Parent Phenol Research Articles

Removal of phenolic compounds from synthetic wastewater using soybean peroxidase

Experiments were conducted to investigate the efficiency of using soybean peroxidase (SBP) to remove several different phenolic compounds from unbuffered synthetic wastewater. The phenol derivatives studied included parent phenol, chlorinated phenols, cresols, 2,4-dichlorophenol and 4,4′-isopropylidenediphenol (commonly known as bisphenol A). Optimum conditions to achieve at least 95% removal of these compounds were determined for the following parameters: pH, SBP dose in the absence and presence of polyethylene glycol (PEG), hydrogen peroxide to substrate ratio, and PEG dose. Experimental results showed that SBP efficiently removed aromatic compounds from synthetic wastewater in the presence of hydrogen peroxide. An increase in the hydrogen peroxide to substrate ratio beyond the optimum resulted in enzyme inactivation in all cases except for bisphenol A. The optimum pH for different phenolic compounds ranged from 5.5 to 8. For each substrate, the optimum enzyme dose in the presence of PEG varied significantly. The studies showed that PEG only slightly reduced the amount of SBP required for 95% removal of the substrate. For most of the substrates, an increase in PEG dose beyond the optimum dose did not significantly change the removal efficiency.

Structure–Hepatic Disposition Relationships for Phenolic Compounds

Phenolic compounds are widely used in therapeutic, environmental, and industrial applications. The present work seeks to define the hepatic disposition of 11 phenolic compounds with varying lipophilicities and molecular weights. The hepatic disposition kinetics were studied in a once-through in situ rat liver perfusion preparation in order to avoid extra-hepatic metabolism and recirculation effects. The phenols were administered using the impulse-response technique and the time course of hepatic venous effluent concentration was examined by moments and a two-compartment dispersion model. While the extraction of the phenolic compounds was relatively independent of lipophilicity, the estimated permeability–surface area (PS) product for influx of solutes into the hepatocytes could be related to the compounds' octanol–buffer partition coefficients (log Papp). This log PS-logPapp relationship was consistent with that reported earlier for another series of solutes with a wide range of lipophilicity. The metabolites produced from each of the phenolic compounds used in this study had mean transit times similar to those of their corresponding parent phenols, suggesting that the metabolites were not trapped in the liver as a consequence of their higher polarity. It is concluded that the strong solute lipophilicity–toxicity and lipophilicity–skin penetration relationships often seen for aqueous solutions of phenols are not evident for the hepatic extraction of these compounds. Such a conclusion is consistent with the hepatic extraction of phenolic compounds being mainly determined by a blood flow limitation in delivery of the phenol to the liver, rather than the intrinsic liver metabolic enzyme activities at the doses injected.

Spectrophotometric Method for the Determination of Polyphenol Oxidase Activity by Coupling of 4-tert-Butyl-o-Benzoquinone and 4-Amino-N,N-Diethylaniline

ABSTRACT We describe a spectrophotometric analytical method for the detection of polyphenol oxidase activity in an aqueous solution. The assay is based on the coupling reaction between 4-tert-butyl-o-benzoquinone, generated during the enzyme-catalyzed reaction acting on 4-tert-butylcatechol, and the aromatic amine, 4-amino-N,N-diethylaniline to yield a blue adduct (λmax 625 nm). This blue adduct exhibited spectral features different from the parent phenol and from the o-quinone. Polyphenol oxidase activities extracted from potatoes, and sunflower seedlings were assayed. The proposed method presents several advantages over the spectrophotometric measurement of 4-tert-butyl-o-benzoquinone. The duration of the linear period was increased, allowing a better determination of its value. The molar extinction coefficient of the blue adduct was higher than that of the 4-tert-butyl-o-benzoquinone; therefore the limitation i8542948 by the comparatively low ɛ for the 4-tert-butyl-o-benzoquinone is overcome. This is of great importance when considering the inertness of the 4-tert-butyl-o-benzoquinone towards some common coupling agents such as 3-methyl-benzothiazolin-2-one hydrazone.

Orthoquinone monoketal chemistry. Experimental and density functional theory studies on orthoquinol acetate rearrangements

The non-dimerizing orthoquinone monoketal, 6-acetoxy-6-methoxy-3-methoxycarbonylcyclohexa-2,4-dienone, conveniently prepared from oxidative acetoxylation of its parent phenol with PhI(OAc) 2 in CH 2Cl 2AcOH (3:1), cleanly undergoes 1,3-acetoxy migrations in the presence of silica gel at room temperature to furnish a 60:40 product mixture conceivably derived from [3,5] and [3,3] sigmatropic rearrangements. Density functional theory calculations indicate that the [3,5] shift is pseudopericyclic, has a remarkably low activation energy of 20.1 kcal/mol, and is favored by 5.4 kcal/mol over the pericyclic [3,3] shift, in qualitative agreement with the experimental observations.

Molecular structure and intramolecular hydrogen bonding in 4,6-dinitroresorcinol and 2,5-dinitrohydroquinone from ab initio molecular orbital calculations

Ab initio molecular orbital calculations using second-order Møller-Plesset (MP2) perturbation theory with the 6-31G ∗ basis set have been performed for 4,6-dinitroresorcinol and 2,5-dinitrohydroquinone. Both molecules are characterized by considerable hydrogen bonding between the nitro and hydroxy groups; pronounced structural changes in other parts of the molecules are observed when compared with the parent phenol and nitrobenzene molecules calculated at the same computational level. These structural changes are consistent with the notion of resonance-assisted hydrogen bonding, also observed in a series of other o-nitrophenols and similar molecules. The geometrical and energetic characteristics of the structures indicate somewhat weaker hydrogen bonding in 2,5-dinitrohydroquinone than in 4,6-dinitroresorcinol, which may be interpreted by the difference in the mutual orientation of the substituent pairs in the two compounds.

Controlled activity polymers. X synthetically tailored monomers and copolymers with hydrolytically-labile pendent esters of allelopathic phenols

Monomers containing hydrolytically-labile ester linkages to allelopathic compounds: phenol, 2-isopropylphenol, 2,6-diisopropylphenol, 2-hydroxybenzoic acid and naphthoic acid were synthesized for incorporation into hydrophilic copolymers. Phenyl acrylate (PA), 2-isopropylphenyl acrylate (IPPA), 2,6-diisopropylphenyl acrylate (DIPPA), 2-acryloxybenzoic acid (2ABA) and 2-acryloxy-1-naphthoic acid (2ANA) were synthesized by esterification of the parent phenol with acryloyl chloride. These monomers were subsequently copolymerized with acrylic acid (AA) using AIBN as initiator in benzene or tetrahydrofuran at 70°C. PA was copolymerized with acrylamide (AM) and N-vinylpyrrolidinone (NVP) using AIBN in tetrahydrofuran and benzene, respectively, at 70°C. Copolymer compositions were determined by 1H NMR, 13C NMR, FTIR and UV-VIS spectroscopy. The copolymerization reactivity ratios were determined from 1H NMR data using Fineman-Ross (F-R), Kelen-Tudos (K-T) and nonlinear least-squares (NLS) methods. Copolymer statistical data were determined from K-T reactivity ratios. The resulting water soluble copolymers are potentially useful as plant growth regulators through the hydrolytic release of phenolic and naphthoic compounds. Selected polymers from these structurally-tailored series were chosen for controlled release studies in aqueous media reported in the subsequent paper of the series.

Influence of Intramolecular Coordination on the Aggregation of Sodium Phenolate Complexes. X-ray Structures of [NaOC(6)H(4)(CH(2)NMe(2))-2](6) and [Na(OC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)(HOC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)](2).

The structural characterization of two new sodium phenolate complexes, containing ortho-amino substituents, enables the influence of intramolecular coordination on the aggregation of sodium phenolate complexes to be determined. Crystals of hexameric [NaOC(6)H(4)(CH(2)NMe(2))-2](6) (1a) are monoclinic, space group P2(1)/c, with a = 11.668(4) Å, b = 18.146(4) Å, c = 14.221(5) Å, beta = 110.76(3) Å, V = 2815.5(16) Å(3), and Z = 2; R = 0.0736 for 2051 reflections with I > 2.0sigma(I). Complex 1a contains a unique Na(6)O(6) core, consisting of two face-fused cubes, with the ortho-amino substituent of each phenolate coordinating to a sodium atom. In addition, two of the phenolate ligands have an eta(2)-arene interaction with an additional sodium atom in the core. Crystals of dimeric [(NaOC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)(HOC(6)H(2)(CH(2)NMe(2))(2)-2,6-Me-4)](2) (2b) are triclinic, space group P&onemacr;, with a = 10.0670(8) Å, b = 10.7121(7) Å, c = 27.131(3) Å, alpha = 92.176(8) degrees, beta = 99.928(8) degrees, gamma = 106.465(6) degrees, V = 2752.1(4) Å(3), and Z = 2; R = 0.0766 for 5329 reflections with I > 2.0sigma(I). Dimeric complex 2b contains two phenolate ligands, which bridge the two sodium atoms, each coordinating with one ortho-amino substituent to a sodium atom, while the second available ortho-amino substituent remains pendant. The coordination sphere of each sodium atom is completed by a (neutral) bidentate O,N-coordinated parent phenol molecule. The second ortho-amino substituent of this neutral phenol is involved in a hydrogen bridge with its acidic hydrogen. On the basis of these two new crystal structures and previously reported solid state structures for sodium phenolate complexes, it is shown that the introduction of first one and then two ortho-amino substituents into the phenolate ligands successively lowers the degree of association of these complexes in the solid state. In this process, the basic Na(2)O(2) building block of the molecular structures remains intact.

Tetramethoxy Calix[4]arenes Revisited: Conformational Control through Self-Assembly

The concept of preorganization in molecular assembly has been well established, and its impact on synthetic supramolecular chemistry is profound.1 Many natural systems thrive on the ability of inherently flexible molecules to self-organize. This process is promoted by a well-defined surrounding architecture and culminates in self-assembly.2 The ability of a protein to find its thermodynamically most stable tertiary structure from a linear sequence of amino acids is an example. Also related is the ability of two flexible, complementary polynucleotide strands to form a double helix. In this paper we demonstrate how flexible molecules can reversibly self-assemble to give a well-defined receptor caVity. The calix[4]arene skeleton3 was chosen as a vehicle for modeling such phenomena. The calixarene platform has recently been exploited for assembly by several laboratories.4,5 Research in our group has explored a unique dimeric binding mode for the calix[4]arene framework which provides for the encapsulation of small molecule guests.5,6 Specifically, urea functions placed on the upper rim of the calix[4]arene permit dimerization to occur through a head-to-tail hydrogen bonding pattern (Figure 1). It is well-known that the calix[4]arenes interconvert between four discrete conformations in solution.3,7 This conformational flexibility can be controlled by alkylation of the phenolic oxygens with substituents larger than ethyl, i.e. reaction of the parent phenol with n-PrBr to give the tetrapropoxy derivative allows the isolation of three stable conformations: the cone (42%), partial cone (55%), and 1,3-alternate (3%).7b We have recently explored derivative 1-1, which uses benzyl ether substituents for such control. In calixarene derivative 1-2 much smaller lower rim substituents are present. The tetramethoxy calix[4]arene has been wellstudied and is defined as a “flexible” system.7,8 It freely interconverts between all four conformations, but the partial cone is the thermodynamically most favorable one.8 Specifically, in the parent tert-butyl system the difference in energy between the partial cone/cone isomers is ∼1.5 kcal/mol, and the barrier to interconversion is on the order of 13 kcal.8c We have found that intermolecular hydrogen bonding through dimerization can be used to driVe the conformational equilibrium exclusiVely to the cone conformer. Since substitution on the upper rim of the calixarene is not known to substantially bias the conformational equilibria,3 the observed conformational selection (self-organization) can be attributed solely to hydrogen bonding effects.

Formation of dichloromethyl phenyl ethers as major products in the photo-Reimer-Tiemann reaction without base

Photolysis of phenols 1a-d in chloroform or carbon tetrachloride afforded the corresponding di- or trichloromethyl phenyl ethers ( 2a-d or 6a-d, respectively). In chloroform, hydroxybenzaldehydes 4a-d or 5 and phenyl formates 3a-d were obtained as minor photoproducts. In carbon tetrachloride, traces of salicyloyl chloride ( 7), phenyl salicylate ( 8) and phenyl p-hydroxybenzoate ( 9) were detected starting from the parent phenol ( 1a). The obtained results agree with the involvement of an electron transfer mechanism.

Reaction of benzotriazole ultraviolet light absorbers with free radicals

The photolysis of benzotriazole ultraviolet light absorber additives (Bz-UVAs) in acrylic/melamine clearcoats suggests that Bz-UVAs are destroyed by clearcoat-driven photooxidation chemistry. Tinuvin 900 is converted to parent benzotriazole and phenol ring oxidation products. Bz-UVAs are not destroyed by photolysis in acrylic/melamine clearcoats in the absence of oxygen. Solution photolysis experiments reveal that Bz-UVAs are not attacked by free radicals generated by thermal decomposition of azoisobutyronitrile (AIBN) or cumene hydroperoxide (CHP) in ethanol or cyclohexane. Bz-UVAs are also not attacked by free radicals generated by photolytic decompostion of AIBN or CHP in cyclohexane. Bz-UVAs, however, are destroyed when AIBN or CHP are photolytically decomposed in ethanol. Photolysis without oxygen leads to Bz-UVA phenol ring solvent and initiator adducts. Photolysis with oxygen leads to cleavage to form free benzotriazole and to destruction of the phenol ring. It is suggested that an excited state of the non-planar Bz-UVA form may be susceptible to free radical attack. Detailed liquid chromatography tandem mass spectrometry (LC/MS/MS) product analysis results are reported in a companion paper.

Nickel-catalysed electrochemical reductive deprotection of allyl ethers

The selective deprotection of a series of functionalized alkyl and aryl allyl ethers to the parent alcohols or phenols, under non-hydrolytic conditions, is effected by the combination of electrochemistry and catalysis by NiII–bipyridine complexes.

Mutagenicity screening of reaction products from the enzyme‐catalyzed oxidation of phenolic pollutants

AbstractPhenol‐oxidizing enzymes such as peroxidases, laccases, and mushroom polyphenol oxidase are capable of catalyzing the oxidation of a wide range of phenolic pollutants. Although the use of these enzymes in waste‐treatment applications has been proposed by a number of investigators, little information exists on the toxicological characteristics of the oxidation products. The enzymes chloroperoxidase, horseradish peroxidase, lignin peroxidase, and mushroom polyphenol oxidase were used in this study to catalyze the oxidation of phenol, several mono‐substituted phenols, and pentachlorophenol. Seventeen reaction mixtures representing selected combinations of enzyme and parent phenol were subjected to mutagenicity screening using the Ames Salmonella typhimurium plate incorporation assay; five selected mixtures were also incubated with the S9 microsomal preparation to detect the possible presence of promutagens. The majority of reaction mixtures tested were not directly mutagenic, and none of those tested with S9 gave a positive response. Such lack of mutagenicity of enzymatic oxidation products provides encouragement for establishing the feasibility of enzyme‐catalyzed oxidation as a waste‐treatment process. The only positive responses were obtained with reaction products from the lignin peroxidase–catalyzed oxidation of 2‐nitrophenol and 4‐nitrophenol. Clear positive responses were observed when strain TA100 was incubated with 2‐nitrophenol reaction‐product mixtures, and when strain TA98 was incubated with the 4‐nitrophenol reaction mixture. Additionally, 2,4‐dinitrophenol was identified as a reaction product from 4‐nitrophenol, and preliminary evidence indicates that both 2,4‐ and 2,6‐dinitrophenol are produced from the oxidation of 2‐nitrophenol. Possible mechanisms by which these nitration reactions occur are discussed.

Evaluation of phenyl carbamates of ethyl diamines as cyclization-activated prodrug forms for protecting phenols against first-bass metabolism

A series of phenyl N-(2-aminoethyl)carbamates derived from various substituted ethyl diamines and phenol was prepared and evaluated as prodrug forms with the aim of protecting phenolic drugs against first-pass metabolism. The stability of the compounds was studied in aqueous buffer solutions and in various biological media. The compounds showed a high stability at lower pH but degraded by a cyclization process at higher pH values with a quantitative release of the parent phenol. The rate of cyclization was not affected by plasma, liver or gut enzymes but depended on the pH value of the medium and on the steric properties of the various substituents. By appropriate selection of the substituents, it is readily feasible to obtain prodrug derivatives having useful rates of cyclization, and hence release of the parent phenolic drug at pH 7.4 and 37°C, corresponding to half-lives of 10–60 min. The results suggest that this prodrug principle involving a non-enzymatic but pH-dependent conversion may be a potentially useful approach to reduce the extent of first-pass metabolism of the vulnerable phenol group.

Insecticidal properties of monoterpenoid derivatives to the house fly (diptera: Muscidae) and red flour beetle (coleoptera: Tenebrionidae)

AbstractMonoterpenoid derivatives were synthesized and their insecticidal activities were evaluated against red flour beetles, Tribolium castaneum (Herbst), in fumigant bioassays and against house flies Musca domestica (L.) in topical, fumigant, and ovicidal bioassays. Acetate derivatives and haloacetate derivatives were compared with each other, and with the parent monoterpenoid to determine structure‐activity relationships. Acetate derivatives were more active than the propionate derivatives of cyclic monoterpenoids in the topical, fumigant, and ovicidal bioassays. Pivalates were topically more insecticidal than acetates to adult house flies, while the acetates had the greater ovicidal activity. Acetates and pivalates were more effective than haloacetates in the topical, red flour beetle fumigation and ovicidal bioassays. Fluoroacetates of cyclic monoterpenoids were the most effective house fly fumigants, followed by acetates, and trichloroacetates. Several derivatives were produced that displayed enhanced activity relative to the parent alcohols or phenols.

Reductive deprotection of aryl allyl ethers with Pd(Ph 3) 4/NaBH 4

Treatment of aryl allyl ethers with catalytic amounts of Pd(PPh 3) 4 and NaBH 4 at room temperature afforded the parent phenol in high yield under non-hydrolytic conditions.

New Spectrophotometric Assay for Polyphenol Oxidase Activity

We describe a convenient and sensitive assay of polyphenol oxidase (PrO, EC 1.14.18.1) consisting of spectrophotometry at 300 nm based on the stoichiometric reaction of cysteine with o-quinones produced during the enzymatic oxidation of phenols. The adduct formed exhibited spectral properties different from those of the parent phenol. PPO activities extracted from apple, pear, and mushroom were assayed. The assay cannot be used with hydroxycinnamoyl derivatives since the cysteinyl adduct compounds exhibited spectral properties similar to those of their parent phenolic substrates. However, the cysteine-coupled method presents several advantages over the measurement of oxygen uptake by polarography or the direct estimation of o-quinone by spectrophotonietry. The duration of the linear period was increased, allowing a better estimation of its value. The zone of proportionality between rates and enzyme quantities was enlarged. The difference in molar extinction coefficients between adduct and phenol at 300 nm ranged between 2000 and 2800 M−1 · cm−1, i.e., two times higher than those of the corresponding o-quinones. Therefore, this assay improves the sensitivity of polyphenol oxidase detection over that of the direct spectrophotometric assay of quinone formation.

1H and 13C NMR studies of proton transfer in intramolecular hydrogen bonds in substituted 2‐diethylaminomethylphenol N‐oxides

AbstractEleven substituted 2‐diethylaminomethylphenol N‐oxides were studied in CDCl3 solutions by 1H and 13C NMR spectroscopy. The 1H chemical shifts of the intramolecular hydrogen‐bonded proton and the Δ14 values obtained from the 13C signals were considered as a function of the pKa values of the parent phenols. The 1H chemical shift of the hydrogen‐bonded proton shows a maximum at pKa ≈ 7. This result agrees well with the turning point of the curve if Δ14 is plotted as a function of the pKa of the parent phenols. All these results agree well with recently obtained Fourier transform IR results. With the system with the strongest hydrogen bond (pKa ≈ 7) a broad, flat, single‐minimum proton potential or a double‐minimum proton potential with a small barrier is present. With this system the deshielding of the proton in the intramolecular hydrogen bond is strongest.

Cyclization-activated phenyl carbamate prodrug forms for protecting phenols against first-pass metabolism

A series of phenyl carbamate esters derived from N-substituted 2-aminobenzamides was prepared and evaluated as prodrug forms with the aim of protecting phenolic drugs against first-pass metabolism following peroral administration. The stability of the derivatives was studied in aqueous buffer solutions and in various biological media. The carbamates showed a relatively high stability at pH 1–6 but underwent an apparent specific base-catalyzed cyclization in neutral and alkaline solution to a 2,4(1 H,3 H)-quinazolinedione with concomitant release of the parent phenol. The rate of this cyclization was not affected by liver, intestinal wall or plasma enzymes but dependent on the p K a of the phenol and the steric and polar properties of the N-substituent within the benzamide moiety. By appropriate selection of this sunstituent it is readily feasible to obtain prodrug derivatives having practically useful rates of cyclization and hence release of the parent phenolic drug at pH 7.4 and 37°C, corresponding to half-lives of 10–60 min. The results suggest that this prodrud principle involving anon-enzymatic but pH-dependent conversion may be a potentially useful approach to reduce the extent of first-pass metabolism of the vulnerable phenol group.

Molecular oxygen and the adsorption of phenols—effect of functional groups

ABSTRACT: This study reveals that the presence of molecular oxygen (oxic conditions) has a significant impact on the exhibited adsorptive capacity of granular activated carbon (GAC) for several phenolic compounds. The increase in the GAC adsorptive capacity under oxic conditions results from polymerization of these adsorbates on the carbon surface. The mechanism of polymer formation is through oxidative coupling of phenolic molecules. The extent of an increase in the GAC adsorptive capacity is in accordance with the ease of oxidation of these compounds. However, substituting a nitro group on the parent phenol molecule suppressed polymerization reactions and no increase in the GAC adsorptive capacity was observed under oxic conditions for these substituents.

Temperature and Pressure Effects on the Reversible Reaction of a Parent Phenol (GH) Corresponding to Galvinoxyl with Aliphatic Amines

Abstract The effects of temperature and pressure on the reversible reaction between GH and aliphatic amines in acetonitrile have been studied spectrophotometrically. The formation of free ions rather than that of ion pairs has been confirmed by the modified Benesi-Hildebrand (B–H) plot. From the plot the equilibrium constants were estimated. From the temperature dependence of the equilibrium constant (K), the heat and entropy of reactions were estimated to be: (ΔH°)av = −44.5 kJ mol−1, and (ΔS°)av = −193 J K−1 mol−1. From the pressure dependence of K the reaction volume (ΔV°)av was estimated to be −40 dm3 mol−1. When unbranched primary amines were used, a side reaction took place for which an explanation has been given.