Ring-opened Form Research Articles

Rational Design of High-Performance Photocontrolled Molecular Switches Based on Chiroptical Dimethylcethrene: A Theoretical Study.

The reversible photo-induced conformation transition of a single molecule with a [5]helicene backbone has garnered considerable interest in recent studies. Based on such a switching process, one can build molecular photo-driven switches for potential applications of nanoelectronics. But the achievement of high-performance reversible single-molecule photoswitches is still rare. Here, we theoretically propose a 13,14-dimethylcethrene switch whose photoisomerization between the ring-closed and ring-open forms can be triggered by ultraviolet (UV) and visible light irradiation. The electronic structure transitions and charge transport characteristics, concurrent with the photo-driven electrocyclization of the molecule, are calculated by the non-equilibrium Green's function (NEGF) in combination with density functional theory (DFT). The electrical conductivity bears great diversity between the closed and open configurations, certifying the switching behavior and leading to a maximum on-off ratio of up to 103, which is considerable in organic junctions. Further analysis confirms the evident switching behaviors affected by the molecule-electrode interfaces in molecular junctions. Our findings are helpful for the rational design of organic photoswitches at the single-molecule level based on cethrene and analogous organic molecules.

An Optical Au3+ Sensor Based on layer-by-layer PEI/PAA-Rho thin Films on ITO.

This study presents the development of a sensitive and selective gold ion (Au3+) sensor utilizing layer-by-layer (LbL) assembled thin films composed of polyethylenimine (PEI) and poly (acrylic acid) (PAA) conjugated with rhodamine (Rho). The first study revealed that the polymeric sensors (PAA-Rho) demonstrated significant selectivity and sensitivity in their colorimetric and fluorescence responses to Au3+ compared to other metal ions. In their spirolactam form, the polymeric sensors were non-fluorescent but could selectively transform into the fluorescent ring-opened amide form upon interaction with Au3+ ions, resulting in fluorescence enhancement and observable color changes. Common co-existing metal ions showed negligible interference in the detection of Au3+. The LbL sensor exhibited a linear increase in absorbance with the addition of bilayers, confirming successful film deposition. Surface morphology analysis using SEM, along with structural confirmation via ATR-FTIR and XRD, further validated the sensor's capability to detect cation. Results demonstrated that the LbL sensor exhibited selectivity for Au3+ ions within the range 1 × 10-6 to 1 × 10-3 M. This approach offers an easily understandable and intrinsically sensitive means for detecting Au3+ ions in both environmental and biological applications.

Revisiting the nature and pharmacodynamics of tacrolimus metabolites

The toxicity of tacrolimus metabolites and their potential pharmacodynamic (PD) interactions with tacrolimus might respectively explain the surprising combination of higher toxicity and lower efficacy of tacrolimus despite normal blood concentrations, described in extensive metabolizers. To evaluate such interactions, we produced tacrolimus metabolites in vitro and characterized them by high resolution mass spectrometry (HRMS, for all) and nuclear magnetic resonance (NMR, for the most abundant, M-I). We quantified tacrolimus metabolites and checked their structure in patient whole blood and peripheral blood mononuclear cells (PBMC). We explored the interactions of M-I with tacrolimus in silico, in vitro and ex vivo. In vitro metabolization produced isoforms of tacrolimus and of its metabolites M-I and M-III, whose HRMS fragmentation suggested an open-ring structure. M-I and M-III open-ring isomers were also observed in patient blood. By contrast, NMR could not detect these open-ring forms. Transplant patients expressing CYP3A5 exhibited higher M-I/TAC ratios in blood and PBMC than non-expressers. Molecular Dynamics simulations showed that: all possible tacrolimus metabolites and isomers bind FKPB12; and the hypothetical open-ring structures induce looser binding between FKBP12 and calcineurins, leading to lower CN inhibition. In vitro, tacrolimus bound FKPB12 with more affinity than purified M-I, and the pool of tacrolimus metabolites and purified M-I had only weak inhibitory activity on IL2 secretion and not at all on NFAT nuclear translocation. M-I showed no competitive effect with tacrolimus on either test. Finally, M-I or the metabolite pool did not significantly interact with tacrolimus MLR suppression, thus eliminating a pharmacodynamic interaction.

A Visible-Light-Responsive Fluorescent Diarylethene Having a Betaine Structure.

As a new molecular scaffold of photoswitchable fluorophore, we developed a photochromic diarylethene containing a betaine structure based on pyridinium N-enolate. A facile reaction of a pyridyl-substituted dithienylperfluorocyclopentene derivative with octafluorocyclopentene constructed the betaine structure. The introduction of the betaine moiety provided the diarylethene molecule with bathochromically shifted optical absorption and fluorescing ability, thus enabling the molecule to function as a visible-light-sensitive turn-off mode photoswitchable fluorophore. The molecule in the open-ring form emitted bright blueish green fluorescence. Upon irradiation with 405 nm light, the molecule underwent cyclization isomerization to form the closed-ring isomer and the fluorescence intensity significantly decreased. The turn-off mode fluorescence photoswitching was observed not only in solution but also in polymer films.

Single-Probe-Based Sensor Array for Fingerprint Recognition of Trivalent Metal Ions and Application in Water Identification.

Abnormal concentration levels of trivalent metal ions (M3+) might hinder their natural biological activities in physiological processes and cause severe health hazards. Herein, a dual-chromophore probe (RhB-TPE) composed of rhodamine and tetraphenylethene (TPE) units was synthesized and explored for discriminating M3+ ions. It exhibited special aggregation and AIE properties in aqueous media. Its ensemble with anionic surfactant SDBS assemblies (RhB-TPE/SDBS) could be utilized as fluorescent sensors for selective and sensitive detection of M3+ ions such as Fe3+, Al3+, and Cr3+ by illustrating quenched TPE emission and switched-on rhodamine emission. Moreover, the use of SDBS assemblies at two concentrations could provide a single-probe-based sensor array and realize four-signal pattern recognition of different concentrations of the three M3+ ions and identify M3+ mixtures or unknown samples. The cross-reactive fluorescence variation was attributed to the M3+ influence on the FRET process from TPE to open-ring form rhodamine in the two ensemble sensors. With the coexistence of Al3+, the optimized RhB-TPE/SDBS ensemble sensor array was successfully applied to differentiate commercially available brand mineral water and purified water, as well as tap water. The present work provides a novel strategy to generate a single-probe-based sensor array and realizes fingerprint recognition of three trivalent metal ions and efficient discrimination of different types of water. The modulation FRET process of a dual chromophore in different surfactant ensembles inspires the future construction of novel and effective sensing platforms.

Predictive Guidelines for Electrocyclization of Dithienylethenes.

Molecular photoswitches undergo a structural transformation upon photoexcitation to interconvert between two or more stable forms. In some cases, the structural rearrangement involves the transition between ring-open and ring-closed forms. In this work, we develop simple guidelines for the design of organic molecules able to undergo photochemical electrocyclization, using electronic structure calculations on dithienylethene (DTE)-based compounds. We conclude that the ability to photocyclize can be predicted from the localization and symmetry of frontier molecular orbitals. These ideas are based on the Woodward-Hoffmann rules but go beyond them, allowing us to address a more general family of chromophores. Our methodology has been experimentally validated in a novel series of quinoline-based DTEs, where the ability for photocyclization depends on specific chemical modifications. We use the DTE scaffold as the workhorse model in our study; however, these simple yet powerful guidelines are expected to be generally valid to guide the design of other diarylethenes.

A sensitive bioanalytical ultra-high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantitation of lactone and carboxylate forms of topotecan in plasma and vitreous.

Topotecan (TPT) is used in the treatment of retinoblastoma, the most common malignant intraocular tumor in children. TPT undergoes pH-dependent hydrolysis of the lactone ring to the ring-opened carboxylate form, with the lactone form showing antitumor activity. A selective, and highly sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the determination of both forms of TPT in one mobile phase composition in plasma and vitreous humor matrices. The method showed an excellent linear range of 0.375-120ng/mL for the lactone. For the carboxylate, the linear range was from 0.75 to 120ng/mL. The matrix effect and the recovery for the lactone ranged from 98.5% to 106.0% in both matrices, for the carboxylate form, it ranged from 94.9% to 101.2%. The dynamics of the transition between TPT lactone and TPT carboxylate were evaluated at different pH environments. The stability of TPT forms was assessed in plasma and vitreous humor at 8 and 37°C and a very fast conversion of lactone to carboxylate form occurred at 37°C in both matrices. The method developed facilitates the investigation of TPT pharmacodynamics and the release kinetics in the development of the innovative local drug delivery systems.

β-cyclodextrin/spiropyran-functionalized optical-driven hydrogel film for bisphenol A detection in food packaging

Bisphenol A (BPA), an endocrine disruptor, is widely used in food packaging materials, including drink containers. Sensitive detection of BPA is crucial to food safety. Herein, we have developed a novel optical-driven hydrogel film sensor for sensitive BPA detection based on the displacement of spiropyran (SP) from β-cyclodextrin (β-CD) cavity by BPA followed by the photochromism of the released SP. The released SP converts to the ring-opened merocyanine form which shows an enhanced red fluorescence in the dark. The sensor demonstrates a linear detection range from 0.1 to 20 μg mL−1 with a limit of detection at 0.027 μg mL−1 and a limit of quantification at 0.089 μg mL−1. Notably, the proposed β-CD/SP hydrogel can be reused due to the reversible isomerization of SP and the reversible host–guest interaction. This sensor also shows good performance for BPA determination in real samples, indicating its great potential for food safety monitoring.

Coumarinyl(pyrrolyl)ethenes for the detection of Pd2+, CN− and F− ions, test strips based on them and logic gates

New coumarinyl(pyrrolyl)ethenes with a 1,3-thiazole bridge were synthesized. When irradiated at 365 nm, a hexatriene-cyclohexadiene rearrangement of the ring-opened form into a colored non-fluorescent ring-closed isomer occurs. The back reaction takes place when exposed to visible light at 540 nm. Furthermore, the compound with terminal 2,4-di-tert-butyl-6-hydroxybenzylidene receptor group represents a multifunctional sensor exhibiting selective chromogenic activity towards palladium(II) ions and CN− and F− anions. This probe interacts with Pd2+ cations with a noticeable naked eye effect - a change in the solution color from yellow to orange. The complexation stoichiometry is 1:1 and the detection limit was found to be 4.5 × 10−7 mol L−1. Similarly, CN− and F− anions cause a contrast naked eye effect with a change in the color of the solution from yellow to rose-red. For convenient detection of the above ions, test strips containing 4-(2-(2-(2,4-di-tert-butyl-6-hydroxybenzylidene)hydrazinyl)-5-(2-oxo-2H-chromen-3-yl)thiazol-4-yl)-1,5-dimethyl-1H-pyrrole-2-carbonitrile have been developed. In addition, a combinatorial molecular logic gate was designed based on multi-controllable photoswitching properties of the obtained probe.

A Nonlinear Photochromic Reaction Based on Sensitizer-Free Triplet-Triplet Annihilation in a Perylene-Substituted Rhodamine Spirolactam.

Nonlinear photochromic reactions that work with weak incoherent light are important for molecular operations with high spatial resolution and multiple photofunctions based on single molecules. However, nonlinear photochromic compounds generally require complex molecular design, restricting accessibility in various fields. Herein, we report nonlinear photochromic properties in a perylene-substituted rhodamine spirolactam derivative (Rh-Pe), which is synthesized from rhodamine B in facile procedures. Direct excitation of Rh-Pe produces the triplet excited state via the charge-transfer (CT) state. The triplet excited state causes triplet-triplet annihilation to bring the generation of the intensely colored ring-open form with nonlinear behavior. Furthermore, green- and red-light-induced photochromism was achieved in Rh-Pe using triplet sensitizers, although Rh-Pe can be directly excited only by ultraviolet and blue light. Our findings are expected to contribute to the development of photofunctional materials showing nonlinear behavior and low-energy light responsivity.

Chemical interaction between the sugar moieties in N, N-di-glycated alanine derivatives

The chemistry of N,N-diglycated amino acids remains unexplored due to their transient nature in the Maillard reaction. Their increased reactivity is attributed to the presence of high concentrations of open ring forms in at least one of their sugar moieties. The N,N-diglycated alanine derivatives were generated in situ via dissociation from their stable precursors the bis[N,N-diglycated alanine]iron(II) complexes, in the alanine/glucose/FeCl2 model system heated at 110 °C for 2 h. The thermal degradations of these complexes were followed in the reaction mixture, using isotope-labelled reactants, such as [13C-3] alanine and [13C–U] glucose, and ESI/qTOF/MS analysis. The N,N-diglycated amino acids exhibited a unique and characteristic chemical interaction between the neighbouring sugar moieties generating hitherto unknown heterocyclic moieties. The origin of these products was tracked by identifying ions incorporating one C-3 atom from alanine and between seven to 12 carbon atoms from the sugar moieties in the same structure. Temperature-dependent FTIR spectra of di-glycated alanine generated through ball milling provided further evidence for their reactivity.

Fast tumor imaging using pH-responsive aggregation of cyanine dyes with rapid clearance

Rapid and selective tumor detection using conventional pH-activatable chemical probes as contrast agents is challenging. Moreover, a large proportion of the contrast agent is usually retained in the body long-term, which causes potential toxicity risks. In this study, we developed a fluorescent sensor, CypH2S, with a pH-sensitive cyclic substructure for detection of acidic tumor microenvironment. Upon pH variation, the sensor underwent structural changes: the closed-ring form, CypH2S-C, exhibited suppressed dye aggregation, while the open-ring form, CypH2S-O, tended to aggregate in aqueous solutions under slightly acidic conditions. Importantly, CypH2S facilitated rapid and selective tumor visualization in a living mouse model via fluorescence imaging of its pH-responsive aggregation with a 1.9-fold tumor/background ratio (< 1 h). Furthermore, prompt clearance of CypH2S from the bloodstream post-tumor detection occurred because of the relatively small size of the aggregates and cell impermeability. These properties would make CypH2S a promising candidate for clinical tumor diagnosis.

Stable ring-opened forms of a spiropyran in the confined space of nanoporous silicas

The structural change of a spiropyran (1,3,3-trimethylindolino-8′-methoxybenzopyrylospiran (MBPS)) to ring-opened forms, such as merocyanine and protonated merocyanine, is spontaneously induced in the confined space of a nanoporous silicas. In general, the ring closing of MBPS occurs easily in liquid media under blue-light illumination or under basic conditions. However, the ring-opened forms are tightly fixed and stable in the nanopores of diameters similar of the molecules owing to the hydrogen-bonding with silanol groups and the strong steric-restriction. The color of the ring-opened forms in the confined space varies with the protonation; therefore, the MBPS trapped in the nanoporous silica with open pores is sensitive to the pH of the surrounding solution.

UV-Light-Induced Morphological Transformation of Spiropyran Assemblies from Irregular Sheet-like Structures to Nanospheres.

Studies on self-assembling systems with a controllable morphology responding to light stimulation are significant for revealing the process and mechanism of assembly. Here, a molecule of spiropyran derivative (SP) possessing photoresponsive assembly morphology is constructed. SP self-assembles into irregular sheet-like structures whose morphology can be significantly transformed into regular nanospheres under continuous ultraviolet light stimulation. The UV-vis absorption spectra indicate that 56% of SP are isomerized from closed-ring form (SPC) to open-ring form (SPO) with color changes from colorless to magenta. Furthermore, theoretical calculations demonstrate that SPO-SPO aggregates possess stronger van der Waals forces than do SPC-SPC aggregates and tend to form stable intermediates combined with SPO isomers. Therefore, the isomerization of SP from SPC to SPO and the differences in intermolecular interactions are important factors in the morphological transition. Our study provides an efficient strategy to modulate the assembled morphology, which holds great promise to be applied in the field of smart materials.

Discovery of ABBV-154, an anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody-Drug Conjugate (iADC).

Stable attachment of drug-linkers to the antibody is a critical requirement, and for maleimide conjugation to cysteine, it is achieved by ring hydrolysis of the succinimide ring. During ADC profiling in our in-house property screening funnel, we discovered that the succinimide ring open form is in equilibrium with the ring closed succinimide. Bromoacetamide (BrAc) was identified as the optimal replacement, as it affords stable attachment of the drug-linker to the antibody while completely removing the undesired ring open-closed equilibrium. Additionally, BrAc also offers multiple benefits over maleimide, especially with respect to homogeneity of the ADC structure. In combination with a short, hydrophilic linker and phosphate prodrug on the payload, this afforded a stable ADC (ABBV-154) with the desired properties to enable long-term stability to facilitate subcutaneous self-administration.

PKa-Tunable fluorescent probes for visualizing minor pH fluctuations in different subcellular organelles and in vivo

Visualizing minor pH fluctuations (0.1–0.2 unit) in subcellular organelles is in great demand for dissecting physiological events in living organism. Here, we judiciously constructed a family of coumarin-indolenium based fluorescent pH probes to visualize minor pH fluctuations (0.1–0.2 unit) in different subcellular organelles. The probe response to pH was based on a nucleophilic addition/elimination reaction induced ring closing/opening process. Notably, pKa values of the probes could be tuned by synergistic effect of multiple approaches, including change of ring size, alteration of nucleophilic ability of nucleophilic group in their ring-opened form, and variation of electrophilic ability of electrophilic atom in their ring-opened form. The probes have been utilized for tracking minor pH fluctuation in mitochondria, lysosome and endoplasmic reticulum (ER). Moreover, acidification of ER under 1,4-Dithiothreitol (DTT) triggered ER stress, which was visualized. In addition, as a proof of concept study, the probes have been applied for imaging pH variation in zebrafish under high level of exogenous CO2.

Photoresponsive Spiropyran and DEGMA-Based Copolymers with Photo-Switchable Glass Transition Temperatures.

Herein, novel photoresponsive spiropyran (SP)-based P(DEGMA-co-SpMA) copolymers with variable percentages of SP fractions are synthesized. The SP group present in these polymers exhibited the abilities of reversible photoisomerism. Their photoresponsive, structural, and thermal properties have been investigated and compared using various characterization techniques. These light-responsive copolymers are found to exhibit photoswitchable glass transition temperature (Tg ), high thermal stability (Td > 250°C), instant photochromism as well as fluorescence upon exposure to UV light. It is demonstrated that the Tg of these synthesized polymers increased when irradiated with UV light (λ = 365nm), as a consequence of the photoisomerization of incorporated SP groups into their merocyanine form. This increase in Tg is attributed to an increase in polarity and a decrease in the overall entropy of the polymeric system when it switches from the ring-closed SP form (less-ordered state) to the ring-opened merocyanine form (more-ordered state). Therefore, such polymers with a unique feature of phototunable glass transition temperatures provide the possibility to be integrated into functional materials for various photoresponsive applications.

Synthesis and Characterization of Multi-Reducing-End Polysaccharides.

Site-specific modification is a great challenge for polysaccharide scientists. Chemo- and regioselective modification of polysaccharide chains can provide many useful natural-based materials and help us illuminate fundamental structure-property relationships of polysaccharide derivatives. The hemiacetal reducing end of a polysaccharide is in equilibrium with its ring-opened aldehyde form, making it the most uniquely reactive site on the polysaccharide molecule, ideal for regioselective decoration such as imine formation. However, all natural polysaccharides, whether they are branched or not, have only one reducing end per chain, which means that only one aldehyde-reactive substituent can be added. We introduce a new approach to selective functionalization of polysaccharides as an entrée to useful materials, appending multiple reducing ends to each polysaccharide molecule. Herein, we reduce the approach to practice using amide formation. Amine groups on monosaccharides such as glucosamine or galactosamine can react with carboxyl groups of polysaccharides, whether natural uronic acids like alginates, or derivatives with carboxyl-containing substituents such as carboxymethyl cellulose (CMC) or carboxymethyl dextran (CMD). Amide formation is assisted using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM). By linking the C2 amines of monosaccharides to polysaccharides in this way, a new class of polysaccharide derivatives possessing many reducing ends can be obtained. We refer to this class of derivatives as multi-reducing-end polysaccharides (MREPs). This new family of derivatives creates the potential for designing polysaccharide-based materials with many potential applications, including in hydrogels, block copolymers, prodrugs, and as reactive intermediates for other derivatives.

Photo-Stimuli-Responsive Dual-Emitting Luminescence of Spiropyran-Encapsulated Metal-Organic Framework for Dynamic Information Encryption.

The development of photo-stimuli-responsive luminescent materials is essential to address emerging demands in encryption security. Here, we report a novel photo-stimuli-responsive dual-emitting luminescent material ZJU-128⊃SP (SP = spiropyran), which was obtained by encapsulating spiropyran molecule into a cadmium-based metal-organic framework (MOF), [Cd3 (TCPP)2 ]·4DMF·4H2 O (ZJU-128, H4 TCPP = 2,3,5,6-tetrakis (4-carboxyphenyl)pyrazine). This MOF/dye composite ZJU-128⊃SP exhibits a blue emission from ligand of ZJU-128 at 447nm and a red emitting around 650nm of spiropyran. Utilizing the photoisomerization of spiropyran from ring-closed to ring-open form under UV light irradiation, significant fluorescence resonance energy transfer process between ZJU-128 and spiropyran is achieved. As a result, the blue emission of ZJU-128 is gradually decreased while the red emission of spiropyran increased. This dynamic fluorescent behavior can fully recover to original state when exposed to visible light (> 405nm). By taking advantage of the time-dependent fluorescence, dynamical anti-counterfeiting pattern and multiplexed coding are successfully developed based on ZJU-128⊃SP film. This work provides an inspiring point for the design of information encryption materials with higher security requirements. This article is protected by copyright. All rights reserved.

A naphthalimide functionalized fluoran with AIE effect for ratiometric sensing Hg2+ and cell imaging application

The pollution caused by mercury ions (Hg2+) poses a potential threat to public health. Therefore, monitoring Hg2+ concentration in the environment is necessary and significant. In this work, a naphthalimide functionalized fluoran dye NAF has been prepared, which shows a new red-shift in emission at 550 nm with the maximum intensity in a mixture of water-CH3CN (v/v = 7/3) due to aggregating induced emission (AIE) effect. Meanwhile, NAF can be employed as a Hg2+ ions sensor, which displays a selective and sensitive response to Hg2+ ions by the reduced fluorescence of naphthalimide fluorophore and increased fluorescence of fluoran group, respectively, showing ratiometric fluorescence signal changes with more than 65-fold emission intensity ratio increase and naked eyes visible color change. In addition, the response time is fast (within 1 min) and the sensing can be conducted in a wide pH range (4.0–9.0). Moreover, the detection limit has been evaluated to be 5.5 nM. The sensing mechanism may be attributed to the formation of a π-extended conjugated system due to the Hg2+ ions-induced conversion of spironolactone to the ring-opened form, partially accompanied by the fluorescence resonance energy transfer (FRET) process. Significantly, NAF exhibits suitable cytotoxicity to living HeLa cells, which allows it to be utilized for ratiometric imaging of Hg2+ ions assisted by confocal fluorescence imaging.