Molecular Dynamic Studies of Dye-Dye and Dye-DNA Interactions Governing Excitonic Coupling in Squaraine Aggregates Templated by DNA Holliday Junctions.

Dye molecules, arranged in an aggregate, can display excitonic delocalization. The use of DNA scaffolding to control aggregate configurations and delocalization is of research interest. Here, we applied Molecular Dynamics (MD) to gain an insight on how dye-DNA interactions affect excitonic coupling between two squaraine (SQ) dyes covalently attached to a DNA Holliday junction (HJ). We studied two types of dimer configurations, i.e., adjacent and transverse, which differed in points of dye covalent attachments to DNA. Three structurally different SQ dyes with similar hydrophobicity were chosen to investigate the sensitivity of excitonic coupling to dye placement. Each dimer configuration was initialized in parallel and antiparallel arrangements in the DNA HJ. The MD results, validated by experimental measurements, suggested that the adjacent dimer promotes stronger excitonic coupling and less dye-DNA interaction than the transverse dimer. Additionally, we found that SQ dyes with specific functional groups (i.e., substituents) facilitate a closer degree of aggregate packing via hydrophobic effects, leading to a stronger excitonic coupling. This work advances a fundamental understanding of the impacts of dye-DNA interactions on aggregate orientation and excitonic coupling.

Structural and optical variation of pseudoisocyanine aggregates nucleated on DNA substrates.

Coherently coupled pseudoisocyanine (PIC) dye aggregates have demonstrated the ability to delocalize electronic excitations and ultimately migrate excitons with much higher efficiency than similar designs where excitations are isolated to individual chromophores. Here, we report initial evidence of a new type of PIC aggregate, formed through heterogeneous nucleation on DNA oligonucleotides, displaying photophysical properties that differ significantly from previously reported aggregates. This new aggregate, which we call the super aggregate (SA) due to the need for elevated dye excess to form it, is clearly differentiated from previously reported aggregates by spectroscopic and biophysical characterization. In emission spectra, the SA exhibits peak narrowing and, in some cases, significant quantum yield variation, indicative of stronger coupling in cyanine dyes. The SA was further characterized with circular dichroism and atomic force microscopy observing unique features depending on the DNA substrate. Then by integrating an AlexaFluorTM647 (AF) dye as an energy transfer acceptor into the system, we observed mixed energy transfer characteristics using the different DNA. For example, SA formed with a rigid DNA double crossover tile (DX-tile) substrate resulted in AF emission sensitization. While SA formed with more flexible non-DX-tile DNA (i.e. duplex and single strand DNA) resulted in AF emission quenching. These combined characterizations strongly imply that DNA-based PIC aggregate properties can be controlled through simple modifications to the DNA substrate's sequence and geometry. Ultimately, we aim to inform rational design principles for future device prototyping. For example, one key conclusion of the study is that the high absorbance cross-section and efficient energy transfer observed with rigid substrates made for better photonic antennae, compared to flexible DNA substrates.

Data-Driven and Multiscale Modeling of DNA-Templated Dye Aggregates.

Dye aggregates are of interest for excitonic applications, including biomedical imaging, organic photovoltaics, and quantum information systems. Dyes with large transition dipole moments (µ) are necessary to optimize coupling within dye aggregates. Extinction coefficients (ε) can be used to determine the µ of dyes, and so dyes with a large ε (>150,000 M−1cm−1) should be engineered or identified. However, dye properties leading to a large ε are not fully understood, and low-throughput methods of dye screening, such as experimental measurements or density functional theory (DFT) calculations, can be time-consuming. In order to screen large datasets of molecules for desirable properties (i.e., large ε and µ), a computational workflow was established using machine learning (ML), DFT, time-dependent (TD-) DFT, and molecular dynamics (MD). ML models were developed through training and validation on a dataset of 8802 dyes using structural features. A Classifier was developed with an accuracy of 97% and a Regressor was constructed with an R2 of above 0.9, comparing between experiment and ML prediction. Using the Regressor, the ε values of over 18,000 dyes were predicted. The top 100 dyes were further screened using DFT and TD-DFT to identify 15 dyes with a µ relative to a reference dye, pentamethine indocyanine dye Cy5. Two benchmark MD simulations were performed on Cy5 and Cy5.5 dimers, and it was found that MD could accurately capture experimental results. The results of this study exhibit that our computational workflow for identifying dyes with a large µ for excitonic applications is effective and can be used as a tool to develop new dyes for excitonic applications.

Interfacing DNA nanotechnology and biomimetic photonic complexes: advances and prospects in energy and biomedicine.

Self-assembled photonic systems with well-organized spatial arrangement and engineered optical properties can be used as efficient energy materials and as effective biomedical agents. The lessons learned from natural light-harvesting antennas have inspired the design and synthesis of a series of biomimetic photonic complexes, including those containing strongly coupled dye aggregates with dense molecular packing and unique spectroscopic features. These photoactive components provide excellent features that could be coupled to multiple applications including light-harvesting, energy transfer, biosensing, bioimaging, and cancer therapy. Meanwhile, nanoscale DNA assemblies have been employed as programmable and addressable templates to guide the formation of DNA-directed multi-pigment complexes, which can be used to enhance the complexity and precision of artificial photonic systems and show the potential for energy and biomedical applications. This review focuses on the interface of DNA nanotechnology and biomimetic photonic systems. We summarized the recent progress in the design, synthesis, and applications of bioinspired photonic systems, highlighted the advantages of the utilization of DNA nanostructures, and discussed the challenges and opportunities they provide.

A Supramolecular Strategy to Engineering a Non-photobleaching and Near-Infrared Absorbing Nano-J-Aggregate for Efficient Photothermal Therapy.

The design of organic photothermal agents (PTAs) for in vivo applications face a demanding set of performance requirements, especially intense NIR-absorptivity and sufficient photobleaching resistance. J-aggregation offers a facile way to tune the optical properties of dyes, thus providing a general design platform for organic PTAs with the desired performance. Herein, we present a supramolecular strategy to build a water-stable, nonphotobleaching, and NIR-absorbing nano-PTA (J-NP) from J-aggregation of halogenated BODIPY dyes (BDP) for efficient in vivo photothermal therapy. Multiple intermolecular halogen-bonding and π-π stacking interactions triggered the formation of BDP J-aggregate, which adsorbed amphiphilic polymer chains on the surface to provide PEGylated sheetlike nano-J-aggregate (J-NS). We serendipitously discovered that the architecture of J-NS was remodeled during a long-time ultrafiltration process, generating a discrete spherical nano-J-aggregate (J-NP) with controlled size. Compared with J-NS, the remodeled J-NP significantly improved cellular uptake efficiency. J-aggregation brought J-NP striking photothermal performance, such as strong NIR-absorptivity, high photothermal conversion efficiency up to 72.0%, and favorable nonphotobleaching ability. PEGylation and shape-remodeling imparted by the polymer coating enabled J-NP to hold biocompatibility and stability in vivo, thereby exhibiting efficient antitumor photothermal activities. This work not only presents a facile J-aggregation strategy for preparing PTAs with high photothermal performance but also establishes a supramolecular platform that enables the appealing optical functions derived from J-aggregation to be applied in vivo.

Near-Infrared Laser-Triggered In Situ Dimorphic Transformation of BF2-Azadipyrromethene Nanoaggregates for Enhanced Solid Tumor Penetration.

The shape of a drug delivery system impacts its in vivo behavior such as circulation time, accumulation, and penetration. Considering the advantages of functional dyes in bioapplications, we synthesize a class of nanoaggregates based on BF2-azadipyrromethene (aza-BODIPY) dyes, which can realize long blood circulation and deep tumor penetration simultaneously in vivo through morphological transformation modulated by a near-infrared (NIR) laser. First, when the temperature increases, the wormlike nanofibers of the aza-BODIPY-1 aggregate, possessing a long blood circulation time, can be transformed into spherical nanoparticles, which are conducive to increasing the penetration in the solid tumor. Second, without any postmodification, the nanofibers exhibit an outstandingly narrow absorption band in the NIR spectral range, so that they possess ideal photothermal properties. Through 655 nm laser irradiation, the intrinsic photothermal effect causes a local temperature increase to ∼48 °C, realizing the transformation of 1-NFs to 1-NPs. Third, the morphological transformation is real-time detected by photoacoustic (PA) imaging. By monitoring the change of the PA signal at a specific wavelength, the in vivo deformation process of nanomaterials can be traced. Consequently, the in situ morphology transformation of aza-BODIPY-based nanomaterials can simultaneously realize long blood circulation and deep penetration, resulting in the enhanced antitumor outcome.

Living Supramolecular Polymerization of an Aza-BODIPY Dye Controlled by a Hydrogen-Bond-Accepting Triazole Unit Introduced by Click Chemistry.

An aza-BODIPY dye 1 bearing two hydrophobic fan-shaped tridodecyloxybenzamide pendants through 1,2,3-triazole linkages was synthesized by a click reaction and characterized. 1 H NMR studies indicated that dye 1 exhibited variable conformations through intramolecular H-bonding interaction, which is beneficial for the polymorphism of aggregation. The thermodynamic, structural, and kinetic aspect of the supramolecular polymerization of dye 1 was investigated by UV/Vis absorption spectroscopy, IR spectroscopy, AFM, TEM, and SEM. Biphasic aggregation pathways of dye 1, leads to the formation of off-pathway, metastable Agg. I and thermodynamically stable Agg. II with distinct H-aggregation spectra and nanoscale morphology. The living manner of the supramolecular polymerization of dye 1 was demonstrated in seeded polymerization experiments with temperature-modulated successive cooling-heating cycles.

Coupled Cooperative Supramolecular Polymerization: A New Model Applied to the Competing Aggregation Pathways of an Amphiphilic aza-BODIPY Dye into Spherical and Rod-Like Aggregates.

Based on our studies on biphasic self-assembly behavior of an amphiphilic BF2 -azadipyrromethene (aza-BODIPY) dye 1, a new analytical model to quantitatively describe the thermodynamic properties of the aggregation involving two competing supramolecular polymerization processes is proposed. In this model, the formation of the metastable as well as the thermodynamically stable aggregates was considered to follow a nucleated polymerization mechanism. The numerical calculation based on the new model gives insight into the formation of different species in such complicate aggregate systems. Moreover, the aggregation of the biphasic self-assembly processes for dye 1 was investigated by concentration-dependent UV/Vis spectroscopy. The experimental data were analyzed by using the new model to evaluate the thermodynamic parameters including aggregation constants, the size of nuclei, and the cooperativity the two types of aggregates.

Exciton Coupling of Merocyanine Dyes from H- to J-type in the Solid State by Crystal Engineering.

A key issue for the application of π-conjugated organic molecules as thin film solid-state materials is the packing structure, which drastically affects optical and electronic properties due to intermolecular coupling. In this regard, merocyanine dyes usually pack in H-coupled antiparallel arrangements while structures with more interesting J-type coupling have been rarely reported. Here we show that for three highly dipolar merocyanine dyes, which exhibit the same π-scaffold and accordingly equal properties as monomers in solution, the solid-state packing can be changed by a simple variation of aliphatic substituents to afford narrow and intense absorption bands with huge hypsochromic (H) or bathochromic (J) shifts for their thin films and nanocrystals. Time-dependent density functional theory calculations show that the energetic offset of almost 1 eV magnitude results from distinct packing motifs within the crystal structures that comply with the archetype H- or J-aggregate structures as described by Kasha's exciton theory.

Optical absorption signature of a self-assembled dye monolayer on graphene.

A well-organized monolayer of alkylated perylene-3,4,9,10-tetracarboxylic-3,4,9,10-diimide (PTCDI) has been formed onto CVD graphene transferred on a transparent substrate. Its structure has been probed by scanning tunnelling microscopy and its optical properties by polarized transmission spectroscopy at varying incidence. The results show that the transition dipoles of adsorbed PTCDI are all oriented parallel to the substrate. The maximum absorption is consistent with the measured surface density of molecules and their absorption cross section. The spectrum presents mainly a large red-shift of the absorption line compared with the free molecules dispersed in solution, whereas the relative strengths of the vibronic structures are preserved. These changes are attributed to non-resonant interactions with the graphene layer and the neighbouring molecules.

Direct Measurement of Energy Migration in Supramolecular Carbocyanine Dye Nanotubes.

Exciton transport lengths in double-walled and bundled cylindrical 3,3'-bis- (2-sulfopropyl)-5,5',6,6'-tetrachloro-1,1'-dioctylbenzimida-carbocyanine (C8S3) J-aggregates were measured using direct imaging of fluorescence from individual aggregates deposited on solid substrates. Regions identified in confocal images were excited with a focused laser spot, and the resulting fluorescence emission was imaged onto an electron multiplying charged coupled device camera. A two-dimensional Gaussian fitting scheme was used to quantitatively compare the excitation beam profile to the broadened aggregate emission profiles. The double-walled tubes exhibit average exciton transport lengths of 140 nm, while exciton transport in the bundled nanotubes was found to be remarkably long, with distances reaching many hundreds of nanometers. A steady-state one-dimensional diffusion model for the broadening of the emission profiles yields diffusion coefficients of 120 nm(2) ps(-1) for the nanotubes and 7000 nm(2) ps(-1) for the aggregate bundles. The level of structural hierarchy dramatically affects the exciton transport capabilities in these artificial light-harvesting systems, and energy migration is not limited to a single dimension in J-aggregate bundles.