Enantiomeric Pairs Research Articles

Chiral Metal Self-Assemblies of Zirconium-Tetrahedra and Their Second Harmonic Generation Activity.

The chirality of metal-organic cages holds enormous potential for novel applications in diverse fields, while it is relatively rare to employ such asymmetric units for the construction of noncentrosymmetric materials. Herein, by self-assembling the 4,4',4''-nitrilotribenzoic acid (H3NBA) with bis(cyclopentadienyl)-zirconium dichloride (Cp2ZrCl2, Cp=η5-C5H5) in different solvent conditions, we have obtained three hierarchical packing modes of metallo-tetrahedra with distinct spatial symmetry groups (designated as Zr-α, Zr-β, and Zr-γ). Among them, Zr-α employs a simple cubic arrangement and is a common centrosymmetric superstructure, which consists of a pair of equimolar metallo-tetrahedra enantiomers in its unit cell. While Zr-β results in conglomerates with spontaneous resolution without using any resolving agents, giving rise to two enantiopure entities separately (Zr-β-P, Zr-β-M). More importantly, Zr-γ breaks the inversion center of symmetry and crystallizes into a racemic yet non-centrosymmetric superstructure with face-centered cubic packing mode. Based on the non-centrosymmetric nature, the hierarchical superstructure Zr-γ displayed good second harmonic generation activities. This work presents a successful instance wherein the reaction solvent induces the modulation of intermolecular packing mode to afford non-centrosymmetric solid materials, which can greatly promote the development of noncentrosymmetric solid (NCS) materials.

Heterocycles and a Sorbicillinoid from the Coral-Derived Fungus Penicillium chrysogenum

A detailed chemical study of the culture of a coral-derived fungus Penicillium chrysogenum resulted in the isolation and identification of four new aromatic heterocycles chrysoquinazolinones A–B (1–2) and chrysobenzothiazoles A–B (3–4), along with a new sorbicillinoid 4-carboxylsorbicillin (5). Chrysoquinazolinones A–B (1–2) combine a quinazolinone fragment with a bicyclo[2.2.2]octane or a pyrrolidone moiety, respectively, demonstrating the unexpected structures of marine natural products. Chrysobenzothiazoles A–B (3–4) possess a benzothiazole system and are the second isolation of this class of skeleton compounds from marine organisms. The existence of the pair of enantiomers (±3) was deduced by chiral HPLC analysis. Their structures and absolute configurations were elucidated by detailed spectroscopic analysis, comparison with the literature data, single-crystal X-ray crystallographic analysis and TDDFT-ECD calculations. Compound 5 exhibited moderate cytotoxicity against K562 and NCI-H446 cell lines, with IC50 values of 15.00 μM and 16.87 μM, respectively.

Isolation of Novel Compounds from Lepidium sativum Seeds and Evaluation of Their Potential Anti-Tumor Activity.

Four undescribed compounds including a pair of enantiomers of a dihydroarylnaphthalene lignan [(±)-1], an arylnaphthalene lignan (2), and an indoleacetic acid ester (3), together with four known compounds (4-7), were isolated from the seeds of Lepidium sativum. Their structures were identified by HRMS and NMR spectroscopic data, and the absolute configuration of these compounds were assigned by ECD data in combination with quantum chemical calculations. Compound (-)-1 had weak inhibitory activity against HeLa cell line with an IC50 value of 60.23±3.51 μM, and compound (+)-1 presented moderate inhibitory effect against HeLa cell line with an IC50 value of 19.99±1.00 μM (IC50 value of the positive control was 0.40±0.02 μM).

Magneto‐Chiral Dichroism of Chiral Lanthanide Complexes in the Context of Richardson's Theory of Optical Activity

AbstractHere we report on the Magneto‐Chiral Dichroism (MChD) detected through visible and near‐infrared light absorption of two enantiomeric pairs of ErIII and TmIII chiral complexes featuring a propeller‐like molecular structure. The magnetic properties show typical features of isolated paramagnetic ions associated with 4I15/2 and 3H6 ground state terms. MChD spectroscopy shows high gMChD dissymmetry factors of ca. 0.12 T−1 and 0.05 T−1 (T=4.0 K and B=1.0 T) for ErIII and TmIII, respectively, associated with the magnetic‐dipole allowed 4I13/2 ← 4I15/2 and 3H5 ← 3H6 transitions. MChD signals of the two complexes were detected up to room temperature and under magnetic fields up to 5.0 T. For the first time, the MChD results are discussed in the context of the Richardson theory of lanthanide optical activity and provide clear indications on the strongest MChD‐active electronic transitions of lanthanide complexes.

Deducing formation routes of oxylipins by quantitative multiple heart-cutting achiral-chiral 2D-LC-MS

Several oxylipins are regulators of inflammation. They are formed by enzymes such as lipoxygenases or cyclooxygenases, but also stereorandomly by autoxidation. Reversed-phase liquid chromatography-tandem-mass-spectrometry (LC-MS/MS) methods for oxylipin quantification do not separate enantiomers. Here, we combine sensitive and selective oxylipin analysis with chiral separation using two-dimensional (2D)-LC-MS/MS. By multiple heart-cutting, the oxylipin peaks are transferred onto a chiral column. 45 enantiomeric pairs of (di-)hydroxy-fatty acids are separated with full gradient elution within 1.80min, yielding lower limits of quantification <1pg on column. Concentrations as well as enantiomeric fractions of oxylipins can be determined, even at low concentrations or at high enantiomeric excess of one isomer. The developed achiral-chiral multiple heart-cutting 2D-LC-MS/MS method offers unprecedented selectivity, enabling a better understanding of the formation route of these lipid mediators. This is demonstrated by distinguishing the formation of hydroxy-fatty acids by (acetylated) cyclooxygenase-2 and radical-mediated autoxidation. Applying the method to human M2-like-macrophages, we show that the so-called specialized pro-resolving mediators (SPM) 5,15-DiHEPE and 7,17-DiHDHA as well as 5,15-DiHETE were present as (S,S)-enantiomers, supporting their enzymatic formation. In contrast, at least eight isomers (including protectin DX but not neutroprotectin D1) of 10,17-DiHDHA are present in immune cells, indicating formation by autoxidation. In human plasma of healthy subjects, none of these dihydroxy-fatty acids are not present. However, we demonstrate that all four isomers quickly form via autoxidation if the samples are stored improperly. Thus, dihydroxy-FA should only be reported as SPM, such as resolvin D5 or resolvin E4, if an enantioselective analysis has been carried out.

Targeted discovery of polyketides with antioxidant activity through integrated omics and cocultivation strategies.

Fungi generate a diverse array of bioactive compounds with significant pharmaceutical applications. However, the chemical diversity of natural products in fungi remains largely unexplored. Here, we present a paradigm for specifically discovering diverse and bioactive compounds from fungi by integrating genome mining with building block molecular network and coculture analysis. Through pangenome and sequence similarity network analysis, we identified a rare type I polyketide enzyme from Penicillium sp. ZJUT-34. Subsequent building block molecular network and coculture strategy led to the identification and isolation of a pair of novel polyketides, (±)-peniphenone E [(±)-1], three known polyketides (2-4), and three precursor compounds (5-7) from a combined culture of Penicillium sp. ZJUT-34 and Penicillium sp. ZJUT23. Their structures were established through extensive spectroscopic analysis, including NMR and HRESIMS. Chiral HPLC separation of compound 1 yielded a pair of enantiomers (+)-1 and (-)-1, with their absolute configurations determined using calculated ECD methods. Compound (±)-1 is notable for its unprecedented structure, featuring a unique 2-methyl-hexenyl-3-one moiety fused with a polyketide clavatol core. We proposed a hypothetical biosynthetic pathway for (±)-1. Furthermore, compounds 2, 5, and 6 exhibited strong antioxidant activity, whereas (-)-1, (+)-1, 3, and four exhibited moderate antioxidant activity compared to the positive control, ascorbic acid. Our research demonstrates a pioneering strategy for uncovering novel polyketides by merging genome mining, metabolomics, and cocultivation methods. This approach addresses the challenge of discovering natural compounds produced by rare biosynthetic enzymes that are often silent under conventional conditions due to gene regulation.IMPORTANCEPolyketides, particularly those with complex structures, are crucial in drug development and synthesis. This study introduces a novel approach to discover new polyketides by integrating genomics, metabolomics, and cocultivation strategies. By combining genome mining, building block molecular networks, and coculturing techniques, we identified and isolated a unique polyketide, (±)-peniphenone E, along with three known polyketides and three precursor compounds from Penicillium sp. ZJUT-34 and Penicillium sp. ZJUT23. This approach highlights the potential of using combined strategies to explore fungal chemical diversity and discover novel bioactive compounds. The successful identification of (±)-peniphenone E, with its distinctive structure, demonstrates the effectiveness of this integrated method in enhancing natural product discovery and underscores the value of innovative approaches in natural product research.

Twist along Central C-C Bonds in a Series of Fully π-Fused Propellanes.

Without stereogenic carbon centers, organic molecules can be chiral when they have large energy barriers for conformational inversion. In this work, conformational behaviors are investigated for a series of tricyclic propellane skeletons with increasing 6-membered-ring peripheral moieties fused with aromatic rings. According to theoretical calculations, trinaphtho[3.3.3]propellane has three vertical naphthalene rings like triptycene shape without torsion along the central C-C single bond. On the other hand, hexabenzo[4.4.4]propellane shows hexaphenylethane-like ca. 60° twist along the bond with large activation energy of 64 kcal mol-1 for twist inversion because of the high congestion caused by three 6-membered-ring loops. Indeed, the [4.4.4]propellane gives a stable pair of chiroptical enantiomers toward heating at 146 °C. By contrast, a hybrid [4.3.3]propellane exhibits fast interconversion between two twisted conformations even at -80 °C.

Magneto-Chiral Dichroism of Chiral Lanthanide Complexes in the Context of Richardson's Theory of Optical Activity.

Here we report on the Magneto-Chiral Dichroism (MChD) detected through visible and near-infrared light absorption of two enantiomeric pairs of ErIII and TmIII chiral complexes featuring a propeller-like molecular structure. The magnetic properties show typical features of isolated paramagnetic ions associated with 4I15/2 and 3H6 ground state terms. MChD spectroscopy shows high gMChD dissymmetry factors of ca. 0.12 T-1 and 0.05 T-1 (T = 4.0 K and B = 1.0 T) for ErIII and TmIII, respectively, associated with their magnetic-dipole allowed 4I13/2 ← 4I15/2 and 3H5 ← 3H6 transitions. MChD signals of the two complexes were detected up to room temperature and under magnetic fields up to 5.0 T. For the first time, the MChD results reported here are discussed in the context of the Richardson theory of lanthanide optical activity and provide clear indications on the strongest MChD-active electronic transitions of lanthanide complexes.

D-π-A Type [7]Helicene-like Imide Derivatives with Tunable Photophysical Properties and Circularly Polarized Luminescence.

Helicenes and their derivatives show great application prospects as circularly polarized luminescence (CPL) materials, but their fluorescence quantum yields (ΦFLs) need a breakthrough urgently. Herein, we reported a series of D-π-A type helical luminescent emitters by combining the [7]helicene-like imide acceptor with five different donors. The obtained five emitters display blue-to-orange luminescence and markedly enhanced ΦFL. Notably, TPA-NiBTI exhibits the maximum ΦFL in solution, while TPE-NiBTI achieves a maximum ΦFL in the solid state. Their two pairs of enantiomers, (P/M)-TPA-NiBTI and (P/M)-TPE-NiBTI, exhibit remarkable CPL activities, and their doped PS film both displayed doubled ΦFLs. Among them, [(P/M)-TPE-NiBTI]-doped PS film exhibits the maximum luminescence dissymmetry factor (|glum|) value of 9.0×10-4 and the maximum ΦFL of 22%. This molecular design strategy presents a promising approach to improving the ΦFL of helicene derivatives, thereby facilitating their potential application into chiral optoelectronic devices.

LC–MS coupled with diagnostic ion strategy facilitated the discovery of 5-methylcoumarin meroterpenoids from Gerbera piloselloides

Plant-derived natural products remain crucial in drug development. However, the identification of undescribed natural products is becoming increasingly challenging. A comprehensive strategy combining LC–MS with diagnostic ions was proposed for the discovery of undescribed 5-methylcoumarin meroterpenoids. Thirteen undescribed 5-methylcoumarin meroterpenoids, including five pairs of enantiomers (1a/1b and 5a/5b–8a/8b), were isolated from the whole plant of Gerbera piloselloides. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated and experimental ECD data and X-ray diffraction analysis. Bioassays conducted on scopolamine-induced injury PC12 cells revealed that compounds 5a/5b, 7a/7b and 8a/8b possessed mild protective effects. Additionally, compounds 2 and 8 showed notable IL-6 inhibition in lipopolysaccharide-induced BEAS-2B cells.

Organic Ferroelastic with Dual-Channel Manipulation Obtained by H/F Substitution.

Ferroelastic materials with high phase transition temperature have broad application prospects in information conversion and storage, shape memory, energy conversion, hyperelasticity, etc. However, most of the current reports focus on inorganic ferroelastic materials. Inorganic ferroelastic materials have the disadvantages of high energy consumption and harmful metals, which limit their application in practical work. In contrast, organic ferroelastic materials have the advantages of structural adjustability, environmental protection, easy processing, low cost, mechanical flexibility, and so on, which have great development potential in new ferroelastic materials. Here, we have successfully designed and synthesized a pair of homochiral enantiomers [(R/S)-4-fluorobenzoic acid-2-amino-2-phenylethanol] (R- and S-F) using the chemical design strategy of H/F substitution. Compared with the non-F substitution [(R/S)-benzoic acid-2-amino-2-phenylethanol] (R- and S-H), they undergo 2F1-type ferroelastic phase transitions at 370 K. Notably, the ferroelastic domains of R/S-F can be controlled through two physical channels that are temperature and stress, showing great potential in dual-channel switches.

Structurally diverse phenylpropanoyl phloroglucinol derivatives from Mallotus philippensis and their anti-bacterial activities

Fifteen undescribed phenylpropanoyl phloroglucinol derivatives featuring modified isoprenyl and/or geranyl units (1–15), in conjunction with thirteen known analogues (16–28), were obtained from the glandular hairs of the fruit of Mallotus philippensis. Meanwhile, fourteen pairs of new enantiomers [(±)-1–9, (±)-11–15] were further resolved by chiral purification. Their structures were determined by comprehensive spectroscopic analyses, single-crystal X-ray diffraction experiments and quantum chemical calculations. Bioactivity evaluation showed that compound 17 exhibited significant anti-bacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MIC of 6 μg/mL, while compounds 3, 4, 8 and 18 displayed moderate effects with MIC of 24, 12, 24, and 12 μg/mL, respectively. The KEGG enrichment analysis of 17 revealed that the phosphotransferase system (PTS) pathway was significantly enriched. In addition, compound 17 was found to affect the amino acids biosynthesis and amino acids/carbohydrate metabolism, and the qRT-PCR verified the accuracy of the transcriptome analysis.

Sesquiterpenes from the fruits of Piper longum L. and their anti-inflammatory activity

The fruits of Piper longum are called long pepper, which are well-known culinary spice as well as traditional medicine. In present work, thirteen sesquiterpenes including four undescribed compounds were isolated from P. longum fruits. Compound 1 was a rare methylated bisabolane-type sesquiterpene. Compounds (−)-3 and (+)-3 were a pair of enantiomers of an uncommon humulane which were separated by chiral HPLC. The absolute configurations of compounds 1–3 were confirmed through the means of spectroscopic data analyses, 13C NMR calculations employing DP4+ probability analyses, and ECD calculations. Compounds 2 and 11 presented moderated inhibitory effect on the NO release in LPS-induced RAW264.7 cells with IC50 values of 30.65 ± 0.90 and 38.48 ± 2.42 μM, respectively. Above results enriched the chemical information of P. longum fruits, and meanwhile provided scientific evidences for the anti-inflammatory function of P. longum fruits.

Structurally diversified sesquiterpenoids from Chloranthus henryi and their neuroprotective activities on H2O2 damaged PC12 cells

Fifteen undescribed sesquiterpenoid monomers, including six pairs of sesquiterpenoid enantiomers (1a/1b-3a/3b and 5a/5b-7a/7b) and three analogues (4, 8, and 9), together with two known sesquiterpenoid dimers (10 and 11) were isolated from the whole plant of Chloranthus henryi Hemsl. Their structures were characterized by spectroscopic data analysis, ECD calculations, and single crystal X-Ray diffractions. Compounds 1a and 1b were highly aromatic cadinane-type sesquiterpenoids. At a concentration of 10μM, compounds 8, 10, and 11 exhibited potent neuroprotective activity against H2O2-induced PC12cell damage. Compounds 10 and 11 significantly decreased the level of ROS. In addition, compound 11 increased the levels of p-AMPK, p-SIRT1, and SIRT3 in the H2O2-induced PC12cell damage via activated the AMPK/SIRT signaling pathway.

Prenylated Flavanone Enantiomers with α-Glucosidase Inhibitory Activity from the Root Bark of Morus alba.

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target α-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

A Chiral Hexa-amino Cyclotriphosphazene for Enantioselective Recognition of Small Organic Compounds.

Chiral recognition and separation studies are of paramount importance in research in view of their applications in asymmetric catalysis and substrate recognition in biological processes. The efficiencies of these processes are governed by the subtle differences in noncovalent interactions between the host and guest molecules. Hexakis(organoamino)phosphazenes are versatile building blocks for host-guest chemistry for their ability to act as both the donor and the acceptor of H-bonds. Herein, we report an enantiomeric pair of cyclotriphosphazenes [P3N3(NHR*)6], [R* = (R)-(CH(CH3)Ph)] (1-R) and [(S)-(CH(CH3)Ph)] (1-S), with chiral α-methylbenzylamino substituents. The chiral recognition capabilities of its R-enantiomer were further probed for several chiral organic compounds containing a range of functional groups. Among these, a remarkable guest selectivity (ξ) value of 2506 was observed for binol (BOL) in favor of its R-enantiomer. DFT-optimized structures of the host-guest pairs suggest that the multiple noncovalent interactions between the molecules in the two unique types of binding sites at the phosphazenes play a crucial role in the observed high binding selectivities.

Chiral mono- and dinuclear CoII and CuII enantiomeric pairs with distinct enantiopure N-donor ligands: Presenting highly enhanced third-harmonic generation responses

Employing Co(hfac)2(H2O)2 and Cu(hfac)2(H2O)2 to react with enantiopure bidentate (1LR/1LS) and bis-bidentate (2LR/2LS) N-donor ligands, respectively, four chiral mono- and dinuclear CoII and CuII enantiomeric pairs formulated as M(hfac)2(1LR)/M(hfac)2 (1LS) (M = CoII, R-1-Co/S-1-Co and CuII, R-1-Cu/S-1-Cu) and M2(hfac)4(2LR)/M2 (hfac)4(2LS) (M = CoII, R-2-Co/S-2-Co and CuII, R-2-Cu/S-2-Cu) were isolated, where 1LR/1LS = (−)/(+)-4,5-pinene-2,2ʹ-bipyridine, 2LR/2LS = (−)/(+)-2,5-bis(4ʹ,5ʹ-pinene-2ʹ-pyridyl)pyrazine and hfac− = hexafluoroacetylacetonate. A study of their nonlinear optical responses reveals that dinuclear CoII and CuII enantiomers based on the symmetric 2LR/2LS ligands with larger π-conjugated systems only display very strong THG (third-harmonic generation) responses, while mononuclear ones based on the asymmetric 1LR/1LS ligands with smaller π-conjugated systems simultaneously present THG and SHG (second-harmonic generation) responses. More remarkably, THG intensities of dinuclear R-2-Co and R-2-Cu are 406 and 372 × α-SiO2, being 6.5 and 8.1 times those of the corresponding mononuclear R-1-Co and R-1-Cu, respectively. Furthermore, THG intensities of R-1-Co and R-1-Cu are 6.4 and 5.9 times those of their corresponding precursors Co(hfac)2(H2O)2 and Cu(hfac)2(H2O)2, respectively. The results indicate continuous large enhancements of the THG intensities from the precursors Co(hfac)2(H2O)2 and Cu(hfac)2(H2O)2 to their mononuclear enantiomers and further to their dinuclear species as the conjugation degrees of their ligands increase.

Herbicidal Sorbicillinoid Analogs Cause Lignin Accumulation in Aspergillus aculeatus TE-65L.

Five new sorbicillinoid derivatives, including (±)-aspersorbicillin A [(±)-1], a pair of enantiomers at C-9, and aspersorbicillins B-D (2-4), together with two known analogs (5 and 6) were isolated from the endophytic fungus Aspergillus aculeatus TE-65L. Their structures including absolute configurations were determined by detailed spectroscopic analyses and electronic circular dichroism calculations. The herbicidal activity of sorbicillinoids on the germ and radicle elongation of various weed types was reported for the first time. Compound 1 displayed significant herbicidal activity against Eleusine indica germ elongation (IC50 = 28.8 μg/mL), while compound 6 inhibited radicle elongation (IC50 = 25.6 μg/mL). Both were stronger than those of glyphosate (66.2 and 30.9 μg/mL, respectively). Further transcriptomic and LC-MS/MS metabolomic analysis indicated that 6 induced the transcriptional expressions of genes related to the lignin biosynthetic pathway, resulting in lignin accumulation. Transmission electron microscopy confirmed the cell wall thickening of seeds treated with 6, suggesting weed growth inhibition. This study reveals new lead compounds for fabricating natural herbicides and expands the agricultural use of sorbicillinoid analogs.

Structural and Magnetic Properties of Dimeric Capsule Assemblies Formed by Cyclic Trinuclear Complexes.

Cyclic trinuclear homo-metal complexes, [{Fe(L3+2Br)py}3] (1) and [{Mn(L3+2Br)}3(py)2 MeOH] (2), along with a hetero-metal complex, [FeMn2(L3+2H)3(DMF)3] (3), were synthesized using asymmetric ditopic ligands (H3L3+2H: 2-(2-hydroxyphenyl)-6-ol-5-(salicylideneamino)benzoxazole, H3L3+2Br: 2-(2-hydrox-5-bromoyphenyl)-6-ol-5-(5-bromosalicylideneamino)benzoxazole). The molecular structure of 1 is characterized by a tripod structure with three-fold symmetry, where an enantiomer pair forms a dimeric capsule with dimensions of approximately 3 × 1.6 × 1.6 nm3. Complexes 2 and 3, which lack three-fold symmetry, exhibit similar molecular structures to previously reported complexes with these ligands, but do not form a capsule structure. Magnetic measurements of 1-3 reveal the presence of significantly weak antiferromagnetic interactions between the metal ions.

Enantioselective optical trapping of chiral nanoparticles by tightly focused fractional vector beams

Enantiomers exhibit markedly different chemical properties although they have the same chemical structure. The identification and separation of enantiomers have been significant issues in biomedicine and chemistry. In this work, we proposed an optical method that selective trapping of enantiomers by using tightly focused fractional vector beams (FVBs). In our proposed model, such a focused beam forms multiple local optical chirality densities (OCDs) with opposite signs at the focal plane. We found that focused FVBs can stably trap the enantiomers at the local positions with the minimum or maximum OCD according to the handedness of enantiomers. The positions and numbers of the trapped enantiomers have a relationship with the fractional topological charge. These results indicate that tightly focused FVBs are an all-optical method capable of dynamic modulation and achieving precise and stable trapping of multiple pairs of enantiomers. Our findings have practical applications in the multi-throughput and multi-sample manipulation of chiral materials.