Catechol Moiety Research Articles

Fast-Curing Mussel-Inspired Adhesive Derived from Vegetable Oil.

The development of functional materials based on renewable resources is of great significance in today's resource shortage. Here, we present an effective way to synthesize a mussel-inspired adhesive from acrylated epoxidized soybean oil (AESO), a renewable and commercially available small molecular material with a molecular weight around 1200 Da, by a one-step esterification reaction with the affordable 3,4-dihydroxybenzoic acid (DHA). By taking advantages of both the double bond and the catechol moiety presented in this small molecular adhesive, a short curing time was achieved with UV irradiation. An average bonding strength around 1.4 MPa at a curing time of only around 10 min on a glass substrate was observed, which reached 3.1 MPa (average 2.8 MPa) at a curing time of 2 h under ambient conditions. The curing time is much shorter, and the bonding strength is obviously stronger than the conditions where conventional oxidation agents such as IO4- or oxidation/coordination agents such as Fe3+ are used as the curing agent. Furthermore, the AESO-g-DHA can be used as an underwater adhesive, and an appreciable bonding strength up to 0.64 MPa was observed, which is superior than most of currently known commercialized glues. Given that the adhesive could be synthesized from low-cost renewable resources in one step, it might be a potential candidate for large-scale practical application.

Self-Assembly and Mechanical Properties of Engineered Protein Based Multifunctional Nanofiber for Accelerated Wound Healing.

The present work reports a new route for preparing tunable multifunctional biomaterials through the combination of synthetic biology and material chemistry. Genetically encoded catechol moiety is evolved in a nanofiber mat with defined surface and secondary reactive functional chemistry, which promotes self-assembly and wet adhesion property of the protein. The catechol moiety is further exploited for the controlled release of boric acid that provides a congenial cellular microenvironment for accelerated wound healing. The presence of 3,4-dihydroxyphenylalanine in the nanofiber mat act as a stimulus to trigger cell proliferation, migration, and vascularization to accelerate wound healing. Electron paramagnetic resonance, NMR, FTIR, and circular dichroism spectroscopy confirm the structural integrity, antioxidant property, and controlled release of boric acid. Fluorescent and scanning electron microscopy reveals the 3D architecture of nanofiber mat, which favors fibroblast growth, endothelial cell attachment, and tube formation, which are the desirable properties of a wound-healing material. Animal studies in the murine wound healing model assert that the multifunctional biomaterial significantly improve re-epithelialization and accelerate wound closure.

Alizarin Grafting onto Ultrasmall ZnO Nanoparticles: Mode of Binding, Stability, and Colorant Studies.

The demand is rising for colorants that are obtained from natural resources, tolerant to industrial processing methods, and meet color quality demands. Herein, we report how relevant properties such as thermal stability and photostability of the natural colorant alizarin can be improved by grafting it onto ZnO nanoparticles (NPs), allowing application in a warm extrusion process for the fabrication of polyamide fibers. For this study, ZnO NPs (diameter 2.0 ± 0.6 nm) were synthesized and subsequently functionalized with alizarin. The alizarin-coated ZnO NPs (i.e., dyed nanoparticles, DNPs) were characterized. Thermogravimetric analysis and ultraviolet–visible (UV–vis) studies revealed that alizarin coating accounts for ∼65% (w/w) of the total mass of the DNPs. A subsequent detailed characterization with Fourier transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), 13C cross-polarization magic angle spinning (CP-MAS) NMR, X-ray photoelectron spectroscopy (XPS), and quantum chemistry studies using various density functional theory (DFT) functionals and basis sets indicated that binding onto the ZnO NPs occurred predominantly via the catechol moiety of alizarin. Importantly, this grafting increased the thermal stability of alizarin with >100 °C, which allowed the processing of the DNPs into polyamide fibers by warm extrusion at 260 °C. Evaluation of the lightfastness of the DNP-dyed nylon fibers revealed that the changes in color quantified via the distance metric ΔE* of alizarin when embedded in a hybrid material were 2.6-fold better compared to nylon fibers that were directly dyed with alizarin. This reveals that the process of immobilization of a natural dye onto ZnO nanoparticles indeed improves the dye properties significantly and opens the way for a wide range of further studies into surface-immobilized dyes.

Interaction of esculetin with aluminium ion by spectroscopic studies and isothermal titration calorimetry: a probable molecule for chelation therapy

The use of aluminium has made significant impact in our life by virtue of its attractive properties. The lack of essentiality of aluminium in biosphere indicated that its accumulation above certain level is undesirous. Esculetin (6,7-dihydroxy coumarin) is an excellent aluminium ion chelator and the chelation interaction was studied by exploiting the absorption and fluorescence behavior of esculetin. In presence of aluminium ion, the absorption band of esculetin was shifted from 350 to 380 nm suggesting the possibility of complex formation. The fluorescence intensity of esculetin at 466 nm was significantly quenched in presence of aluminium ion. The fluorescence quenching was interpreted in terms of chelation-quenched fluorescence (CHQF) mechanism where the strong Lewis acid character of aluminium ion accepts electrons from the chelating catechol moiety of the excited esculetin. From the absorption and fluorescence changes the association constant was estimated in the order of 105 M −1. The association constant was further evaluated by isothermal titration calorimetry (ITC) and there was close agreement to that of obtained from spectroscopic studies. Form ITC studies, the binding enthalpy and binding entropy were estimated as −20.6 kcal/mol and −46.7 cal/mol/K respectively. The complex was less toxic compared to the individual complexing agents when studied in Chinese hamster ovary cells. Considering the present investigation, esculetin can be a probable molecule for chelation therapy where rapid complex formation ability of esculetin will help to reduce the aluminium accumulation through chelation and water soluble nature of the complex will help for faster elimination from the system. Communicated by Ramaswamy H. Sarma

Synthesis and Properties of Cationic Gradient Brush Copolymers Carrying PEO Side Chains and Catechol Moieties

AbstractSynthesis and study of brush copolymers carrying long PEO side chains and catechol moieties are reported. Kinetics of reversible‐addition‐fragmentation chain‐transfer copolymerization of 2‐(dimethylamino) ethyl methacrylate (DMAEMA) and poly(ethylene glycol) methyl ether methacrylate (PEOMEMA) is studied by size exclusion chromatography (SEC) and 1H NMR spectroscopy, which allow calculating not only copolymerization rate but also the evolution of copolymer composition during copolymerization. Molecular weight Mn and dispersity Ð of the copolymers are determined by SEC with triple detection. Well defined gradient copolymers p(DMAEMA‐co‐PEOMEMA) of various composition with degree of polymerization close to 100 and Ð less than 1.18 are synthesized. For attachment of catechol moieties and introduction of positive charge, DMAEMA units are quaternized with 2‐chloro‐3,4‐dihydroxyacetophenone. The use of tetrahydrofuran as a solvent for that reaction allows obtaining the degree of quaternization close to 100%. Positively charged catechol brush copolymers and their solutions are characterized by 1H NMR, fourier‐transform infrared spectroscopy), and ultraviolet–visible spectroscopy, potentiometric titration, and water contact angle measurements, and their properties are compared with those of similar neutral catechol brush copolymers.

Mussel-inspired poly(γ-glutamic acid)/nanosilicate composite hydrogels with enhanced mechanical properties, tissue adhesive properties, and skin tissue regeneration

It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H2O2, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. Statement of significanceRecently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.

Effects of clovamide and its related compounds on the aggregations of amyloid polypeptides.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are common diseases in the elderly, and the increasing number of patients with these diseases has become a serious health problem worldwide. The aggregation and development of plaque of amyloid polypeptides (amyloid β; Aβ and human islet amyloid polypeptide; hIAPP, amylin) are found in the brains of patients with AD and the pancreas of patients with T2D and are considered to be, in part, the causes of both diseases, respectively. Therefore, preventing amyloid aggregation may be a promising therapeutic strategy for preventing AD and T2D. In addition, the disaggregation of the already aggregated amyloid polypeptides is expected to contribute to the prevention and treatment of both diseases as amyloid polypeptide aggregations begin several decades before the onset of disease. Therefore, in this study, we investigated the hIAPP aggregation inhibitory activity and Aβ42/hIAPP disaggregation activity of clovamide which had shown inhibitory activity against Aβ42 aggregation in our previous studies. In addition, active sites were identified (structure-activity relationship analysis) using clovamide-related compounds in which hydroxyl groups of these compounds were either eliminated or methylated. Our results showed that the compounds with one or two catechol moieties showed strong hIAPP aggregation inhibitory activity and Aβ42/hIAPP disaggregation activity; and the non-catechol type compounds showed little or no activity. This suggests that the catechol moiety is important in amyloid polypeptide aggregation inhibition and disaggregation. Thus, clovamide and its related compounds may be promising therapeutic strategies for inhibiting amyloid polypeptide-related pathology in AD and T2D.

The chemical interaction between the neurotransmitter dopamine and the antipsychotic drugs olanzapine and quetiapine

Mental disorders like schizophrenia affect about 0.7% of the world population. Nowadays, the treatment consists of atypical antipsychotic drugs, mainly olanzapine and quetiapine. In this paper, we observed the chemical interaction between both olanzapine and quetiapine, antipsychotic drugs, with dopamine in phosphate buffer solutions at physiological pH using cyclic and differential voltammetry techniques, UV–Vis and EPR spectra. A solution containing both antipsychotic drugs and dopamine resulted in a shift of dopamine's redox processes, hindering its electrochemical oxidation. The chemical interaction was voltametrically investigated and a mechanism is proposed. In addition, it was observed that the reactions of both drugs with DA are first-order, presenting kinetic rate constants of 1.5 10 −2 s −1 and 9.0 10 −3 s −1 for olanzapine and quetiapine, respectively, at pH = 7.4. To further evaluate the chemical reaction, a minimalist model between PIPES molecule and catechol was proposed and tested. The model presented a similar signal decrease and kinetic rate constant to those observed for both olanzapine and quetiapine reaction with dopamine, reinforcing the data obtained which strongly suggests that the chemical reaction occurs between piperazine and catechol moieties. • Neurotransmitter dopamine reacts with antipsychotic drugs olanzapine and quetiapine; • The reaction occurs between the catechol and piperazine moieties from dopamine and the antipsychotics, respectively • A mechanism to the reactions involving both olanzapine and quetiapine with dopamine is proposed; • The reaction rate constants were obtained.

L-Dopa in small peptides: an amazing functionality to form supramolecular materials.

l-Dopa (3,4-dihydroxyphenylalanine) is a chiral amino acid generated via biosynthesis from l-tyrosine in plants and some animals. The presence of multiple interacting sites makes l-Dopa a multifunctional building block for the preparation of supramolecular materials. The possibility to form hydrogen bonds and the presence of the aromatic ring allow l-Dopa molecules to interact through a series of non-covalent interactions. The additional presence of the catechol moiety really makes this compound unique: not only does it have implications in the self-assembly process of Dopa itself and with other substrates, but also it highly increases the number of applications of the final material, since it works as an antioxidant, radical trapper, metal chelator, reducing agent and adhesive. l-Dopa and catechol containing derivatives have been extensively introduced inside both synthetic and natural polymers to obtain amazing functional materials. In this review we report the preparation of small peptides containing l-Dopa, focusing on the supramolecular materials that can be obtained with them, ranging from fibrils to fibres, gels, films and coatings, all having the different applications mentioned above and many others.

Reactivity of Flavonoids Containing a Catechol or Pyrogallol Moiety with Metal‐Free and Metal‐Associated Amyloid‐β

Aggregates of both metal‐free amyloid‐β (Aβ) and metal‐bound Aβ (metal–Aβ) are accumulated in the brain affected by Alzheimer's disease. To control metal‐free and metal‐bound Aβ species, chemical reagents capable of modulating their aggregation profiles have been developed. As an effort, the reactivity of natural products such as flavonoids with metal‐free Aβ and metal–Aβ has been investigated to identify their use as chemical reagents and structural features essential for such reactivity. This review illustrates the effects of flavonoids containing a catechol or pyrogallol group on metal‐free and metal‐mediated Aβ aggregation pathways. In addition, the studies regarding the structure–activity relationship of flavonoids against metal‐free Aβ or metal–Aβ are discussed.

Synthesis, Structural, and Physicochemical Characterization of a Ti6 and a Unique Type of Zr6 Oxo Clusters Bearing an Electron-Rich Unsymmetrical {OON} Catecholate/Oxime Ligand and Exhibiting Metalloaromaticity.

The chelating catechol/oxime ligand 2,3-dihydroxybenzaldehyde oxime (H3dihybo) has been used to synthesize one titanium(IV) and two zirconium(IV) compounds that have been characterized by single-crystal X-ray diffraction and 1H and 13C NMR, solid-state UV-vis, and ESI-MS spectroscopy. The reaction of TiCl4 with H3dihybo and KOH in methanol, at ambient temperature, yielded the hexanuclear titanium(IV) compound K2[TiIV6(μ3-O)2(μ-O)3(OCH3)4(CH3OH)2(μ-Hdihybo)6]·CH3OH (1), while the reaction of ZrCl4 with H3dihybo and either nBu4NOH or KOH also gave the hexanuclear zirconium(IV) compounds 2 and 3, respectively. Compounds 1-3 have the same structural motif [MIV6(μ3-Ο)2(μ-Ο)3] (M = Ti, Zr), which constitutes a unique example with a trigonal-prismatic arrangement of the six zirconium atoms, in marked contrast to the octahedral arrangement of the six zirconium atoms in all the Zr6 clusters reported thus far, and a unique Zr6 core structure. Multinuclear NMR solution measurements in methanol and water proved that the hexanuclear clusters 1 and 3 retain their integrity. The marriage of the catechol moiety with the oxime group in the ligand H3dihybo proved to be quite efficient in substantially reducing the band gaps of TiO2 and ZrO2 to 1.48 and 2.34 eV for the titanium and zirconium compounds 1 and 3, respectively. The application of 1 and 3 in photocurrent responses was investigated. ESI-MS measurements of the clusters 1 and 3 revealed the existence of the hexanuclear metal core and also the initial formation of trinuclear M3 (M = Ti, Zr) building blocks prior to their self-assembly into the hexanuclear M6 (M = Ti, Zr) species. Density functional theory (DFT) calculations of the NICSzz scan curves of these systems revealed that the triangular M3 (M = Ti, Zr) metallic ring cores exhibit pronounced metalloaromaticity. The latter depends upon the nature of the metallic center with NICSzz(1) values equal to -30 and -42 ppm for the Ti (compound 1) and Zr (compound 2) systems, respectively, comparable to the NICSzz(1) value of the benzene ring of -29.7 ppm calculated at the same level of theory.

Isolation and Structural Confirmation of Xanthone Isomers from Dryopteris ramosa (Hope) C. Chr. and Their In Vitro Antioxidant Mechanism

The long history of using plant species as medicines worldwide provides clues for the search for bioactive phytochemicals. One of the important traditional medicinal plant species of Pakistan is Dryopteris ramosa (Dryopteridaceae). The fronds of Dryopteris ramosa are traditionally used for the treatment of gastric ulcer and constipation. The crude methanol extract and aqueous fraction of Dryopteris ramosa exhibited strong free radical scavenging potential. Two xanthonoid compounds, mangiferin and isomangiferin, were isolated from the aqueous fraction of Dryopteris ramosa by chromatographic techniques (CC Sephadex LH20, followed by MPLC and purified by preparative TLC). Their structures were confirmed by spectroscopic analysis MS, NMR (1H, 13C, HSQC and HMBC). This is the first report on isolation of mangiferin and isomangiferin from Dryopteris genus though previously reported in other fern genera, e.g., Cystopteris, Acystopteris, Gymnocarpium and Asplenium. The antioxidant potential of mangiferin (60.34 ± 0.14 μg/mL) and isomangiferin (55.98 ± 0.39 μg/mL) was comparable to ascorbic acid (57.97 ± 0.93 μg/mL), thus representing promising antioxidant agents against oxidative stress. The investigation of the mechanism of free radical scavenging by mangiferin and isomangiferin showed that the catechol moiety was involved in quenching of free radicals. This study justified the traditional use of Dryopteris ramosa confirming the pharmacological properties of isolated compounds. Further phytochemical studies on Dryopteris ramosa are needed for identification of new bioactive phytochemicals in this plant of ethnobotanical relevance.

Design and Synthesis of Bio-Inspired Polyurethane Films with High Performance.

In the present work, the synthesis of segmented polyurethanes functionalized with catechol moieties within the hard or the soft segment is presented. For this purpose, a synthetic route of a new catechol diol was designed. The direct insertion of this catechol-free derivative into the rigid phase led to segmented polyurethanes with low performance (σmax ≈ 4.5 MPa). Nevertheless, when the derivative was formally located within the soft segment, the mechanical properties of the corresponding functionalized polyurethane improved considerably (σmax ≈ 16.3 MPa), owing to a significant increase in the degree of polymerization. It is proposed that this difference in reactivity could probably be attributed to a hampering effect of this catecholic ring during the polyaddition reaction. To corroborate this hypothesis, a protection of the aromatic ring was carried out, blocking the hampering effect and avoiding secondary reactions. The polyurethane bearing the protected catechol showed the highest molecular weight and the highest stress at break described to date (σmax ≈ 66.1 MPa) for these kind of catechol-functionalized polyurethanes. Therefore, this new approach allows for the obtention of high-performance polyurethane films and can be applied in different sectors, benefiting from the molecular adhesion introduced by the catechol ring.

Boc‐Protection on L‐DOPA: an Easy Way to Promote Underwater Adhesion

The ability of mussels to adhere to underwater surfaces has attracted a lot of attention from the scientific community. As proteins containing L‐DOPA (3,4‐dihydroxyphenyl‐l‐alanine) are involved in their adhesion, a common strategy to synthesize adhesives is the incorporation of this amino acid into other compounds. Herein, we report a study on four compounds of the family of Bocx‐(L‐DOPA)n‐OMe (x = 1–3; n = 1,2), that we prepared through simple synthetic steps. Three of them showed the capability of underwater adhesion: while they are not adhesive in the dry phase, the adhesiveness is triggered when the dried sample is immersed in water or any aqueous solutions. The introduction of protecting groups stabilizes L‐DOPA, preventing the oxidation of the catechol moiety, and enhances the hydrophobicity, helping the removal of water from the surface to bind. These molecules show good adhesiveness, with different properties, so they may be all used as adhesives for different purposes. These outcomes pave the way for new applications for these materials as green and biocompatible adhesives.

Supramolecular Caffeic Acid and Bortezomib Nanomedicine: Prodrug Inducing Reactive Oxygen Species and Inhibiting Cancer Cell Survival.

Phenolics from plant materials have garnered attention in nanomedicine research, due to their various medicinal properties. Caffeic acid, a phenolic compound that is abundant in coffee beans, has been proven to have anticancer effects, due to its reactive oxygen species (ROS)-inducing properties. Here, a supramolecular nanomedicine was designed using caffeic acid molecule and the synthetic anticancer drug bortezomib, via catechol–boronic acid conjugation and Fe(III) ion crosslinking. Bortezomib is a proteasome-inhibiting drug and its boronic acid functional group can bind to caffeic acid’s catechol moiety. By having a nanoparticle formulation that can deliver bortezomib via intracellular endocytosis, the catechol–boronic acid conjugation can be dissociated, which liberates the boronic acid functional group to bind to the 26S proteasome of the cell. The ROS-inducing property of caffeic acid also complements the bortezomib payload, as the latter suppresses the survival mechanism of the cell through NF-κB inhibition.

Metal Chelates of Petunidin Derivatives Exhibit Enhanced Color and Stability.

Anthocyanins with catechol (cyanidin) or pyrogallol (delphinidin) moieties on the B-ring are known to chelate metals, resulting in bluing effects, mainly at pH ≤ 6. Metal interaction with petunidin, an O-methylated anthocyanidin, has not been well documented. In this study, we investigated metal chelation of petunidin derivatives in a wide pH range and its effects on color and stability. Purple potato and black goji extracts containing >80% acylated petunidin derivatives (25 μM) were combined with Al3+ or Fe3+ at 0 μM to 1500 μM in buffers of pH 3–10. Small metal ion concentrations triggered bathochromic shifts (up to ~80nm) at an alkaline pH, resulting in vivid blue hues (hab 200°–310°). Fe3+ caused a larger bathochromic shift than Al3+, producing green colors at pH 8-9. Generally, metal ions increased the color stability and half-life of petunidin derivatives in a dose-dependent manner, particularly at pH 8. Petunidin derivative metal chelates produced a wide range of colors with enhanced stability.

Iron-crosslinked Rososome with robust stability and high drug loading for synergistic cancer therapy

Development of liposomal nanomedicine with robust stability, high drug loading and synergistic efficacy is a promising strategy for effective cancer therapy. Here, we present an iron-crosslinked rosmarinic liposome (Rososome) which can load high contents of drugs (including 25.8% rosmarinic acid and 9.04% doxorubicin), keep stable in a high concentration of anionic detergent and exhibit synergistic anti-cancer efficacy. The Rososomes were constructed by rosmarinic acid-lipid conjugates which not only work synergistically with doxorubicin by producing reactive oxygen species but also provide catechol moieties for the iron cross-linkages. The cross-linkages can lock the payloads tightly, endowing the crosslinked Rososome with better stability and pharmacokinetics than its non-crosslinked counterpart. On the syngeneic mouse model of breast cancer, the iron-crosslinked Rososomes exhibit better anticancer efficacy than free rosmarinic acid, doxorubicin, non-crosslinked Rososome and commercial liposomal formulation of doxorubicin (DOXIL). This study introduces a novel strategy for the development of liposomes with robust stability, high drug loading and synergistic anti-cancer efficacy.

Effects of different ester chains on the antioxidant activity of caffeic acid

Caffeic acid ester derivatives have been widely found in propolis extract and plants. In this work, the effect of ester groups with different aromatic and alkyl chains on the antioxidant activity of caffeic acid was performed on the double H+/e– process using DFT calculations. We found that 1) O3–H3⋯O4 intramolecular hydrogen-bonds exist in the catechol moiety of the investigated compounds, which have the same strength and are closed shell interactions, weak-strength and electrostatic in nature, making the 4–OH more favourable than 3–OH to trap free radicals. 2) In weak polarity phases, caffeic acid and its derivatives prefer to perform the double H+/e– processes via the dHAT mechanism. In the polar phases, the SdPLdET mechanism is more favoured. The first step of these mechanisms is more possible in 4–OH groups. 3) The ester group with different aromatic and alkyl chains would enhance the antioxidant capacities of caffeic acid.

Antioxidant studies by hydrodynamic voltammetry and DFT, quantitative analyses by HPLC-DAD of clovamide, a natural phenolic compound found in Theobroma Cacao L. beans

Clovamide (trans-clovamide, (2S)-3-(3,4-dihydroxyphenyl)-2-[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino]propanoic acid) is a naturally occurring caffeoyl conjugate and a potent antioxidant found in the phenolic fraction of Theobroma Cacao L. beans. This work quantified clovamide content in single-origin cocoa beans at different production stages (raw, roasted, and winnowed side and end products) by high-performance liquid chromatography with diode array detector (HPLC-DAD). We analyzed the antioxidant activities of clovamide and these extracts by measuring their superoxide radical scavenging capabilities in a Rotating Ring-Disk Electrode (RRDE) electrochemical system against in-situ generated superoxide radical. Our studies concluded a positive correlation between clovamide concentration and the overall antioxidant activities of beans, with the roasting step showing a reduction effect on both. The subsequent refining steps recover the clovamide concentration. Antioxidant studies on clovamide alone by RRDE and density functional theory (DFT) studies led to the conclusion that it is a powerful oxygen radical scavenger, partially contributed by its molecular catechol moieties.

Free radical scavenging potency of ellagic acid and its derivatives in multiple H+/e‒ processes

The reaction energetics of the multiple free radical scavenging mechanisms of ellagic acid and its derivatives were studied by DFT method. Ellagic acid and its derivatives that bear catechol or guaiacyl moieties can proceed multiple free radical scavenging processes. Intramolecular hydrogen-bonds were found in the most stable geometries of the investigated compounds and can influence the antioxidant activity of the related groups and hydrogen atom/proton loss sequence. The stronger hydrogen-bond, the weaker antioxidant activity of the hydrogen atom/proton-donating group. The preferred mechanisms vary among different phases. All of the investigated compounds prefer to trap free radicals by multiple HAT mechanisms in gas and benzene phases. The second HAT reaction preferably occurs in the same catechol or guaiacyl unit of the first HAT group with the formation of stable quinone or benzodioxole. The catechol and guaiacyl moieties not only retain high free radical scavenging ability of the parent compounds but even show increased potency for the second and fourth H+/e‒ reactions. In water phase, ellagic acid and its derivatives would proceed consecutively PL reactions from the OH groups. The formed di/tri/tetra-anion would proceed one/four electron transfers following with single/double SPLET mechanism and electron donation reactions until forming the stable quinone or benzodioxole.