Hydroxyl Derivatives Research Articles

Application of Hydroxyaromatic Aldehydes in Ultra-Efficient and Metal-Free Photocatalytic E→Z Isomerization of Olefin.

The strategy of photocatalyzed E→Z isomerization of olefins to access thermodynamically less stable Z-alkenes has recently received considerable attention. Here, we have discovered a sensitizer of hydroxyaromatic aldehyde that can rapidly achieve olefin E→Z isomerization under blue light irradiation. Notably, 2-hydroxybenzene-1,3,5-tricarbaldehyde, when assisted by blue light, can achieve efficient and selective conversion within just 5 minutes (Z/E=92 : 8). The reaction can be successfully scaled up to gram scale, and exhibits remarkable reactivity toward various derivatives of ethyl cinnamate (27 examples) and other olefins. Furthermore, the former can be directly cyclized by a hydroxyl derivative to produce 4-substituted coumarin. The prominent preponderance of this method includes being metal-free, efficient, convenient, no by-products and achieving high selectivity. Correlation of sensitizer triplet energy (ET) and preliminary mechanistic experiments indicate that the accomplishment of this reaction is based on the selective excitation mechanism.

Analysis of pentacyclic triterpenoids and phytosterols in cloudberry (Rubus chamaemorus L.) by LC-MS/MS.

Cloudberry (Rubus chamaemorus L.) is a plant rich in various biologically active compounds. In this work, the composition and concentrations of pentacyclic triterpenoids (PCTs) and phytosterols in various parts of cloudberries were studied using high-performance liquid chromatography-tandem mass spectrometry by multiple reaction monitoring mode (MRM, targeted analysis) and precursor ion scan mode (non-targeted analysis and semi-quantitative determination). Moderately polar fractions of cloudberry leaves, sepals and berries extracts are rich in β-sitosterol glycoside and various triterpenoid acids, among which tormentic acid (∼190-1800 μg/g dw part of cloudberries) and its hydroxyl derivatives (∼3.1-470 μg/g dw part of cloudberries) predominate. Non-polar fractions are characterised by the presence of amyrins (0.76-110 μg/g dw part of cloudberries), β-sitosterol (62-750 µg/g dw part of cloudberries) and β-sitosterol glycoside (∼92-360 μg/g dw sepals).

The new pincer-type NHCs obtained by synthesizing Ag(I)-NHC complexes with various tails containing hydroxyl or acetate derivatives: Structural properties and in vitro antibacterial activities

This article discusses the synthesis, chemistry, and uses of transition metal complexes containing functionalized N-Heterocyclic carbenes (NHCs). NHCs were obtained by coupling functional group compounds containing ethyl acetate, propyl acetate, and ethanol to the 5,6-dimethylbenzimidazole compound. Thermogravimetric analysis (TGA), FT-IR, and solution (1H and 13C) NMR spectroscopy were used to characterize the elements in these compounds, and Rietveld analysis using X-ray powder diffraction (XPD) and ICP (Inductively Coupled Plasma) data was used to determine their structures. Major uses include catalyst modification and immobilization using a functional group to immobilize catalysts on a 5,6-dimethylbenzimidazole derivative support. The effects of the drug ampicillin were compared with the antimicrobial activities of 3a-c and 4a-c determined by the minimum inhibitory concentration (MIC; μg/ml). The MIC value of the compound bis(1,3-bis(3-ethoxy-3-oxopropyl)-5,6-dimethyl-1H-3λ4-benzo[d]imidazol-2-ylidene)silver(I)hexafluorophosphate (4b) was measured as 0.25 ± 2.05 μg/mL. This value indicates that this complex has strong antibacterial abilities.

Albusamides A-G: Hydroxylated Fatty Amine Derivatives from the Deep-Sea-Derived Actinomycete Streptomyces albus 228DD-066 and Their Cytotoxic Activity.

A series of new hydroxylated fatty amine derivatives, albusamides A-G (1-7), along with four known compounds (8-11), which are reported for the first time from a natural source, were isolated from the culture broth of Streptomyces albus 228DD-066 derived from a deep-sea sediment sample gathered off the coast of Dokdo Island, Republic of Korea. Their structures were elucidated through the comprehensive analysis of 1D and 2D NMR spectra and HRESIMS, and absolute configurations were determined using the modified Mosher's method. Biological evaluations against solid and blood cancer cell lines revealed that these new metabolites have moderate to strong cytotoxic activity. Compound 3 exhibited high cytotoxic activity with GI50 values ranging from 0.4 to 0.6 μM against solid cancer cell lines and exhibited the strongest cytotoxicity (GI50 value = 0.2 μM) against the WSU-DLCL2 blood cancer cell line.

Photochemical method for preparation of benzo[a]pyrano[3,2‐c]phenazin‐4‐ones from quinoxalines with 4‐pyranone unit

AbstractPhotochemical properties of terarylenes with quinoxalines bridge unit and allomaltol fragment was investigated. We have demonstrated that starting compounds with hydroxyl group in 3‐hydroxy‐4‐pyranone substituent does not undergo any photoinduced transformations. Wherein, conversion to methoxy derivatives allows one to realize photochemical 6π‐electrocyclization for considered quinoxalines. Based on data of x‐ray analysis the observed difference in reactivity is connected with the presence of hydrogen bond in hydroxyl derivatives. As a result of carried out research photochemical approach to novel benzo[a]pyrano[3,2‐c]phenazin‐4‐ones was implemented.

Theoretical Insight into Psittacofulvins and Their Derivatives

Psittacofulvins are polyenal dyes responsible for coloring parrot feathers and protecting them against photo-oxidation, harmful radicals, and bacterial degradation. To explain the unusual properties of these compounds, the thermodynamic and global chemical activity descriptors characterizing four natural and three synthetic psittacofulvins, as well as their hydroxyl, carboxyl and dialdehyde derivatives, were determined. To this aim, the DFT method at the B3LYP/QZVP theory level and the C-PCM solvation model were used. The calculations enabled the selection of the projected compounds for the greatest bioactivity and potential applicability as multifunctional ingredients in medicines, cosmetics, supplements, and food, in which they may play a triple role as preservative, radical scavenger, and coloring agent. The results obtained provide arguments for the identification of a fifth psittacofulvin within the parrot feather pigment, characterized by ten conjugated double bonds (docosadecaenal).

Molecular origin for pH-responsive wormlike micelles of zwitterionic surfactants triggered by aromatic acid derivatives

Introduction of aromatic acid derivatives (AADs) into zwitterionic surfactants is an efficient method to prepare wormlike micelles with pH-controllable viscosity; however, the coincident molecular origin of AAD/zwitterionic surfactant binary mixtures remains unclear. Herein, the self-assembly of hydroxyl derivatives of benzoic acid (BA) and cetyldimethyl betaine (BS-16) mixtures in water was systematically assessed, and various factors, such as the molecular structure, molar ratio of AAD and BS-16, and solution pH, were investigated. The structure–property relationship of AAD/BS-16 binary mixtures was established, which provided the molecular origin for the effect of AAD on micellar microstructures and the pH-induced morphological transitions. The ortho-substituted hydroxyl moiety in the BA molecule facilitated the formation of larger wormlike micelles, whereas the effect of the meta-substituted moiety was less significant. The para-substituted hydroxyl moiety in BA did not favor micellar growth. This moiety exhibited similar characteristics to the increasing hydroxyl moiety number in the AAD molecules or solution pH where the negative effects of steric hindrance and electrostatic interactions of molecules in micelles are dominant.

2'-Hydroxychalcone Induces Autophagy and Apoptosis in Breast Cancer Cells via the Inhibition of the NF-κB Signaling Pathway: In Vitro and In Vivo Studies.

2'-Hydroxychalcone is a hydroxyl derivative of chalcones, which are biosynthetic precursors of flavonoids and rich in the human diet. The anticancer activity of 2'-hydroxychalcone has been reported in several cancers but remains to be investigated in breast cancer. In the current study, 2'-hydroxychalcone showed significant cytotoxicity against breast cancer cell lines MCF-7 and CMT-1211. It could inhibit breast cancer cell proliferation, migration, and invasion in vitro and suppress tumor growth and metastasis in vivo. Mechanistic investigation revealed that the NF-κB pathway was significantly inhibited by 2'-hydroxychalcone treatment accompanied by an excessive intracellular accumulation of reactive oxygen species, induction of endoplasmic reticulum stress, and activation of JNK/MAPK. In addition, 2'-hydroxychalcone elevated the autophagic levels in breast cancer cells equipped with increasing numbers of autophagy vesicles and complete autophagic flux. Finally, autophagy-dependent apoptosis was observed in 2'-hydroxychalcone-induced cell death. In conclusion, 2'-hydroxychalcone enhances the autophagic levels and induces apoptosis in breast cancer cells, which could be contributed to the inhibition of the pro-survival NF-κB signaling, indicating a promising potential for 2'-hydroxychalcone in future anticancer drug development.

Substitution and Orientation Effects on the Crystallinity and PFAS Adsorption of Olefin-Linked 2D COFs.

Solid phase adsorbents with high removal affinity for per- and polyfluoroalkyl substances (PFAS) in aqueous environments are sought. We report the synthesis and investigation of COF-I, a new covalent organic framework (COF) with a good affinity for PFAS adsorption. COF-I was synthesized by the condensation reaction between 2,4,6-trimethyl-1,3,5-triazine and 2,3-dimethoxyterephthaldehyde and fully characterized. In addition to the high crystallinity and surface area, COF-I showed high hydrolytic and thermal stability. Further, we converted its hydrophobic surface to a hydrophilic surface by converting the ortho-methoxy groups to hydroxyl derivatives and produced a new hydrophilic olefin-linked two-dimensional (2D) COF. We experimentally measured the crystallinity of both COFs by X-ray diffraction and used atomistic simulations coupled with cross-polarization/magic angle spinning solid-state nuclear magnetic resonance (CP/MAS ssNMR) to determine the relative amounts of AA-stacking and AB-stacking present. COF-I, with its hydrophobic surface and methoxy groups in the ortho positions, showed the best PFAS adsorption. COF-I reduced the concentration of perfluorooctanoic acid from 20 to 0.069 μg L-1 and to 0.052 μg L-1 for perfluorooctanesulfonic acid. These amounts are lower than the U.S. Environmental Protection Agency advisory level (0.070 μg L-1). High efficiency, fast kinetic adsorption, and reusability of COF-I are advantages of COF-I for PFAS removal from water.

METABOLIC PROFILE OF 4F-MDMB-BICA IN HUMAN URINE

The purpose of the study is to study the metabolic profile of the cannabimimetic 4F-MDMB-BICA in the urine of consumers and to identify markers of 4F-MDMB-BICA use using gas chromatography with a mass spectrometric detector (GC-MS) and liquid chromatography with tandem mass spec-trometry (LC-MS/ MS) in the urine of consumers of psychoactive substances, for chemical-toxicological and forensic chemical analysis. Material and methods. The study of urine samples of 4F-MDMB-BICA cannabimimetic users using enzymatic hydrolysis in combination with solid-phase extraction and gas chromatography with mass spectrometric detection showed that the 4F-MDMB-BICA marker and, in some cases, its nor-metabolite are detected in the urine of consumers. The 4F-MDMB-BICA nor-metabolite is a common biotransformation product for the cannabimimetics 4F-MDMB-BICA and 5F-MDMB-PICA, resulting from the hydrolysis of the ester bond and N-dealkylation of the heterocyclic core. Results. 35 compounds were identified by liquid chromatography with tandem mass spectrometry, including the original parent 4F-MDMB-BICA, 31 metabolites of biotransformation phases I and II, and 3 metabolite artifacts; it was found that the latter are the product of intramolecular cyclization of 4F-MDMB-BICA metabolites. 16 previously undescribed compounds, including 15 metabolites and one artifact were identified. The putative structures, mass spectra and some characteristics of the identified compounds are given, including retention time, MRM transitions, and relative peak area of the substance. Conclusion. From the presented data, it can be seen that the main pathways of 4F-MDMB-BICA metabolism in the human body are hydrolysis of the ester group, hydroxylation of alkyl radicals and the heterocyclic core, oxidative defluorination, and N-dealkylation. The hydrolysis products of the ester bond and hydroxyl derivatives are subsequently conjugated with glucuronic acid.

Interactions of Cyclodextrins and their Hydroxyl Derivatives with Etodolac: Solubility and Dissolution Enhancement.

Poor solubility and dissolution rate of drugs are largely responsible for erratic drug absorption and limited oral bioavailability. Etodolac (ETO) is a non-steroidal anti-inflammatory drug (NSAID) that is classified as BCS class II (dissolution rate-dependent absorption). ETO has high safety and efficacy in pain relief and control of inflammation. ETO is commercially available as (400- 600 mg) tablets; poor solubility and dissolution rate of ETO could result in variable oral absorption and inconsistent analgesic responses. The aim of this study was to improve solubility and dissolution rates of ETO by complexation with cyclodextrins (CDs). Four different CDs namely β-, γ-, HP β-CDs, and HP γ-CDs were prepared using three different methods; solvent evaporation (CO), freeze-drying (FD), and physical mixing (PM). The prepared drug: excipient mixtures were investigated for aqueous solubility, as well as via</i> DSC, XRD, FTIR, SEM, dissolution, and docking. The results revealed a solubility phase diagram of the AL type, indicating a 1:1 complexation of ETO: CD. These results agreed with our molecular docking calculations. DSC, FTIR, XRD, and SEM results confirmed the formation of an inclusion complex. The complexation efficiency, solubility, and dissolution enhancement were in the order of HPγ-CD > γ -CD > HPβ-CD > β-CD. FD method was superior to both CO and PM. Superior dissolution enhancements of ETO were recorded for the FD mixture (up to 90% dissolved in less than 10 min). In conclusion, γ- and hydroxypropyl γ-derivative of cyclodextrins can be considered a promising excipient for enhancement of dissolution rates concerned for ETO.

Molecular Mechanisms Regulating Phenylpropanoid Metabolism in Exogenously-Sprayed Ethylene Forage Ramie Based on Transcriptomic and Metabolomic Analyses.

Ramie (Boehmeria nivea [L.] Gaud.), a nutritious animal feed, is rich in protein and produces a variety of secondary metabolites that increase its palatability and functional composition. Ethylene (ETH) is an important plant hormone that regulates the growth and development of various crops. In this study, we investigated the impact of ETH sprays on the growth and metabolism of forage ramie. We explored the mechanism of ETH regulation on the growth and secondary metabolites of forage ramie using transcriptomic and metabolomic analyses. Spraying ramie with ETH elevated the contents of flavonoids and chlorogenic acid and decreased the lignin content in the leaves and stems. A total of 1076 differentially expressed genes (DEGs) and 51 differentially expressed metabolites (DEMs) were identified in the leaves, and 344 DEGs and 55 DEMs were identified in the stems. The DEGs that affect phenylpropanoid metabolism, including BGLU41, LCT, PER63, PER42, PER12, PER10, POD, BAHD1, SHT, and At4g26220 were significantly upregulated in the leaves. Ethylene sprays downregulated tyrosine and chlorogenic acid (3-O-caffeoylquinic acid) in the leaves, but lignin biosynthesis HCT genes, including ACT, BAHD1, and SHT, were up- and downregulated. These changes in expression may ultimately reduce lignin biosynthesis. In addition, the upregulation of caffeoyl CoA-O-methyltransferase (CCoAOMT) may have increased the abundance of its flavonoids. Ethylene significantly downregulated metabolites, affecting phenylpropanoid metabolism in the stems. The differential 4CL and HCT metabolites were downregulated, namely, phenylalanine and tyrosine. Additionally, ETH upregulated 2-hydroxycinnamic acid and the cinnamyl hydroxyl derivatives (caffeic acid and p-coumaric acid). Cinnamic acid is a crucial intermediate in the shikimic acid pathway, which serves as a precursor for the biosynthesis of flavonoids and lignin. The ETH-decreased gene expression and metabolite alteration reduced the lignin levels in the stem. Moreover, the HCT downregulation may explain the inhibited lignin biosynthesis to promote flavonoid biosynthesis. In conclusion, external ETH application can effectively reduce lignin contents and increase the secondary metabolites of ramie without affecting its growth and development. These results provide candidate genes for improving ramie and offer theoretical and practical guidance for cultivating ramie for forage.

Flavonols affect the interrelated glucosinolate and camalexin biosynthetic pathways in Arabidopsis thaliana.

Flavonols are structurally and functionally diverse biomolecules involved in plant biotic and abiotic stress tolerance, pollen development, and inhibition of auxin transport. However, their effects on global gene expression and signaling pathways are unclear. To explore the roles of flavonol metabolites in signaling, we performed comparative transcriptome and targeted metabolite profiling of seedlings from the flavonol-deficient Arabidopsis loss-of-function mutant flavonol synthase1 (fls1) with and without exogenous supplementation of flavonol derivatives (kaempferol, quercetin, and rutin). RNA-seq results indicated that flavonols modulate various biological and metabolic pathways, with significant alterations in camalexin and aliphatic glucosinolate synthesis. Flavonols negatively regulated camalexin biosynthesis but appeared to promote the accumulation of aliphatic glucosinolates via transcription factor-mediated up-regulation of biosynthesis genes. Interestingly, upstream amino acid biosynthesis genes involved in methionine and tryptophan synthesis were altered under flavonol deficiency and exogenous supplementation. Quercetin treatment significantly up-regulated aliphatic glucosinolate biosynthesis genes compared with kaempferol and rutin. In addition, expression and metabolite analysis of the transparent testa7 mutant, which lacks hydroxylated flavonol derivatives, clarified the role of quercetin in the glucosinolate biosynthesis pathway. This study elucidates the molecular mechanisms by which flavonols interfere with signaling pathways, their molecular targets, and the multiple biological activities of flavonols in plants.

Magnetic Seed Treatment Modulates Phenolic and Fatty Acid Metabolism of Sunflower under Water Scarcity

Environmental and anthropogenic activities are pushing the earth towards warmer years, which is reducing agricultural land and causing water scarcity. It is well documented that sunflower (being drought tolerant) crops can be grown under water deficit conditions with some additional supportive priming applications to compensate for drought-induced challenges. However, finding the most efficient and eco-friendly priming tools is always a top priority among researchers to improve plant growth, adaptive traits, and productivity. In this study, an experiment was performed on oil-producing crops (sunflower) using seed magnetic treatment. The seeds were subjected to 0.1, 0.2, and 0.3 Tesla for 20 min, respectively. Plants were exposed to water limitation (100 and 50%) after 30 days of germination. Sunflower showed its tolerance to water limitation by maintaining the majority of growth parameters, nutritive value, metabolizable energy, and higher proline content. Nevertheless, a reduction in the achene number per capitulum, capitulum weight, chlorophyll, catalase activity, unsaturated to saturated fatty acids, anthocyanin, and hydroxyl derivatives of cinnamic acid supported our hypothesis about the need for some supportive techniques. Better metabolic adjustment and percentage of oil yield were manifested by 0.3 T magnetic seed treatment, which was used for phenolic and fatty acid profiling. To conclude, magnetic treatment of seeds may improve their primary metabolic capacity and antioxidation potential, which in turn may activate their secondary metabolism as evidenced by an excess of gallic acid, quercetin, benzoic acid, curcumin acid, sinapic acid, and chlorogenic acid.

Screening eco-friendliness tire antioxidants alternatives: functional 2,2,4-trimethyl-1,2-dihydroquinoline derivatives design and toxicity evaluation.

Antioxidants which are indispensable functional additives used in rubber tires, are released into aquatic habitats from tire wear particles (TWP), collected in water bodies, and threaten the aquatic ecosystem. This study aimed to design eco-friendly derivatives of 2,2,4-trimethyl-1,2-dihydroquinoline (TMQ) with increased antioxidant activity to use as tire antioxidants. Initially, seventy highly efficient derivatives of TMQ were designed by hydroxylation modifications at multiple sites. The antioxidant activity of hydroxyl derivatives was characterized based on DFT method and compared with TMQ. Twenty derivatives showing a significant (greater than 9%) increase in antioxidant activity compared to TMQ were selected for the next stage. The toxicity risk of these twenty TMQ derivatives was assessed using various toxicokinetic methods. Finally, six TMQ derivatives with significantly lower toxicity risk compared to that of TMQ were evaluated for potential developmental toxicity. They were characterized using molecular docking and molecular dynamics techniques to assess the developmental toxicity risk in silver salmon by absorption of their ROO·, HO·, O2·- and O3 derivatives. TMQ-6 and TMQ-48 showed the lowest toxicity among all TMQ derivatives by a rather large margin. The study throws light on the path of future endeavors to develop highly efficient and greener tire antioxidants.

Degradation mechanism of surface sulfidization and hydrophobicity by Fe(III) in the flotation of cerussite

Unavoidable metal ions commonly exist in the pulp during flotation. These ions can affect the floatability of minerals, and they can also result in the differences in the surface features between different minerals. In this study, how Fe3+ affected the flotation behavior of cerussite was investigated by micro-flotation tests. The corresponding adsorption characteristics of the sulfidizing agent and collector on the surfaces of cerussite were investigated by surface-analysis techniques. The results of micro-flotation tests showed that the floatability of cerussite significantly decreased when Fe3+ was added before Na2S and xanthate. The flotation recovery of cerussite decreased compared with that obtained without participation of Fe3+. Additionally, the results of xanthate and Na2S adsorption tests, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS) and zeta potential measurements verified that Fe3+ and its hydrophilic hydroxyl derivatives (Fe-OH compounds) resulted in reduced amounts and reactive activities of S-bearing species adsorbed on the surfaces of cerussite. This decreased the adsorption capacity of subsequently added xanthate, resulting in the difficulty in effectively recovering cerussite in the sulfidization-xanthate system.

New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors.

In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC50 > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H2O2-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders.

Antioxidant and anti-α-glucosidase activities of biotransformable dragon’s blood via predicted data mining approach

Bacillus megaterium tyrosinase (BmTYR) has been proven an applicable biocatalyst in the ortho-hydroxylation of flavonoids, which usually possess higher antioxidant activity than their precursors. With a predicted data mining approach (PDMA), putative novel bioactive flavonoids from known precursors may be good candidates for biotransformation by BmTYR. Two flavonoid precursors (loureirin A and loureirin B) were confirmed via this approach, which are the commercial constituents of the Chinese medicine dragon’s blood. These two flavonoids were then biotransformed by BmTYR for validation. The results found two novel flavonoids (3′-hydroxyloureirin A and 3′-hydroxyloureirin B), which gained 2.5 and 1.6 times of the antioxidant activity of ascorbic acid, respectively. In addition, all four flavonoids—loureirin A, loureirin B, and the two 3′-hydroxyl derivatives—possessed 4–22 times the anti-α-glucosidase activity of acarbose, a clinical anti-diabetes drug. A further kinetic analysis revealed that the inhibition mode of the four α-glucosidase inhibitors was non-competitive, and their kinetic constants (Ki values) were 64.3 ± 2.5 μM, 308.7 ± 10.4 μM, 69.4 ± 2.8 μM, and 325.3 ± 12.6 μM, respectively. The high antioxidant and anti-α-glucosidase activity suggest that the two novel flavonoids have potential future applications in pharmacology and biotechnology.

Analytical Toolbox to Unlock the Diversity of Oxidized Lipids.

ConspectusLipids are diverse class of small biomolecules represented by a large variety of chemical structures. In addition to the classical biosynthetic routes, lipids can undergo numerous modifications via introduction of small chemical moieties forming hydroxyl, phospho, and nitro derivatives, among others. Such modifications change the physicochemical properties of a parent lipid and usually result in new functionalities either by mediating signaling events or by changing the biophysical properties of lipid membranes. Over the last decades, a large body of evidence indicated the involvement of lipid modifications in a variety of physiological and pathological events. For instance, lipid (per)oxidation for a long time was considered as a hallmark of oxidative stress and related proinflammatory signaling. Recently, however, with the burst in the development of the redox biology field, oxidative modifications of lipids are also recognized as a part of regulatory and adaptive events that are highly specific for particular cell types, tissues, and conditions.The initial diversity of lipid species and the variety of possible lipid modifications result in an extremely large chemical space of the epilipidome, the subset of the natural lipidome formed by enzymatic and non-enzymatic lipid modifications occurring in biological systems. Together with their low natural abundance, structural annotation of modified lipids represents a major analytical challenge limiting the discovery of their natural variety and functions. Furthermore, the number of available chemically characterized standards representing various modified lipid species remains limited, making analytical and functional studies very challenging. Over the past decade we have developed and implemented numerous analytical methods to study lipid modifications and applied them in the context of different biological conditions. In this Account, we outline the development and evolution of modern mass-spectrometry-based techniques for the structural elucidation of modified/oxidized lipids and corresponding applications. Research of our group is mostly focused on redox biology, and thus, our primary interest was always the analysis of lipid modifications introduced by redox disbalance, including lipid peroxidation (LPO), oxygenation, nitration, and glycation. To this end, we developed an array of analytical solutions to measure carbonyls derived from LPO, oxidized and nitrated fatty acid derivatives, and oxidized and glycated complex lipids. We will briefly describe the main analytical challenges along with corresponding solutions developed by our group toward deciphering the complexity of natural epilipdomes, starting from in vitro-oxidized lipid mixtures, artificial membranes, and lipid droplets, to illustrate the diversity of lipid modifications in the context of metabolic diseases and ferroptotic cell death.

Supramolecular Organization in Salts of Riluzole with Dihydroxybenzoic Acids—The Key Role of the Mutual Arrangement of OH Groups

Intermolecular interactions, in particular hydrogen bonds, play a key role in crystal engineering. The ability to form hydrogen bonds of various types and strengths causes competition between supramolecular synthons in pharmaceutical multicomponent crystals. In this work, we investigate the influence of positional isomerism on the packing arrangements and the network of hydrogen bonds in multicomponent crystals of the drug riluzole with hydroxyl derivatives of salicylic acid. The supramolecular organization of the riluzole salt containing 2,6-dihydroxybenzoic acid differs from that of the solid forms with 2,4- and 2,5-dihydroxybenzoic acids. Because the second OH group is not at position 6 in the latter crystals, intermolecular charge-assisted hydrogen bonds are formed. According to periodic DFT calculations, the enthalpy of these H-bonds exceeds 30 kJ·mol-1. The positional isomerism appears to have little effect on the enthalpy of the primary supramolecular synthon (65-70 kJ·mol-1), but it does result in the formation of a two-dimensional network of hydrogen bonds and an increase in the overall lattice energy. According to the results of the present study, 2,6-dihydroxybenzoic acid can be treated as a promising counterion for the design of pharmaceutical multicomponent crystals.