Large Two-photon Cross-section Research Articles

Azaacene Diradicals Based on Non-Kekulé Meta-Quinodimethane with Large Two-Photon Cross-Sections in the Infrared Spectral Region.

Non-Kekulé quinoidal azaacences m-A (1a,b) were synthesized and compared to their para- and ortho-quinodimethane analogues. m-Adisplay high diradical characters (1b: y0 = 0.88) due to their meta-quinodimethane (m-QDM) topology. Electron paramagnetic, nuclear magnetic resonance spectroscopies and supraquantum interference device measurements in combination with quantum-chemical calculations revealed singlet ground states for m-A with singlet-triplet gaps ΔEST (0.13-0.25kcalmol-1) and thermally populated triplet states. These non-Kekulé structures are over all void of zwitterionic character and possess record high two-photon absorption cross sections over a broad spectral range in the near-infrared.

Two Dicyanostilbene-Based Two-Photon Fluorescence Environmentally Sensitive Probes with Large Two-Photon Absorption Cross Sections and Two-Photon Triple Fluorescence

The unusually sensitive solvatochromism of 2,5-dicyano-4-methyl-4’-dimethylaminostilbene (1a) whose emission maximum varies from 445 nm in cyclohexane to 641 nm in DMSO are described. 1a with remarkably large two-photon cross sections exhibits very strong polarity-, viscosity-, and temperature-dependence of fluorescence, and can be used to detect polarities, viscosities, and temperature. The successful application of 1a provides a brilliant prototype for the developments of ideal two-photon fluorescence probes.

Large two-photon cross sections and low-threshold multiphoton lasing of CdS/CdSe/CdS quantum shells.

Colloidal quantum shells are spherical semiconductor quantum wells, which have shown strong promise as optical materials, particularly in classes of experiments requiring multiple excitons. The two-photon properties of CdS/CdSe/CdS quantum shell samples are studied here to demonstrate large non-linear absorption cross-sections while retaining advantageous multiexciton physics conferred by the geometrical structure. The quantum shells have large two-phonon cross sections (0.4-7.9 × 106 GM), which highlights their potential use in upconversion imaging in which large per particle two-photon absorption is critical. Time-resolved measurements confirmed that the quantum shells have long biexciton lifetime (>10 ns in the largest core samples reported here) and large gain bandwidth (>300 meV). The combination of these attributes with large two-photon cross sections makes the CdS/CdSe/CdS quantum shells excellent gain media for two-photon excitation. With a broad gain bandwidth and long gain lifetime, quantum shell solids support multimodal amplified spontaneous emission from excitons, biexcitons, and higher excited states. Thresholds for amplified spontaneous emission and lasing, which are as low as 1 mJ cm-2, are comparable to, or lower than, the thresholds reported for other colloidal materials.

Coumarin-based two-photon AIE fluorophores: Photophysical properties and biological application

Based on the coumarin skeleton, we deliberately designed two groups of fluorophores, termed as Coum-R and Naph-Coum-R, using the diphenylamino group as the electron donor, which displayed long-wavelength emissions (red spectral region), large Stokes shift (up to 204 nm), superior AIE performance, and large two-photon absorbance cross-sections (as high as 365 GM). The electron-withdrawing substituents at the 3-position of these dyes could induce a significant red-shift in their emission spectra. Preliminary imaging experiments demonstrated the capability of these dyes as two-photon fluorophores for specifically staining lipid droplets in living cells.

A dual-site colorimetric fluorescent probe for rapid detection of hydrazine/hypochlorite and its application in two-photon fluorescent bioimaging

A colorimetric two-photon multianalyte sensor with spirobifluorene motif was developed. Along with the addition of hypochlorite/hydrazine to a solution of the probe, a colorimetric change from yellow to colorless and a fluorescence enhancement (Under 365 nm UV light) can be observed by ‘naked-eye’. The detection limits are 28 nM for hypochlorite and 12 nM for hydrazine, respectively. The molecule has large two-photon cross-section value of 220GM and has been successfully applied to two-photon imaging of hypochlorite / hydrazine in live cells. As far as we know, a two-photon fluorescent probe capable of detecting reactive oxygen species and reducing agent, and a colorimetric two-photon fluorescent probe for hypochlorite is reported for the first time. In addition, the detection limit for hydrazine is much lower than those of most hydrazine fluorescent probes reported in the literature.

Photophysical properties and bioimaging application of an aminonaphthalimide-squaraine non-conjugated system

An aminonaphthalimide-squaraine non-conjugated system was designed and synthetized with the purpose of preparing fluorescent molecule in the 650–700 nm region that could operate via energy transfer (ET) between covalently linked naphthalimide and squaraine chromophores. The photophysical properties of the new fluorescent system were explored with the aim of understanding the ET in one- and two-photon excitation modes. The spectroscopic techniques employed in the characterization includes; absorption, fluorescence, quantum yields and fluorescence lifetime measurements in different solvents. The effect of polarity of solvents on efficiencies of ET were evaluated using one- and two-photon excited fluorescence. The optical behavior of the non-conjugated system was compared with its individual squaraine and naphthalimide moieties. The two-photon absorption (TPA) spectrum of the molecule was obtained between 750 and 1040 nm, with the largest two-photon cross section (δTPA)above 4200 GM. Finally, the applicability of the molecule for fluorescence imaging in the one- and two-photon excitation mode was demonstrated in N13 Microglial cells. The in vitro and in vivo confocal microscopy studies indicated that the non-conjugated system efficiently accumulated in the cytoplasm suggesting it could be utilized as a subcellular probe.

Ground-State Proton-Transfer (GSPT)-Assisted Enhanced Two-Photon Uncaging from a Binol-based AIE-Fluorogenic Phototrigger.

We demonstrated for the first time without any chemical modification the two-photon absorption (TPA) cross-section can be enhanced and red-shifted to the near-infrared (NIR) region by the ground-state proton-transfer (GSPT) process. Using GSPT, we developed a simple binol-based aggregation-induced emission (AIE)-fluorogenic phototrigger having a large two-photon uncaging cross-section in the "phototherapeutic window". As a proof of concept, we showed our phototrigger for the release of two different anticancer drugs in the NIR region.

Doppler-free two-photon cavity ring-down spectroscopy of a nitrous oxide ( N2O ) vibrational overtone transition

We report Doppler-free two-photon absorption of N2O at λ = 4.53 μm, measured by cavity ring-down spectroscopy. High power was achieved by optical self-locking of a quantum cascade laser to a linear resonator of finesse , and accurate laser detuning over a 400 MHz range was measured relative to an optical frequency comb. At a sample pressure of p = 0.13 kPa, we report a large two-photon cross-section per molecule of cm4 s for the Q(18) rovibrational transition at a resonant frequency of ν 0 = 66179400.8 MHz.

A mitochondria-targetable two-photon fluorescent probe with a far-red to near-infrared emission for sensing hypochlorite in biosystems

Hypochlorite (ClO−), one of reactive oxygen species (ROS), is closely related with many physiological and pathological processes. Especially as one of cellular reactive oxygen species in mitochondria, ClO− can induce mitochondrial permeability, which leads to apoptosis. Thus, developing an effective method which is able to sense ClO− in mitochondria is important. Although fluorescent probe has become a powerful tool for imaging ClO− in mitochondria, most of them suffered from phototoxicity to biosamples, autofluorescence, and photobleaching phenomenon due to their short-wavelength excitations and emissions. Based on advantages of two-photon fluorescent probe and far-red to NIR fluorescent probe, a mitochondria-targetable two-photon fluorescent probe with a turn-on signal in far-red to NIR region, Mito-TP-ClO, was developed for ClO− in this paper. Mito-TP-ClO is consisted of a triphenylphosphonium cations as a mitochondria-targetable unit and a structure of dibenzoylhydrazine as a response unit to ClO−. Mito-TP-ClO exhibited a high sensitivity and a high selectivity to ClO−, with a linear range from 6.0 × 10−8 to 1.0 × 10−5 M and a detection limit of 2.5 × 10−8 M. Due to its large two-photon cross section (267 GM) and far-red to NIR emission, Mito-TP-ClO exhibits excellent performances including low autofluorescence, photostable fluorescence signal, and deep tissue penetration (230 μM). Moreover, Mito-TP-ClO was successfully used to detect endogenous ClO− in bacteria-infected cells and inflammatory mouse model, which confirmed that Mito-TP-ClO is a powerful tool to monitor ClO− in mitochondria and study on effects of hypochlorite on mitochondria.

Stilbene-Based Two-Photon Thermo- Solvatochromic Fluorescence Probes with Large Two-Photon Absorption Cross Sections and Two- Photon Triple Fluorescence: Detection of Solvent Polarities, Viscosities, and Temperature

The unusually sensitive solvatochromism of 2,5-dicyano-4-methyl-4’-dimethylaminostilbene (P1) whose emission maximum varies from 445 nm in cyclohexane to 641 nm in DMSO are described. 1a with remarkably large two-photon cross sections exhibits very strong polarity-, viscosity-, and temperature-dependence of fluorescence, and can be used to detect polarities, viscosities, and temperature. The successful application of P1 provides a brilliant prototype for the developments of ideal two-photon fluorescence probes.

A two-photon fluorescent probe derived from spirobifluorene for fast sensing of hypochlorite and mercury ions

A two-photon fluorescent probe derived from spirobifluorene has been developed. The probe exhibits large two-photon cross-section value. It displayed fast response toward ClO− / Hg2+ with high sensitivity and selectivity, exhibiting fluorescence enhancement. In the case of TPA, the detection limit of SPF-S is 11nM for ClO− and 24nM for Hg2+, which is lower than that obtained with one-photon fluorescence. Moreover, the present probe was successfully applied to the two-photon fluorescence imaging of ClO− and Hg2+ in living cells. This work indicated that the compound is an excellent fluorescence probe for the detection of Hg2+ and ClO− and provides a two-photon fluorescence probe for ClO−, which is rarely reported till now.

Synthesis and application of ratio fluorescence probe for chloride.

As chloride ions (Cl-) play a vital role in maintaining normal physiological activity, detection of chloride ions is quite urgent. Hence, we developed chloride fluorescence probes to highly selectively and sensitively monitor chloride ions. The probe M2 with single emission has a high fluorescence quantum yield (Φ = 45%), and it is capable of quantitative detection of Cl- under physiological conditions (pH = 7.4) and pH = 5.0 with a linear range of 0.1-4.0mM; nevertheless, it is of the switch-off type. We further synthesized a ratiometric fluorescent probe MY with M2 as raw material, which featured excellent selectivity and anti-interference, and large two-photon cross section (555 GM). The probe is conveniently used to detect Cl- in water samples and biological samples including human sweat, serum, and urine samples, indicating it holds great promise for chloride detection and biological application. Graphical abstract ᅟ.

Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars.

Inflammatory breast cancer (IBC) is rare, but it is the most aggressive subtype of breast cancer. IBC has a unique presentation of diffuse tumor cell clusters called tumor emboli in the dermis of the chest wall that block lymph vessels causing a painful, erythematous, and edematous breast. Lack of effective therapeutic treatments has caused mortality rates of this cancer to reach 20%–30% in case of women with stage III–IV disease. Plasmonic nanoparticles, via photothermal ablation, are emerging as lead candidates in next-generation cancer treatment for site-specific cell death. Plasmonic gold nanostars (GNS) have an extremely large two-photon luminescence cross-section that allows real-time imaging through multiphoton microscopy, as well as superior photothermal conversion efficiency with highly concentrated heating due to its tip-enhanced plasmonic effect. To effectively study the use of GNS as a clinically plausible treatment of IBC, accurate three-dimensional (3D) preclinical models are needed. Here, we demonstrate a unique in vitro preclinical model that mimics the tumor emboli structures assumed by IBC in vivo using IBC cell lines SUM149 and SUM190. Furthermore, we demonstrate that GNS are endocytosed into multiple cancer cell lines irrespective of receptor status or drug resistance and that these nanoparticles penetrate the tumor embolic core in 3D culture, allowing effective photothermal ablation of the IBC tumor emboli. These results not only provide an avenue for optimizing the diagnostic and therapeutic application of GNS in the treatment of IBC but also support the continuous development of 3D in vitro models for investigating the efficacy of photothermal therapy as well as to further evaluate photothermal therapy in an IBC in vivo model.

Dicyanostilbene-based Two-photon Thermo-solvatochromic Fluorescence Probes with Two-photon Triple Fluorescence

The unusually sensitive solvatochromism of the two-photon fluorescence fluorophore of 2,5-dicyano-4-methyl-4’-dimethylaminostilbene (P1) whose emission maximum varies from 445 nm in cyclohexane to 641 nm in DMSO are described. P1 with remarkably large two-photon cross sections exhibits very strong polarity-, viscosity-, and temperature-dependence of fluorescence, and can be used to detect polarities, viscosities, and temperature. P1 presents a two-photon triple fluorescence.

Easily prepared ruthenium-complex nanomicelle probes for two-photon quantitative imaging of oxygen in aqueous media

Easily prepared, biocompatible, and oxygen-sensitive optical probes with a large two-photon cross-section: towards inexpensive quantitative oxygen imaging in vivo.

Computational screening of one- and two-photon spectrally tuned channelrhodopsin mutants

Optogenetics is by now a well-established field within neuroscience where neuro-response is controlled at the molecular level using the photochemical properties of channelrhodopsin (ChR). In this study the recently published X-ray structure of retinal inside the ChR binding pocket serves as the basis for conducting high-level polarizable embedding quantum mechanical/molecular mechanical (QM/MM) mutation studies with the aim of providing insight into the tuning mechanisms of this remarkable protein. The levels of theory applied are the recently developed PERI-CC2 and PE-DFT approaches. Their computational efficiency makes it possible to rapidly carry out a large number of spectral calculations. This is exploited to construct in silico mutated ChR variants which are characterized in terms of the location of the relevant excitation energy and the magnitude of the two-photon absorption cross section. In turn, this allows us to pinpoint the amino acids that have the largest electrostatic effect on the studied excited state properties. We show that a single/double site mutation strategy in ChR does not perturb the electronic properties of retinal to a degree that satisfies the experimental demand for a significant red-shift. With respect to non-linear absorption we conjecture that the recently synthesized ChETA variant possesses an even larger two-photon cross section than the C1C2 variant and it is thus an ideal candidate for further studies on the two-photon activation of ChR.

Two-photon fluorescence probes for imaging of mitochondria and lysosomes

Novel biocompatible cyanines show not only a very large two-photon cross-section of up to 5130 GM at 910 nm in aqueous medium for high-contrast and -brightness two-photon fluorescence live cell imaging but also highly selective subcellular localization properties including localization of mitochondria and lysosomes.

Two-photon absorption of metal–organic DNA-probes

We report remarkable multiphoton absorption properties of DNA intercalating ruthenium complexes: (1) [Ru(phen)(2)dppz](2+); (2) [(11,11'-bidppz)(phen)(4)Ru(2)](4+); (3) [11,11'-bipb(phen)(4)Ru(2)](4+). Two-photon spectra in the range from 460 to 1100 nm were measured using the Z-scan technique. In particular, complex 2 was found to exhibit very strong two- and three-photon absorption properties, which could be an effect of symmetric charge transfer from the ends towards the middle of the conjugated dimeric orbital system. We propose that these molecules could provide a new generation of DNA binding nonlinear chromophores for wide applications in biology and material science. The combination of a large two-photon cross section and strong luminescence quantum yields for the molecules when intercalated makes the compounds uniquely bright and photo-stable probes for two-photon luminescence imaging and also promising as enhanced photosensitizers in two-photon sensitizing applications.

Photosensitizer-doped conjugated polymer nanoparticles with high cross-sections for one- and two-photon excitation

We report a novel nanoparticle that is promising for photodynamic therapy applications, which consists of a π-conjugated polymer doped with a singlet oxygen photosensitizer. The nanoparticles exhibit highly efficient collection of excitation light due to the large excitation cross-section of the polymer. A quantum efficiency of singlet oxygen production of 0.5 was determined. Extraordinarily large two-photon excitation cross-sections were determined, indicating promise for near infrared multiphoton photodynamic therapy. Gel electrophoresis of DNA after near-UV irradiation in the presence of nanoparticles indicated both purine base and backbone DNA damage.

Alternating copolymers of 2,6-bis(p-dihexylaminostyryl)anthracene-9,10-diyl and N-octylcarbazole with large two-photon cross sections

We report the synthesis, thermal, one- and two-photon properties of poly(2,6-bis(p-dihexylaminostyryl)anthracene-9,10-diyl-alt-N-octylcarbazole-3,6-/2,7-diyl) (P1/P2). The as-synthesized polymers exhibit number-average molecular weights of 1.7 × 104 for P1 and 2.1 × 104 g/mol for P2. They emit strong one- and two-photon excitation fluorescence with the peak around 502 nm, and the fluorescence quantum yields around 0.76 in chloroform. In film state, P1 and P2 show different red-shift emission with the peaks at 512 nm and 523 nm, respectively. The DSC measurement reveals that as-synthesized polymers are all amorphous aggregates with the glass transition temperatures of 131 °C for P1 and 152 °C for P2. The solution two-photon absorption (TPA) properties of P1 and P2 in chloroform are measured by the two-photon-induced fluorescence method using femtosecond laser pulses (120 fs). The TPA cross sections (δ) are measured over the range of 700–900 nm. The maximal δ of P1 and P2 all appear at ∼800 nm and are 1010 GM and 940 GM per repeating unit, respectively. This suggests that no notable interactions among structure units that impair their fluorescence and TPA properties, and the polymers with large δ can be obtained by using the high TPA-active units as building blocks. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010