Electronic Circular Dichroism Research Articles

Anisotropy Factor Spectra for Weakly Allowed Electronic Transitions in Chiral Ketones.

Quantum chemical calculations of one-photon absorption, electronic circular dichroism and anisotropy factor spectra for the A-band transition of fenchone, camphor and 3-methylcyclopentanone (3MCP) are reported. While the only weakly allowed nature of the transition leads to comparatively large anisotropies, a proper theoretical description of the absorption for such a transition requires to account for non-Condon effects. We present experimental data for the anisotropy of 3MCP in the liquid phase and show that corresponding Herzberg-Teller corrections are critical to reproduce the main experimental features. The results obtained with our comprehensive theoretical model highlight the importance of the vibrational degree of freedom, paving the way for a deeper understanding of the dynamics in electronic circular dichroism.

J-Aggregation of Chlorophyll-a Derivatives Inserting Fluorinated Phenylene Linker

Abstract Chlorophyll(Chl)-a derivatives inserting an ethynylene and fluorinated phenylene linker between the chlorin π-skeleton and hydroxymethyl group were prepared as chlorosomal Chl models. The self-aggregation of these derivatives was investigated by means of electronic absorption and circular dichroism spectroscopy. The spectroscopic results revealed that the electronic interactions between the chlorin core and the peripheral fluorinated aromatic π-systems had a large effect on the optical properties of the synthetic Chl-a derivative self-assemblies.

Sesquiterpenes and Lignans From the Branches and Leaves of Wikstroemia micrantha.

One new sesquiterpene wikstromicrol (1), 1 new lignan (7R, 8S, 8'S)-9-acetoxyl (-)-isolariciresinol (8), and 12 known compounds were isolated from the branches and leaves of Wikstroemia micrantha. The structures of new compounds were elucidated by extensive interpretation of spectroscopic data and quantum chemical calculations of electronic circular dichroism spectra. The bioactivity assay showed that compounds 6 and 7 had weak cytotoxicity against MCF-7, HCT-116, and HL-60 cell lines with IC50 values ranging from 33.84 to 49.15µM, whereas compound 8 exhibited moderate cytotoxicity against HCT-116 cell line with an IC50 value of 16.54µM.

Derailment of the Biosynthesis via an Acid-Mediated Intramolecular Cyclo-rearrangement Leads to a Novel Cytochalasin Skeleton.

Cytochalasins are notable for their structural diversity and broad range of biological activities. The gene cluster responsible for the biosynthesis of cytochalasins bearing diverse polycycles was identified in Phomopsis sp. DHS-48. Characterization of the cluster indicated that only the 5/6/11-tricycle can be biosynthetically produced. The chemical space of cytochalasins was expanded by acid-mediated intramolecular cyclo-rearrangement of the 5/6/11-tricycle, and three new cytochalasins, phomoparagins D-F (13, 17, and 18, respectively), with diversified polycycles were obtained, among which compound 13 featured an unprecedented 5/6/5/7/6-pentacycle. Their structures and absolute configurations were established by spectroscopic analysis (1D, 2D NMR), electronic circular dichroism calculations, and a single-crystal X-ray diffraction experiment. The compounds inhibited the growth of HeLa and RKO cell lines with IC50 values ranging from 0.8 to 47.3 μM. Cytoskeleton staining experiments and molecular docking models revealed that compound 13 showed cytotoxicity by targeting F-actin.

New eremophilane-type sesquiterpenoid and new chromanone isolated from marine derived fungus Humicola sp. GXIMD02070

Chemical investigation of a marine-derived fungus Humicola sp. GXIMD02070 resulted in the isolation of one new eremophilane-type sesquiterpenoid (1), one new chromanone analogue (2), and three previously described metabolites, namely chaetosemin D (3), butyrolactone I (4), and isoochracinic acid (5). Their structures were elucidated by comprehensive analyses of the spectroscopic methods, quantum chemical calculation of NMR, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited inhibitory effects on NO production with EC50 value of 82.04 ± 0.12 μM and 100.2 ± 0.13 μM, respectively, indicating moderate anti-inflammatory activity.

Chemical components of Salvia cavaleriei and their anti-inflammatory effect via NF-κB signaling pathway.

In this study, with the aimed to explore the anti-inflammatory ingredients of Salvia cavaleriei, a phytochemical study with bioactive guided isolation for this plant have been taken. As a result, two pairs of new phenylacetic acid enantiomers, (±) cavalvia A (±1) and B (±2), and one previously undescribed germacrane-type sesquiterpenoid, salviesquiten A (3), along with ten known ones (4-13) were isolated from the ethyl acetate portion of 95 % ethanol extract. Their chemical structures were established based on UV, IR, MS and NMR spectroscopic analyses, as well as PD4+ probability analysis and electronic circular dichroism (ECD) methods. Anti-inflammatory bioassay showed that compound 6 exhibited significant effect against LPS-induced NO production in the RAW264.7 macrophages model, with the IC50 value of 3.40 ± 0.24 μM. Furthermore, compound 6 significantly suppressed the production of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and the protein expression of the enzymes iNOS and COX-2 in a concentration-dependent manner. And further investigation showed that 6 exerts anti-inflammatory effect via NF-κB signaling pathway.

Cycloartane-type triterpenoids from Combretum quadrangulare Kurz with PCSK9 secretion inhibitory activities.

Nine previously undescribed (1-9) and seven known (10-16) cycloartane-type triterpenoids were isolated and characterized from Combretum quadrangulare Kurz using physicochemical and spectroscopic methods. The absolute configurations of these compounds were determined through modified Mosher's method and quantum chemical calculation of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Their inhibitory activities against PCSK9 secretion were assessed, and a plausible structure-activity relationship was delineated. Compounds 2, 14, and 15 exhibited notable inhibitory effects on PCSK9 mRNA and protein levels, and significant PCSK9 mRNA inhibition was observed when co-treated with atorvastatin. Compound 15 showed the most potent activity, markedly enhancing LDL uptake compared to the negative control. In vivo pharmacokinetic studies confirmed that compound 15 exhibited higher distribution in the liver than plasma, where PCSK9 is predominantly synthesized. These findings emphasize the potential significance of the cycloartane-type triterpenoid scaffold in discovering PCSK9 inhibitors.

Terpenoids and steroids from the whole plants of Euphorbia wallichii and their protective effects on STZ-induced damage in INS-1 cells.

The research on the whole plant of Euphorbia wallichii led to the identification of two undescribed compounds, (1R,4S,5S,10S)-10-hydroxyacorenone B and (5R,9R,18S,20S,25R,26S,27S,28R)-D:C-friedolupane-3-oxo-7-ene. Together with 32 known compounds. Their chemical structures were determined through detailed spectroscopic data analyses and electronic circular dichroism measurements. The terpenoids and steroids found in Euphorbia wallichii have been identified to exhibit a diverse array of biological activities. However, their underlying antidiabetic effects have not yet been examined. In this study, the effects of terpenoid and steroid compounds on promoting the proliferation of INS-1 cells and protecting STZ-induced pancreatic β-cell damage were evaluated. Bioassays have demonstrated that compounds 32 and 33 exhibited a noteworthy protective effect on INS-1 cells against STZ-induced injury, as well as promoted the proliferation of INS-1 cells. As a whole, compounds 32 and 33 might be potentially beneficial for the treatment of diabetes.

Nidustrin A, cysteine-retained emestrin with a unique 18-membered macrocyclic lactone from the endophytic fungus Aspergillus nidulans.

Nidustrin A (1), the first cysteine-retained emestrin featuring a unique sulfur-containing 18-membered macrocyclic lactone, along with four biogenetically related compounds (2-5), and one known analogue secoemestrin C (6), were isolated from the large-scale culture of Aspergillus nidulans, an endophytic fungus derived from the Whitmania pigra. Compounds 2 and 3 represent the second examples of noremestrin besides the previously reported noremestrin A, and the single crystal X-ray diffraction analysis of compound 2 provided solid evidence for the intriguing skeleton of noremestrin. Their structures were determined by extensive spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compounds 2-4 exhibited inhibitory activity against concanavalin A-induced T lymphocyte proliferation with IC50 values from 2.95 to 24.5μM, respectively. Compound 4 could protect the liver from hepatocyte apoptosis in ConA-induced liver injury and showed moderate cytotoxic activities with IC50 values ranging from 3.26 to 15.70μM.

Sesquiterpene lactones from Artemisia porrecta Krasch.ex Poljakov and their anti-inflammatory, cytotoxic and anti-vitiligo activities.

This experiment focused on investigating the chemical constituents of the plant Artemisia porrecta Krasch.ex Poljakov, resulting in the isolation and characterization of twenty-seven sesquiterpene lactones belonging to the eudesmanolides, germacronolides, melampolides, and heliangolide types. These compounds include ten undescribed sesquiterpene lactones, Porrectolide A-I, 11-epi-Deacetylherbolide D and seventeen known ones. All known compounds were isolated from this plant for the first time. Their structures were established by 1D, 2D NMR spectroscopic and HR-ESI-MS data, electronic circular dichroism, and single crystal X-ray diffraction analysis. Evaluations of the anti-inflammatory activity revealed that 6 had moderate anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells with the IC50 value of 14.57±0.24 μM.

An Unusual Meroterpenoid and Two New Steroids from Fungus Penicillium fellutanum and Their Bioactivities.

An unusual clathrate-type meroterpenoid isoatlantinone A (1), two new steroids acrocalysterols E (2) and F (3), together with fifteen known compounds (4-18) were separated from a plant-associated fungus Penicillium fellutanum. Their structures and absolute configurations were established based on spectroscopic data (NMR and HRESIMS), electronic circular dichroism (ECD) and modified Mosher's method. Notably, compound 1 represents an unusual highly oxygenated meroterpenoid derivative with a unique caged bioxatetracyclo-[6.3.2.01,6.01,12]-tridecane ring system. All compounds were assessed in vitro for antifungal and cytotoxic activities. Intriguingly, compound 16 exhibited potent antifungal activity against Fusarium culmorum with MIC value of 50 mM, similar to the positive control carbendazim. Furthermore, compound 3 displayed potent cytotoxic effects on HCC-1806, and IC50 value of 18.15 ± 1.05 μM, and compound 6 exhibited remarkable cytotoxic activities on RKO, with the IC50 value of 11.61 ± 0.19 μM. Thus, strain Penicillium fellutanum represents a novel resource of these bioactive compounds to be exploited.

Immunomodulatory Potential of a Bibenzyl-dihydrophenanthrene Derivative Isolated from Calanthe cardioglossa.

Bibenzyls and dihydrophenanthrenes exhibit promising immunomodulatory effects in various human diseases. In this study, we isolated one new dihydrophenanthrene derivative (1), two new bibenzyl-dihydrophenanthrene derivatives (2, 3) along with 12 known compounds (4-15) from the methanol extract of Calanthe cardioglossa. These compounds were identified by using physicochemical analyses and spectroscopic methods. The three new compounds possess enantiomeric forms, and their configurations were determined by comparing the experimental electronic circular dichroism (ECD) spectra to data from the literature. The immunomodulatory activity of the isolated compounds was assessed in THP-1 monocytes and human peripheral blood mononuclear cells (PBMCs) derived from multiple sclerosis (MS) patients. Notably, five of the isolated compounds significantly reduced the TNF-α levels in LPS-stimulated THP-1 monocytes. Furthermore, calancardin B (2) exhibited a significant reduction in TNF-α levels in both THP-1 monocytes and CD14+ monocytes from MS PBMCs.

Bioactive sorbicillinoid derivatives from an endophytic fungus Trichoderma citrinoviride

Three new sorbicillinoid derivatives, citrinsorbicillinol A-C (1–3), along with three known compounds, such as trichosorbicillin G (4), dibutyl phthalate (5), and 3-(4-methoxyphenyl) propanoic acid (6), were isolated from the endophyte Trichoderma citrinoviride of Coptis chinensis. Their structures were elucidated through extensive analyses of spectroscopic data, computer-assisted structure elucidation (ACD/Structure Elucidator), density functional theory (DFT) calculations of the nuclear magnetic resonance (NMR) spectra, and electronic circular dichroism (ECD). Biologically, compounds 1–4 exhibited potential antioxidant activity, as assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, with IC50 values ranging from 27.8 to 89.6 μM. In particular, compounds 2 and 3 demonstrated radical scavenging activity comparable to that of the positive control, ascorbic acid, with IC50 values of 27.8 and 31.2 μM, respectively. Moreover, compound 1 exhibited potential anti-inflammatory activity by inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, with an IC50 value of 52.7 μM. These findings underscore the therapeutic potential of the new sorbicillinoid derivatives for antioxidant and anti-inflammatory applications.

Artemisieverolides A—G, Sesquiterpenoid Trimers from Artemisia sieversiana and Their Antihepatic Fibrosis Activity

Comprehensive SummaryArtemisieverolides A—G (1—7), seven unreported sesquiterpenoid trimers, were isolated from Artemisia sieversiana (Asteraceae), and elucidated by comprehensive spectral data and electronic circular dichroism (ECD) calculations. Compounds 1, 2, 4 and 6 were unambiguously determined by the single‐crystal X‐ray diffraction. Artemisieverolide A (1) was an unprecedented guaianolide sesquiterpenoid trimer featuring a rare 5/7/4/7/5 carbon skeleton biogenetically derived from [2+2] cycloaddition and a 2‐methylbicyclo[2.2.1]‐2‐heptene ring through a Diels‐Alder (D‐A) reaction. Artemisieverolides B—G (2—7) were guaianolide sesquiterpenoid trimers generated by two D‐A reactions. Compounds 3, 4, and 5 exhibited inhibitory activities on the proliferation of HSC‐LX‐2 with the IC50 values of 52.6, 58.4, and 54.8 μmol/L, and were about 3 folds more active than silybin (IC50 = 149.4 μmol/L). Furthermore, compounds 2 and 7 suppressed the expression of collagen I in TGF‐β1‐stimulated HSC‐LX‐2.

Dihydroaurones and Isoflavan Derivatives from the Roots of Glycyrrhiza asymmetrica.

As a continuation of our pharmacognostic studies on different Glycyrrhiza species growing in Türkiye, the phytochemical investigation of the roots of Glycyrrhiza asymmetrica Hub.-Mor., a licorice species endemic to Türkiye, was carried out. This study yielded twenty-three secondary metabolites (1-23) including nine previously unreported compounds: two dihydroaurone-3-enoic acids, licoaurone A (1) and licoaurone B (2), isoflavan hydroxypreglabridin (3), isoflavanone cyclodeoxykievitone (4), flavanone-3-ol glycyasymmetrol (5), and four bi-isoflavans, glycyasymmetrica A-D (6-9). The structures of isolated compounds were established by NMR and MS experiments. The relative configurations (6-9) were assigned by a combined quantum mechanical/NMR approach, comparing the experimental 13C/1H NMR chemical shift data and the related predicted values. The absolute configurations of compounds 1-9 were assigned by comparison of their experimental electronic circular dichroism curves with the TDDFT-predicted curves. All isolated compounds were also evaluated for their cytotoxic activity against MCF-7, HeLa, HepG2, and A549 cancer cell lines by using MTT assay.

Photophysical and Chiroptical Properties of Pyrazino-Phenanthroline-Helicene Derivative and its Rhenium(I) Complex.

A novel coordination motif comprising [4]helicene fused with pyrazino-phenanthroline (H4PP) has been synthesized and reacted with ReCl(CO)5 to yield its rhenium(I) complex (Re-H4PP). Absorption and emission spectroscopic analysis conducted in dichloromethane and 2-methyltetrahydrofuran reveals that combining pyrazino-phenanthroline with helicene visibly affects the photophysical attributes of both the resulting ligand and its Re(I) complex as compared to their non-helicene analogues, and even more importantly leads to relatively high photoluminescence quantum yield values, especially in the case of H4PP (29%). Chiroptical studies through electronic circular dichroism and circularly polarized luminescence performed on enantiomerically enriched samples of Re-H4PP show the chiral nature of low-energy excited states affording notable glum values that amplify at cryogenic temperatures. Insights into experimental results are provided via first-principles quantum-chemical calculations showing important role of intra-ligand charge-transfer (ILCT) and metal-to-ligand (MLCT) states in determining photophysical features of these systems.

Two new terpenoids from the leaves and twigs of Croton cnidophyllus and their anti-AD activities.

A new oleanane-type triterpenoid, 3β-acetyl-15α-hydroxy-oleanane-13β,28-olide (1), and a new clerodane furanoditerpenoid, cnidophyllin A (2), together with eleven known compounds (3-13) were isolated and identified from the 95% EtOH extract of the leaves and twigs of Croton cnidophyllus. Except for compounds 3 and 7, all other compounds were isolated for the first time from C. cnidophyllus. The structures of the new compounds were ascertained through a comprehensive application of spectroscopic techniques, including both 1D and 2D NMR, IR, and HR-ESI-MS, while their absolute configurations were validated either through single-crystal X-ray diffraction analysis or via electronic circular dichroism (ECD) calculations. Meanwhile, the single-crystal X-ray diffraction data of 8 has been reported for the first time. Additionally, the in vivo anti-Alzheimer's disease (AD) activities of compounds 3-13 were assessed using the Caenorhabditis elegans AD pathology model. Among all the isolated compounds, compounds 4 and 7-13 significantly delayed the paralysis of the worms with AD-like symptoms, which may be potential candidates for anti-AD drugs.

Halogenated meroterpenoids with antifungal activities from the Deep-Sea-Derived fungus Acremonium sclerotigenum guided by the genomic and OSMAC strategy.

Thirteen new meroterpenoids, acremorins A-M (1, 2, 4, 6, 7 and 9-16), together with three known analogues (3, 5 and 8) were isolated from the deep-sea-derived fungus Acremonium sclerotigenum LW14 guided by the genomic and OSMAC strategy. Their structures and absolute configurations were established by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD experiments, and a single-crystal X-ray diffraction experiment. Compounds 2, 4, 6 and 9 represent the rare brominated ascochlorins. Compounds 1/3 and 2/4 are two pairs of epimers isomerized at C-19. Compounds 1 and 2 are the first examples of ascochlorins which have the 19S configuration in the cyclohexanone moiety. Compounds 3/7, 8/10 and 11/12 are three pairs of epimers isomerized at C-12, C-18 and C-15, respectively. Compounds 7-10 showed moderate antifungal activity against Cryptococcus gattii 3271G1 with the same MIC values of 8μg/mL. The treatment with compound 7 led to a significant reduction in the cell wall thickness, rarefaction of cytoplasm, and damage to the structural integrity of organelles in C. gattiii 3271G1. Further RNA sequencing (RNA seq) analysis indicated that compound 7 exerted its anti-C. gattiii effect by up-regulating the biosynthesis and RNA binding of ribosomes, while concurrently inhibiting RNA and nucleic acid metabolism and ATPase activity.

(aS)-Glucosciadopitysin, a New Biflavonoid Glycoside from the Leaves of Ginkgo biloba and Osteogenic Activity of Bioflavonoids.

The leaves of Ginkgo biloba have been used in treating freckles and effectively reducing cough and sputum in folk medicines. Recently, investigations into the correlation between ginkgo leaves and the proliferative activity of osteogenic differentiation have been conducted. However, bioactive compounds that enhance osteogenesis or exhibit osteoporosis prevention from G. biloba have not been fully identified. Phytochemical investigation of the MeOH extract of G. biloba leaves led to the isolation and identification of a new biflavonoid glycoside, (aS)-glucosciadopitysin (1), along with five flavonoids (2-6), through LC/MS-guided isolation approach. The structure of the new compound 1 was elucidated by the spectroscopic methods, including 1D and 2D NMR analysis, as well as HR-ESIMS. The absolute configuration of sugar moiety was established through acid hydrolysis, followed by chemical derivatization reaction and the axial chirality arising from the biaryl system with substituents was determined by electronic circular dichroism (ECD) calculations. The isolated flavonoids (1-6) were tested for their effects on mesenchymal stem cell (MSC) differentiation at 20 μM using Oil Red O and alkaline phosphatase (ALP) staining. Ginkgetin (2) was further evaluated for osteogenic activity on C3H10T1/2 cells at concentrations of 1, 2.5, 5, and 10 μM for 10 days. ALP staining and RT-PCR assessed the gene expression of osteogenic markers ALP and osteopontin (OPN). Ginkgetin (2) demonstrated the strongest osteogenic activity, significantly increasing the expression of ALP (12.5-fold) and OPN (4.0-fold) at 10 μM, comparable to the positive control, oryzativol A. Ginkgetin (2) shows potential as a therapeutic agent for osteopenia by promoting osteogenesis in MSCs, suggesting its promising role in treating osteoporosis.

Chemical Constituents of the Deep-Sea-Derived Penicillium citrinum W22 and Their Ferroptosis Inhibitory Activity.

One new monomeric citrinin analog (1) and 42 known compounds (2-43) were isolated from Penicillium citrinum W22. The structure of 1 was determined by detailed analysis of the 1D and 2D nuclear magnetic resonance (NMR), HRESIMS, and time-dependent density functional theory (TD-DFT)-based electronic circular dichroism (ECD) calculation. Penicitrinol A (2) and methyl 2-(2-acetyl-3,5-dihydroxy-4,6-dimethylphenyl) acetate (11) significantly inhibited renin-angiotensin system-selective lethal 3 (RSL3)-induced ferroptosis with half maximal effective concentration (EC50) values of 1.6 and 34.0µM, respectively.