the dyes. In relation, theoretical results are in good accordance with our experimental observations. Finally, ZnPc derivatives were used as a donor component and PC61BM as an acceptor material in BHJ solar cells, displaying a maximum power conversion efficiency of 0.8%. Compared with ZnPcs 1–2, ZnPc 3–4 based cells showed an inferior photovoltaic performance. These results are promising and should encourage further studies on BHJ solar cells using near-infrared absorbing and non-aggregated ZnPcs.

Photochemical CO2 Reduction Using Rhenium(I) Tricarbonyl Complexes with Bipyridyl‐Type Ligands with and without Second Coordination Sphere Effects

AbstractThe effect of phenyl, phenol, aniline, amino, and CF3 substituents of the 2,2′‐bipyridine ligand in fac‐ReCl(L)(CO)3 (L=2,2′‐bipyridine derivative) catalysts on photochemical CO2 reduction in dimethylacetamide is examined, in order to understand the structure‐function relationships and to compare the catalytic activities with the previously published electrochemical results. All complexes including ReCl(bpy)(CO)3 have similar excited‐state lifetimes and emission spectra, but complex 1 with the Ph‐NH2 moiety exhibits a significantly larger molar absorption coefficient for its metal‐to‐ligand charge transfer (MLCT) band. All complexes we tested produce CO with only a negligible amount of H2 and formate in self‐sensitized systems in the presence of triethanolamine (TEOA) and in some cases, BIH (1,3‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐benzo[d]‐imidazole). The presence of the Ph‐NH2 moiety (complex 1) has a beneficial effect on both electrochemical and photochemical activity, allowing a turnover number (TON) of 32 and 120 for photochemical CO production (without and with BIH, respectively). In the case of the Ph‐OH group in the second coordination sphere (complexes 4 and 6), these complexes are active for photochemical CO2 reduction, despite the formation of a stable 6‐coordinate Re‐OPh intermediate via reductive deprotonation as previously observed under electrochemical conditions. Overall, BIH accelerates the rate of formation of the one‐electron reduced species (OERS) of the Re catalysts and allows higher turnover frequency (TOF) and TON for CO formation. The X‐ray structures of complexes 1 and 4 were determined to have distorted octahedral Re centres, and show π‐π stacking interactions with neighboring molecules as well as intramolecular hydrogen bonds to the internal chloride ligands. The unusually high absorptivity of the MLCT absorption of complex 1 has been explained by TD‐DFT calculations.

Eight coordinated mononuclear dysprosium complexes of heptadentate aminophenol ligands: the influence of the phenol substituents and the ancillary donors on the magnetic relaxation.

The mononuclear complexes [Dy(3Br,5Cl-H3L1,1,4)(D)]·solvate (D = H2O, solvate = 0.25MeOH, 1W·0.25MeOH; D = Py without solvate, 1Py), and [Dy(3NO2,5Br-H3L1,1,4)(H2O)] (2W) were isolated. The crystal structures of 1W·0.25MeOH, 1Py and 2W·2CH3C6H5 show that the DyIII ion is octacoordinated, in N4O4 or N5O3 environments, with distorted geometries, between square antiprism, biaugmented trigonal prism and triangular dodecahedral. A similar environment for the metal ion is shown in the chiral crystals of the diamagnetic yttrium analogue [Y(3Br,5Cl-H3L1,1,4)(MeOH)] (3M), which were spontaneously resolved. Magnetic analyses of the three dysprosium complexes, and their diluted analogous 1W@Y, 1Py@Y and 2W@Y, reveal that none of them seem to relax through an Orbach mechanism at Hdc = 0. However, the three complexes show Orbach relaxation under Hdc = 1000 Oe, and 1Py is the in-field SIM with the highest energy barrier among these complexes, with a Ueff value of 358 K. Analysis of ac magnetic data shows that the electron-withdrawing substituents on the phenol rings of the aminophenol ligands, as well as the auxiliary oxygen donors from water ligands, reduce the energy barriers of the complexes, which is attributed to a charge reduction in the coordinating atoms of the aminophenol donor. Ab initio calculations support the experimental results.

Quinone Methide-Based Organophosphate Hydrolases Inhibitors: Trans Proximity Labelers versus Cis Labeling Activity-Based Probes.

Quinone methide (QM) chemistry is widely applied including in enzyme inhibitors. Typically, enzyme-mediated bond breaking releases a phenol product that rearranges into an electrophilic QM that in turn covalently modifies protein side chains. However, the factors that govern the reactivity of QM-based inhibitors and their mode of inhibition have not been systematically explored. Foremost, enzyme inactivation might occur in cis, whereby a QM molecule inactivates the very same enzyme molecule that released it, or by trans if the released QMs diffuse away and inactivate other enzyme molecules. We examined QM-based inhibitors for enzymes exhibiting phosphoester hydrolase activity. We tested different phenolic substituents and benzylic leaving groups, thereby modulating the rates of enzymatic hydrolysis, phenolate-to-QM rearrangement, and the electrophilicity of the resulting QM. By developing assays that distinguish between cis and trans inhibition, we have identified certain combinations of leaving groups and phenyl substituents that lead to inhibition in the cis mode, while other combinations gave trans inhibition. Our results suggest that cis-acting QM-based substrates could be used as activity-based probes to identify various phospho- and phosphono-ester hydrolases, and potentially other hydrolases.