Exploring the Potential of Terpenoids as a Possible Treatment for Cancer: Structure-Activity Relationship and Mechanistic Studies.

Cancer stands as a significant global health challenge due to its mortality rates and the complexities involved in its treatment. Addressing issues, such as metastasis, recurrence, chemoresistance, and treatment-related toxicity, remains pivotal in cancer therapy advancement. Therefore, exploration of novel therapeutic agents has emerged as a priority. As the risk of cancer continues to rise, effective measures must be taken to combat it. One promising approach is to explore natural remedies, such as terpenoids, which have demonstrated anticancer activity. Utilizing terpenoids could aid in the development of potent compounds to fight cancer. By studying the structural makeup of various terpenoid derivatives from previous research, we can identify which structural groups are essential for their anticancer activity. This understanding of the structure-activity relationship is crucial for developing new, effective anticancer agents based on terpenoids. Terpenoids, a diverse class of plant-derived secondary metabolites composed of multiple isoprene units, have garnered attention for their potential anticancer and pharmacological qualities. Some terpenoids exhibit notable anticancer effects by concentrating on several stages of cancer development. They show promise in blocking the initiation of early carcinogenesis by the induction of cell cycle arrest, the inhibition of cancer cell differentiation, and the induction of apoptosis. This study delves into the investigation of specific terpenoids showcasing promising anticancer activity against prevalent malignancies, including breast, colon, ovarian, and lung cancers. The study also explores the relationship between the structure and activity of these compounds, which sheds light on how effective they are against a variety of cancer cell types. The comprehensive discussion centres on elucidating terpenoids with substantial potential for combating diverse cancer types, offering insights into their structural features and promising anticancer mechanisms.

Chemical Composition, Antioxidant Capacity, and Anticancerous Effects against Human Lung Cancer Cells of a Terpenoid-Rich Fraction of Inula viscosa.

Inula viscosa is a widely used plant in traditional Mediterranean and Middle Eastern medicine for various illnesses. I. viscosa has been shown to have anticancer effects against various cancers, but its effects against lung cancer have been under limited investigation. At the same time, I. viscosa is rich in terpenoids whose anti-lung cancer effects have been poorly investigated. This study aimed to examine the potential anticancer properties of methanolic and aqueous extracts of stems and leaves of I. viscosa and its terpenoid-rich fraction against human lung cancer A549 cells. Results showed that the methanolic extracts of I. viscosa had significantly higher polyphenol and flavonoid content and radical scavenging capacity than the aqueous extracts. In addition, leaves methanolic extracts (IVLM) caused the highest reduction in viability of A549 cells among all the extracts. IVLM also reduced the viability of human ovarian SK-OV-3, breast MCF-7, liver HepG2, and colorectal HCT116 cancer cells. A terpenoid-rich I. viscosa fraction (IVL DCM), prepared by liquid-liquid separation of IVLM in dichloromethane (DCM), displayed a substantial reduction in the viability of A549 cells (IC50 = 27.8 ± 1.5 µg/mL at 48 h) and the panel of tested cancerous cell lines but was not cytotoxic to normal human embryonic fibroblasts (HDFn). The assessment of IVL DCM phytochemical constituents using GC-MS analysis revealed 21 metabolites, highlighting an enrichment in terpenoids, such as lupeol and its derivatives, caryophyllene oxide, betulin, and isopulegol, known to exhibit proapoptotic and antimetastatic functions. IVL DCM also showed robust antioxidant capacity and decent polyphenol and flavonoid contents. Furthermore, Western blotting analysis indicated that IVL DCM reduced proliferation (reduction of proliferation marker Ki67 and induction of proliferation inhibitor proteins P21 and P27), contaminant with P38 MAP kinase activation, and induced the intrinsic apoptotic pathway (P53/BCL2/BAX/Caspase3/PARP) in A549 cells. IVL DCM also reduced the migration of A549 cells, potentially by reducing FAK activation. Future identification of anticancer metabolites of IVL DCM, especially terpenoids, is recommended. These data place I. viscosa as a new resource of herbal anticancer agents.

Production of Terpene Trilactones from Cell and Organ Cultures of Ginkgo biloba.

Ginkgo biloba is an ancient plant that has survived up until the present day. Gingko biloba is a rich source of valuable secondary metabolites, particularly terpene trilactones (TTLs) such as ginkgolides and bilobalides, which are obtained from the leaves and seeds of the plant. TTLs have pharmacological properties, including anticancer, anti-dementia, antidepressant, antidiabetic, anti-inflammatory, anti-hypertensive, antiplatelet, immunomodulatory, and neuroprotective effects. However, ginkgo is a very-slow-growing tree that takes approximately 30 years to reach maturity. In addition, the accumulation of TTLs in these plants is affected by age, sex, and seasonal and geographical variations. Therefore, plant cell cultures have been established in ginkgo to produce TTLs. Extensive investigations have been conducted to optimize the culture media, growth regulators, nutrients, immobilization, elicitation, and precursor-feeding strategies for the production of TTLs in vitro. In addition, metabolic engineering and synthetic biology methods have been used for the heterologous production of TTLs. In this review, we present the research strategies applied to cell cultures for the production of TTLs.

Chemical constituents with their alpha-glucosidase inhibitory activity from the whole plant of Ceratophyllum demersum.

From Ceratophyllum demersum growing in Vietnam, twelve compounds were isolated and structurally elucidated, including six previously undescribed compounds, demersones A-D (1-4), acetylvelutins A and B (8 and 9), together with six known compounds, (+)-cyclocolorenone (5), 1-hydroxycyclocolorenone (6), 10-hydroxycyclocolorenone (7), retusin (10), betulinic acid (11), and lupeol (12). The chemical structures and stereochemistry of 1-12 were identified through analysis of spectroscopic data (1D and 2D NMR and HRESIMS), ECD data, and DFT calculation. Notably, this is the first time that humulene-type (1 and 2), guaiane-type (3), and aromadendrane-type (4-7) sesquiterpenoids have been reported in this genus. Compounds 8 and 9 are the first examples of 8-acetoxyflavones found in nature. Upon evaluation of the alpha-glucosidase of 1-3 and 5-12, it was found that 12 exhibited the highest potential with an IC50 value of 15.4 ± 1.1 µM. The molecular docking of 3 and 8 was further studied.

Potential Application of Plant-Derived Compounds in Multiple Sclerosis Management.

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration, resulting in significant disability and reduced quality of life. Current therapeutic strategies primarily target immune dysregulation, but limitations in efficacy and tolerability highlight the need for alternative treatments. Plant-derived compounds, including alkaloids, phenylpropanoids, and terpenoids, have demonstrated anti-inflammatory effects in both preclinical and clinical studies. By modulating immune responses and promoting neuroregeneration, these compounds offer potential as novel adjunctive therapies for MS. This review provides insights into the molecular and cellular basis of MS pathogenesis, emphasizing the role of inflammation in disease progression. It critically evaluates emerging evidence supporting the use of plant-derived compounds to attenuate inflammation and MS symptomology. In addition, we provide a comprehensive source of information detailing the known mechanisms of action and assessing the clinical potential of plant-derived compounds in the context of MS pathogenesis, with a focus on their anti-inflammatory and neuroprotective properties.

Terpenoids and steroids from aerial parts of Achillea alpina L. as PTP1B inhibitors: Kinetic analysis and molecular docking studies.

Achillea alpina L. (Alpine yarrow) is a noteworthy herb in the genus Achillea with many uses in vegetables and traditionally used to treat stomach disorders. In our continuous research on the chemical constituents and biological activities of medicinal plants, ten previously undescribed terpenoids including eight eudesmane-type sesquiterpenes (1-8), one nor-eudesmane-type sesquiterpene (9), one cyclo-geraniol derivative (10), and twenty-one known compounds were isolated and structurally elucidated from the aerial parts of A. alpina. Structures and absolute configurations of the undescribed terpenoids were identified using comprehensive spectroscopic analysis (NMR, HRESI-MS, and CD data) and computational methods (ECD and NMR calculation). Enzyme inhibitory assays showed that the isolated sesquiterpene (19), triterpene (22), and sterol (26) were protein tyrosine phosphatase 1B (PTP1B) inhibitors with IC50 values ranging from 14.87 to 23.09 µM in comparison with positive control - ursolic acid, showing IC50 value of 5.93 ± 0.16 µM. Further enzyme kinetics and molecular docking studies were performed to provide valuable insights into their mechanism of action.

Beyond the Scent: New Evidence about Micromorphological, Phytochemical and Biological Features of Plumeria rubra 'Tonda Palermitana' (Apocynaceae).

Plumeria rubra L. is an ornamental Caribbean plant widely known for its ethnobotanical uses and pharmacological activities. The 'Tonda Palermitana' cultivar, on which no data are to date available, is commonly cultivated in Sicily. The aim of our study was to characterize the micro-morphological features of leaves and flowers of this cultivar by light and Scanning Electron Microscopy and to investigate the phytochemical profile and the biological properties of their food-grade extracts (LE and FE, respectively) by LC-DAD-ESI-MS analysis and different in vitro assays. Numerous branched laticifers were observed, and their secretion contained alkaloids and lipophilic compounds as confirmed by histological analyses. Phytochemical analyses showed the presence of alkaloids (9%), terpenoids (13%) and fatty acids (6%), together with a very abundant presence of iridoids (28%) and polyphenols (39%). The most notable biological activity of both extracts appears to be the antioxidant one, showing half-inhibitory concentrations (IC50) about 5 times lower than those detected in anti-inflammatory assays (383.74 ± 5.65 and 232.05 ± 2.87 vs. 1981.23 ± 12.82 and 1215.13 ± 10.15, for FE and LE, respectively), with LE showing the best, and statistically significant (p < 0.001), biological activity. These results allow us to speculate promising nutraceutical and cosmeceutical applications for this old Sicilian cultivar.

Secondary Metabolites of Fomitopsis betulina: Chemical Structures, Biological Activity and Application Prospects.

Fomitopsis betulina, as a macrofungus with both medicinal and dietary applications, is renowned for its rich content of bioactive substances. The recent advancements in research have significantly enhanced our understanding of its polysaccharides, cellulose-degrading enzymes, and wide range of secondary metabolites. This paper provides a comprehensive review of the artificial cultivation techniques and the chemical profiling of over 100 secondary metabolites identified in F. betulina, including terpenoids, phenols, and various other classes. These compounds exhibit notable pharmacological activities, such as anti-cancer, anti-inflammatory, antimicrobial, antiviral, and anti-malarial effects. Moreover, this review delves into the genomic analysis of F. betulina, focusing on the prediction and classification of terpene synthases, which play a crucial role in the biosynthesis of these bioactive compounds. This insight is instrumental for potentially facilitating future biochemical studies and pharmaceutical applications. Through this review, we aim to solidify the foundation for future in-depth studies and the development of new drugs derived from this promising natural resource.

Combined Metabolome and Transcriptome Analyses of Maize Leaves Reveal Global Effect of Biochar on Mechanisms Involved in Anti-Herbivory to Spodoptera frugiperda.

Fall armyworm (FAW, Spodoptera frugiperda) has now spread to more than 26 Chinese provinces. The government is working with farmers and researchers to find ways to prevent and control this pest. The use of biochar is one of the economic and environmentally friendly strategies to increase plant growth and improve pest resistance. We tested four v/v combinations of bamboo charcoal with coconut bran [BC1 (10:1), BC2(30:1), BC3(50:1)] against a control (CK) in maize. We found that plant height, stem thickness, fresh weight and chlorophyll content were significantly higher in BC2, in addition to the lowest FAW survival %. We then compared the metabolome and transcriptome profiles of BC2 and CK maize plants under FAW herbivory. Our results show that the levels of flavonoids, amino acids and derivatives, nucleotides and derivatives and most phenolic acids decreased, while terpenoids, organic acids, lipids and defense-related hormones increased in BC-grown maize leaves. Transcriptome sequencing revealed consistent expression profiles of genes enriched in these pathways. We also observed the increased expression of genes related to abscisic acid, jasmonic acid, auxin and MAPK signaling. Based on these observations, we discussed the possible pathways involved in maize against FAW herbivory. We conclude that bamboo charcoal induces anti-herbivory responses in maize leaves.

Hormetic and transcriptomic responses of the toxic alga Prymnesium parvum to glyphosate.

Growth of the toxic alga Prymnesium parvum is hormetically stimulated with environmentally relevant concentrations of glyphosate. The mechanisms of glyphosate hormesis in this species, however, are unknown. We evaluated the transcriptomic response of P. parvum to glyphosate at concentrations that stimulate maximum growth and where growth is not different from control values, the zero-equivalent point (ZEP). Maximum growth occurred at 0.1 mg l-1 and the ZEP was 2 mg l-1. At 0.1 mg l-1, upregulated transcripts outnumbered downregulated transcripts by one order of magnitude. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the upregulated transcriptome is primarily associated with metabolism and biosynthesis. Transcripts encoding heat shock proteins and co-chaperones were among the most strongly upregulated, and several others were associated with translation, Redox homeostasis, cell replication, and photosynthesis. Although most of the same transcripts were also upregulated at concentrations ≥ZEP, the proportion of downregulated transcripts greatly increased as glyphosate concentrations increased. At the ZEP, downregulated transcripts were associated with photosynthesis, cell replication, and anion transport, indicating that specific interference with these processes is responsible for the nullification of hormetic growth. Transcripts encoding the herbicidal target of glyphosate, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), were upregulated at concentrations ≥ZEP but not at 0.1 mg l-1, indicating that disruption of EPSPS activity occurred at high concentrations and that nullification of hormetic growth involves the direct interaction of glyphosate with this enzyme. Results of this study may contribute to a better understanding of glyphosate hormesis and of anthropogenic factors that influence P. parvum biogeography and bloom formation.

Development of GC-MS coupled to GC-FID method for the quantification of cannabis terpenes and terpenoids: Application to the analysis of five commercial varieties of medicinal cannabis.

Cannabis terpenes and terpenoids are among the major classes of pharmacologically active secondary metabolites of therapeutic interest. Indeed, these hydrocarbon molecules, responsible for the characteristic aroma of cannabis flowers, are thought to be involved in a synergistic effect known as the "entourage effect", together with cannabinoids. Numerous analytical studies have been carried out to characterize the terpene and terpenoid contents of some cannabis varieties, but they have not proposed any real quantification or have described a limited number of analytical standards or average response factors, which may have led to over- or underestimation of the real content of the cannabis flowers. Real and reliable quantification is necessary to justify the entourage effect. Here, we report a rigorous and precise GC-FID and GC-MS method for the identification and quantification of cannabis terpenes and terpenoids. This method is distinguished by the use of a high number of analytical standards, the determination of retention indices for all compounds studied, an exhaustive comparison of databases and scientific literature, the use of relevant response factors, and internal calibration for reliable results. It was applied to the study of terpenic compounds in five commercial varieties of medicinal cannabis produced by Bedrocan International: a CBD-rich (Bedrolite®), a THC/CBD balanced (Bediol®), and three THC-dominant (Bedrocan®, Bedica® and Bedrobinol®). Two extraction solvents are described (ethanol and hexane) to compare their selectivity towards target molecules, and to describe as exhaustively as possible the terpenic profile of the five pharmaceutical-grade varieties. Twenty-three standards were used for accurate dosages. This work highlights that the choice of solvent and the analysis method reliability are critical for the study of these terpenic compounds, regarding their contribution to the entourage effect.

Unveiling novel insights: geraniol's enhanced anti-candida efficacy and mechanistic innovations against multidrug-resistant candida strains.

OBJECTIVES: This study addressed the need for new treatments for severe Candida infections, especially resistant strains. It evaluated the antifungal potential of geraniol alone and with fluconazole against various Candida spp., including resistant strains, and investigated geraniol's mechanism of action using flow cytometry. METHODS: The research assessed the inhibitory effects of geraniol on the growth of various Candida species at concentrations ranging from 110 to 883 µg/ml. The study also explored the potential synergistic effects when geraniol was combined with fluconazole. The mechanism of action was investigated through flow cytometry, with a particular emphasis on key enzymes associated with plasma membrane synthesis, membrane permeability changes, mitochondrial membrane depolarization, reactive oxygen species (ROS) induction, and genotoxicity. RESULTS: Geraniol demonstrated significant antifungal activity against different Candida species, inhibiting growth at concentrations within the range of 110 to 883 µg/ml. The mechanism of action appeared to be multifactorial. Geraniol was associated with the inhibition of crucial enzymes involved in plasma membrane synthesis, increased membrane permeability, induction of mitochondrial membrane depolarization, elevated ROS levels, and the presence of genotoxicity. These effects collectively contributed to cell apoptosis. CONCLUSIONS: Geraniol, alone and in combination with fluconazole, shows promise as a potential therapeutic option for Candida spp. INFECTIONS: Its diverse mechanism of action, impacting crucial cellular processes, highlights its potential as an effective antifungal agent. Further research into geraniol's therapeutic applications may aid in developing innovative strategies to address Candida infections, especially those resistant to current therapies.

Terpenoids: Unlocking Their Potential on Cancer Glucose Metabolism.

Cancer incidence has increased globally and has become the leading cause of death in the majority of countries. Many cancers have altered energy metabolism pathways, such as increased glucose uptake and glycolysis, as well as decreased oxidative phosphorylation. This is known as the Warburg effect, where cancer cells become more reliant on glucose to generate energy and produce lactate as an end product, even when oxygen is present. These are attributed to the overexpression of key glycolytic enzymes, glucose transporters, and related signaling pathways that occur in cancer cells. Therefore, overcoming metabolic alterations in cancer cells has recently become a target for therapeutic approaches. Natural products have played a key role in drug discovery, especially for cancer and infectious diseases. In this review, we are going to focus on terpenoids, which are gradually gaining popularity among drug researchers due to their reported anti-cancer effects via cell cycle arrest, induction of apoptosis, reduction of proliferation, and metastasis. This review summarizes the potential of 13 terpenoid compounds as anti-glycolytic inhibitors in different cancer models, primarily by inhibiting the glucose uptake and the generation of lactate, as well as by downregulating enzymes associated to glycolysis. As a conclusion, disruption of cancer cell glycolysis may be responsible for the anti-cancer activity of terpenoids.

Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas.

Biosynthesis of sodorifen with a unique C16-bicyclo[3.2.1]octene framework requires an S-adenosyl methionine-dependent methyltransferase SodC and terpene cyclase SodD. While bioinformatic analyses reveal a wide distribution of the sodCD genes organization in bacteria, their functional diversity remains largely unknown. Herein, two sodorifen-type gene clusters, pcch and pcau, from Pseudomonas sp. are heterologously expressed in Escherichia coli, leading to the discovery of two C16 terpenoids. Enzymatic synthesis of these compounds is achieved using the two (SodCD-like) pathway-specific enzymes. Enzyme assays using different combinations of methyltransferases and terpene synthases across the pcch, pcau, and sod pathways reveal a unifying biosynthetic mechanism: all three SodC-like enzymes methylate farnesyl pyrophosphate (FPP) with subsequent cyclization to a common intermediate, pre-sodorifen pyrophosphate. Structural diversification of this joint precursor solely occurs by the subsequently acting individual terpene synthases. Our findings expand basic biosynthetic understanding and structural diversity of unusual C16-terpenoids.

Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukaemia/lymphoma (IX): active principles from Juniperus rigida.

During the screening of novel chemotherapeutic candidates from plants against adult T-cell leukaemia/lymphoma (ATL), we found that extracts of plants in the Solanaceae, Annonaceae, Apocynaceae, and Rutaceae families showed anti-proliferative activity in the MT-1 and MT-2 cell lines. We have isolated active compounds from these plants in the present research because Cupressaceae plants showed potent anti-proliferative activity in the cell lines. We attempted to isolate the active compounds from the leaves of Juniperus rigida. Using activity-guided fractionation, we isolated 22 compounds, including seven terpenoids, three aromatic compounds, two iridoids, five lignans, and five biflavonoids. The anti-proliferative activities of five diterpenoids were moderate, and those of two biflavonoids were stronger. A lignan (compound 13) showed the strongest activity. These compounds are promising candidates for the treatment of ATL.

Recent Advances in Naturally Occurring [4+2] Type Terpenoid Dimers Assembled through Unmatched-electron-demand Cycloaddition.

Terpenoid dimers of the [4+2] type, which are naturally occurring compounds biosynthetically derived from the [4+2] cycloaddition of two synthons, have garnered considerable attention due to their complex molecular structures, diverse biological activities, and intriguing biosynthetic pathways. We have previously summarized the advancements in three types of [4+2] terpenoid dimers. In this review, we will focus on the lesser-explored class of [4+2] terpenoid dimers which assembled from two electron-deficient synthons via the unmatched-electron-demand Diels-Alder reaction  (UMEDDA). We will summarize their sources, biological activities, proposed biosynthesis, and chemical syntheses. Finally, a summary and outlook for this fascinating class of compounds will be presented.

Therapeutic Potential of Terpenoids in Cancer Treatment: Targeting Mitochondrial Pathways.

BACKGROUND: In recent decades, natural compounds have been considered a significant source of new antitumor medicines due to their unique advantages. Several in vitro and in vivo studies have focused on the effect of terpenoids on apoptosis mediated by mitochondria in malignant cells. RECENT FINDINGS: In this review article, we focused on six extensively studied terpenoids, including sesquiterpenes (dihydroartemisinin and parthenolide), diterpenes (oridonin and triptolide), and triterpenes (betulinic acid and oleanolic acid), and their efficacy in targeting mitochondria to induce cell death. Terpenoid-induced mitochondria-related cell death includes apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and necrosis caused by mitochondrial permeability transition. Apoptosis and autophagy interact in meaningful ways. In addition, in view of several disadvantages of terpenoids, such as low stability and bioavailability, advances in research on combination chemotherapy and chemical modification were surveyed. CONCLUSION: This article deepens our understanding of the association between terpenoids and mitochondrial cell death, presenting a hypothetical basis for the use of terpenoids in anticancer management.

A New 19(10→9)Abeo-Euphane Triterpenoid with Other Terpenoid Components from Trichilia dregeana Leaves and Their NO Production Inhibitory Activities in LPS-Stimulated RAW 264.7 Macrophages.

Trichilia dregeana Sond. (Meliaceae) is a plant used in traditional medicine to treat wounds. The anti-inflammatory potential of the ethyl acetate leaf extract and the presence of euphane-type triterpenes in this extract have recently been reported by our group. Further investigation of the remaining subfractions of the ethyl acetate fraction afforded a new 19(10→9)abeo-euphane-type triterpenoid (1), along with six known terpenoids (2-7). The structure of the new compound was elucidated by analyses of the HR-ESI-MS, 1D and 2D NMR data and by comparisons with previously reported data. We investigated the ability of the compounds to modulate the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 macrophages. The known compounds 3 and 6 exhibited moderate (IC50 72.06 µM) and mild (IC50 98.84 µM) inhibitory activities, respectively, without cytotoxic effects on the cells. These results, in conjunction with our previous findings, emphasize the significant role of terpenoid components in the anti-inflammatory efficacy of T. dregeana leaves and indicate that the rare 3,10-epoxy-19(10→9)abeo-euphane triterpenoids could serve as a chemotaxonomic marker for T. dregeana.

Palladium-catalyzed C(sp3)-H activation in a monoterpene-based compound under mild conditions: a combined experimental and theoretical mechanistic study.

The first example of the palladium-catalyzed sp3 C-H bond activation in a monoterpene-based compound has been observed in the reaction of PdCl2 with a (+)-3-carene-based ligand HL (HL = N-((1aS,3S,7bR)-1,1,3-trimethyl-7-phenyl-5-(pyridin-2-yl)-1a,2,3,7b-tetrahydro-1H-cyclopropa[f]quinolin-3-yl)acetamide), which yielded the [PdLCl] complex. In contrast to the vast majority of C(sp3)-H activation reactions which require prolonged heating and mixing due to the inert character of the corresponding bond, the reaction reported herein proceeds rapidly under mild conditions. A theoretical insight into the ligand deprotonation has been performed by DFT calculations. The mechanism of the C-H activation involves (i) simultaneous coordination of the CH3 group of HL to the Pd2+ ion and decoordination of the Cl- anion with consequent formation of a Cl⋅⋅⋅H-N hydrogen bond with the amide group, (ii) approximation of the out-of-sphere Cl- anion to one of the hydrogen atoms of the CH3 group mediated by the crane motion of the amide group and (iii) the ejection of the HCl molecule, which increases the entropy of the system and serves as a driving force for the reaction.

Characterization of Camphene- and Fenchol-Based Hydrophobic Eutectic Solvents and Their Application in Aldehyde Extraction.

Binary terpenoid-based eutectic systems consisting of the natural substances camphene (CA), fenchol (FE), thymol (TH), menthol (ME), dodecanoic acid (DA), and 1-dodecanol (DO) are synthesized and screened for their Solid-Liquid Equilibrium (SLE) and eutectic compositions. Out of nine eutectic systems, 13 solvent compositions at eutectic points and next to them, in addition to the reference solvent, TH:ME, are synthesized and applied for the solvent extraction of the aromatic aldehydes vanillin (VAN), syringaldehyde (SYR), and p-hydroxybenzaldehyde (HYD) from an acidic aqueous model solution. The extraction efficiency is determined from aldehyde concentrations measured by High-Performance Liquid Chromatography (HPLC), taking into consideration mutual solubility measured by Karl Fischer titration (KF) and a Total Organic Carbon-analysis (TOC). Physicochemical properties, such as the density, viscosity, and stability of the solvents, are evaluated and discussed. Additionally, 1H-NMR measurements are performed to verify hydrogen bonding present in some of the solvents. The results show that all synthesized eutectic systems have a strong hydrophobic character with a maximum water saturation of ≤2.21 vol.% and solvent losses of ≤0.12 vol.% per extraction step. The hydrophobic eutectic solvents based on CA exhibit lower viscosities, lower mutual solubility, and lower extraction efficiency for the aromatic aldehydes when compared with FE-based solvents. The highest extraction efficiencies for VAN (>95%) and for SYR (>93%) at an extraction efficiency of 92.61% for HYD are achieved by the reference solvent TH:ME (50:50 mol.%). With an extraction efficiency of 93.08%, HYD is most preferably extracted by the FE-DO-solvent (80:20 mol.%), where the extraction efficiencies for VAN and SYR reach their maximum at 93.37% and 90.75%, respectively. The drawbacks of the high viscosities of 34.741 mPas of the TH:ME solvent and 31.801 mPas of the FE-DO solvent can be overcome by the CA-TH solvent, which has a viscosity of 3.436 mPas, while exhibiting extraction efficiencies of 71.92% for HYD, >95% for VAN, and >93% for SYR, respectively.