NIR-II emissive donor-acceptor-donor fluorophores for dual fluorescence bioimaging and photothermal therapy applications.

Fluorescence bioimaging with near-infrared II (NIR-II) emissive organic fluorophores has proven to be a viable noninvasive diagnostic technique. However, there is still the need for the development of fluorophores that possess increased stability as well as functionalities that impart stimuli responsiveness. Through strategic design, we can synthesize fluorophores that possess not only NIR-II optical profiles but also pH-sensitivity and the ability to generate heat upon irradiation. In this work, we employ a donor-acceptor-donor (D-A-D) design to synthesize a series of NIR-II fluorophores. Here we use thienothiadiazole (TTD) as the acceptor, 3-hexylthiophene (HexT) as the π-spacer and vary the alkyl amine donor units: N,N-dimethylaniline (DMA), phenylpiperidine (Pip), and phenylmorpholine (Morp). Spectroscopic analysis shows that all three derivatives exhibit emission in the NIR-II region with λemimax ranging from 1030 to 1075 nm. Upon irradiation, the fluorophores exhibited noticeable heat generation through non-radiative processes. The ability to generate heat indicates that these fluorophores will act as theranostic (combination therapeutic and diagnostic) agents in which simultaneous visualization and treatment can be performed. Additionally, biosensing capabilities were supported by changes in the absorbance properties while under acidic conditions as a result of protonation of the alkyl amine donor units. The fluorophores also show minimal toxicity in a human mammary cell line and with murine red blood cells. Overall, initial results indicate viable NIR-II materials for multiple biomedical applications.

Symmetric dicyanobenzothiadiazole (DCBT) dyes with a 1.5 eV excited state reduction potential range.

Strong molecular photooxidants are important in many disciplines including organic synthesis and renewable energy. In these fields, strongly oxidizing chromophores are employed to drive various transformations from challenging bond formations to energy storage systems. A range of photooxidant strengths are needed to drive these processes. A series of 8 symmetrically bisarylated 5,6-dicyano[2,1,3]benzothiadiazole (DCBT) dyes were studied for their tunability toward breadth of light absorption and photooxidant strength. The dye oxidation strength and light absorption tunability is the result of appending various aryl substituents on the periphery of the DCBT core which shows remarkable tunability of the final chromophore. The dyes are studied via steady-state absorption and emission, time-correlated single photon counting, computational analysis, and cyclic voltammetry. In changing the peripheral aryl substituents via electronics, sterics, and π-conjugation length, a series of dyes are arrived at with a dramatic 1.5 eV range in oxidizing strength and >200 nm (0.95 eV) absorption maxima tunability. Furthermore, two dyes in the series exhibit strong oxidizing strength while still approaching red light absorbance (>650 nm onset) which provides unique opportunities for the use of lower energy light to affect chemical transformations. Ultimately, this series provides options for photooxidations that allow for energetic tuning and selectivity for a given chemical transformation.

Synthesis and Characterization of Novel Thienothiadiazole-Based D-π-A-π-D Fluorophores as Potential NIR Imaging Agents.

As fluorescence bioimaging has increased in popularity, there have been numerous reports on designing organic fluorophores with desirable properties amenable to perform this task, specifically fluorophores with emission in the near-infrared II (NIR-II) region. One such strategy is to utilize the donor-π-acceptor-π-donor approach (D-π-A-π-D), as this allows for control of the photophysical properties of the resulting fluorophores through modulation of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels. Herein, we illustrate the properties of thienothiadiazole (TTD) as an effective acceptor moiety in the design of NIR emissive fluorophores. TTD is a well-known electron-deficient species, but its use as an acceptor in D-π-A-π-D systems has not been extensively studied. We employed TTD as an acceptor unit in a series of two fluorophores and characterized the photophysical properties through experimental and computational studies. Both fluorophores exhibited emission maxima in the NIR-I that extends into the NIR-II. We also utilized electron paramagnetic resonance (EPR) spectroscopy to rationalize differences in the measured quantum yield values and demonstrated, to our knowledge, the first experimental evidence of radical species on a TTD-based small-molecule fluorophore. Encapsulation of the fluorophores using a surfactant formed polymeric nanoparticles, which were studied by photophysical and morphological techniques. The results of this work illustrate the potential of TTD as an acceptor in the design of NIR-II emissive fluorophores for fluorescence bioimaging applications.

Guest-Host Raman under Liquid Nitrogen Spectroscopy for the Acquisition of Improved Vibrational Spectra of Solids.

Guest-host Raman under liquid nitrogen spectroscopy (GHRUNS) is introduced whereby solid-state guest molecules are isolated inside cage-like host environments for the facile acquisition of their Raman spectra. This convenient method features reduced fluorescence, the analysis of populations in their ground states, and increased signal to noise ratios. Samples are also preserved through the reduction of thermal degradation and oxidation. To demonstrate the benefits of this new method, Raman spectra of the ubiquitous molecule C60 inside a cage of water ice are presented. Using this technique, a new normal mode of C60 is elucidated. The GHRUNS methodology is of interest to those seeking to acquire and characterize the vibrational spectra, structure, and properties of emissive, air-sensitive molecules.

Probing halogen bonding interactions between heptafluoro-2-iodopropane and three azabenzenes with Raman spectroscopy and density functional theory.

The potential formation of halogen bonded complexes between a donor, heptafluoro-2-iodopropane (HFP), and the three acceptor heterocyclic azines (azabenzenes: pyridine, pyrimidine, and pyridazine) is investigated herein through normal mode analysis via Raman spectroscopy, density functional theory, and natural electron configuration analysis. Theoretical Raman spectra of the halogen bonded complexes are in good agreement with experimental data providing insight into the Raman spectra of these complexes. The exhibited shifts in vibrational frequency of as high as 8 cm-1 for each complex demonstrate, in conjunction with NEC analysis, significant evidence of charge transfer from the halogen bond acceptor to donor. Here, an interesting charge flow mechanism is proposed involving the donated nitrogen lone pair electrons pushing the dissociated fluorine atoms back to their respective atoms. This mechanism provides further insight into the formation and fundamental nature of halogen bonding and its effects on neighboring atoms. The present findings provide novel and deeper characterization of halogen bonding with applications in supramolecular and organometallic chemistry.

Raman Spectroscopic and Quantum Chemical Investigation of the Pyridine-Borane Complex and the Effects of Dative Bonding on the Normal Modes of Pyridine.

The pyridine-borane (PyBH3) complex was analyzed by Raman vibrational spectroscopy and density functional theory to elucidate its structural and vibrational properties and to compare these with those for neat pyridine (Py). The borane-nitrogen (BN) bond length, the BN dative bond stretching frequency, and the effects of dative-bonded complex formation on Py are presented. Rather than having a single isolated stretching motion, the complex exhibits multiple BN dative bond stretches that are coupled to Py's vibrations. These modes exhibit large shifts that are higher in energy relative to neat Py, similar to previous observations of Py/water mixtures. However, significantly higher charge transfer was observed in the dative-bonded complex when compared to the hydrogen-bonded complex with water. A linear relationship between charge transfer and shifts to higher frequencies of pyridine's vibrational modes agrees well with earlier observations. The present work is of interest to those seeking a stronger relationship between charge-transfer events and concomitant changes in molecular properties.