Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity

Neurogenerative diseases, such as Parkinson’s disease, are associated, not only with the selective loss of dopamine (DA), but also with the accumulation of reactive catechol-aldehyde, 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is formed as the immediate oxidation product of cytoplasmic DA by monoamine oxidase. DOPAL is well known to exhibit toxic effects on neuronal cells. Both catecholic and aldehyde groups seem to be associated with the neurotoxicity of DOPAL. However, the exact cause of toxicity caused by this compound remains unknown. Since the reactivity of DOPAL could be attributed to its immediate oxidation product, DOPAL-quinone, we examined the potential reactions of this toxic metabolite. The oxidation of DOPAL by mushroom tyrosinase at pH 5.3 produced conventional DOPAL-quinone, but oxidation at pH 7.4 produced the tautomeric quinone-methide, which gave rise to 3,4-dihydroxyphenylglycolaldehyde and 3,4-dihydroxybenzaldehyde as products through a series of reactions. When the oxidation reaction was performed in the presence of ascorbic acid, two additional products were detected, which were tentatively identified as the cyclized products, 5,6-dihydroxybenzofuran and 3,5,6-trihydroxybenzofuran. Physiological concentrations of Cu(II) ions could also cause the oxidation of DOPAL to DOPAL-quinone. DOPAL-quinone exhibited reactivity towards the cysteine residues of serum albumin. DOPAL-oligomer, the oxidation product of DOPAL, exhibited pro-oxidant activity oxidizing GSH to GSSG and producing hydrogen peroxide. These results indicate that DOPAL-quinone generates several toxic compounds that could augment the neurotoxicity of DOPAL.

Ruminant-Waste Protein Hydrolysates and Their Derivatives as a Bio-Flocculant for Oil Sands Tailing Management

Reclamation of tailings ponds is a critical issue for the oil industry. After years of consolidation, the slurry in tailings ponds, also known as fluid fine tailings, is mainly comprised of residual bitumen, water, and fine clay particles. To reclaim the lands that these ponds occupy, separation of the solid particles from the liquid phase is necessary to facilitate water removal and recycling. Traditionally, synthetic polymers have been used as flocculants to facilitate this process, but they can have negative environmental consequences. The use of biological polymers may provide a more environmentally friendly approach to flocculation, and eventual soil remediation, due to their natural biodegradability. Peptides derived from specified risk materials (SRM), a proteinaceous waste stream derived from the rendering industry, were investigated to assess their viability for this application. While these peptides could achieve >50% settling within 3 h in bench-scale settling tests using kaolinite tailings, crosslinking peptides with glutaraldehyde greatly improved their flocculation performance, leading to a >50% settling in only 10 min. Settling experiments using materials obtained through different reactant ratios during crosslinking identified a local optimum molar reactant ratio of 1:32 (peptide amino groups to glutaraldehyde aldehyde groups), resulting in 81.6% settling after 48 h. Taken together, these data highlight the novelty of crosslinking waste-derived peptides with glutaraldehyde to generate a value-added bioflocculant with potential for tailings ponds consolidation.

Synthesis and antiprotozoal activity of 2-phenoxy derivatives of pyridine

The aim of the present work is to synthesize phenoxypyridine derivatives and to screen substances with a high level of biological activity within the series of synthesized compounds, which is essential for solving the problem of overcoming the growing drug resistance of bacteria and protozoa. The interaction of 2-chloro-5-nitro- and 2-chloro-3-nitro-pyridine with aromatic aldehydes containing phenolic hydroxyl gave 15 pyridine series aryl ethers in high yields when reacted in dimethylformamide (DMFA) or dimethyl sulfoxide (DMSO) in the presence of bases. In the reaction we used phenolic derivative of kojic acid (compound 1 of Table 1), a number of benzene series aldehydes with different substituents: 3-methoxy-4-hydroxybenzaldehyde (compound 2 of Table 1), 4-hydroxybenzaldehyde (compound 3 of Table 1), 2,4-dihydroxybenzaldehyde (compound 5 of Table 1), 3-methoxy-4-hydroxybenzaldehyde (compound 7 of Table 1 ), salicylic aldehyde (compound 11 of Table 1), 3,4-dihydroxybenzaldehyde (compound 12 of Table 1), vanillin (compound 13 of Table 1), and compound 15 (Table 1) of the benzene series with two hydroxyl and aldehyde groups. As well as benzene-type aldehydes, the methyl ester of salicylic acid (compound 4 of Table 1), 4-hydroxymethylphenol (compound 6 of Table 1), 4-acetylphenol (compound 8 of Table 1), and 3-hydroxy benzoic acid (compound 14 of Table 1) were used. In the reaction, in addition to the above compounds, 7-hydroxycoumarin (compound 9 of Table 1) and semicarbazide-4-hydroxybenzaldehyde (compound 10 of Table 1) were also used. Their purification was performed by recrystallization from organic solvents (ethyl acetate, benzene, ethanol, and isopropanol). The obtained compounds were studied as part of the institute's search for compounds to expand the range of active substances with protistoсid and antibacterial activity with low toxicity. Synthesized compounds have pronounced antiprotozoal activity against Colpoda steinii. the most active compound contains a nitro group in the 3rd position of the pyridine ring as well as an aldehyde and hydroxyl group in the benzene ring. The minimum protistocidal concentration of this compound is 0.9 µg/ml, which is 60 fold more active than toltrazuril and 8 fold more active than chloroquine. This compound is recommended for extended toxicological and pharmacological studies.

PECULIARITIES OF SYNTHESIS AND ANTIMICROBIAL PROPERTIES OF GUANIDINE-CONTAINING CAR-BOXYMETHYLCELLULOSE DERIVATIVES

The article presents data on the synthesis and antimicrobial properties of guanidine-containing carboxymethylcellulose derivatives with different physical and chemical characteristics. The regularities of the reaction of nucleophilic substitution of aldehyde groups of modified Na-carboxymethylcellulose (Na-CMC) by guanidine under different conditions are studied. Based on the results obtained, it was found that the limit replacement of reactive electrophilic groups with nucleophilic reagent depends on the pH value of the medium, molar ratio of guanidine and the degree of oxidation of cellulose ester. By varying the reaction conditions and the number of aldehyde groups in the oxidized Na-CMC composition, the azometin derivatives differing in the content of nitrogen-containing fragments in the polymer chain were obtained. Chemical restoration of labile azomethine bonds was performed and water-soluble derivatives containing strong amino-bound guanidine groups were synthesized. The study shows and substantiates the influence of structural indices (degree of substitution, quantitative guanidine content, pKα values and nature of counterion) of macromolecular systems on antibacterial and antifungal properties. The developed approach of synthesis opens prospects for creation of antimicrobial derivatives with regulated physical and chemical characteristics and set biologically active properties.

Serial Extraction Technique of Rich Antibacterial Compounds in Sargassum cristaefolium Using Different Solvents and Testing their Activity

Background: S. cristaefolium is the brown seaweed extracted using the serial technique with different solvents. Methods: S. cristaefolium powder (50 mesh) was extracted with hexane, ethyl acetate, and methanol respectively. The S. cristaefolium powder residue had been dried before being re-extracted with the next different solvents. Three serial extracts were obtained and named as the 1-stage extract, 2-stage extract, and 3-stage extract. Besides, a single-step extract (extraction using only methanol) was also produced to compare with three serial extracts in antibacterial activity tests (against E. coli and S. aureus). The three serial extracts were detected their antibacterial compounds using GC-MS, LC-HRMS, and FT-IR. Results: The 3-stage extract had the highest extraction yield. On S. aureus, the inhibition zone in all extracts was not significantly different. On E.coli, the highest inhibition zone (5.42±0.14 mm) was the 3-stage extract, indeed it is higher than both antibiotic and a single-step extract. Phenol, 9-Tricosene(Z)-, palmitic acid, and oleamide were contained in all extracts. Other antibacterial compound types, both the 1-stage and 2-stage extracts contained 8 types whilst the 3-stage extract contained the most types (12 types). Particularly, hexyl cinnamic aldehyde and betaine were detected only in the 3-stage extract with the dominant area. The carboxylic acid groups were detected in all extracts to confirm the fatty acid structure. Several cinnamic aldehyde groups were detected only in the 3-stage extract. Conclusions: Thus, the extraction technique serially could produce the 3-stage extract which has the strongest antibacterial activity and the richest antibacterial compounds.

Structure elucidation of the novel carotenoid gemmatoxanthin from the photosynthetic complex of Gemmatimonas phototrophica AP64

Gemmatimonas phototrophica AP64 is the first phototrophic representative of the bacterial phylum Gemmatimonadetes. The cells contain photosynthetic complexes with bacteriochlorophyll a as the main light-harvesting pigment and an unknown carotenoid with a single broad absorption band at 490 nm in methanol. The carotenoid was extracted from isolated photosynthetic complexes, and purified by liquid chromatography. A combination of nuclear magnetic resonance (1H NMR, COSY, 1H-13C HSQC, 1H-13C HMBC, J-resolved, and ROESY), high-resolution mass spectroscopy, Fourier-transformed infra-red, and Raman spectroscopy was used to determine its chemical structure. The novel linear carotenoid, that we have named gemmatoxanthin, contains 11 conjugated double bonds and is further substituted by methoxy, carboxyl and aldehyde groups. Its IUPAC-IUBMB semi-systematic name is 1′-Methoxy-19′-oxo-3′,4′-didehydro-7,8,1′,2′-tetrahydro- Ψ, Ψ carotene-16-oic acid. To our best knowledge, the presence of the carboxyl, methoxy and aldehyde groups on a linear C40 carotenoid backbone is reported here for the first time.

Oxi-HA/ADH Hydrogels: A Novel Approach in Tissue Engineering and Regenerative Medicine

Hyaluronic acid (HA) is a natural polyelectrolyte abundant in mammalian connective tissues, such as cartilage and skin. Both endogenous and exogenous HA produced by fermentation have similar physicochemical, rheological, and biological properties, leading to medical and dermo-cosmetic products. Chemical modifications such as cross-linking or conjugation in target groups of the HA molecule improve its properties and in vivo stability, expanding its applications. Currently, HA-based scaffolds and matrices are of great interest in tissue engineering and regenerative medicine. However, the partial oxidation of the proximal hydroxyl groups in HA to electrophilic aldehydes mediated by periodate is still rarely investigated. The introduced aldehyde groups in the HA backbone allow spontaneous cross-linking with adipic dihydrazide (ADH), thermosensitivity, and noncytotoxicity to the hydrogels, which are advantageous for medical applications. This review provides an overview of the physicochemical properties of HA and its usual chemical modifications to better understand oxi-HA/ADH hydrogels, their functional properties modulated by the oxidation degree and ADH concentration, and the current clinical research. Finally, it discusses the development of biomaterials based on oxi-HA/ADH as a novel approach in tissue engineering and regenerative medicine.

Hydrogel Films Based on Chitosan and Oxidized Carboxymethylcellulose Optimized for the Controlled Release of Curcumin with Applications in Treating Dermatological Conditions

Cross-linked chitosan (CS) films with aldehyde groups obtained by oxidation of carboxymethyl cellulose (CMC) with NaIO4 were prepared using different molar ratios between the CHO groups from oxidized carboxymethyl cellulose (CMCOx) and NH2 groups from CS (from 0.25:1 to 2:1). Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy demonstrated the aldehyde groups’ presence in the CMCOx. The maximum oxidation degree was 22.9%. In the hydrogel, the amino groups’ conversion index value increased when the -CHO/-NH2 molar ratio, cross-linking temperature, and time increased, while the swelling degree values decreased. The hydrogel films were characterized by scanning electron microscopy (SEM) and FTIR analysis. The curcumin encapsulation efficiency decreases from 56.74% to 16.88% when the cross-linking degree increases. The immobilized curcumin release efficiency (REf%) and skin membrane permeability were evaluated in vitro in two different pH solutions using a Franz diffusion cell, and it was found to decrease when the molar ratio -CH=O/NH2 increases. The curcumin REf% in the receptor compartment was higher at pH = 7.4 (18%- for the sample with a molar ratio of 0.25:1) than at pH = 5.5 (16.5%). The curcumin absorption in the skin membrane at pH = 5.5 (47%) was more intense than at pH = 7.4 (8.6%). The curcumin-loaded films’ antioxidant activity was improved due to the CS presence.

Structure elucidation of the novel carotenoid gemmatoxanthin from the photosynthetic complex of Gemmatimonas phototrophica AP64

Gemmatimonas phototrophica AP64 is the first phototrophic representative of bacterial phylum Gemmatimonadetes. The cells contain photosynthetic complexes with bacteriochlorophyll a as the main light-harvesting pigment. In addition, the complexes contain a carotenoid with a single broad absorption band at 490 nm in methanol. A combination of nuclear magnetic resonance, high-resolution mass spectroscopy and Fourier-transformed infra-red spectroscopy was used to determine the chemical structure of G. phototrophica light-harvesting carotenoid that we have named gemmatoxanthin. It is a novel linear carotenoid containing 11 conjugated double bonds and further substituted by methoxy, carboxyl and aldehyde group. Its IUPAC-IUBMB semi-systematic name is 1’-Methoxy-19’-oxo-3’,4’-didehydro-7,8,1’,2’-tetrahydro- Ψ, Ψ carotene-16-oic acid. To our best knowledge, the presence of the carboxyl, methoxy and aldehyde groups on a linear C40 carotenoid backbone is reported here for the first time.

Flow-Through PolyHIPE Silver-Based Catalytic Reactor

Catalytic reactors performing continuously are an important step towards more efficient and controllable processes compared to the batch operation mode. For this purpose, homogenous high internal phase emulsion polymer materials with an immobilized silver catalyst were prepared and used as a continuous plug flow reactor. Porous material with epoxide groups was functionalized to bear aldehyde groups which were used to reduce silver ions using Tollens reagent. Investigation of various parameters revealed that the mass of deposited silver depends on the aldehyde concentration as well as the composition of Tollens reagent. Nanoparticles formed on the pore surface showed high crystallinity with a cuboctahedra crystal shape and highly uniform surface coverage. The example of the 4-nitrophenol catalytic reduction in a continuous process was studied and demonstrated to be dependent on the mass of deposited silver. Furthermore, productivity increased with the volumetric silver density and flow rate, and it was preserved during prolonged usage and storage.