ECD Spectra Research Articles

Theoretical study of nimetazepam, a real-life chiral molecule without an asymmetric carbon atom

We investigate the potential energy landscape and the spectroscopic properties of the nimetazepam molecule using a density functional theory approach. Our calculations show that despite the lack of a chiral carbon atom or a stereochemically active bond, this molecule exhibits two conformational enantiomers, M and P. For the isomerization process we find an activation energy of 16.7 kcal/mol. The conformers are inseparable at room temperature, and consequently, the nimetazepam drug exists as a racemic mixture. The theoretical spectroscopic analysis of these enantiomers including IR, VCD, NMR, UV-Vis, and ECD has been performed, to identify suitable experimental techniques to detect the individual stereoisomers. The infrared spectrum of nimetazepam agrees well with the experimentally observed one, and vibrational bands have been assigned. Moreover, the 1H and 13C NMR experimental chemical shifts have been well reproduced using the gauge independent atomic orbital method. The calculations suggest a dynamic 1H NMR effect that can be used to follow the isomerization process. The TD-DFT approach enables us to simulate the UV-Vis spectra, and the obtained results coincide satisfactorily with the observed spectrum. The M and P conformers show a complementary behavior in their predicted VCD and ECD spectra.

LC-MS-guided isolation of 2-(2-phenylethyl)chromone dimers from red soil agarwood of Aquilaria crassna

Six new 2-(2-phenylethyl)chromone dimers (1–6) were isolated from ethyl ether extract of red soil agarwood of Aquilaria crassna from Vietnam by LC-MS-guided fractionation procedure. Their structures were unambiguously elucidated based on HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by comparison of the experimental and computed ECD spectra. Compound 6 displayed cytotoxicity against the human myeloid leukemia cell line (K562) with an IC50 value of 39.49 μM.

A full set of 8,4′-oxy-8′-phenylneolignan stereoisomers from Sophora tonkinensis and their absolute configurations by TDDFT

A full set of 8,4′-oxy-8′-phenylneolignans with four chiral carbons, named (+)/(−)-leptolepisols D1‒D2 and (+)/(−)-sophorols A‒F, were isolated from the roots and rhizomes of Sophora tonkinensis Gagnep., including 14 previously undescribed stereoisomers, along with 2 known leptolepisol D diastereomers. Their planar structures and relative configurations were elucidated by detailed spectroscopic analysis (HRESIMS and NMR). Based on a highly accurate conformer filtering protocol at low computational cost, the absolute configurations of full set 8,4′-oxy-8′-phenylneolignans were completely assigned by TDDFT calculations of ECD spectra for the first time. Furthermore, (+)/(−)-sophorol A, (−)-sophorol B, and (−)-sophorol E could moderately suppress the lipopolysaccharide-induced nitric oxide production in murine macrophages at 10 μM, with inhibitory ratios of 48.4–52.9%.

Tunable Excimer Circularly Polarized Luminescence in Isohexide Derivatives from Renewable Resources.

Organic compounds showing circularly polarized luminescence (CPL) are at the forefront of novel applications and technologies. Here we show the synthesis and chiroptical properties of pyrene and perylene derivatives of inexpensive chiral scaffolds: isomannide and isosorbide. Low‐intensity ECD spectra were obtained, suggesting the absence of chromophore interaction in the ground state, except in the case of isomannide bis‐perylenecarboxylate, whose ECD spectrum showed a positive exciton couplet. All isomannide derivatives, with the only exception of the one containing a pyrenecarboxylate and a perylenecarboxylate, exhibited excimer CPL spectra, whereas isosorbide derivatives did not show any CPL. Isomannide derivatives bearing two pyrenecarboxylate or two pyrenylacetate groups showed positive CPL emission with dissymmetry factors up to 10−2, which depends on the conformational freedom of the appended units. The CPL sign, Stokes shift and order of magnitude of dissymmetry factor were reproduced by excited‐state calculations on a representative compound. Interestingly, the mixed derivative containing pyrenic units with different spacing from the isomannide scaffold showed an oppositely signed excimer band with respect to the homo‐substituted derivatives.

Spirovetivane- and Eudesmane-Type Sesquiterpenoids Isolated from the Culture Media of Two Cyanobacterial Strains.

As part of a study examining polar metabolites produced by cyanobacterial strains, we examined media extracts of a Calothrix sp. (strain R-3-1) and a Scytonema sp. (strain U-3-3). The cell mass of each was separated from the media, and HP20 resin was added for adsorption of secreted metabolites, a relatively unexplored area of cyanobacterial chemistry. HPLC-UV-LCMS-guided isolation led to the discovery of seven sesquiterpenoid compounds with five new, one known, and one previously isolated as the methyl ester. Through a complement of 1D and 2D NMR spectroscopic techniques, the planar structures and relative configurations of the seven compounds were elucidated. Spironostoic acid (1), 11,12-didehydrospironostoic acid (2), and 12-hydroxy-2-oxo-11-epi-hinesol (4) are spirovetivane-type compounds from R-3-1, while stigolone (5), 11R,12-dihydroxystigolone (6), and 11S,12-dihydroxystigolone (7) are three eudesmane-type compounds from U-3-3. Circular dichroism was utilized to decipher the absolute configurations of new compounds 1, 2, 4, 5, 6, and 7. Due to the structural variety observed among the spirovetivane- and eudesmane-type compounds in the literature and often a lack of clarity in how determinations were made, computational spectra and model compounds were used to support the interpretation of ECD and NMR spectra. A straightforward process to determine the configuration of these systems is presented.

π‐Extended Helical Nanographenes: Synthesis and Photophysical Properties of Naphtho[1,2‐a]pyrenes**

AbstractA mild and efficient synthesis of a broad scope of substituted naphtho[1,2‐a]pyrene derivatives was accomplished in good yields using an InCl3/AgNTf2‐mediated two‐fold alkyne benzannulation reaction. HPLC enantiomeric separation was achieved and the interconversion barriers have been determined. The ECD spectra of two derivatives were recorded and interpreted through TD‐DFT calculations. Raman spectra were also recorded and predicted through DFT calculations.

Spectroscopic investigation on 1,2-substituted ferrocenes with only planar chirality: How chiroptical data are related to absolute configuration and to substituents

Single enantiomers of three 1,2-substituted ferrocene derivatives, i.e. 1-methoxymethyl-2-hydroxymethylferrocene (1), 1-formyl-2-hydroxymethylferrocene (2) and 1-iodo-2-hydroxymethylferrocene (3), sharing the common hydroxymethyl substituent and the presence of planar chirality only, were investigated for their spectroscopic (IR and UV) and chiroptical (VCD and ECD) properties. Both enantiomers of 1 were obtained for the first time in optically pure form by lipase-catalyzed kinetic resolution of the corresponding racemate (±)-1 and separately converted into formyl derivatives (+)-2 and (–)-2.The experimental spectroscopic and chiroptical data were compared with DFT calculated spectra and excellent correspondence was found for all compounds, allowing one to confirm the previously assigned absolute configurations. The common features in the VCD spectra of a doublet between 940 and 965 cm−1 and the short-wavelength (about 200 nm) doublet and the longest wavelength band in the ECD spectra were analyzed to test whether they may be taken as markers of the absolute configuration (AC). The predominance of conformers with intramolecular hydrogen bond for the first two investigated compounds is predicted by conformational analysis and also confirmed by NMR.

A new butenolide with antifungal activity from solid co-cultivation of Irpex lacteus and Nigrospora oryzae

A new antifungal butenolide irperide (1) along with five known compounds were isolated from the co-culture of endophyte Irpex lacteus and pathogenic Nigrospora oryzae. The structure of 1, including the absolute configuration, was elucidated by analysis of NMR, HR-ESI-MS data and ECD spectra. Compounds 1, 4 and 6 exhibited significant antifungal activity against Aspergillus fumigatus, with MIC values of 1, 2 and 1 μg/mL, respectively.

Lignans with α-glucosidase, protein tyrosine phosphatase 1B, and aldose reductase inhibitory activities from the fruits of Viburnum cylindricum

Viburnum cylindricum Buch.-Ham. ex D. Don is widely cultivated in China due to its considerable economic value. In this study, the EtOAc fraction (VCFE) of V. cylindricum fruits (VCF) was first reported to obviously reduce postprandial blood glucose levels in normal and diabetic ICR mice at 100 mg/kg, and significantly inhibit α-glucosidase, PTP1B, and AR activities in vitro. In order to clarify its antidiabetic components, nine undescribed lignans, including seven 9,9′-epoxylignans, viburindrins A−G (1−7), one rare variable 9,9′-epoxylignan, viburindrin H (8), and one furofuran lignan, viburindrin I (9), were isolated from VCFE by bioassay-guided fractionation, and their structures including absolute configurations were identified by comprehensive spectroscopic analyses and the comparison of the experimental and calculated ECD spectra. Compounds 1−8 exhibited significant inhibitory activities against these enzymes. Among them, compounds 1, 4, and 8 possessed the most potent inhibitory effects on α-glucosidase, PTP1B, and AR with the IC50 values of 14.21, 6.14, and 1.08 μM, respectively. In addition, their inhibitory kinetics and molecular modeling analyses were also investigated. These results uncovered that VCF with the active lignans could be the potential resource for the improvement and treatment of diabetes and related complications.

Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour

Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A−D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC50 values of 2.61, 1.19, and 1.74 μM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 μg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC50 of 20.06 μM) and α-glycosidase inhibitor (IC50 of 17.18 μM), while tabernamine, ervahanine B, and ervadivaricatine B only showed α-glycosidase inhibitory activities with IC50 values in the range of 0.95–4.61 μM.

Diverse diterpenoids with α-glucosidase and β-glucuronidase inhibitory activities from Euphorbia milii

Four undescribed regular rosane-type diterpenoids euphominoids M−P and three undescribed rearranged rosane-type diterpenoids euphomilones C-E were isolated from the whole plants of Euphorbia milii Des Moul., along with nine known compounds. Their structures were elucidated by detailed interpretation of the NMR and mass spectroscopy. The absolute configurations were established by single-crystal X-ray diffraction experiments, as well as comparative analyses of calculated and experimental ECD spectra. Euphominoid M featured a highly oxygenated ring A and a rare four-membered oxygen ring while euphomilones C-E possessed 7/5/6 or 5/7/6 fused ring systems, which were rarely occurring in rosane-type diterpenoids. In the in-vitro bioassays, 19-norrosa-1,3,5(10),15-tetraene-2,3-diol and antiquorin showed more potent α-glucosidase inhibitory activity than the positive control acarbose while euphominoid C exhibited significant inhibitory activity against both α-glucosidase and β-glucuronidase. To the best of our knowledge, it was the first time that rosane-type diterpenoids were reported as β-glucuronidase inhibitors.

Cadinane-Type Sesquiterpenoids with Cytotoxic Activity from the Infected Stems of the Semi-mangrove Hibiscus tiliaceus

Eight new cadinane sesquiterpenoids (1-8), along with two known compounds (9 and 10), were isolated from infected stems of the semi-mangrove plant, Hibiscus tiliaceus. The structures of compounds 1-8 were elucidated through the analysis of their 1D and 2D NMR and MS data, and their absolute configurations were determined by comparing their experimental and calculated ECD spectra and by single-crystal X-ray diffraction. The two confused known compounds (9 and 10) were resolved using single-crystal X-ray crystallography. Compounds 1-3 have novel norsesquiterpene carbon skeletons arising from a ring contraction rearrangement. All obtained isolates were evaluated against the HepG2 and Huh7 cell lines, and compounds 1b, 2b, 4, 6, and 8 showed cytotoxic activity toward both cell lines, with IC50 values ranging from 3.5 to 6.8 μM.

New Secondary Metabolites from the Marine-Derived Fungus Talaromyces mangshanicus BTBU20211089.

Seven new compounds, namely talaromanloid A (1), talaromydene (2), 10-hydroxy-8-demethyltalaromydine and 11-hydroxy-8-demethyltalaromydine (3 and 4), talaromylectone (5), and ditalaromylectones A and B (6 and 7), together with seven known compounds were identified from a marine-derived fungus, Talaromyces mangshanicus BTBU20211089, which was isolated from a sediment sample collected from the South China Sea. Their chemical structures were determined using spectroscopic data, including HRESIMS, 1D, and 2D NMR techniques. The absolute configurations of 1 and 2 were elucidated by comparing experimental and calculated ECD spectra. Compounds 1, 2, 6, and 7 are new compounds possessing a novel carbon skeleton. Compound 6 is a dimeric molecule of 3 and 9. Compound 7 shared a unique structure of the cyclized dimer of 3 and 4. All the compounds were tested for their bioactivities against Staphylococcus aureus, Escherichia coli, and Candida albicans.

Anti-inflammatory Dimeric Tetrahydroxanthones from an Endophytic Muyocopron laterale.

Twelve new dimeric tetrahydroxanthones, muyocoxanthones A-L (1-12), were isolated from the endophytic fungus, Muyocopron laterale. Their structures were characterized on the basis of the interpretation of NMR and HRESIMS data. The absolute configurations of 1-10 and 12 were unambiguously determined by ECD spectrum data and single-crystal X-ray diffraction analysis. Compounds 2, 6, and 11 showed inhibitory activity against the LPS-induced production of nitric oxide (NO) in RAW 264.7 cells with IC50 values of 5.2, 1.3, and 5.1 μM, respectively.

Cover Feature: Electronic Circular Dichroism Imaging (ECD i ) Casts a New Light on the Origin of Solid‐State Chiroptical Properties (Chem. Eur. J. 4/2022)

Thanks to the concept of synchrotron radiation ECD imaging (SR-ECDi) applied to the active pharmaceutical ingredient Finasteride, we obtained an exclusive insight into the critical role played by the anisotropy of local domains in solid-state ECD spectra. Our findings open a new way to interpret solid-state chiroptical measurements and will broaden their application to probing and mapping solid chiral materials. More information can be found in the Research Article by M. Górecki, L. Di Bari, et al. (DOI: 10.1002/chem.202103632).

Physico-Chemical Properties and DFT Calculations of 2-Methoxy – 4 - (Prop-1-En-1-Yl) Phenol (ISOEUGENOL) Using Gausssian Basis Set

<p>Physico-chemical properties plays an important role in determining toxicity of a material hence were calculated using acdlab/chemsketch and the data predicted is generated using ACD/Labs Percepta Platform - PhysChem Module. Gaussian 09, RevisionA.01, software package was used for the theoretical quantum chemical calculations of 2-methoxy -4-(prop-1-en-1-yl) phenol commonly called Isoeugenol. DFT/B3LYP/6-311G (d, p) basis was used to perform geometric optimization and vibrational frequency determination of the molecule. The statistical thermochemical calculations of the molecule were done at DFT/B3LYP/6-311G (d, p) basis set to calculate the standard thermodynamic functions: heat capacity (CV), entropy (S) and Enthalpy (E). DFT/B3LYP/6-311G (d, p) basis set was used to calculate the various NLO properties like dipole moment (µ), mean linear polarizability (α), anisotropic polarizability (Δα), first order hyperpolarizability (β), second order hyperpolarizability (γ) in terms of x, y, z components for Isoeugenol (2-methoxy -4-(prop-1-en-1-yl) phenol. Same basis set was used to carry out Mulliken population analysis. UV-Visible absorption spectra, ECD spectra, electronic transitions, vertical excitation energies and oscillator strengths of Isoeugenol (2-methoxy -4-(prop-1-en-1-yl) phenol) were computed by Time Dependent DFT (TD-DFT) method using the same basis set. FMO analysis, Molecular electrostatic potential study was also done using the same basis set.</p>

Rhabdastrenones A-D from the sponge Rhabdastrella globostellata.

Three new isomalabaricanes (1–3), a new α-pyrone derivative (4), together with four known isomalabaricane analogs rhabdastrellin G (5), isogeoditin A (6), stelliferin A (7), and (13E)-isogeoditin A (8) were isolated from the marine sponge Rhabdastrella globostellata. Their chemical structures were determined by HR-ESI-MS, 1D and 2D-NMR spectroscopic data analysis. The absolute configurations were identified by Mo2(OAc)4 induced ECD spectra and TD-DFT theoretical calculated ECD spectra. Compound 6 exhibited weak cytotoxic effects against HepG2 and SKMel2 cell lines with the IC50 values of 7.53 ± 0.70 and 9.93 ± 0.95 μM, respectively.

Streptoglycerides E-H, Unsaturated Polyketides from the Marine-Derived Bacterium Streptomyces specialis and Their Anti-Inflammatory Activity.

Four new streptoglycerides E–H (1–4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1–4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1–4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC50 values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.

New dimeric chromanone derivatives from the mutant strains of Penicillium oxalicum and their bioactivities.

Three new chromanone dimer derivatives, paecilins F–H (1–3) and ten known compounds (4–13), were obtained from the mutant strains of Penicillium oxalicum 114-2. Their structures were elucidated by extensive analysis of spectroscopic data and comparison with reported data, and the configurations of 1–3 were resolved by quantum chemical calculations of NMR shifts and ECD spectra. Compounds 5 and 11 showed significant anti-influenza A virus activities with IC50 values of 5.6 and 6.9 μM, respectively. Compounds 8 and 9 displayed cytotoxic activities against the MIA-PaCa-2 cell line with IC50 values of 2.6 and 2.1 μM, respectively. Compound 10 exhibited antibacterial activities against Bacillus cereus with a MIC value of 4 μg mL−1.

Structurally diverse biflavonoids from Dysosma versipellis and their bioactivity.

Five pairs of new biflavonoid enantiomers, (±)-dysosmabiflavonoids A-E (1-5), two new biflavonoids, dysosmabiflavonoids F-G (6-7), and four biosynthetically related precursors (8-11) were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by extensive spectroscopic analysis, including HR-ESI-MS and 2D NMR. Their absolute configurations were determined by comparison of the calculated and experimental ECD spectra. All isolated compounds were evaluated for AChE inhibitory activity. Compounds 6 and 7 exhibited more potent inhibitory activities with IC50 values of 1.42 and 0.73 µM, respectively, than their biosynthetically related precursors kaempferol (8, 17.90 µM) and quercetin (9, 3.96 µM). The preliminary structure-activity relationship study indicated that the connection mode of biflavonoid subunits, oxidation degree of the C ring, and 3,4-dihydroxy group of the B ring were important structural factors for AChE inhibitory activity. Racemates 1-5 and their corresponding levorotatory and dextrorotatory enantiomers were tested for their potential to impede the generation of NO in lipopolysaccharide-stimulated RAW264.7 cells, and their mushroom tyrosinase inhibitory effect. Racemate 1 displayed more potent mushroom tyrosinase inhibitory activity (IC50, 28.27 µM) than the positive control kojic acid (IC50, 32.59 µM). D. versipellis may have therapeutic potential for melanogenesis disorders and neurodegenerative diseases.