Fluorescence Imaging Research Articles

A dual-responsive fluorescent probe for cellular hypoxia and tumor imaging based on nitroreductase and viscosity synergy

Nitroreductase (NTR), an enzyme that operates within the cytoplasm, relies on flavin mononucleotide or flavin adenine dinucleotide for its activity. In tumor cells, hypoxic conditions often lead to an increase in NTR levels. Consequently, the development of fluorescent probes capable of detecting NTR activity is crucial for the monitoring of hypoxia in biological systems. This study presents the one-step synthesis of a near-infrared fluorescent probe, DSM-NO2. The probe was highly sensitive to NTR and caused a fluorescence enhancement by 50-fold, with a detection limit as low as 1 ng/mL. Under hypoxic conditions in tumor cells, not only does NTR increase, but the cellular viscosity also rises. In high-viscosity environments, the fluorescence enhancement could reach up to 220-fold, and the detection limit could be further reduced to 55 pg/mL. The reaction mechanism was thoroughly investigated using mass spectrometry, molecular docking, and theoretical calculations. Moreover, the probe was successfully applied in the real-time monitoring and visualization analysis of NTR during the growth of Escherichia coli and in the hypoxic state of cancer cells. Additionally, through nebulized inhalation, the probe was successfully employed for in situ fluorescent imaging studies in a murine model of lung cancer.

Audit of Antimicrobial Prescribing Trends in 1447 Outpatient Wound Assessments: Baseline Rates and Impact of Bacterial Fluorescence Imaging.

Background/Objectives: In the field of wound care, the prescription of antibiotics and antimicrobials is haphazard and irrational, which has led to unchecked overprescribing. Recent Joint Commission guidelines mandate that hospital outpatient clinics develop and implement antimicrobial stewardship programs (ASPs). Yet few ASPs exist in wound clinics across the United States (US). Understanding baseline prescribing practices and rates in the US is a critical first step toward rational antimicrobial use and effective ASPs. Methods: This prospective study was conducted across eight outpatient wound clinics from January-December 2022. Data from consecutive patients attending single-time-point initial visits were recorded, including clinical findings, antimicrobial prescribing trends, and sampling practices. Results: A total of 1438 wounds were included; 964 were assessed by clinical examination (standard of care, SoC), and 474 by clinical examination plus fluorescence imaging. SoC patients were prescribed more concurrent medications on average than fluorescence patients (1.4 vs. 1 per patient). Prescriptions were preferentially topical in the fluorescence group (92% vs. 64%, p > 0.0001), and systemic antibiotics represented 36% of the single items prescribed under SoC (vs. 8% in fluorescence group p < 0.0001). Conclusions: Fluorescence imaging provided objective and actionable information at the bedside, which led to a decrease in the use of antibiotics. Real-time diagnostic technologies are essential in establishing a meaningful ASP.

Quantitative assessment of early caries lesion activity using novel dye-enhanced fluorescence imaging

ObjectivesThis study aimed to evaluate the validity of the dye-enhanced quantitative light-induced fluorescence (DEQLF) method for assessing early enamel caries activity. MethodsSeventy extracted human teeth with early enamel caries on smooth surfaces were included. Two dentists evaluated the caries activity using the Nyvad system followed by the DEQLF method. The teeth were hydrated with distilled water for 60 s, dehydrated with compressed air for 10 s, and stained with 100 μM fluorescein sodium solution for 10 s. White and fluorescent images were captured using a QLF-D 2+ Billuminator. The change in fluorescence (ΔΔG) was calculated using image analysis software. Independent-sample t-tests were performed to evaluate the difference in ΔΔG between active and inactive lesions for both DEQLF and conventional quantitative light-induced fluorescence (QLF) methods. Receiver operating characteristic (ROC) curve analysis was used to assess the validity of ΔΔG for distinguishing lesion activity using the area under the ROC curve (AUROC). ResultsAmong the 70 caries lesions, 33 were active and 37 were inactive. Using the DEQLF method, the ΔΔG for active lesions (3.8 ± 5.6) was significantly higher than that for inactive lesions (1.0 ± 2.5) (P < 0.05). With the conventional QLF method, there was no significant difference in ΔΔG between active (-1.1 ± 1.7) and inactive (-1.3 ± 1.7) lesions. DEQLF-derived ΔΔG demonstrated an AUROC of 0.72, a sensitivity of 0.67, and a specificity of 0.76. ConclusionsApplying the DEQLF method to human teeth enabled the quantitative assessment of lesion activity based on dye penetration. DEQLF-derived ΔΔG values showed significant differences based on lesion activity status and demonstrated high validity in distinguishing lesion activity. Clinical significanceClinicians can use the DEQLF method, which involves applying a fluorescent dye for 10 s prior to conventional QLF, to objectively quantify and distinguish the activity status of early enamel caries, potentially replacing the traditional reliance on subjective visual assessments.

Selective Interaction of Chiral Carbon Dots with Nucleic Acids: A Promising Nanosensing Platform.

Carbon dots (CDs) represent an emerging class of nanomaterials that combine outstanding photoluminescent properties with low toxicity and excellent biocompatibility. These unique features have garnered significant interest for potential applications in sensing as well as nanovectors for bioactive compounds. Within this context, the possibility of synthesizing chiral carbon dots (CCDs) has paved the way for a plethora of bioapplications in their interaction with chiral biomolecules. In this study we report the synthesis and characterization of CCDs with opposite chiralities and their selective interaction with nucleic acids. A systematic study on their interaction with different oligonucleotides (ODNs) using UV-vis, photoluminescence, and circular dichroism analyses highlighted how the chiral surface of the CCDs induces distinct spectroscopic responses in CCDs-ODN conjugates. These findings establish the foundation for innovative applications of CCDs as nanosensors and nanocarriers for nucleic acids. Additionally, the antioxidant properties of CCDs were investigated, highlighting their dual potential as both sensing and preservative nanomaterials for genetic material. Our results suggest significant implications for the development of chiral-specific diagnostic tools, drug delivery systems, and therapeutic agents. Furthermore, these properties open new avenues for the use of CCDs in antibiotic residue detection, fluorescence imaging, and photodynamic therapy.

Indocyanine Green (ICG) Fluorescence in the Assessment of Vascularity of Anastomotic Margins in Colorectal Surgery in a Lower Middle-Income Country (LMIC) Hospital.

One of the uses of indocyanine green (ICG) in the surgical field is the evaluation of the anastomotic margins in colorectal surgery. This is of particular importance because fluorescence imaging may aid in detecting vascular compromise, allowing the surgeon to change the resection margin thereby decreasing the chance of an anastomotic leak. To date, there has been no study with its use locally. This study aimed to determine whether the use of ICG can safely identify if the margins of resection are well-vascularized in patients undergoing left-sided colon or rectal surgery, which in turn may reduce anastomotic leak rates. Through a retrospective study design, the investigators gathered data of patients who underwent left-sided colon or rectal surgery. The groups were divided into those with and without the use of ICG and a comparative data on the anastomotic leak rates were analyzed. Eighty-six (86) patients with similar patient characteristics, tumor staging, and surgical approach were compared. Both the leak rates identified during the initial hospital stay and at 30 days post-operatively were lower in those where ICG was used (p=0.035, p=0.047, respectively) than those where ICG was not used. ICG fluorescence imaging may reduce the anastomotic leak rates in patients undergoing colorectal surgery.

Thiophene appended schiff base probe for selective ‘turn-on’ response for copper (ii) ion and their applications in live cell imaging Thiophene appended schiff base probe for selective ‘turn-on’ response for copper (ii) ion and their applications in live cell imaging

In this research, we have synthesized a thiophene Schiff base from 5-phenyl thiophene-2-carboxaldehyde and 2-thiophene carboxylic acid hydrazide and characterized by using FT-IR NMR, HRMS and SC-XRD analysis techniques. The probe exhibited a selective turn-on fluorescence response for Cu2+ over 20 other common metal ions in a CH3CN (9:1, v/v) solution. The Job’s plot represents a 1:1 binding complexation mode and further DFT study was carried out to aid in understanding the geometric structure and interaction of the ligand and Cu2+. The detection limit (LOD) and limit of quantification (LOQ) were found to be 20 nM and 69 nM respectively. Furthermore, the probe’s sensing ability was tested in HeLa cells and their fluorescence imaging also supported the effective turn-on response towards Cu2+ ion.

A Water‐Soluble Fluorescent Probe Derived from Pyridine‐2,6‐Dicarboxylic Acid: Synthesis, Interaction with Ions, and Two‐Photon Microscopy

AbstractTwo‐photon excited fluorescence is a process in which the excited fluorophore relaxes and emits fluorescence after two‐photon absorption. Combined with appropriate two‐photon fluorescent probes, two‐photon microscopy enables observation deep inside tissue without damage. Former reports showed that the two‐photon absorption cross sections of donor–acceptor (D–A) dipoles, as well as D‐π‐D and D–A–D quadrupoles can be strengthened by using strong D–A groups. In this study, a novel water‐soluble fluorescent probe with D‐π‐A structure containing pyridine‐2,6‐dicarboxylic acid unit was synthesized. The maximum excitation wavelength and emission wavelength of the probe in aqueous solution were 328 nm and 471 nm, respectively. The fluorescence emitted by the probe can be quenched by various metal cations. The pyridyl N and carboxyl O in the probe formed chelates with Cu2+, which resulted in a fluorescence quenching response, and showed a linear relationship between fluorescent intensity and Cu2+ concentration with wide linear range and low limit of detection. CCK‐8 tests showed the probe had no obvious toxicity to 4T1 cells in the range of 0.4–50 μmol L−1, and the cell survival rate was above 86 %. The probe had a large two‐photon absorption cross section ranging from 680 nm to 820 nm. The two‐photon absorption cross section reached 100 GM at 760 nm of excitation wavelength. By means of microscopic imaging of 4T1 cells stained with the probe, one‐photon fluorescence represented blue emission, while two‐photon fluorescence represented bright green emission. The probe was proved to have good cell permeability, and preferred to target nucleus, showing application potential in two‐photon fluorescence imaging technology.

Multiscale study on fatigue healing performance and molecular healing behavior of self-healing SBS modified bitumen

Self-healing polymer modified bitumen based on dynamic chemical bonds is a potential approach to improve the durability of bitumen pavement and save fossil energy. Herein, a novel self-healing SBS modified bitumen on the basis of dynamic disulfide bonds and hydrogen bonds was prepared. Firstly, an aliphatic disulfide (A-ALD) with disulfide bonds and hydrogen bonds was synthesized. Then A-ALD/SBS modified bitumen (A-ALD/SMB) was prepared by blending A-ALD and SBS modified bitumen. The chemical structure and microstructure of A-ALD/SMB were evaluated. In addition, the self-healing performance of A-ALD/SMB at the macroscopic scale and the self-healing behavior at the molecular scale were investigated by a combination of fatigue healing test and molecular dynamics (MD) simulation. The chemical structure analysis showed the formation of disulfide bonds and hydrogen bonds in A-ALD, and A-ALD was successfully attached to the CC bonds in SBS. Fluorescent images revealed that a better network structure appeared in A-ALD/SMB and formed a two-phase continuous morphology. The optimal dosage of A-ALD in SBS modified bitumen was 0.6 %. The fatigue healing test results indicated that A-ALD markedly enhanced the self-healing ability of SBS modified bitumen, and prolonging resting time and raising healing temperature can increase the self-healing performance of A-ALD/SMB. When the damage degree, healing temperature, and resting time were 30 %, 30 °C, and 60 min, respectively, the healing rate of A-ALD/SMB was 98.5 %, which was 30.2 % higher than SMB. The MD simulation results showed that the A-ALD enhanced the molecular diffusion capacity of SBS modified bitumen, and crack healing time of A-ALD/SMB was earlier than that of SMB under the same conditions. When the healing temperature was 40 °C, the time for the A-ALD/SMB and SMB molecular chain segments to start contacting and healing was 27 ps and 49 ps, respectively, which was improved by 44.9 % for A-ALD/SMB compared to SMB. Furthermore, the self-healing behavior of A-ALD/SMB at the molecular scale was consistent with the self-healing performance at the macroscopic scale under different healing temperatures and damage degrees. This study provided a theoretical basis for exploring the self-healing mechanism of SBS modified bitumen.

Fluorescent Self-Assembled Complexes Based on Glyco-Functionalized G-Quadruplexes as a Targeted Delivery Platform.

Targeted delivery systems combined with the stimuli-responsive release of drug molecules hold noteworthy promise for precision medicine, enabling treatments with enhanced effectiveness and reduced adverse effects. An ideal drug delivery platform with versatile targeting moieties, the capability of combinational payloads, and simple preparation is highly desirable. Herein, we developed pH-sensitive fluorescent self-assembled complexes (SACs) of a galactose-functionalized G-quadruplex (G4) and a coumarin carboxamidine derivative as a targeted delivery platform through the nanoprecipitation method. These SACs selectively targeted hepatocellular carcinoma (HepG2) cells in fluorescence imaging after a short incubation and exerted specific anticancer effects in an appropriate dose range. Co-delivery of 1 μM prodrug floxuridine oligomers and 16 μg/mL SACs (minimal hemolytic effect) significantly reduced the cytotoxicity of the nucleoside anticancer drug on normal cells (NIH/3T3), kept up to 70% alive after 72-h incubation, and improved anticancer efficacy compared to SACs alone. This strategy can be extended to ratiometric multidrug delivery through self-assembly for targeted combinational therapy.

Multiplexed Shortwave Infrared Imaging Highlights Anatomical Structures in Mice

AbstractMultiplexed fluorescence in vivo imaging remains challenging due to the attenuation and scattering of visible and traditional near infrared (NIR‐I, 650–950 nm) wavelengths. Fluorescence imaging using shortwave infrared (SWIR, 1000–1700 nm, a.k.a. NIR‐II) light enables deeper tissue penetration due to reduced tissue scattering as well as minimal background autofluorescence. SWIR‐emitting semiconductor quantum dots (QDs) with tunable emission peaks and optical stability are powerful contrast agents, yet few imaging demonstrations exclusively use SWIR emission beyond two‐color imaging schemes. In this study, we engineered three high quality lead sulfide/cadmium sulfide (PbS/CdS) core/shell QDs with distinct SWIR emission peaks ranging from 1100–1550 nm for simultaneous three‐color imaging in mice. We first use the exceptional photostability of QDs to non‐invasively track lymphatic drainage with longitudinal imaging, highlighting the detailed networks of lymphatic vessels with widefield imaging over a 2 hr period. We then perform multiplexed imaging with all three QDs to distinctly visualize the lymphatic system and spatially overlapping vasculature networks, including clearly distinguishing the liver and spleen. This work establishes optimized SWIR QDs for next generation multiplexed and longitudinal preclinical imaging, unlocking numerous opportunities for preclinical studies of disease progression, drug biodistribution, and cell trafficking dynamics in living organisms.

Super-resolved fluorescence imaging utilising accessible stochastic optical reconstruction microscopy (easySTORM) implemented on a low-cost, modular open-source (openFrame) microscope

Abstract Optical super-resolution microscope is a powerful tool for the life sciences, including cell biology and pathology yielding information on, e.g., biological structure and protein distribution in the nano-scale range. In recent years, there has been an exponential rise in the interest to apply super-resolution microscopes in diverse areas, but its wider utility is hindered by the cost of purchasing and maintaining super-resolved microscopes. In this paper we present the implementation of easySTORM, an accessible implementation of stochastic optical reconstruction microscopy (STORM) at Indian Institute of Technology Guwahati (IITG), India, in a flexible, user friendly and cost-effective manner using a state-of-the-art, modular, open-source, optical microscope platform called: "openFrame". Providing comparable imaging performance to commercial optical super-resolution microscopes, the openFrame-based implementation of easySTORM uses in-expensive multimode diode lasers and industry grade CMOS cameras, and the open-source and modular nature of the instrument makes it easy to maintain and to upgrade. To demonstrate its successful implementation at IITG, we image quantum dots and actin-tubulin structure in both normal and cancer cells, resolved features separated by a few tens of nanometers. This work demonstrates that openFrame-enabled easySTORM instrumentation can be widely accessible to provide affordable, research grade super-resolution microscopy capability for academic and medical research.&amp;#xD;

Red-Emitting Coumarin-Derived fluorescent probe for thiol detection and indirect recognition of β-Lactamase

Biothiols, comprising cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play a pivotal role in maintaining the delicate redox balance essential for life processes, intricately intertwined with the well-being of living organisms. Deviations in their concentrations can precipitate a range of diseases. Herein, we presented a novel fluorescent probe, DIcou-DNBS, derived from coumarin, which possessed red emission and a substantial Stokes shift (122 nm), tailored for biothiol detection. DIcou-DNBS demonstrated rapid-responsiveness (6 min) towards Cys, Hcy and GSH with detection limits of 0.015 µM, 0.032 µM and 0.059 µM, respectively. Furthermore, its excellent biocompatibility enabled successful applications in biothiol fluorescence imaging of living cells and zebrafish. Beyond biothiol sensing, DIcou-DNBS leveraged its unique property to indirectly detect β-lactamases, making it a valuable tool in inhibitor screening and susceptibility testing of both sensitive (Staphylococcus aureus ATCC 29213) and resistant (Enterobacter cloacae ATCC 13047) bacterial strains. This assay system anticipates to furnish a potent instrument for visualization studies across biological and medical domains.

Dual-responsive two-photon probe for specific lipid droplets near-infrared fluorescence imaging in the brain of epileptic mice

Abnormal lipid metabolism in glial cells is a key pathological feature of epilepsy. The identification of lipid droplets (LDs) is essential for investigating lipid metabolism, disease progression, and potential therapeutic interventions. Two-photon imaging technology enables real-time visualization of the spatial distribution and temporal dynamics of LDs in epilepsy models. In this study, we developed a novel two-photon excited dual-responsive near-infrared fluorescent probe, CabA, based on viscosity and polarity, to monitor dynamic changes in LDs. The fluorescence of CabA at 670 nm exhibits a significant increase in response to low polarity and high viscosity due to the twisted intramolecular charge transfer and intramolecular charge transfer mechanisms. The LDs-targeting capability of CabA at the cellular level and the process of LDs generation between neurons and astrocytes during the pathological advancement of epilepsy have been validated. In situ synchronous imaging experiments in epileptic and normal mice using CabA revealed abnormal LDs accumulation in the brain during seizures. Two-photon fluorescence imaging further demonstrated LDs accumulation in the brains of epileptic mice at a penetration depth of 100 μm. This study offers a valuable tool for enhancing the understanding of LDs in physiological and pathological processes, potentially aiding in the early diagnosis of epilepsy.

Highly specific GSH-triggered bifunctional molecules to enable precise imaging and targeted therapy of cancer

The utilization of diagnostic-integrated molecules can enable targeted delivery and controlled release to significantly enhance therapeutic effectiveness and minimize toxic effects. Herein, we developed a novel class of glutathione (GSH)-activated bifunctional molecules that respond to elevated levels of GSH in tumor microenvironment. These bifunctional molecules retained the pharmacodynamic effects of parent molecules and mitigated cytotoxicity. Meanwhile, controlled release was monitored using fluorescent signals, enabling detection of drug distribution and accumulation in situ and in real time. Moreover, the correlation between GSH levels and fluorescence intensity offers the possibility of monitoring the effectiveness of responsive drugs. In conclusion, bifunctional molecules, as novel diagnostic-integrated molecules with both fluorescence imaging and therapeutic effects, exhibited potential applications in cancer therapy and imaging.

Intelligent luminescent microneedle and hydrogel patches for visual monitoring of lactic acid and dopamine

Dopamine (DA) and lactic acid (LA) are vital biochemical indicators of neurotransmitters and tissue oxidation monitoring, which can comprehensively assess the neurological and physical conditions. The combination of fluorescent sensor and artificial intelligence shows great potentials in monitoring and quantizing of human biochemicals. Herein, a Tb3+ functionalized hydrogen-bonded organic framework material (Tb@ME-TPA) is synthesized based on coordination post-synthesis modification, and its sensing mechanism for DA and LA is investigated by experiments and theoretical calculations. For visual detection of DA and LA in actual environment, Tb@ME-TPA is fabricated into PVA films and microneedle patches, which hold the advantages of high efficiency, sensitivity and anti-interference. In addition, microneedles-based probe for minimally invasive sensing of DA in the dermal interstitial fluid along with a portable smartphone platform are designed to monitor with high accuracy. Furthermore, an intelligent back-propagation neural network model based on fluorescence image recognition is constructed, which can combine optical sensing of LA with deep learning by computer, greatly improving the efficiency and accuracy. This work not only presents a novel idea for the integration of fluorescent materials, smartphones and deep learning, but also provides an effective method for the prediction of diseases as well as the real-time monitoring of overall well-being.

Sensitive Cancer Hypoxia Detection via a Dual-Locking Fluorescence Response System Using Two Hypoxia Indicators.

Hypoxia is intricately associated with various diseases, including ischemia, vascular disorders, and cancer. Particularly in cancer cells, hypoxia promotes tumor growth, cell proliferation, migration, and invasion and enhances treatment resistance, making its detection crucial for cancer diagnosis and therapy. However, methods for detecting hypoxia are limited, often relying on single-detection systems. In this study, we developed a dual-lock-based fluorescent probe that selectively exhibits strong green fluorescence under hypoxic conditions due to simultaneous activity of nitroreductases (NTRs) and hydrogen sulfide (H2S), with a high signal-to-background ratio. The biocompatibility and photophysical properties of the probes were thoroughly investigated through both extracellular and intracellular experimental analyses. Among the synthesized naphthalimide-based probes, the dual-detection probe DNNC demonstrated excellent selectivity and sensitivity to the simultaneous activity of NTR/H2S compared to other single-detection probes. The performance of DNNC was applied to various organ-derived cancer cells and tumor tissue models such as HeLa cell sparoids, enabling spatiotemporal confocal fluorescence imaging and quantitative analysis of hypoxic levels in cancer. Our development of DNNC is expected to significantly advance cancer diagnosis and treatment by molecularly detecting hypoxia associated with cancer aggressiveness, therapy resistance, and unfavorable prognosis.

Fast and Artifact-Free Excitation Multiplexing Using Synchronized Image Scanning.

Multicolor fluorescence microscopy is an essential tool to visualize structures and dynamics in the life and materials sciences. However, the near-simultaneous acquisition of labels differing in excitation spectrum is difficult and renders such measurements prone to artifacts. We present a simple strategy to provide quasi-simultaneous fluorescence imaging with multiple excitation wavelengths by using an optical element to displace the sample image on the sensor at a rate that is much faster than the image acquisition rate and synchronizing this with the illumination. The emission elicited by the different wavelengths can then be encoded into the point-spread function of the imaging or visualized as multiple distinct images. In doing so, our approach can eliminate or mitigate artifacts caused by temporal aliasing in conventional sequential imaging. We demonstrate the use of our system to uncover hidden emissive states in single quantum dots and for the imaging of Ca2+ signaling in neurons.

Modeling the differential functional responses and selectivity of a marine copepod to nano/microplastics in mixture

Nano- and microplastics (NMPs) pollution is widespread in the oceans, posing potential risks to marine species. This study examined the accumulation capacity and selectivity potentials of NMPs by a marine copepod Parvocalanus crassirostris under different food mixtures by modeling the combined biokinetic and functional response. We investigated two sizes of NMPs (200 nm and 5 µm) across a concentration gradient (0 - 5000 µg/L) and varying diatom abundances (0, 104, 105 cells/mL). Fluorescence imaging and quantification revealed that P. crassirostris actively ingested NMPs at low concentration. Accumulation increased with NMPs concentration but eventually saturated due to gut capacity limits, following a Holling type II functional response (i.e., hyperbolic curve). Our novel functional response model estimated the key parameters and demonstrated that the maximum accumulation reached 5.3 % of dry weight with averaged half-saturation constants of 229 µg/L. The size of NMPs did not significantly affect the total accumulation or satiety levels. The presence of diatoms influenced the feeding selectivity and decreased the microplastic accumulation by 73 % at 105 cells/mL, while facilitating nanoplastic accumulation by 81 % at 104 cells/mL. This study enhanced our understanding of NMPs bioavailability and environmental fate in marine ecosystems.

Synthesis of Alkene Atropisomers with Multiple Stereogenic Elements via Catalytic Asymmetric Rearrangement of 3‐Indolylmethanols

AbstractCatalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3‐indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non‐covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3‐indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry.

Synthesis of Alkene Atropisomers with Multiple Stereogenic Elements via Catalytic Asymmetric Rearrangement of 3-Indolylmethanols.

Catalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3-indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non-covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3-indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry.