Non-conjugated Research Articles

Rapid Synthesis of Propargyl‐γ‐Modified Peptide Nucleic Acid Monomers for Late‐Stage Functionalization of Oligomers

AbstractThe exceptional hybridization properties of peptide nucleic acids (PNAs) coupled with the ease of their synthesis has made this artificial nucleic acid mimetic a desirable platform for diagnostics, therapeutics and supramolecular engineering. PNA backbone modifications have been extensively explored to finetune physicochemical properties and for conjugation of functional molecules. Here, we detail the synthesis of a universal γ‐propargyl‐PNA backbone from serine, and its acylation with the four DNA canonical nucleobases. The availability of serine as d or l enantiomer provide simple accesses to PNA oligomers for hybridization with natural oligonucleotides or for orthogonal hybridization circuitry. We show that late‐stage conjugation enables optimization of the physicochemical properties. This approach is appealing due to its orthogonality to Fmoc‐SPPS, its flexibility and ease for introducing diversity by on‐resin copper(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC). We exemplified the utility of these novel monomers with PNA based hybridization chain reactions (HCRs).

The Synthesis of a Multiple D-A Conjugated Macrocycle and Its Application in Organic Photovoltaic.

As a novel class of materials, D-A conjugated macrocycles hold significant promise for chemical science. However, their potential in photovoltaic remains largely untapped due to the complexity of introducing multiple donor and acceptor moieties into the design and synthesis of cyclic π-conjugated molecules. Here, we report a multiple D-A ring-like conjugated molecule (RCM) via the coupling of dimer molecule DBTP-C3 as a template and thiophenes in high yields. RCM exhibits a narrow optical gap (1.33 eV) and excellent thermal stability, and shows a remarkable photoluminescence yield (ΦPL ) of 11.1 % in solution, much higher than non-cyclic analogues. Organic solar cell (OSC) constructed with RCM as electron acceptor shows efficient charge separation at donor-acceptor band offsets and achieves a power conversion efficiency (PCE) of 14.2 %-approximately fourfold higher than macrocycle-based OSCs reported so far. This is partly due to low non-radiative voltage loss down to 0.20 eV and a high electroluminescence yield (ΦEL ) of 4×10-4 . Our findings emphasize the potential of D-A cyclic conjugated molecules in advancing organic photovoltaic technology.

In-depth exploration of polysubstituted BOPHYs Dyes: Synthesis, photophysical, electrochemical, and theoretical properties

A family of new highly substituted and symmetrical BOPHYs with modulated optoelectronic properties was synthetized. The strategy consisted in the formation of pyrroles substituted with electron-donor or -withdrawing groups through the cycloaddition reaction between Fischer carbene and oxazolones. The absorption spectra of all compounds present a main peak due to the HOMO-LUMO electronic transition, as supported by the theoretical study. The maximum has large absorption coefficient ε (∼104 M−1cm−1) and is in the green region from 514 to 531 nm, red shifted with respect to unsubstituted BOPHY. The dihedral angle between the two bridged rings in the BOPHY core affects the degree of puckering, depending on the chemical modulation. The fluorescence spectra present excitonic features and pure color according to the CIE coordinates, from green, orange to almost red. Inside the family, the Stokes shift (Δν) follows the same trend as the maxima, and inversely with the fluorescence quantum yield (φ), being the most fluorescent (φ = 85%) the BOPHY with the lowest Stokes shift (Δν) (R1 = phenyl and R2 = methyl). BOPHYs are more difficult to oxidize and reduce than BODIPYs, displaying a shift in the anodic and cathodic potentials in regard to BODIPYs. The delocalization of charges in BOPHYs does not extend with an additional = N–BF2 nucleus, thus BOPHYs rather present a higher band gap reveling that are less conjugated molecules than mononucleous = N–BF2.

A systematic investigation of luminescent schiff bases: Photophysical and DFT studies

Conjugated molecular materials with fused rings are of considerable interest in area of organic electronics, because of their excellent charge carrier mobility and high stability. A highly Conjugated new Schiff base molecules have been designed, synthesized from p-hydroxyacetophenone, 1-naphthaldehyde and o-dianisidine, and characterized by standard spectroscopic techniques such as FT IR, NMR and Mass Spectral studies. DFT studies are performed to optimise the geometry of the molecule to study the electronic properties. From the DFT studies, the energy gap between first singlet and triplet excited state are found to be 0.102 eV, the value confirmed that molecule possessed better intersystem crossing ability. In order to evaluate the photostability of the molecule, the photophysical properties in various solvents (DMF, DMSO, acetonitrile, and ethanol) at different intervals of time were investigated systematically to demonstrate the relationships between molecular structures and photophysical properties. The results obtained indicated that the molecule showed good stability towards in DMSo medium as compared to the other solvents. The studies of electronic, optical and structural properties of the compound SB proves it to be a more efficient functional photovoltaic organic materials.

Pyrene-TEMPO-Modified Carbon Electrodes for Organic Radical Lithium-Ion Batteries

Organic radical batteries (ORBs) are a promising alternative to traditional lithium-ion batteries (LIBs) because of their environmentally friendly materials and potential to be low-cost, light weight, and mechanically flexible. Among ORB materials, stable organic radical polymers have great potential as high energy density and high power density cathode materials due to their small molecular weight and fast, reversible redox reactions. A stable radical polymer for LIB applications contains an organic radical unit with redox potentials suitable for the LIB anode or cathode that is immobilized on an electrode via a main chain polymer. Conductive and light-weight polymer main chains are necessary to ensure fast electron transfer to the current collector, without adding significant weight to the cell. Despite extensive research, organic radical materials present some key challenges which limit their present use in electrochemical cells. Many polymer backbones are non-conductive, leading to increased electrode resistance and poor cell performance at high charge/discharge rates. Many organic radical materials also have relatively low thermal stability and low packing density. Moreover, many organic radicals are soluble in typical organic battery electrolytes, resulting in capacity fading.In this research, we apply pyrene as a polymer backbone to 2,2,6,6-tetramethyl-piperidine-1-oxyl radical (TEMPO) for the first time in LIB applications to reduce the solubility of the active organic radical and enable π−π stacking interactions with aromatic carbons. We prepared a surface-immobilized p–TEMPO on fullerene C60 and graphene foam (GF) electrodes via π−π stacking interactions to increase electrode conductivity. Pyrene is used to modify certain carbon allotropes via π−π stacking interactions. It was hypothesized that this approach would enable strong bond formation of the TEMPO radical with the electrode, while providing a non-destructive and simple modification approach of conductive carbon surfaces. The successful conjugation of pyrene and TEMPO molecules was established by NMR spectroscopy. The redox activity of p-TEMPO in LIB electrolytes was validated in solution. The non-covalent attachment of p-TEMPO to fullerene C60 and GF electrodes was established by XPS. The mechanisms and reversibility of the TEMPO redox reaction was then explored for p-TEMPO immobilized on the carbon electrodes. While both electrodes showed diffusion-limited current, and quasi-reversible reactions, C60-p-TEMPO has better reversibility and less resistance than GF-p-TEMPO. C60-p-TEMPO electrodes exhibit exceptional cycling stability over 600 cycles. These results are outstanding as the C60 has a high tendency to dissolve in LIB electrolytes. LIB half-cell testing identified challenges and opportunities for the p-TEMPO-modified electrodes. C60-p-TEMPO discharge capacity at ~5C rate is comparable to PTMA-based literature, however no distinct TEMPO response was observed in the charge or discharge curves. GF-p-TEMPO electrodes showed a TEMPO response in cycle 1 only, suggesting possible p-TEMPO dissolution in the electrolyte. Overall, the results show that the use of a noncovalent immobilization method allows facile preparation of p-TEMPO functionalized electrodes and demonstrates the potential of p-TEMPO noncovalent bonding in organic LIB applications. Figure 1

Generalizable Electrochemical Biosensors Using DNA-Analyte Conjugates Integrated with Pneumatic Oscillators for Microfluidic Workflow Automation

Sensors based on electrochemical (EC) readout offer low cost, miniaturization, and adaptability to the point-of-care (POC). Nonetheless, most EC sensors are specialized to a particular target, and there remains a need for a robust EC biosensor platform for the multitude of biomarkers that are not EC-active, do not undergo enzymatic conversion, or are not suited for potentiometry [1,2]. While aptamer-based EC sensors have been proven for sensing in living animals with temporal resolution of a few seconds [3], most method development has been target-focused, lacking generalizability [4]. Presently, the clinical EC toolbox is a conglomerate of targeted methods, and there is a pressing need to develop a single EC platform amenable to rapid, generalizable, quantitative readout of multiple classes of clinically relevant targets. A direct, generalized EC sensing approach with minimal added reagents or amplification steps is preferred [5,6]. Our group has been working to address this need and expand to more analyte classes for several years, and in 2019 we designed a versatile DNA-nanostructure architecture attached to gold electrode surfaces [6]. In this work, we will discuss our efforts to expand the generalizability of our sensor platform, chiefly through custom synthesis of varied DNA-analyte bioconjugates to incorporate within the DNA-nanostructure, specifically DNA-peptide and DNA-small molecule conjugates. Using the same DNA nano-architecture, sensors have been validated in 98% human serum for a variety of targets, several encompassing the human clinical range—a peptide drug (exendin-4) [7], a larger protein (creatine kinase), and smaller molecules or steroid hormones (testosterone, estradiol, progesterone, cortisol). Overall, this new DNA nanostructure platform provides a generalizable sensor with minimal workflow, direct-readout, and the capability to expand EC sensing to a wide variety of clinically important analytes. These sensors can measure antibodies directly without any reagent addition, and the small-molecule or peptide sensors require just a two-step workflow. While the workflow is minimal, the EC measurements benefit from well-controlled solution pH, ionic strength, etc. As such, automated fluidic handling can enhance the user-friendliness of the sensors while maintaining measurement quality. We will also discuss several advancements in automating microfluidic flow control, leveraging digital circuit analogies to develop on-chip pneumatic circuits [8,9]. Using devices fabricated by inexpensive, resin-based 3D printers, we have developed robust pneumatic oscillators that can control on-chip valves for pumping solutions to the EC sensors. The oscillators are automated and tunable from 0.5 to 100 Hz and can pump multiple solutions on microdevices with only a single vacuum input line. Antibody reagents and samples can be mixed automatically then introduced to the electrode, and buffer washes can be included to improve measurement consistency. Ultimately, by integrating this automated microfluidic control with our generalizable EC sensors in the future, many different analytes should be measurable consistently and in a user-friendly manner.

Peptide Hydrogels and Nanostructures Controlling Biological Machinery.

Peptides are versatile building blocks for the fabrication of various nanostructures that result in the formation of hydrogels and nanoparticles. Precise chemical functionalization promotes discrete structure formation, causing controlled bioactivity and physical properties for functional materials development. The conjugation of small molecules on amino acid side chains determines their intermolecular interactions in addition to their intrinsic peptide characteristics. Molecular information affects the peptide structure, formation, and activity. In this Perspective, peptide building blocks, nanostructure formation mechanisms, and the properties of these peptide materials are discussed with the results of recent publications. Bioinstructive and stimuli-responsive peptide materials have immense impacts on the nanomedicine field including drug delivery, cellular engineering, regenerative medicine, and biomedicine.

Polyethylene Glycol-Mediated Directional Conjugation of Biological Molecules for Enhanced Immunoassays at the Point-of-Care.

Rapid and reliable point-of-care (POC) diagnostic tests can have a significant impact on global health. One of the most common approaches for developing POC systems is the use of target-specific biomolecules. However, the conjugation of biomolecules can result in decreased activity, which may compromise the analytical performance and accuracy of the developed systems. To overcome this challenge, we present a polymer-based cross-linking protocol for controlled and directed conjugation of biological molecules. Our protocol utilizes a bifunctional thiol-polyethylene glycol (PEG)-hydrazide polymer to enable site-directed conjugation of IgG antibodies to the surface of screen-printed metal electrodes. The metal surface of the electrodes is first modified with thiolated PEG molecules, leaving the hydrazide groups available to react with the aldehyde group in the Fc fragments of the oxidized IgG antibodies. Using anti-Klebsiella pneumoniae carbapenemase-2 (KPC-2) antibody as a model antibody used for antimicrobial resistance (AMR) testing, our results demonstrate a ~10-fold increase in antibody coupling compared with the standard N-hydroxysuccinimide (NHS)-based conjugation chemistry and effective capture (>94%) of the target KPC-2 enzyme antigen on the surface of modified electrodes. This straightforward and easy-to-perform strategy of site-directed antibody conjugation can be engineered for coupling other protein- and non-protein-based biological molecules commonly used in POC testing and development, thus enhancing the potential for improved diagnostic accuracy and performance.

Formation of whey protein isolate–dextran conjugates by Maillard reaction with ethanol-water pretreatment

A simple, efficient, and low-cost Maillard reaction method was developed through ethanol-water pretreatment. The formation of whey protein isolate (WPI)–dextran conjugates was confirmed using the degree of glycosylation, ultraviolet absorbance, browning intensity, color, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The significant conformational changes were illuminated because of the higher wavenumber shift of absorption peaks of FTIR amide I, II, and III bands, the reduction of fluorescent signal, and the decrease of surface hydrophobicity. Scanning electron microscopy revealed the morphological transition of WPI from a smooth sphere to an inhomogeneous block structure with rough and uneven surface before and after covalent grafting of dextran. The strong steric hindrance and abundant hydrophilic hydroxyl groups from covalently conjugated dextran dramatically inhibited the aggregation between conjugate molecules which exhibited low turbidity and good solubility in a wide pH range from 2.0 to 10.0. Emulsifying activity and emulsifying stability of WPI were significantly improved after glycosylation. This work will be beneficial to control the formation of light-colored Maillard reaction products under high substrate concentration, high reaction rate, and low water content at mild temperatures for short processing time, and to facilitate the large-scale preparation of glycosylated protein with desirable physicochemical properties.

Hybrid organic/inorganic interface: in situ and ex situ characterization in terms of structure, morphology, electronic and magnetic properties

Organic conjugated molecules are promising media to host spin-polarized carriers, due to their weak spin relaxation mechanisms. Here, we fabricated a metal–hybrid organic–inorganic complex oxide heterostructure made of Fe–Phthalocyanine (FePc): Co(0.5 nm)/FePc(0; 0.5; 1 nm)/La0.67Sr0.33MnO3/SrTiO3 and investigated the interface structure and chemical bonding, and overall magnetic properties. Details about the Co/FePc and FePc/LSMO interfaces were obtained through X-ray photoelectron and absorption characterizations. The combined in-situ and ex-situ magnetic measurements of the heterostructure indicates the contribution of FePc and Co moments to the overall magnetic response. Moreover, these measurements indicate that the LSMO bulk magnetic properties were not canceled out by the surface treatment, but favored the formation of a magnetic dead layer. The hybrid heterostructure presents a modification of the saturation magnetization attributed to the contribution of the molecular layer. The present results are a step forward in the engineering of hybrid organic/inorganic interfaces.

Antibody Polymer Conjugates (APCs) for Active Targeted Therapeutic Delivery.

Antibody drug conjugates (ADCs) are poised to have an enormous impact on targeted nanomedicine, especially in many cancer pathologies. The reach of the current format of ADCs is limited by their low drug-to-antibody ratio (DAR) because of the associated physiochemical instabilities. Here, we design antibody polymer conjugates (APCs) as a modular strategy to utilize polymers to address ADC's shortcomings. We show here that conjugation of polymer-based therapeutic molecules to antibodies helps increase the DAR, owing to the hydrophilic comonomer in the polymer that helps in masking the increased hydrophobicity caused by high drug loading. We show that the platform exhibits cell targetability and selective cell killing in multiple cell lines expressing disease-relevant antigens, viz., HER2 and EGFR. The ability to use different functionalities in the drug as the handle for polymer attachment further demonstrates the platform nature of APCs. The findings here could serve as an alternative design strategy for the next generation of active targeted nanomedicine.

Stable Deep‐Blue Electroluminescence from Hierarchical Crystalline Structure Based on Planar Conformational Terfluorenes: Benefits of Preventing Defect Structures Formation

AbstractLiner‐type organic conjugated molecules with 1D π‐electron delocalization present conformation‐dependent intramolecular optoelectronic behavior. Significantly different from non‐planar ones, the coplanar conformational backbone of π‐conjugated molecules can enhance intramolecular π‐electron delocalization and dominate intermolecular π‐electron coupling, which are the fundamental parameters for improving their optoelectronic properties. Herein, the effect of the formation of coplanar conformation on intermolecular packing and optoelectrical properties of liner‐type steric terfluorene (DSFX‐SFSO) toward solution‐processed deep‐blue organic light‐emitting diodes (OLEDs) is systematically demonstrated. Firstly, uniform and continuous crystalline films based on the planar conformational DSFX‐SFSO molecules are achieved via thermal annealing at 160 °C, which can avoid microscale crystallization processing. Contrary to amorphous ones, these hierarchical crystalline films present robust deep‐blue emission with an efficiency of > 60%, due to the suppression of defect structures. More interestingly, this hierarchical crystalline film has a stable and efficient deep‐blue electroluminescence (CIE: 0.15, 0.09) without the obvious defective green‐band emission, even at 500 mA cm−2, also further confirming the excellent and perfect molecular landscape to obtain single‐chromophore excitonic behavior from single planar‐terfluorene segments. Therefore, obtaining a uniform hierarchical structure based on planar conformational molecules is an effective strategy to optimize the optoelectrical properties for optoelectronic applications.

Electronic coarse-graining of long conjugated molecules: Case study of non-fullerene acceptors.

By considering only one electronic state per molecule, charge transport models of molecular solids neglect intramolecular charge transfer. This approximation excludes materials with quasi-degenerate spatially separated frontier orbitals, such as non-fullerene acceptors (NFAs) and symmetric thermally activated delayed fluorescence emitters. By analyzing the electronic structure of room-temperature molecular conformers of a prototypical NFA, ITIC-4F, we conclude that the electron is localized on one of the two acceptor blocks with the mean intramolecular transfer integral of 120meV, which is comparable with intermolecular couplings. Therefore, the minimal basis for acceptor-donor-acceptor (A-D-A) molecules consists of two molecular orbitals localized on the acceptor blocks. This basis is robust even with respect to geometry distortions in an amorphous solid, in contrast to the basis of two lowest unoccupied canonical molecular orbitals withstanding only thermal fluctuations in a crystal. The charge carrier mobility can be underestimated by a factor of two when using single site approximation for A-D-A molecules in their typical crystalline packings.

Donor-acceptor-donor small molecules for fluorescence/photoacoustic imaging and integrated photothermal therapy.

Here, a D-A-D type fluorescent conjugated molecule with a high molar absorption coefficient and emission at 1120 nm in the near-infrared region was synthesized. Conjugated molecules and two polyethylene glycol polymers with different lipophilic ends are assembled into water-soluble nanoparticles to improve their biocompatibility. Then, their physical and chemical properties were studied and compared. Compared with phospholipid-based PEG, styrene-based PEG can reduce the π-π stacking between molecules and the quenching caused by molecular aggregation. It has more advantages in particle size and fluorescence performance and can be better used in biological imaging. In addition, the Nano-particles have good photo-thermal conversion efficiency; the temperature rises to 62.8°C after 980 nm irradiation for 6 min, which can be used as a potential near-infrared II photothermal therapeutic agent. In vivo imaging experiments confirmed that nanomaterials have fluorescence, photoacoustic dual-modal imaging and good biological safety. STATEMENT OF SIGNIFICANCE: In this work, we constructed D-A-D type dual donor fluorescent molecules using BBTD, CPDT and EDOT, and used amphiphilic polymers to improve their biocompatibility. Compared with DSPE NPs, PS-NPs can reduce intermolecular π-π stacking and increase quantum yield (QY=0.98 %). Deep penetration and low biological toxicity make it have biomedical value and realize the integration of multi-functional collaborative imaging. This work can still be further improved and supplemented, and the molecular structure can be optimized to improve its application in biomedical imaging.

Extremely Electron‐Withdrawing Lewis‐Paired CN Groups for Organic p‐Dopants

AbstractP‐type chemical doping (p‐doping) is a key technique to modulate the optical, electrical, and electronic properties of organic semiconductors. However, typical functional groups in organic p‐dopants have insufficient electron‐withdrawing strength, and the inevitable diffusion of dopants in host matrices degrades doping stabilities. Herein, we utilize extremely electron‐withdrawing Lewis‐paired CN groups as a new class of building blocks for designing unprecedentedly strong organic p‐dopants with excellent doping stability. Various Lewis acids are paired with CN‐functionalized conjugated molecules in the solution state, which strengthens the electron‐withdrawing properties of CN groups almost twofold. The large dopants afford outstanding doping stability against continuous heating and long‐term atmospheric exposure, which is promising for practical applications in devices. Given the broad applicability of this simple combinatorial approach, it may impact many fields of (opto)electronics.

Extremely Electron-Withdrawing Lewis-Paired CN Groups for Organic p-Dopants.

P-type chemical doping (p-doping) is a key technique to modulate the optical, electrical, and electronic properties of organic semiconductors. However, typical functional groups in organic p-dopants have insufficient electron-withdrawing strength, and the inevitable diffusion of dopants in host matrices degrades doping stabilities. Herein, we utilize extremely electron-withdrawing Lewis-paired CN groups as a new class of building blocks for designing unprecedentedly strong organic p-dopants with excellent doping stability. Various Lewis acids are paired with CN-functionalized conjugated molecules in the solution state, which strengthens the electron-withdrawing properties of CN groups almost twofold. The large dopants afford outstanding doping stability against continuous heating and long-term atmospheric exposure, which is promising for practical applications in devices. Given the broad applicability of this simple combinatorial approach, it may impact many fields of (opto)electronics.

Foldamer Nanotubes Mediated Label-Free Detection of Protein-Small Molecule Interactions.

Development of miniaturized lab-on-chip devices for the detection of rapid and specific small molecule-protein binding interactions at very low concentrations holds significant importance in drug discovery and biomedical applications. Here, the label-free detection of small molecule-protein interactions is reported on the surface functionalizable nanotubes of α,γ-hybrid peptide helical foldamers using nanoscale capacitance and impedance spectroscopy. The 12-helix conformation of the α,γ-hybrid peptide observed in the single crystals, self-assembled into nanotubes in an aqueous environment with exposed cysteine thiols for small molecule conjugation. The binding of streptavidin to the covalently linked biotin on the surface of nanotubes was detected at the picomolar concentrations. No change in the capacitance and impedance were observed in the absence of either immobilized biotin or protein streptavidin. The functionalizable hybrid peptide nanotubes reported here pave the way for the label-free detection of various small molecule protein interactions at very low concentrations.

Phenylboronic Ester-Bridged Chitosan/Myricetin Nanomicelle for Penetrating the Endothelial Barrier and Regulating Macrophage Polarization and Inflammation against Ischemic Diseases.

The brain and liver are more susceptible to ischemia and reperfusion (IR) injury (IRI), which triggers the reactive oxygen species (ROS) burst and inflammatory cascade and results in severe neuronal damage or hepatic injury. Moreover, the damaged endothelial barrier contributes to proinflammatory activity and limits the delivery of therapeutic agents such as some macromolecules and nanomedicine despite the integrity being disrupted after IRI. Herein, we constructed a phenylboronic-decorated chitosan-based nanoplatform to deliver myricetin, a multifunctional polyphenol molecule for the treatment of cerebral and hepatic ischemia. The chitosan-based nanostructures are widely studied cationic carriers for endothelium penetration such as the blood-brain barrier (BBB) and sinusoidal endothelial barrier (SEB). The phenylboronic ester was chosen as the ROS-responsive bridging segment for conjugation and selective release of myricetin molecules, which meanwhile scavenged the overexpressed ROS in the inflammatory environment. The released myricetin molecules fulfill a variety of roles including antioxidation through multiple phenolic hydroxyl groups, inhibition of the inflammatory cascade by regulation of the macrophage polarization from M1 to M2, and endothelial injury repairment. Taken together, our present study provides valuable insight into the development of efficient antioxidant and anti-inflammatory platforms for potential application against ischemic disease.

Visualizing the multi-level assembly structures of conjugated molecular systems with chain-length dependent behavior

It remains challenging to understand the structural evolution of conjugated polymers from single chains to solvated aggregates and film microstructures, although it underpins the performance of optoelectrical devices fabricated via the mainstream solution processing method. With several ensemble visual measurements, here we unravel the morphological evolution process of a model system of isoindigo-based conjugated molecules, including the hidden molecular assembly pathways, the mesoscale network formation, and their unorthodox chain dependence. Short chains show rigid chain conformations forming discrete aggregates in solution, which further grow to form a highly ordered film that exhibits poor electrical performance. In contrast, long chains exhibit flexible chain conformations, creating interlinked aggregates networks in solution, which are directly imprinted into films, forming interconnective solid-state microstructure with excellent electrical performance. Visualizing multi-level assembly structures of conjugated molecules provides a deep understanding of the inheritance of assemblies from solution to solid-state, accelerating the optimization of device fabrication.

Doubly Strapped Zwitterionic NIR‐I and NIR‐II Heptamethine Cyanine Dyes for Bioconjugation and Fluorescence Imaging

AbstractHeptamethine cyanine dyes enable deep tissue fluorescence imaging in the near infrared (NIR) window. Small molecule conjugates of the benchmark dye ZW800‐1 have been tested in humans. However, long‐term imaging protocols using ZW800‐1 conjugates are limited by their instability, primarily because the chemically labile C4′‐O‐aryl linker is susceptible to cleavage by biological nucleophiles. Here, we report a modular synthetic method that produces novel doubly strapped zwitterionic heptamethine cyanine dyes, including a structural analogue of ZW800‐1, with greatly enhanced dye stability. NIR‐I and NIR‐II versions of these doubly strapped dyes can be conjugated to proteins, including monoclonal antibodies, without causing undesired fluorophore degradation or dye stacking on the protein surface. The fluorescent antibody conjugates show excellent tumor‐targeting specificity in a xenograft mouse tumor model. The enhanced stability provided by doubly strapped molecular design will enable new classes of in vivo NIR fluorescence imaging experiments with possible translation to humans.