As functional liquid media, natural deep eutectic solvent (NADES) species can dissolve natural or synthetic chemicals of low water solubility. Moreover, the special properties of NADES, such as ...biodegradability and biocompatibility, suggest that they are alternative candidates for concepts and applications involving some organic solvents and ionic liquids. Owing to the growing comprehension of the eutectic mechanisms and the advancing interest in the natural eutectic phenomenon, many NADES applications have been developed in the past several years. However, unlike organic solvents, the basic structural unit of NADES media primarily depends on the intermolecular interactions among their components. This makes NADES matrices readily influenced by various factors, such as water content, temperature, and component ratio and, thus, extends the metabolomic challenge of natural products (NPs). To enhance the understanding of the importance of NADES in biological systems, this review focuses on NADES properties and applications in NP research. The present thorough chronological and statistical analysis of existing report adds to the recognition of the distinctiveness of (NA)DES, involves a discussion of NADES-related observations in NP research, and reportes applications of these eutectic mixtures. The work identifies potential areas for future studies of (NA)DES by evaluating relevant applications, including their use as extraction and chromatographic media as well as their biomedical relevance. The chemical diversity of natural metabolites that generate or participate in NADES formation highlights the growing insight that biosynthetically primordial metabolites (PRIMs) are as essential to the biological function and bioactivity of unrefined natural products as the biosynthetically more highly evolutionary metabolites (HEVOs) that can be isolated from crude mixtures.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
This work assesses the current instrumentation, method development, and applications in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as ...countercurrent separation (CCS). The article provides a critical review of the CCS literature from 2007 since our last review (J. Nat. Prod. 2008, 71, 1489–1508), with a special emphasis on the applications of CCS in natural products research. The current state of CCS is reviewed in regard to three continuing topics (instrumentation, solvent system development, theory) and three new topics (optimization of parameters, workflow, bioactivity applications). The goals of this review are to deliver the necessary background with references for an up-to-date perspective of CCS, to point out its potential for the natural product scientist, and thereby to induce new applications in natural product chemistry, metabolome, and drug discovery research involving organisms from terrestrial and marine sources.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are ...responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as invalid metabolic panaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence–bioactivity–effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base.
The visualization of latent fingerprints often involves the use of a chemical substance that creates a contrast between the fingerprint residues and the surface on which the print was deposited. The ...chemical-aided visualization techniques can be divided into two main categories: those that chemically react with the fingerprint residue and those that adhere to the fingerprint residue by intermolecular forces. A plethora of empirically effective fingerprint revelation methods have been developed but the chemistry is often incompletely understood. This article briefly describes the chemical rationale of most fingerprint visualization techniques practiced today. This material is suitable for a forensic chemistry course or for an introductory chemistry course to introduce the relevance of chemistry in law enforcement. This material may also apply to an organic or biochemistry course when discussing noncovalent intermolecular interactions.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
•The GUESSmix was utilized to evaluate solvent system polarity and selectively characteristics.•Solvent system polarity was described by three methods, including a new GUESSmix Polarity ...Index.•Solvent system selectivity was evaluated by calculating the pairwise comparison methodology.•2D Reciprocal Shifted Symmetry (ReSS2) plots were created to visually compare polarity and selectivity.
Rational solvent system selection for countercurrent chromatography and centrifugal partition chromatography technology (collectively known as countercurrent separation) studies continues to be a scientific challenge as the fundamental questions of comparing polarity range and selectivity within a solvent system family and between putative orthogonal solvent systems remain unanswered. The current emphasis on metabolomic investigations and analysis of complex mixtures necessitates the use of successive orthogonal countercurrent separation (CS) steps as part of complex fractionation protocols. Addressing the broad range of metabolite polarities demands development of new CS solvent systems with appropriate composition, polarity (π), selectivity (σ), and suitability. In this study, a mixture of twenty commercially available natural products, called the GUESSmix, was utilized to evaluate both solvent system polarity and selectively characteristics. Comparisons of GUESSmix analyte partition coefficient (K) values give rise to a measure of solvent system polarity range called the GUESSmix polarity index (GUPI). Solvatochromic dye and electrical permittivity measurements were also evaluated in quantitatively assessing solvent system polarity. The relative selectivity of solvent systems were evaluated with the GUESSmix by calculating the pairwise resolution (αip), the number of analytes found in the sweet spot (Nsw), and the pairwise resolution of those sweet spot analytes (αsw). The combination of these parameters allowed for both intra- and inter-family comparison of solvent system selectivity. Finally, 2-dimensional reciprocal shifted symmetry plots (ReSS2) were created to visually compare both the polarities and selectivities of solvent system pairs. This study helps to pave the way to the development of new solvent systems that are amenable to successive orthogonal CS protocols employed in metabolomic studies.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated ...health claims lacks a rigorous scientific foundation. CBD’s reputation as a cure-all puts it in the same class as other “natural” panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the “natural” label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.
Much confusion exists about the chemical composition of widely sold Cannabis sativa products that utilize the cannabidiol (CBD) acronym and related terms such as “CBD oil”, “CBD plus hemp oil”, “full ...spectrum CBD”, “broad spectrum CBD”, and “cannabinoids”. Their rational chemical and subsequent biological assessment requires both knowledge of the chemical complexity and the characterization of significant individual constituents. Applicable to hemp preparations in general, this study demonstrates how the combination of liquid–liquid-based separation techniques, NMR analysis, and quantum mechanical-based NMR interpretation facilitates the process of natural product composition analysis by allowing specific structural characterization and absolute quantitation of cannabinoids present in such products with a large dynamic range. Countercurrent separation of a commercial “CBD oil” yielded high-purity CBD plus a more polar cannabinoid fraction containing cannabigerol and cannabidivarin, as well as a less polar cannabinoid fraction containing cannabichromene, trans-Δ9-tetrahydrocannabinol, cis-Δ9-tetrahydrocannabinol, and cannabinol. Representatives of six cannabinoid classes were identified within a narrow range of polarity, which underscores the relevance of residual complexity in biomedical research on cannabinoids. Characterization of the individual components and their quantitation in mixed fractions were undertaken by TLC, HPLC, 1H (q)NMR spectroscopy, 1H iterative full spin analysis (HiFSA), 13C NMR, and 2D NMR. The developed workflow and resulting analytical data enhance the reproducible evaluation of “CBD et al.” products, which inevitably represent complex mixtures of varying molecular populations, structures, abundances, and polarity features.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
The notion of data transparency is gaining a strong awareness among the scientific community. The availability of raw data is actually regarded as a fundamental way to advance science by promoting ...both integrity and reproducibility of research outcomes. Particularly, in the field of natural product and chemical research, NMR spectroscopy is a fundamental tool for structural elucidation and quantification (qNMR). As such, the accessibility of original NMR data, i.e., Free Induction Decays (FIDs), fosters transparency in chemical research and optimizes both peer review and reproducibility of reports by offering the fundamental tools to perform efficient structural verification. Although original NMR data are known to contain a wealth of information, they are rarely accessible along with published data. This viewpoint discusses the relevance of the availability of original NMR data as part of good research practices not only to promote structural correctness, but also to enhance traceability and reproducibility of both chemical and biological results.
Much uncertainty exists in science and herbal products referencing turmeric (T), turmeric extract (TE), curcuminoid-enriched turmeric extract (CTE), further processed curcuminoid-enriched materials ...(CEM), or curcumin as a single-chemical entity. To facilitate the rational chemical and biological assessment of turmeric-derived NPs, we introduced the DESIGNER approach of Depleting and Enriching Select Ingredients to Generate Normalized Extract Resources to Curcuma longa preparations. Countercurrent separation of a commercial CTE yielded four key materialslipophilic metabolites; purified curcumin (“purcumin”); a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin (“purcuminoids”); and hydrophilic metabolitesand enabled production of a curcuminoid-free TE (“nocumin”). Their characterization utilized TLC, 1H (q)NMR spectroscopy, and HPLC.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
The flowering tops of Trifolium pratense L., popularly known as red clover, are used in ethnic Western and Traditional Chinese medicine, in a variety of preparations, including infusions, decoctions ...and tinctures. Red clover has been reported to be helpful for treatment of menopausal symptoms, premenstrual syndrome, mastalgia, high cholesterol, and other conditions.
The aims were to compare the chemical dynamics between traditional preparations of infusions, decoctions, and tinctures, as well as to identify the chemical variability over time in a traditional red clover tincture. For this purpose, eight isoflavone aglycones as well as two glucosides, ononin and sissotrin, were used as marker compounds.
Quantitative NMR (qHNMR), LC-MS-MS, and UHPLC-UV methods were used to identify and quantitate the major phenolic compounds found within each extract.
Infusions, decoctions and tinctures were shown to produce different chemical profiles. Biochanin A and formononetin were identified and quantified in infusion, decoction, and tinctures of red clover. Both infusion and decoction showed higher concentrations of isoflavonoid glucosides, such as ononin and sissotrin, than 45% ethanolic tinctures. Dynamic chemical variability (“dynamic residual complexity”) of the red clover tincture was observed over time (one-month), with biochanin A and formononetin reaching peak concentrations at around six days.
Insight was gained into why different formulation methods (infusions, decoctions, and tinctures) are traditionally used to treat different health conditions. Moreover, the outcomes show that tinctures, taken over a period of time, are dynamic medicinal formulations that allow for time-controlled release of bioactive compounds.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
