Spiro Structure Research Articles

Spiro‐Based Thermally Activated Delayed Fluorescence Emitters for Organic Light‐Emitting Diodes

AbstractSpiro structures, possessing unique π‐electron systems, large steric hindrance, high glass transition temperature, and chemical stability, serve as critical structural building blocks in constructing thermally activated delayed fluorescence (TADF) emitters. The incorporation of various heteroatoms such as oxygen, sulfur, and nitrogen in 9,9′‐spirobifluorene generates diverse spiro structures like spiro[fluorene‐9,9′‐xanthene], spiro[fluorene‐9,9′‐thioxanthene], and spiro[acridine‐9,9′‐fluorene]. Based on the charge transfer characteristics, TADF emitters built upon spiro structures can be classified into various types, including twisted intramolecular charge transfer, through‐space charge transfer, multiresonance, and exciplex‐type TADF emitters. This review systematically highlights the recent progress in the research on TADF emitters comprised of spiro‐structured aromatics. It intricately explores the molecular design strategies, material synthesis methods, understanding of photophysical attributes, and analysis of organic light‐emitting diode performance. Concurrently, it sketches out the challenges faced in the commercial application stage while providing an outlook for potential research trajectories.

From Intercalation to External Binding: Ru(II) Complexes with a Spiro Ligand for TAR RNA Selective Binding and HIV-1 Reverse Transcriptase Inhibition.

As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.

Carbonyl‐Based Narrowband Emitters Peripherally Decorated by Sulfone‐Containing Spiro Structures

AbstractSulfone group plays a pivotal role in narrowing emission spectra, while, precise modification with sulfone group for carbonyl‐based narrowband emitters that maintain high color purity remains challenging. Herein, a comprehensive exploration of the function of the sulfone group is performed with various sulfur valences and positions fused into traditional carbonyl‐based narrowband emission unit QAO, namely SpiroS‐QAO, SpiroSO2‐QAO, SpiroO‐QAO, and SpiroOSO2‐QAO. A rigid molecular skeleton with a spiro structure as an intramolecular lock enables the four emitters to exhibit narrowband emissions. After full oxidization of sulfur, the emission band of SpiroSO2‐QAO is further narrowed, with full width at half maximum of 32 nm, compared to that of 43 nm for sulfane‐decorated SpiroS‐QAO, which is attributed to the suppressed C─S bond‐length variation by the introduction of sulfone group. Nearly identical spectra of SpiroO‐QAO and SpiroOSO2‐QAO suggest that the sulfone group should be directly linked to the emission core to maximize its function. Maximum external quantum efficiencies of 30.8%, 30.3%, and 29.2% are achieved for SpiroO‐QAO, SpiroOSO2‐QAO, and SpiroS‐QAO‐based sensitized organic light‐emitting diodes with highly efficient thermally activated delayed fluorescence assistant host. These results offer a comprehensive understanding of the sulfone group embedded into the narrowband emission core with respect to the narrowing emission band.

Boosting the Reactivity of Bis-Lactones to Enable Step-Growth Polymerization at Room Temperature.

The development of new sustainable polymeric materials endowed with improved performances but minimal environmental impact is a major concern, with polyesters as primary targets. Lactones are key monomers thanks to ring-opening polymerization, but their use in step-growth polymerization has remained scarce and challenging. Herein, we report a powerful bis(γ-lactone) (γSL) that was efficiently prepared on a gram scale from malonic acid by Pd-catalyzed cycloisomerization. The γ-exomethylene moieties and the spiro structure greatly enhance its reactivity toward ring-opening and enable step-growth polymerization under mild conditions. Using diols, dithiols, or diamines as comonomers, a variety of regioregular (AB)n copolymers with diverse linkages and functional groups (from oxo-ester to β-thioether lactone and β-hydroxy-lactame) have been readily prepared. Reaction modeling and monitoring revealed the occurrence of an original trans-lactonization process following the first ring-opening of γSL. This peculiar reactivity opens the way to regioregular (ABAC)n terpolymers, as illustrated by the successive step-growth polymerization of γSL with a diol and a diamine.

Microwave Facilitated Discovery of Substituted 1,2,4-triazaspiro[4.5] dec-2-en-3-amines: Biological and Computational Investigations

Background: Tuberculosis is an effectual infectious disease caused by the spread of tu-bercular bacteria within the lungs via droplets of coughs and sneezes. In 2021, 1.6 million people died due totuberculosis, which is the 13th leading killer disease and 2nd leading after COVID-19 infectious disease. Objective: Many drugs are available as antitubercular drug, but still, requires more efficacious drug molecules with lower toxicity, side effects and small-sized molecules. To fulfill said prospective, computational study such as molecular docking and ADMET studies guides towards an ideal drug molecule with small -sized, unique spiro structures. Methods: Conventional and microwave-initiated Reaction of cyclohexanone, hydrazine carbothio-amide, and 2-amino-4-methoxy-6-methyl-1,3,5-triazine affords compound 1, which is subjected to the Schiff base reaction with diverse aldehydes. All structures are defined using IR, 1H NMR, 13C NMR, and mass spectroscopy. The entire series is exposed to in vitro antibacterial and antitubercu-lar and in silico molecular docking and ADMET studies. Results: Compounds 2c and 2b have been established to be potential antibacterial agents, whereas compounds 2d, 2e, 2j, 2k and 2l are extremely effective against tubercular strains. Furthermore, molecular docking of related molecules is performed, and compounds 2d, 2e, 2j, 2k, and 2l have higher affinities toward antitubercular proteins. ADMET parameters such as water solubility, SA score, PCaco2 value, and TPSA values are satisfactory. Conclusion: The microwave method has been proven to be a greener method as compared to the con-ventional heating method. Comparative results of in vitro analysis are obtained with referenced anti-bacterial drugs and antitubercular drugs. In silico observations supports their in vitro assessments. Appraisal obtained from the ADMET study leads to the formation of ideal drug molecules.

Introducing Spiro-locks into the Nitrogen/Carbonyl System towards Efficient Narrowband Deep-blue Multi-resonance TADF Emitters.

The current availability of multi-resonance thermally activated delayed fluorescence (MR-TADF) materials with excellent color purity and high device efficiency in the deep-blue region is appealing. To address this issue in the emerged nitrogen/carbonyl MR-TADF system, we propose a spiro-lock strategy. By incorporating spiro functionalization into a concise molecular skeleton, a series of emitters (SFQ, SOQ, SSQ, and SSeQ) can enhance molecular rigidity, blue-shift the emission peak, narrow the emission band, increase the photoluminescence quantum yield by over 92 %, and suppress intermolecular interactions in the film state. The referent CZQ without spiro structure has a more planar skeleton, and its bluer emission in the solution state redshifts over 40 nm with serious spectrum broadening and a low PLQY in the film state. As a result, SSQ achieves an external quantum efficiency of 25.5 % with a peak at 456 nm and a small full width at half maximum of 31 nm in a simple unsensitized device, significantly outperforming CZQ. This work discloses the importance of spiro-junction in modulating deep-blue MR-TADF emitters.

Introducing Spiro‐locks into the Nitrogen/Carbonyl System towards Efficient Narrowband Deep‐blue Multi‐resonance TADF Emitters

AbstractThe current availability of multi‐resonance thermally activated delayed fluorescence (MR‐TADF) materials with excellent color purity and high device efficiency in the deep‐blue region is appealing. To address this issue in the emerged nitrogen/carbonyl MR‐TADF system, we propose a spiro‐lock strategy. By incorporating spiro functionalization into a concise molecular skeleton, a series of emitters (SFQ, SOQ, SSQ, and SSeQ) can enhance molecular rigidity, blue‐shift the emission peak, narrow the emission band, increase the photoluminescence quantum yield by over 92 %, and suppress intermolecular interactions in the film state. The referent CZQ without spiro structure has a more planar skeleton, and its bluer emission in the solution state redshifts over 40 nm with serious spectrum broadening and a low PLQY in the film state. As a result, SSQ achieves an external quantum efficiency of 25.5 % with a peak at 456 nm and a small full width at half maximum of 31 nm in a simple unsensitized device, significantly outperforming CZQ. This work discloses the importance of spiro‐junction in modulating deep‐blue MR‐TADF emitters.

Relationships between the structure of spiro[[2]benzopyran-1,1′-cyclohexan]-4′-amines and their σ1 receptor affinity and selectivity

A set of 31 secondary and tertiary amines of type 5 was synthesized by reductive amination of ketones 6 and 22–24 with amines and NaBH(OAc)3. Usually, cis-configured amines display higher σ1 affinity than trans-configured analogs. Elongation of the distance between the amino moiety and the terminal phenyl ring from one to three CH2 moieties increased the σ1 affinity. Tertiary amines with one small N-substituent are well tolerated by the σ1 receptor. Within this class of compounds, the cyclohexylpiperazines trans-21a (Ki(σ1) = 6.3 nM) and cis-21b (Ki(σ1) = 4.4 nM) show very high σ1 affinity and selectivity over related receptors (σ2 receptor, MOR, DOR, KOR). On the other hand, the cis-configured p-fluorophenylpiperazine cis-20b was identified as high-affinity σ2 ligand (Ki(σ2) = 11 nM) with considerable selectivity over σ1 receptor, MOR, DOR and KOR. Very high MOR affinity (Ki = 2.3 nM), but only moderate affinity towards both σ receptor subtypes was detected for the cis-configured piperidine cis-17b without aryl moiety at the piperidine ring. Thus, cis-17b represents a novel MOR chemotype with high MOR affinity and high selectivity over both σ receptors, DOR and KOR.

Constructing Four-Membered Heterocycles by Cycloisomerization

Four-membered heterocycles are highly sought after in modern drug discovery as they provide beneficial properties to the target molecules. Despite tremendous efforts by the synthetic research community, there is a need for a simple and new method to incorporate these motifs into the design molecules. Herein, we reveal a cycloisomerization strategy for the construction of oxetane and azetidine rings via metal hydride hydrogen atom transfer/radical polar crossover, which is challenging both enthalpically and entropically. This method is suitable for synthesizing polysubstituted four-membered heterocycles. This mild and functional-group tolerant reaction has a broad substrate scope, including the spiro structure, which is an important motif in drug discovery research. Various four-membered heterocyclic building blocks can be synthesized by product derivatization. We also discuss the reaction mechanism, focusing on the four-membered ring formation, by deuterium experiments and DFT studies.

Tetrahomo corona[4]arene-based spirophanes: synthesis, structure, and properties.

In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo corona[4]arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient SNAr reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo i-corona[4]arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry.

Indirect Control of Donor/Acceptor Interactions for Highly Efficient Space‐Confined Thermally Activated Delayed Fluorescence Emitters

AbstractConformational engineering is essential to further reinforce the luminescent properties of thermally activated delayed fluorescence (TADF) materials featuring through‐space charge transfer (TSCT) characteristics. Herein, two TSCT‐TADF emitters (8MeDM‐B and 8FDM‐B) with the methyl and fluorine moieties substituted at the C8 site of the rigid spiro‐fluorene bridge is reported. Derivation of the C8 site is first proposed to control the molecular configuration with the ability to indirectly tune the intramolecular interaction between donor and acceptor groups. As a result, 8MeDM‐B and 8FDM‐B both present small singlet‐triplet energy gaps, fast reverse intersystem crossing rates, and high photoluminescence quantum yields. Interestingly, the smaller fluorine atom not the bigger methyl group exhibits more evident electrostatic repulsive force onto the central donor and thus rectifies the central spiro structure. Consequently, the high external quantum efficiency values of 28.8% and 31.7% for 8MeDM‐B and 8FDM‐B‐based electroluminescence devices are achieved, respectively. This study offers a measure for enhancing TSCT‐TADF emitters without directly modifying the donor or acceptor.

Solution-processable through-space charge-transfer emitters via solubilizing groups modification

The solubility of luminescent materials is a key parameter to improve the electroluminescent performances of solution-processed organic light-emitting diodes (OLEDs). The through-space charge transfer (TSCT) materials provide an alternative to introduce the solubilizing groups (SGs) to the linker. Herein, the tert-butyl and n-hexyl groups are introduced as SGs at C7 positions of spiro structure, named C6-DMB and tBu-DMB, away from the acceptor. This has no influence on the photophysical properties of the parent TSCT molecule. Highly efficient solution-processed OLEDs were demonstrated with the maximum external quantum efficiencies of 21.0% and 21.7%, respectively. To the best of our knowledge, these are champions in the state-of-the-art solution-processed OLEDs with TSCT emitters. This work confirmed our conjecture of constructing highly efficient soluble emitters by transforming an outstanding TSCT material from thermal evaporation to solution-processed OLEDs with SGs simply integrated on the ‘bridge’ linker.

Chemistry Teacher Trainees’ use of Molecular Models in Learning Spiro and Bicyclic Compounds

The study diagnosed chemistry teacher trainees’ difficulties in naming and writing structures of spiro and bicyclic compounds. The case study design was conducted in a constructivist environment to enhance chemistry teacher trainees’ ability to construct, represent, and interpret the structural formulae of spiro and bicyclic compounds. Purposive sampling technique was employed to select 126 1st-year chemistry teacher trainees from University of Education, Winneba for the study. The results revealed that chemistry teacher trainees had difficulties in naming and writing structural formulae of spiro and bicyclic compounds. However, through the effective use of molecular model kits in teaching naming and writing structures of spiro and bicyclic compounds, these chemistry teacher trainees became conscious of IUPAC rules for naming and writing spiro and other cyclic compounds. A t-test conducted indicated that a statistical significance difference existed between students’ performance before the implementation of the intervention and after the intervention. It is recommended that chemistry teachers should adopt the use of molecular model kits in teaching concepts of organic nomenclature.

Polyketides with anti-inflammatory activity from Rhodiola tibetica endophytic fungus Alternaria sp. HJT-Y7

Seven undescribed polyketides with particular ortho-trisubstituted benzo[c]furan and benzo[c]oxepin spiro structures were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. HJT-Y7. Structural elucidations of these compounds were determined mainly by NMR and HR-ESI-MS analysis. An assumed polyketide biosynthetic pathway of these isolates was proposed. Two undescribed compounds and four known compounds showed significant inhibitory effects on LPS-induced NO production in RAW 264.7 cells without cytotoxicity at their effective concentrations.

Abstract 1781: Up284, a novel inhibitor to treat quadruple negative breast cancer

Abstract Quadruple negative breast cancer (QNBC), lacking the expression of ER (estrogen receptor), PR (progesterone receptor), HER2 (human epidermal growth factor receptor 2) and AR (androgen receptor), is the breast cancer subtype with the worst prognosis, and QNBC disproportionately afflicts African Americans. It has no standard-of-care treatment targets and thus efficacious and safe treatments are urgently sought for this unmet medical need, and to address the disparity in breast cancer outcomes. The current proposal is motivated by data showing elevated expression of proteasome subunit RPN13 is associated with both African American race and lower survival in QNBC patients, that RPN13 selectively targeted by a small molecule Up284 developed by Up Therapeutics. Both triple negative breast cancer and QNBC cell lines show evidence of greater vulnerability to proteasome inhibitors. However, licensed 20S proteasome inhibitors, e.g. bortezomib, have proven ineffective against solid tumors, with emergence of resistance, and dose limiting toxicities including thrombocytopenia and neutropenia. Up284 has a target and structure designed to overcome the limitations of the licensed drugs with respect to drug resistance. Up284 blocks substrate recognition and deubiquitination rather than just one of the three 20S catalytic activities), poor activity against solid tumors (Up284 has a novel spiro structure with evidence of improved drug access to tumor as compared to peptide-based 20S inhibitors), key toxicities of thrombocytopenia and neutropenia (unlike 20S inhibitors, Up284 does not target the immunoproteasome expressed by hematopoietic cells and does not show these toxicities). Up284 shows broad anticancer activity in vitro, including against QNBC lines with a robust therapeutic index, a promising safety profile and pharmacodynamics, and the ability to control xenograft tumor. By inhibiting proteasome ubiquitin receptor RPN13 function and its associated deubiquitinase activity, Up284 triggers more rapid accumulation and increased molecular weight polyubiquinated protein aggregates than is induced by 20S inhibitors. These toxic misfolded protein aggregates produce an unresolved ER stress, activate the canonical Unfolded Protein Response (UPR) signaling cascade and more rapidly triggers apoptosis than 20S inhibitor. The safety parameters and promising efficacy of Up284 against breast cancer lines encourages us to validate Up284 efficacy in more QNBC lines and animal models. We discuss Up284 efficacy and pharmacological analysis in our presentation. Citation Format: Balasubramanyam Karanam, Clayton Yates, Ravi Anchoori. Up284, a novel inhibitor to treat quadruple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1781.

Modulation of Properties by Ion Changing Based on Luminescent Ionic Salts Consisting of Spirobi(boron ketoiminate).

We report development of luminescent ionic salts consisting of the boron ketoiminate structure, which is one of the robust skeletons for expressing aggregation-induced emission (AIE) properties. From the formation of the boron-centered spiro structure with the ketoiminate ligands, we obtained stable ionic salts with variable anions. Since the ionic salts show Tms below 100 °C, it was shown that these salts can be classified as an ionic liquid. By using PF6 anion, the single crystal—which is applicable for X-ray crystallography—was obtained. According to the optical measurements, it was proposed that electronic interaction should occur through the boron center. Moreover, intense emission was observed both in solution and solid. Finally, we demonstrated that the emission color of the PF6 salt was altered from crystal to amorphous by adding mechanical forces. Based on boron complexation and intrinsic solid-state luminescent characters, we achieved obtainment of emissive ionic materials with environmental responsivity.

Steric Modulation of Spiro Structure for Highly Efficient Multiple Resonance Emitters.

A multiple resonance thermally activated delayed fluorescence (MR-TADF) molecule with a fused, planar architecture tends to aggregate at high doping ratios, resulting in broad full width at half maximum (FWHM), redshifting electroluminescence peaks, and low device efficiency. Herein, we propose a mono-substituted design strategy by introducing spiro-9,9'-bifluorene (SBF) units with different substituted sites into the MR-TADF system for the first time. As a classic steric group, SBF can hinder interchromophore interactions, leading to high device efficiency (32.2-35.9 %) and narrow-band emission (≈27 nm). Particularly, the shield-like molecule, SF1BN, seldom exhibits a broadened FWHM as the doping ratio rises, which differs from the C3-substituted isomer and unhindered parent emitter. These results manifest an effective method for constructing highly efficient MR-TADF emitters through a spiro strategy and elucidate the feasibility for steric modulation of the spiro structure in π-framework.

Steric Modulation of Spiro Structure for Highly Efficient Multiple Resonance Emitters

AbstractA multiple resonance thermally activated delayed fluorescence (MR‐TADF) molecule with a fused, planar architecture tends to aggregate at high doping ratios, resulting in broad full width at half maximum (FWHM), redshifting electroluminescence peaks, and low device efficiency. Herein, we propose a mono‐substituted design strategy by introducing spiro‐9,9′‐bifluorene (SBF) units with different substituted sites into the MR‐TADF system for the first time. As a classic steric group,SBFcan hinder interchromophore interactions, leading to high device efficiency (32.2–35.9 %) and narrow‐band emission (≈27 nm). Particularly, the shield‐like molecule,SF1BN, seldom exhibits a broadened FWHM as the doping ratio rises, which differs from the C3‐substituted isomer and unhindered parent emitter. These results manifest an effective method for constructing highly efficient MR‐TADF emitters through a spiro strategy and elucidate the feasibility for steric modulation of the spiro structure in π‐framework.

Discovery of novel spiro compound as RAF kinase inhibitor with in vitro potency against KRAS mutant cancer

The development of RAF inhibitors targeting cancers with wild type RAF kinase and/or RAS mutation has been challenging due to the paradoxical activation of the RAS-RAF-MEK-ERK cascade following RAF inhibitor treatment. Herein is the discovery and optimization of a series of RAF inhibitors with a novel spiro structure. The most potent spiro molecule 9 showed excellent in vitro potency against b/c RAF enzymes and RAS mutant H358 cancer cells with minimal paradoxical RAF signaling activation. Compound 9 also exhibited good drug-like properties as demonstrated by in vitro cytochrome P450 (CYP), liver microsome stability (LMS) data and moderate oral pharmacokinetics (PK) profiles in rat and mouse.

Photoacid-Enabled Synthesis of Indanes via Formal [3 + 2] Cycloaddition of Benzyl Alcohols with Olefins

An environmentally friendly and highly diastereoselective method for synthesizing indanes has been developed via a metastable-state photoacid system containing catalytic protonated merocyanine (MEH). Under visible-light irradiation, MEH yields a metastable spiro structure and liberated protons, which facilitates the formation of carbocations from benzyl alcohols, thus delivering diverse molecules in the presence of various nucleophiles. Mainly, a variety of indanes could be easily obtained from benzyl alcohols and olefins, and water is the only byproduct.