Click Synthesis of Tweezer Dyads for H-Bond Assisted Cooperativity in Tandem Uncaging Systems.

"Tandem" uncaging systems, in which a photolabile protecting group (PPG) is sensitized by an energy-harvesting antenna, may increase the photosensitivity of PPGs by several orders of magnitude for two-photon (2P) photorelease. Yet, they remain poorly accessible because of arduous multi-step synthesis. In this work, we design efficient tandem uncaging systems by (i) using a convenient assembly of the building blocks relying on click chemistry, (ii) H-bonding induced proximity thus facilitating (iii) photoinduced electron transfer (PeT) as a cooperative mechanism. A strong two-photon absorber electron-donating quadrupolar antenna and various electron-accepting PPGs (mDEAC, MNI or MDNI) were clicked stepwise onto a "tweezer-shaped" pyrido-2,6-dicarboxylate platform whose H-bonding and p-stacking abilities were exploited to keep the antenna and the PPGs in close proximity. The different electron acceptor ability of the PPGs led to dyads with wildly different behaviors. Whilst the MDNI and MNI dyads showed poor dark stability or no photo-uncaging ability due to their too high electron accepting character, the mDEAC dyad benefited from optimum redox potentials to promote PeT and slow down charge recombination, resulting in enhanced uncaging quantum yield (Fu=0.38) compared to mDEAC (Fu=0.014). The unique resulted in large 2P photo-sensitivity in the near-infrared window (240 GM at 710 nm).

The Intermode Polariton Parametric Scattering Laser in a Strong Coupled Microcavity Via Two-Photon Absorption.

Exciton-polaritons, hybrid quasiparticles from the strong coupling of excitons and cavity photons in semiconductor microcavities, offer a platform for exploring quantum coherence and nonlinear optical properties. The unique polariton parametric scattering (PPS) laser is of interest for its potential in quantum technologies and nonlinear devices. However, direct resonant excitation of polaritons in strong-coupling microcavities is challenging. This study proposes an innovative two-photon absorption (TPA) pump mechanism to address this. We observe TPA-driven PPS lasing in a strongly coupled microcavity at room temperature. High K-value exciton injections promote coherent stimulated emission of polariton scattering through intermode channels. Angle-resolved spectra confirm a TPA process, showing evolution from pump-state to signal-state. Hanbury Brown-Twiss measurement of second-order correlation g2(τ) of signal state indicates a phase transition from a classical thermal state to a quantum coherent state. Theoretical modeling provides insights into the physical mechanisms of PPS. Our work advances nonlinear phenomena exploration in strongly coupled light-matter systems, contributing to quantum polaritonics and nonlinear optics.

Advances in two-photon absorption photodynamic therapy of glioma based on porphyrin-based metal-organicframework composites.

Gliomas of the brain are characterised by high aggressiveness, high postoperative recurrence rate, high morbidity and mortality, posing a great challenge to clinical treatment. Traditional treatments include surgery, radiotherapy and chemotherapy; they also have significant associated side effects, leading to difficulties in tumour resection and recurrence. Photodynamic therapy has been shown to be a promising new strategy to help treat malignant tumours of the brain. It irradiates the tumour site at a specific wavelength to activate a photosensitiser, which selectively accumulates at the tumour site, triggering a photochemical reaction that destroys the tumour cells. It has the advantages of being minimally invasive, highly targeted and with few adverse reactions, and is expected to be well used in anti-tumour therapy. However, the therapeutic effect of traditional PDT is limited by the weak tissue penetration ability of photosensitiser, hypoxia and immunosuppression in the tumour microenvironment. This paper reviews the current research status on the therapeutic principle of photodynamic therapy in glioma and the mechanism of tumour cell injury, and also analyses the advantages and disadvantages of the current application in glioma treatment, and clarifies the analysis of ideas to improve the tissue penetration ability of photosensitizers. It aims to provide a feasible direction for the improvement of photodynamic therapy for glioma and a reference for the clinical treatment of deep brain tumours.

Augmenting the effect of solvents on optical nonlinearity by spectroscopic, DFT, solvatochromism and z-scan studies of push-pull chalcone: (2E)-1-(4-ethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one.

In this article, the structural and nonlinear optical behaviour of a chalcone derivative, (2E)-1-(4-ethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one have been studied. FT-IR, FT-Raman, and NMR spectroscopy were analyzed to validate the molecular structure. To predict the nonlinear optical characteristics of the chalcone, the DFT approach was used and the experimental results were corroborated by the computations. The bathochromic shift is obtained in linear absorbance spectra and is validated using TD-DFT. Also, the broad emission in the blue region demonstrates the blue light emission property of the sample. Using the finite-field method, the dipole moments, polarizability, first-order and second-order hyperpolarizability parameters have been computed. Ground and excited state dipole moments were quantified by solvatochromism. The third-order nonlinear optical characteristics of chalcone in polar and non-polar solvent media were examined using the open/closed-aperture z-scan technique. The chalcone displayed considerable two-photon absorption with a positive nonlinear absorption coefficient and a positive index of refraction due to the self-focussing effect. Furthermore, the optical limiting study manifests that the investigated chalcone might well be favourable for NLO applications.

Near-infrared two-photon absorption and excited state dynamics of a fluorescent diarylethene derivative.

Near-infrared two-photon absorption and excited state dynamics of a fluorescent diarylethene (fDAE) derivative were investigated by time-resolved absorption and fluorescence spectroscopies. Prescreening with quantum chemical calculation predicted that a derivative with methylthienyl groups (mt-fDAE) in the closed-ring isomer has a two-photon absorption cross-section larger than 1000 GM, which was experimentally verified by Z-scan measurements and excitation power dependence in transient absorption. Comparison of transient absorption spectra under one-photon and simultaneous two-photon excitation conditions revealed that the closed-ring isomer of mt-fDAE populated into higher excited states deactivates following three pathways on a timescale of ca. 200 fs: (i) the cycloreversion reaction more efficient than that by the one-photon process, (ii) internal conversion into the S1 state, and (iii) relaxation into a lower state (S1' state) different from the S1 state. Time-resolved fluorescence measurements demonstrated that this S1' state is relaxed to the S1 state with the large emission probability. These findings obtained in the present work contribute to extension of the ON-OFF switching capability of fDAE to the biological window and application to super-resolution fluorescence imaging in a two-photon manner.

Thio and Seleno-Psoralens as Efficient Triplet Harvesting Photosensitizers for Photodynamic Therapy.

The Psoralen (Pso) molecule finds extensive applications in photo-chemotherapy, courtesy of its triplet state forming ability. Sulfur and selenium replacement of exocyclic carbonyl oxygen of organic chromophores foster efficient triplet harvesting with near unity triplet quantum yield. These triplet-forming photosensitizers are useful in Photodynamic Therapy (PDT) applications for selective apoptosis of cancer cells. In this work, we have critically assessed the effect of the sulfur and selenium substitution at the exocyclic carbonyl (TPso and SePso, respectively) and endocyclic oxygen positions of Psoralen. It resulted in a significant redshifted absorption spectrum to access the PDT therapeutic window with increased oscillator strength. The reduction in singlet-triplet energy gap and enhancement in the spin-orbit coupling values increase the number of intersystem crossing (ISC) pathways to the triplet manifold, which shortens the ISC lifetime from 10-5 s for Pso to 10-8 s for TPso and 10-9 s for SePso. The intramolecular photo-induced electron transfer process, a competitive pathway to ISC, is also considerably curbed by exocyclic functionalizations. In addition, a maximum of 115 GM of two-photon absorption (2PA) with IR absorption (660-1050 nm) confirms that the Psoralen skeleton can be effectively tweaked via single chalcogen atom replacement to design a suitable PDT photosensitizer.

Dual-Criteria Decision Analysis by Multiphotonic Effects in Nanostructured ZnO.

Simultaneous interrogation of pump and probe beams interacting in ZnO nanostructures of a two-wave mixing is proposed for dual-path data processing of optical signals by nonlinear optical effects. An enhancement in third-order nonlinear optical properties was exhibited by Al-doped ZnO thin films. Multiphoton absorption and nonlinear refraction were explored by the z-scan technique at 532 nm with nanosecond pulses. The evolution of the optical Kerr effect in the ZnO thin films was analyzed as a function of the incorporation of Al in the sample by a vectorial two-wave mixing method. Electrical and photoconductive effects were evaluated to further characterize the influence of Al in the ZnO solid samples. Potential applications of nonlinear optical parameters for encoding and encrypting information in light can be envisioned.

Quasi-intrinsic thiobase derivatives as potential targeted photosensitizers in two-photon photodynamic therapy.

In this study, a set of potential quasi-intrinsic photosensitizers for two-photon photodynamic therapy (PDT) are proposed based on the unnatural 2-amino-8-(1'-ß-ᴅ-2'-deoxyribofuranosyl)-imidazo[1,2-ɑ]-1,3,5-triazin-4(8H)-one (P), which is paired with the 6-amino-5-nitro-3-(1'-ß-ᴅ-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and can specifically recognize breast and liver cancer cells. Herein, the effects of sulfur substitution and electron-donating/electron-withdrawing groups on the photophysical properties in aqueous solution are systematically investigated. The one- and two-photon absorption spectra evidence that the modifications could result in red-shifted absorption wavelength and large two-photon absorption cross-section, which contributes to selective excitation and provides effective PDT for deep-seated tissues. To ensure the efficient triplet state population, the singlet-triplet energy gaps and spin-orbit coupling constants were examined, which is responsible for a rapid intersystem crossing rate. Furthermore, these thiobase derivatives are characterized by the long-lived T1 state and the large energy gap for radiationless transition to ensure the generation of cytotoxic singlet oxygen.

Two spirobifluene-based turn-on fluorescent probes for highly selective detection of Cysteine and the applications in cells two-photon fluorescence imaging.

Two spirobifluene-based fluorescent probes SPF1 and SPF2, were designed and synthesized. The probes displayed "turn-on" fluorescence response for Cysteine. One of the challenges in developing a Cysteine probe is to secure high selectivity. SPF1/SPF2 can discriminate Cysteine from GSH as well as Hcy, and showed high substrate selectivity. The detection limit of SPF1 is 36 nM, which is excellent comparing with other optical sensors for Cysteine. The sensing mechanism of SPF1/SPF2 was verified by experimental data and theoretical calculations. There was a good linear relationship between the fluorescence intensity of SPF1/SPF2 and the concentration of Cysteine. The MTT tests indicated that SPF1/SPF2 had low cytotoxicity and good biocompatibility. Theoretical calculations demonstrated that SPF1, SPF2, and their related reaction products with Cysteine exhibited good two-photon absorption properties. Finally, SPF1/SPF2 had been successfully applied to the imaging of Cysteine in living cells under two-photon excitation.

Two-Photon Absorbing Dendrimers and Their Properties-An Overview.

This review describes the two-photon absorption properties of dendrimers, which are arborescent three-dimensional macromolecules differing from polymers by their perfectly defined structure. The two-photon absorption process is a third order non-linear optical property that is attractive because it can be used in a wide range of applications. In this review, dendrimers that were studied for their two-photon absorption properties are first described. Then, the use of dendritic TPA chromophores for light harvesting, photopolymerization, optical power limitation, cell imaging, singlet oxygen generation, and photodynamic therapy is described. This review thus proposes an overview of the properties and possible applications of two-photon absorbing dendrimers.

Near-Infrared Light-Excited Quinolinium-Carbazole Small Molecule as Two-Photon Fluorescence Nucleic Acid Probe.

This article reports three new two-photon absorption (TPA) materials that are quinolinium-carbazole derivates. They are 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (M4), 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (H2), and 3-(N-methyl-4-ethylquinolinium iodide)-9-ethylcarbazole (H4). Their TPA cross-sections are 491, 515, and 512 GM, respectively. Under the excitation of near-infrared light, their fluorescence emission is about 650 nm. The compounds can stain nucleic acid DNA with the same level of nuclear localization as Hoechst 33342. Under continuous irradiation with a near-infrared laser, the three new compounds showed less fluorescence decay than DAPI, and the average fluorescence decay rates were 0.016%/s, 0.020%/s, and 0.023%/s. They are expected to become new two-photon fluorescent probes of nucleic acid DNA because of their excellent performance.

Theoretical study on photoinduced charge transfer in one-photon and two-photon absorption of branching oligofluorenes.

Oligofluorenes have been identified as very promising two-photon absorption (TPA) materials and present great application potential for the fabrication of nonlinear optical devices, but the TPA mechanism and corresponding electron excitation properties have not been studied. Here, the photoinduced charge transfer characteristics of V-shaped and Y-shaped branching oligofluorenes that consist of two and three fluorene units in each branch during one-photon absorption (OPA) and TPA processes are analyzed theoretically using the density functional theory and visualization sum-over-states model. The calculated results show that the OPA intensity and TPA cross-section are significantly enhanced by increasing the branch length or changing the structure from V-shaped to Y-shaped. The long-distance charge transfer only occurs on the second transition of TPA at high excited states. Compared to Y-shaped molecules, V-shaped structures exhibit a stronger cooperative effect among the different branches.

Near-Infrared Light-Driven Photocatalysis with an Emphasis on Two-Photon Excitation: Concepts, Materials, and Applications.

Efficient utilization of sunlight in photocatalysis is widely recognized as a promising solution for addressing the growing energy demand and environmental issues resulting from fossil fuel consumption. Recently, there have been significant developments in various near-infrared (NIR) light-harvesting systems for artificial photosynthesis and photocatalytic environmental remediation. This review provides an overview of the most recent advancements in the utilization of NIR light through the creation of novel nanostructured materials and molecular photosensitizers, as well as modulating strategies to enhance the photocatalytic processes. A special focus is given to the emerging two-photon excitation NIR photocatalysis. The unique features and limitations of different systems are critically evaluated. In particular, it highlights the advantages of utilizing NIR light and two-photon excitation compared to UV-visible irradiation and one-photon excitation. Ongoing challenges and potential solutions for the future exploration of NIR light-responsive materials are also discussed.

A Curious Case of Two-Photon Absorption in n-Helicene and n-Phenylene, n=6-10: Why n=7 is Different?

n-Helicenes and n-Phenylenes are interesting examples of twisted molecules, where although the atoms are connected through conjugated π ${\pi }$ -bonds, the π ${\pi }$ -conjugation is largely hindered by the twisted nature of the bonds. Such structures provide a unique opportunity to study the effect of twisted π ${\pi }$ -system on non-linear optical properties. In this work, we studied the two-photon absorption in donor-acceptor substituted n-helicenes and n-phenylenes employing the state-of-the-art RI-CC2 method and reported a unique feature we observed in n=7 systems. We found that both 7-helicene and 7-phenylene systems exhibit largest two-photon absorption than other members in their respective classes. Furthermore, using generalized few-state model, we provided a detailed microscopic mechanism of this unique observation involving participation of different transition dipole moment vectors and their relative orientations.

Nanothermometer Based on Polychlorinated Trityl Radicals Showing Two-Photon Excitation and Emission in the Biological Transparency Window: Temperature Monitoring of Biological Tissues.

Nanothermometers are emerging probes as biomedical diagnostic tools. Especially appealing are nanoprobes using NIR light in the range of biological transparency window (BTW) since they have the advantages of a deeper penetration into biological tissues, better contrast, reduced phototoxicity and photobleaching. This article reports the preparation and characterization of organic nanoparticles (ONPs) doped with two polychlorinated trityl radicals (TTM and PTM), as well as studies of their electronic and optical properties. Such ONPs having inside isolated radical molecules and dimeric excimers, can be two-photon excited showing optimal properties for temperature sensing. Remarkably, in TTM-based ONPs the emission intensity of the isolated radical species is unaltered increasing temperature, while the excimer emission intensity decreases strongly being thereby able to monitor temperature changes with an excellent thermal absolute sensitivity of 0.6-3.7% K-1 in the temperature range of 278-328 K. The temperature dependence of the excimeric bands of ONPs are theoretically simulated by using electronic structure calculations and a vibronic Hamiltonian model. Finally, TTM-doped ONPs as ratiometric NIR-nanothermometers are tested with two-photon excitationwith enucleated pig eye sclera, as a real tissue model, obtaining a similar temperature sensitivity as in aqueous suspensions, demonstrating their potential as NIR nanothermometers for bio applications.

Crystallography, Charge Transfer, and Two-Photon Absorption Relations in Molecular Cocrystals for Two-Photon Excited Fluorescence Imaging.

Two-photon excited fluorescence imaging requires high-performance two-photon absorption (TPA) active materials, which are commonly intramolecular charge transfer systems prepared by traditional chemical synthesis. However, this typically needs harsh conditions and new methods are becoming crucial. In this work, based on a collaborative intermolecular charge transfer (inter-CT) strategy, three centimeter-sized organic TPA cocrystals are successfully obtained. All three cocrystals exhibit a mixed stacking arrangement, which can effectively generate inter-CT between the donor and acceptor. The ground and excited state characterizations compare their inter-CT ability: 1,2-BTC > 2D-BTC > 1D-BTC. Transient absorption spectroscopy detects TCNB•-, indicating that the TPA mechanism arises from molecular polarization caused by inter-CT. Meanwhile, 1,2-BTC exhibits the highest excited-state absorption and the longest excited-state lifetime, suggesting a stronger TPA response. First-principles calculations also confirm the presence of inter-CT interactions, and the significant parameter Δµ which can assess the TPA capability indicates that inter-CT enhances the TPA response. Besides, cocrystals also demonstrate excellent water solubility and two-photon excited fluorescence imaging capabilities. This research not only provides an effective method for synthesizing TPA crystal materials and elucidates the connection between inter-CT ability and TPA property but also successfully applies them in the fields of multi-photon fluorescence bioimaging.

Giant Star-shaped meso-substituted Fluorescent Porphyrins with Fluorenyl-containing Arms Designed for Two-photon Oxygen Photosensitization.

In the continuation of previous studies on carbon-rich meso-tetraarylporphyrins featuring 2,7-fluorene units at their periphery, the effect of changing the peripheral dendritic arms for linear arms on their oxygen-photosensitizing ability, their fluorescence and their two-photon absorption (2PA) properties is now analyzed. Thus, starburst porphyrins possessing up to twenty conjugated fluorenyl units were isolated and studied. More precisely, a series of five new free-base porphyrins featuring fully conjugated arms incorporating an increasing number of fluorenyl groups connected via 1,2-alkenyl spacers were synthesized, along with their Zn(II) complexes. Upon excitation in the arm-centred π-π* absorption band, an efficient energy transfer takes place from the peripheral fluorenyl units to the central porphyrin core, leading to intense red-light emission and oxygen photosensitization by the latter. More interestingly, while the linear optical properties of these porphyrins were only slightly improved compared to those of their dendrimer analogues for photodynamic therapy (PDT) or fluorescence imaging, their 2PA cross-sections were much more significantly boosted, evidencing the key role played by different structures on nonlinear optical properties. Finally, by comparison with other porphyrin-based two-photon photosensitizers reported in the literature, we show that these new "semi-disconnected" starburst systems exhibit a remarkable trade-off between intrinsic 2PA, fluorescence and oxygen photosensitization.

BF2-Functionalized Benzothiazole Amyloid Markers: Effect of Donor Substituents on One- and Two-Photon Properties.

Investigation of amyloids with the aid of fluorescence microscopy provides crucial insights into the development of numerous diseases associated with the formation of aggregates. Here, we present a series of BF2-functionalized benzothiazoles with electron-donating methoxy group(s), which are tested as amyloid fluorescent markers. We evaluate how the position of donor functional group(s) influences optical properties (fluorescence lifetime (τ) and fluorescence quantum yield (FQY)) in a solution and upon binding to amyloids. We elucidate the importance of surrounding environmental factors (hydrogen-bonding network, polarity, and viscosity) on the observed changes in FQY and evaluate how the localization of a donor influences radiative and nonradiative decay pathways. We conclude that a donor attached to the benzothiazole ring contributes to the increment of radiative decay pathways upon binding to amyloids (kr), while the donor attached to the flexible part of a molecule (with rotational freedom) contributes to a decrease in nonradiative decay pathways (knr). We find that the donor-acceptor-donor architecture allows us to obtain 58 times higher FQY of the dye upon binding to bovine insulin amyloids. Finally, we measure two-photon absorption (2PA) cross sections (σ2) of the dyes and their change upon binding by the two-photon excited fluorescence (2PEF) technique. Measurements reveal that dyes that exhibit the increase/decrease of σ2 values when transferred from highly polar solvents to CHCl3 present a similar behavior upon amyloid binding. Our 2PA experimental values are supported by quantum mechanics/molecular mechanics (QM/MM) simulations. Despite this trend, the values of σ2 are not the same, which points out the importance of two-photon absorption measurements of amyloid-dye complexes in order to understand the performance of 2P probes upon binding.

Anti-Stokes Luminescence in Multi-Resonance-Type Thermally-Activated Delayed Fluorescence Molecules.

Photon-upconversion in organic molecular systems is one of the promising technologies for future energy harvesting systems because these systems can generate excitons that possess higher energy than excitation energy. The photon-upconversion caused by absorbing ambient heat as additional energy is particularly interesting because it could ideally provide a light-driving cooling system. However, only a few organic molecular systems have been reported. Here, we report the anti-Stokes photoluminescence (ASPL) derived from hot-band absorption in a series of multi-resonance-type thermally-activated delayed fluorescence (MR-TADF) molecules. The MR-TADF molecules exhibited an anti-Stokes shift of approximately 0.1 eV with a high PL quantum yield in the solution state. The anti-Stokes shift corresponded well to the 1-0 vibration transition from the ground state to the excited singlet state, and we further evaluated a correlation between the activation energy for the ASPL intensity and the TADF process. Our demonstration underlines that MR-TADF molecules have become a novel class of ASPL materials for various future applications, such as light-driving cooling systems.

Photoswitchable Molecular Units with Tunable Nonlinear Optical Activity: A Theoretical Investigation.

The first-, second-, and third-order molecular nonlinear optical properties, including two-photon absorption of a series of derivatives, involving two dithienylethene (DTE) groups connected by several molecular linkers (bis(ethylene-1,2-dithiolato)Ni- (NiBDT), naphthalene, quasilinear oligothiophene chains), are investigated by employing density functional theory (DFT). These properties can be efficiently controlled by DTE switches, in connection with light of appropriate frequency. NiBDT, as a linker, is associated with a greater contrast, in comparison to naphthalene, between the first and second hyperpolarizabilities of the "open-open" and the "closed-closed" isomers. This is explained by invoking the low-lying excited states of NiBDT. It is shown that the second hyperpolarizability can be used as an index, which follows the structural changes induced by photochromism. Assuming a Förster type transfer mechanism, the intramolecular excited-state energy transfer (EET) mechanism is studied. Two important parameters related to this are computed: the electronic coupling (VDA) between the donor and acceptor fragments as well as the overlap between the absorption and emission spectra of the donor and acceptor groups. NiBDT as a linker is associated with a low electronic coupling, VDA, value. We found that VDA is affected by molecular geometry. Our results predict that the linker strongly influences the communication between the open-closed DTE groups. The sensitivity of the molecular nonlinear optical properties could assist with identification of molecular isomers.