Computational chemistry facilitates the development of second near-infrared xanthene-based dyes.

CONTEXT: The dyes in the second near-infrared (NIR-II) region play a crucial role in advancing imaging technology. However, developing small-molecule dyes in NIR-II poses a significant bottleneck to meet the substantial demands in biological fields, which may be attributed to the lack of a rational design strategy. Herein, we designed a series of rhodamine analogs with more red-shifted emission by replacing the oxygen-bridge atom in xanthene-based dyes with -C(CH3)2, -Si(CH3)2, -SO2, and -P(O)Ph. We investigated the frontier molecular orbital, electrostatic potential surfaces, the interaction region indicator, electron-hole distribution, and absorption and emission spectrum of xanthene-based dyes using (time-dependent) density functional theory. Our results demonstrated that these designed small molecular dyes exhibit long emission wavelengths covering 1377-1809 nm. We expected these findings to enable the targeted design of long-wavelength rhodamines. METHOD: Geometry optimization of dyes in the ground and excited states was carried out at ω-B97XD/Def2SVP level using Gaussian 16 A03. The absorption and emission wavelengths were evaluated using 13 functional, including TPSSH, O3LYP, B3LYP*, B3LYP, PBE0, MPW1B95, PBE-1/3, PBE38, MPWB1K, MN15, BHandHLYP, ω-B97XD, and CAM-B3LYP.

Biomedical-Optical-Window Tailored Cyanines for Steerable Inflammatory Bowel Disease Theranostic.

Tailored photophysical properties and chemical activity is the ultimate pursuit of functional dyes for in vivo biomedical theranostics. In this work, the independent regulation of the absorption and fluorescence emission wavelengths of heptamethine cyanines is reported. These dyes retain near-infrared fluorescence emission (except a nitro-modified dye) while feature variable absorption wavelengths ranging from 590 to 860 nm. This enables to obtain customized functional dyes that meet the excitation and fluorescence wavelength requirements defined by the optical properties of tissues for in vivo biomedical applications. Typically, a nitro-modified photothermal active derivative Cy-Mu-7-9 is used, which features strong absorption at 810 nm in PBS, a wavelength that balanced the tissue penetration depth and non-specific photothermal effect, to realize non-destructive inflammatory bowel disease (IBD) therapy via photothermal induced up-regulation of heat shock protein 70 in the intestinal epithelial cells. The corresponding amino-modified dye Cy-Mu-7-9-NH2, which can be formed in health enteric cavity by Cy-Mu-7-9 after oral administration, is a fluorescence compound with the emission of 800 nm in PBS. Based on the IBD sensitive transformation of Cy-Mu-7-9 and Cy-Mu-7-9-NH2, in vivo IBD theranostic and therapeutic effect evaluation is realized via the synergy of fluorescence imaging and photothermal therapy for the first time.

Data-driven machine learning models for predicting the maximum absorption and emission wavelengths of single benzene fluorophores.

Single benzene fluorophores (SBFs) have garnered significant research attention due to their ease of preparation, seamless diffusion into biological samples, and low molecular weight. Accurately predicting the molecular photophysical properties, specifically the maximum absorption and emission wavelengths, is pivotal in advancing functional SBFs. In this study, we introduce a machine-learning model to estimate the maximum absorption and emission wavelengths of SBFs precisely. This model leverages a Full Connect Neural Network and computational chemistry and is tailored to address the challenges associated with a relatively small dataset (81 SBFs). Remarkably, our model (SBFs-ML) demonstrates impressive accuracy, yielding a mean relative error of 1.54 % and 2.93 % for SBFs' maximum absorption and emission wavelengths, respectively. Importantly, the SBFs-ML was bullied based on only three descriptors, resulting in strong interpretability. Experimental results have strongly corroborated these predictions. Our prediction methods are poised to facilitate significantly the efficient design and creation of SBFs.

Modulation of intramolecular freedom for tuning fluorescence imaging and photooxidation of amyloid-ß aggregates.

Alzheimer's disease (AD) is distinguished by amyloid-ß (Aß) deposition and plaque formation, prompting significant interest in fluorescence imaging and photooxidation of Aß aggregates for diagnostic and intervention purposes. However, the molecular engineering required to modulate fluorescence imaging and photooxidation of Aß presents notable challenges. Here, we present the design of four small molecules (BTD-SZ, BTD-YD, BTD-TA-SZ, and BTD-TA-YD) aimed at investigating the influence of intramolecular freedom of movement on imaging and photooxidation. Notably, BTD-SZ exhibits exceptional fluorescence properties, offering promising potential for non-invasive detection of Aß plaques in vivo. Furthermore, by converting dimethylamine into triphenylamine to restrict intramolecular freedom of movement in the aggregate state, we synthesized a photosensitizer denoted as BTD-TA-SZ. This compound demonstrates aggregation-induced photooxidation (AIP), effectively impeding Aß aggregation under light irradiation in vivo. Thus, the modulation of intramolecular freedom of movement emerges as a pivotal molecular engineering strategy for developing photosensitizers for the diagnosis and intervention of AD, offering insights into innovative approaches for combating this debilitating condition.

Polarity-Driven Fluorescence Monitoring of Lipid Droplet Dynamics in Dry Eye Disease.

The emergence of lipid droplets (LDs) has been recognized as cellular markers of ocular surface hyperosmosis, which is recognized as a fundamental mechanism driving dry eye disease (DED), while their dynamics during DED progression and therapy remains unlocked. For this purpose, an LD-specific fluorescent probe P1 is presented in this work that exhibits highly selective and sensitive emission enhancement in response to a decreased ambient polarity (Δf) from 0.209 to 0.021. The hydrophobic nature of P1 enables specific staining of LDs, facilitating visualization of changes in polarity within these cellular structures. Utilizing P1, we observe a decrease in polarity accompanied by an increase in the size and number of LDs in hyperosmotic human corneal epithelial cells (HCECs). Furthermore, interplays between LDs and cellular organelles such as mitochondria and the Golgi apparatus are visualized, suggesting the underlying pathogenesis in DED. Notably, the variations of LDs are observed after the inhibition of ferroptosis or activation of autophagy in hyperosmotic HCECs, implying the great potential of LDs as indicators for the design and efficacy evaluation of DED drugs regarding ferroptosis or autophagy as targets. Finally, LDs are confirmed to be overproduced in corneal tissues from DED mice, and the application of clinical eye drops effectively impedes these changes. This detailed exploration underscores the significant roles of LDs as an indicator for the deep insight into DED advancement and therapy.

Ternary choline chloride/benzene sulfonic acid/ethylene glycol deep eutectic solvents for oxidative desulfurization at room temperature.

Deep eutectic solvents (DESs) have been extensively studied as promising green solvents to attain a better removal efficiency of sulfide. A new DES system formed from choline chloride (ChCl), benzene sulfonic acid (BSA), and ethylene glycol (EG) as a class of ternary DESs was prepared and used in the oxidative desulfurization (ODS) of different sulfides. Ternary DESs have distinct advantages such as volatility and high activity compared with organic acid-based binary DESs. Under the optimum conditions with VDES/VOil = 1 : 5, O/S (molar ratio of oxygen to sulfur) = 5, and T = 25 °C, the desulfurization efficiencies of dibenzothiophene (DBT), 4,6-dimethyldibenzothiophene (4,6-DMDBT), and benzothiophene (BT) were all achieved to 100% in 2 h. Through experimental and density functional theory (DFT) calculation methods, this new system as a class of ternary DESs shows good stability and excellent desulfurization performance at room temperature. The investigation of this study could supply a new idea of ternary DESs for oxidative desulfurization.

Highly Efficient Blue Organic Light Emitting Diodes Based on Cyclohexane-Fused Quinoxaline Acceptor.

Exploring blue organic light emitting diodes (OLED) is an important but challenging issue. Herein, to achieve blue-shifted emission, cyclohexane is fused to quinoxaline to weaken the electron-withdrawing ability and conjugation degree of the acceptor. As a result, blue to cyan fluorescent emitters of Me-DPA-TTPZ, tBu-DPA-TTPZ, and TPA-TTPZ were designed and synthesized with donors of diphenylamine and triphenylamine, which exhibit high photoluminescence quantum yields and good thermal stability. In OLEDs with emitters of TPA-TTPZ, the sensitized and nonsensitized devices demonstrate deep-blue (449 nm) and blue (468 nm) emission with maximum external quantum efficiency and CIE coordinates of 6.1%, (0.15, 0.10) and 5.1%, (0.17, 0.22), respectively, validating their potential as blue emitters in OLEDs.

Blending Low-Frequency Vibrations and Push-Pull Effects Affords Superior Photoacoustic Imaging Agents.

Photoacoustic imaging (PAI), a state-of-the-art noninvasive in vivo imaging technique, has been widely used in clinical disease diagnosis. However, the design of high-performance PAI agents with three key characteristics, i.e., near-infrared (NIR) absorption (λabs >800 nm), intense PA signals, and excellent photostability, remains a challenging goal. Herein, we present a facile but effective approach for engineering PAI agents by amplifying intramolecular low-frequency vibrations and enhancing the push-pull effect. As a demonstration of this blended approach, we constructed a PAI agent (BDP1-NEt2 ) based on the boron-dipyrromethene (BODIPY) scaffold. Compared with indocyanine green (ICG, an FDA-approved organic dye widely utilized in PAI studies; λabs =788 nm), BDP1-NEt2 exhibited a UV/Vis-NIR spectrum peaked at 825 nm, superior in vivo PA signal intensity and outstanding stability to offer improved tumor diagnostics. We believe this work provides a promising strategy to develop the next generation of PAI agents.

Spontaneously Blinking Rhodamine Dyes for Single-Molecule Localization Microscopy.

Single-molecule localization microscopy (SMLM) has found extensive applications in various fields of biology and chemistry. As a vital component of SMLM, fluorophores play an essential role in obtaining super-resolution fluorescence images. Recent research on spontaneously blinking fluorophores has greatly simplified the experimental setups and extended the imaging duration of SMLM. To support this crucial development, this review provides a comprehensive overview of the development of spontaneously blinking rhodamines from 2014 to 2023, as well as the key mechanistic aspects of intramolecular spirocyclization reactions. We hope that by offering insightful design guidelines, this review will contribute to accelerating the advancement of super-resolution imaging technologies.

Molecular Principles of the Excited-State Intramolecular Thiol Proton Transfers in 3-thiolflavone Derivatives.

The excited-state intramolecular proton transfer (ESIPT) effect has attracted considerable attention due to its potential applications in photoluminescent materials. However, only a few theoretical reports have investigated the ESIPT process involving sulfur-hydrogen bonds. Herein, we systematically investigated the ESIPT effect of three 3-thiolflavone derivatives containing sulfur-hydrogen bonds with M06-2X functional combined Def2-TZVP basis set. The intramolecular sulfur-hydrogen bonds were confirmed in the ground and excited states via analyzing the bond lengths, interaction energies, and infrared vibrational spectra. Besides, we demonstrated that the electron-withdrawing group led to a more stable tautomer compared to the electron-donating group. Conversely, the electron-donating group played a crucial role in reducing the energy barrier of the ESIPT reaction due to the strengthening of the hydrogen bond in the excited state. Interestingly, the substituent group can determine the excited-state electronic properties of keto tautomers. Specifically, the electron-withdrawing group caused significant improvement in the nπ* transition configuration, significantly reducing the radiation rate. The electron-donating group increased the proportion of the ππ* transition configuration, thus, the keto tautomer had bright emission. We expect these findings to open new avenues for designing potential luminescent materials.

Restriction of photoinduced electron transfer as a mechanism for the aggregation-induced emission of a trityl-functionalised maleimide fluorophore.

The restriction of intramolecular motion (RIM) and restricted access to a conical intersection (RACI) have been accepted as general working mechanisms for aggregation-induced emission (AIE) phenomena. However, as the family of AIE molecules grows, the RIM and RACl mechanisms cannot be used to fully understand some AIE phenomena. Herein, the restriction of the photoinduced electron transfer (RPET) state is proposed to rationalize the AIE phenomena of trityl-functionalised maleimide molecule based on density functional theory calculations. The "state-crossing from a locally excited to an electron transfer state" (SLEET) model was employed to predict the ON/OFF molecular PET in solution and solid states. According to the SLEET model, we showed that a non-emissive electron transfer excited state leads to the fluorescence quenching of trityl-functionalised maleimide in solution. However, due to the reduced polarity of the environment in aggregates, the electron transfer state is thermodynamically inaccessible, and a low-lying locally excited state exhibits intense emission. These findings provide a theoretical foundation to understand the working mechanisms of AIE molecules and the design of new AIEgens. We expect that the RPET mechanism can be used to screen potential AIEgens using the SLEET model.

Enlarging the Stokes Shift by Weakening the π-Conjugation of Cyanines for High Signal-to-Noise Ratiometric Imaging.

The signal-to-noise ratio (SNR) is one of the key features of a fluorescent probe and one that often defines its potential utility for in vivo labeling and analyte detection applications. Here, it is reported that introducing a pyridine group into traditional cyanine-7 dyes in an asymmetric manner provides a series of tunable NIR fluorescent dyes (Cy-Mu-7) characterized by enhanced Stokes shifts (≈230 nm) compared to the parent cyanine 7 dye (<25 nm). The observed Stokes shift increase is ascribed to symmetry breaking of the Cy-Mu-7 core and a reduction in the extent of conjugation. The fluorescence signals of the Cy-Mu-7 dyes are enhanced upon confinement within the hydrophobic cavity of albumin or via spontaneous encapsulation within micelles in aqueous media. Utilizing the Cy-Mu-7, ultra-fast in vivo kidney labeling in mice is realized, and it is found that the liver injury will aggravate the burden of kidney by monitoring the fluorescence intensity ratio of kidney to liver. In addition, Cy-Mu-7 could be used as efficient chemiluminescence resonance energy transfer acceptor for the reaction between H2 O2 and bisoxalate. The potential utility of Cy-Mu-7 is illustrated via direct monitoring fluctuations in endogenous H2 O2 levels in a mouse model to mimic emergency room trauma.

CO2 Photoactivation Study of Adenine Nucleobase: Role of Hydrogen-Bonding Traction.

The discovery and in-depth study of non-biocatalytic applications of active biomolecules are essential for the development of biomimicry. Here, the effect of intermolecular hydrogen-bonding traction on the CO2 photoactivation performance of adenine nucleobase by means of an adenine-containing model system (AMOF-1-4) is uncovered. Remarkably, the hydrogen-bonding schemes around adenines are regularly altered with the increase in the alkyl (methyl, ethyl, isopropyl, and tert-butyl) electron-donating capacity of the coordinated aliphatic carboxylic acids, and thus, lead to a stepwise improvement in CO2 photoreduction activity. Density functional theory calculations demonstrate that strong intermolecular hydrogen-bonding traction surrounding adenine can obviously increase the adenine-CO2 interaction energy and, therefore, result in a smoother CO2 activation process. Significantly, this work also provides new inspiration for expanding the application of adenine to more small-molecule catalytic reactions.

Monomer and Excimer Emission in a Conformational and Stacking-Adaptable Molecular System.

A design strategy that combines molecular conformation, alkyl chain length, and charge-transfer effects has been developed to obtain conformational and stacking-adaptable donor-acceptor-π type molecules for precisely regulating the monomer and excimer emission in a single luminous platform under different environments. These fluorophores can exhibit bright monomer emissions when they are in the dispersed state based on their planar conformation. However, when the luminous molecules with short alkyl side chains are in the crystalline state, their molecular conformation can become distorted, further inducing strong intermolecular interactions and staggered π-π stacking for bright excimer emission. More importantly, their dispersed and aggregated states can be reversibly regulated in a phase-change fatty acid matrix, to achieve temperature-responsive fluorescence for temperature monitoring and advanced information encryption.

Near-Infrared Photooxygenation Theranostics Used for the Specific Mapping and Modulating of Amyloid-ß Aggregation.

The photooxygenation of amyloid-ß (Aß) protein is considered a promising strategy against Alzheimer's disease (AD). The inhibition of Aß aggregation or depolymerization of Aß aggregates can effectively alleviate and improve the condition of AD. Herein, we report a series of "off-on" near-infrared quinolinium photosensitizers (QM20-QM22) based on D-π-A structures using a target-sensing catalyst activation (TaSCAc) strategy. They exhibit turn-on fluorescence when bonded to Aß aggregates and generate singlet oxygen to achieve the specific imaging and photooxygenation of Aß aggregates, leading to attenuated Aß aggregates, enhancing their clearance through the microglial lysosomal pathway, decreasing their neurotoxicity. This study will shed light on the development of the photooxygenation of misfolded proteins for the treatment of neurodegenerative diseases.

All-in-One Theranostic Platforms: Deep-Red AIE Nanocrystals to Target Dual-Organelles for Efficient Photodynamic Therapy.

Aggregation-induced emission (AIE) nanoparticles have been widely applied in photodynamic therapy (PDT) over the past few years. However, amorphous nanoaggregates usually occur in their preparation, resulting in loose packing with disordered molecular structures. This still allows free intramolecular motions, thus leading to limited brightness and PDT efficiency. Herein, we report deep-red AIE nanocrystals (NCs) of DTPA-BS-F by following the facile method of nanoprecipitation. It is observed that DTPA-BS-F NCs possess not only a high photoluminescence quantum yield value of 8% in the deep-red region (600-850 nm) but also an impressive reactive oxygen species (ROS) generation efficiency of up to 69%. Moreover, DTPA-BS-F NCs targeting dual-organelles of lysosomes and nucleus to generate ROS are also achieved, thus boosting the PDT effect in cancer therapy both in vitro and in vivo. This work provides high-performance AIE NCs to simultaneously target two organelles for efficient photodynamic therapy, indicating their promising application in all-in-one theranostic platforms.

An Approach to Developing Cyanines with Upconverted Photosensitive Efficiency Enhancement for Highly Efficient NIR Tumor Phototheranostics.

Upconverted reactive oxygen species (ROS) photosensitization with one-photon excitation mode is a promising tactic to elongate the excitation wavelengths of photosensitive dyes to near-infrared (NIR) light region without the requirement of coherent high-intensity light sources. However, the photosensitization efficiencies are still finite by the unilateral improvement of excited-state intersystem crossing (ISC) via heavy-atom-effect, since the upconverted efficiency also plays a decisive role in upconverted photosensitization. Herein, a NIR light initiated one-photon upconversion heavy-atom-free small molecule system is reported. The meso-rotatable anthracene in pentamethine cyanine (Cy5) is demonstrated to enrich the populations in high vibrational-rotational energy levels and subsequently improve the hot-band absorption (HBA) efficiency. Moreover, the spin-orbit charge transfer intersystem crossing (SOCT-ISC) caused by electron donated anthracene can further amplify the triplet yield. Benefiting from the above two aspects, the 1 O2 generation significantly increases with over 2-fold improved performance compared with heavy-atom-modified method under upconverted light excitation, which obtains efficient in vivo phototheranostic results and provides new opportunities for other applications such as photocatalysis and fine chemical synthesis.

Green-Solvent-Processable Low-Cost Fluorinated Hole Contacts with Optimized Buried Interface for Highly Efficient Perovskite Solar Cells.

Solution-processed hole contact materials, as an indispensable component in perovskite solar cells (PSCs), have been widely studied with consistent progress achieved. One bottleneck for the commercialization of PSCs is the lack of hole contact materials with high performance, cost-effective preparation, and green-solvent processability. Therefore, the development of versatile hole contact materials is of great significance. Herein, we report two novel donor-acceptor (D-A)-type hole contact molecules (FMPA-BT-CA and 2FMPA-BT-CA) with low cost and alcohol-based processability by utilizing a fluorination strategy. We showed that the fluorine atoms lead to the lowered highest occupied molecular orbital (HOMO) energy levels and larger dipole moments for FMPA-BT-CA and 2FMPA-BT-CA. Moreover, fluorination also improves the buried interfacial interaction between hole contacts and perovskite. As a result, a remarkable power conversion efficiency (PCE) of 22.37% along with good light stability could be achieved for green-solvent-processed FMPA-BT-CA-based inverted PSC devices, demonstrating the great potential of environmentally compatible hole contacts for highly efficient PSCs.

Revealing the Sole Impact of Acceptor's Molecular Conformation to Energy Loss and Device Performance of Organic Solar Cells through Positional Isomers.

Two new fused-ring electron acceptor (FREA) isomers with nonlinear and linear molecular conformation, m-BAIDIC and p-BAIDIC, are designed and synthesized. Despite the similar light absorption range and energy levels, the two isomers exhibit distinct electron reorganization energies and molecular packing motifs, which are directly related to the molecular conformation. Compared with the nonlinear acceptor, the linear p-BAIDIC shows more ordered molecular packing and higher crystallinity. Furthermore, p-BAIDIC-based devices exhibit reduced nonradiative energy loss and improved charge transport mobilities. It is beneficial to enhance the open-circuit voltage (VOC ) and short-current current density (JSC ) of the devices. Therefore, the linear FREA, p-BAIDIC yields a relatively higher efficiency of 7.71% in the binary device with PM6, in comparison with the nonlinear m-BAIDIC. When p-BAIDIC is incorporated into the binary PM6/BO-4Cl system to form a ternary system, synergistic enhancements in VOC , JSC , fill factor (FF), and ultimately a high efficiency of 17.6% are achieved.

Pushing the Efficiency of High Open-Circuit Voltage Binary Organic Solar Cells by Vertical Morphology Tuning.

The tuning of vertical morphology is critical and challenging for organic solar cells (OSCs). In this work, a high open-circuit voltage (VOC ) binary D18-Cl/L8-BO system is attained while maintaining the high short-circuit current (JSC ) and fill factor (FF) by employing 1,4-diiodobenzene (DIB), a volatile solid additive. It is suggested that DIB can act as a linker between donor or/and acceptor molecules, which significantly modifies the active layer morphology. The overall crystalline packing of the donor and acceptor is enhanced, and the vertical domain sizes of phase separation are significantly decreased. All these morphological changes contribute to exciton dissociation, charge transport, and collection. Therefore, the best-performing device exhibits an efficiency of 18.7% with a VOC of 0.922 V, a JSC of 26.6 mA cm-2 , and an FF of 75.6%. As far as it is known, the VOC achieved here is by far the highest among the reported OSCs with efficiencies over 17%. This work demonstrates the high competence of solid additives with two iodine atoms to tune the morphology, particularly in the vertical direction, which can become a promising direction for future optimization of OSCs.