The application of two-photon absorption (2PA) materials is a classical research field and has recently attracted increasing interest. It has generated a demand for new dyes with high 2PA cross-sections. In this short review, we briefly cover the structure-2PA property relationships of organic fluorophores, organic-inorganic nanohybrids and metal complexes explored by our group. (1) The two-photon absorption cross-section (δ) of organic fluorophores increases with the extent of charge transfer, which is important to optimize the core, donor-acceptor pair, and conjugation-bridge to obtain a large δ value. Among the various cores, triphenylamine appears to be an efficient core. Lengthening of the conjugation with styryl groups in the D-π-D quadrupoles and D-π-A dipoles increased δ over a long wavelength range than when vinylene groups were used. Large values of δ were observed for extended conjugation length and moderate donor-acceptors in the near-IR wavelengths. The δ value of the three-arm octupole is larger than that of the individual arm, if the core has electron accepting groups that allow significant electronic coupling between the arms; (2) Optical functional organic/inorganic hybrid materials usually show high thermal stability and excellent optical activity; therefore the design of functional organic molecules to build functional organic-inorganic hybrids and optimize the 2PA properties are significant. Advances have been made in the design of organic-inorganic nanohybrid materials of different sizes and shapes for 2PA property, which provide useful examples to illustrate the new features of the 2PA response in comparison to the more thoroughly investigated donor-acceptor based organic compounds and inorganic components; (3) Metal complexes are of particular interest for the design of new materials with large 2PA ability. They offer a wide range of metals with different ligands, which can give rise to tunable electronic and 2PA properties. The metal ions, including transition metals and lanthanides, can serve as an important part of the structure to control the intramolecular charge-transfer process that drives the 2PA process. As templates, transition metal ions can assemble simple to more sophisticated ligands in a variety of multipolar arrangements resulting in interesting and tailorable electronic and optical properties, depending on the nature of the metal center and the energetics of the metal-ligand interactions, such as intraligand charge-transfer (ILCT) and metal-ligand charge-transfer (MLCT) processes. Lanthanide complexes are attractive for a number of reasons: (i) their visible emissions are quite long-lived; (ii) their absorption and emission can be tuned with the aid of appropriate photoactive ligands; (iii) the accessible energy-transfer path between the photo-active ligands and the lanthanide ion can facilitate efficient lanthanide-based 2PA properties. Thus, the above materials with excellent 2PA properties should be applied in two-photon applications, especially two-photon fluorescence m...

In this study, three-photon absorbing cyclometalated iridium(III) complexes (Ir-H, Ir-8C, and Ir-O) were rational designed and synthesized through fine-tuning of an auxiliary ligand. The long alkoxy chains in Ir-8C and...

The synergy of multiphoton fluorescence imaging (MP-FI) and magnetic resonance imaging (MRI) provides an imaging platform with high resolution and unlimited penetration depth for early disease detection. Herein, two kinds of terpyridine–Mn­(II) complexes (FD–Mn–O 2 NO and FD–Mn–FD) possessing seven and six coordination modes, respectively, were designed rationally for photodynamic therapy (PDT) guided by MP-FI/MRI. The complexes obtain different multiphoton fluorescence/magnetic resonance properties by adjusting the number of terpyridine ligands. Among them, FD–Mn–FD exhibits the following superiorities: (1) The optimal three-photon excitation wavelength of FD–Mn–FD falls at 1450 nm (NIR-II), which brings high sensitivity and deep tissue penetration in MP-FI. (2) FD–Mn–FD has effective longitudinal relaxation efficiency (r 1 = 2.6 m M–1 s–1), which can be used for T 1-weighted MRI, overcoming the problems of limited tissue penetration depth and low spatial resolution. (3) FD–Mn–FD generates endogenous 1O2 under irradiation by 808 nm light, thereby enhancing the PDT effect in vitro and in vivo. To the best of our knowledge, the complex FD–Mn–FD is the first complex to guide PDT through MP-FI/MRI, providing a blueprint for accurate and effective early detection and timely treatment of the complex in the early stages of cancer.

In this work, a series of multiphoton terpyridine agents (ZA, ZA-Mex, and ZA-Hex) for fluorescence lifetime imaging microscopy (FLIM) are designed and synthesized. The results from photophysical property research reveal that ZA-Hex, as an N-hexylated terpyridine salt, has stronger three-photon aggregation-induced emission (AIE) properties compared to ZA-Mex due to enhanced intramolecular charge transfer (ICT) performance. All three terpyridine derivatives possess suitable fluorescence intensities and stable fluorescence lifetimes under different pH conditions (pH = 4.0–8.0), thereby performing multiphoton fluorescence lifetime imaging. For biological imaging applications, it is found that ZA shows good lipid droplet (LD) turn-on fluorescence performance, and ZA-Hex could easily accumulate in mitochondria with high specificity. This is the first report of terpyridine salts as three-photon AIE probes used for multiphoton FLIM imaging.

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With the advantages of deeper penetration depth and lower biological damage, multi-photon AIE probes are widely used in the field of multi-photon therapy. We develop a series of carbazole terpyridine...

Herein, we have synthesized a series of three-photon fluorescent Pt­(II) complexes targeting a tumor-associated biothiol, cysteine (Cys), which allows it to be detected without any interference from other intracellular proteins. We focused on how to significantly improve the fluorescence response of Cys via regulating the recognition units in probes. The reaction of K2PtCl4 with L-CH 3 or L-COOEt in DMSO solution gave Lyso-Pt-CH 3 and Lyso-Pt-COOEt, respectively, which present four-coordinated square-planar geometries in mononuclear structures. Lyso-Pt-CH 3 consists of a Cys aptamer labeled with typical aggregation-induced emission (AIE) characteristics, which shows strong three-photon absorption cross section (3PA) only in the presence of Cys. It was found that Lyso-Pt-CH 3 displayed a perfect signal-to-noise ratio for imaging lysosomes and for rapid detection of Cys. Using Lyso-Pt-CH 3 , Cys-related cellular mechanisms were proposed. We confirm that cystine (Cyss) could be absorbed in cells through cystine/glutamate antiporters (system xc –) and is then converted to Cys under the effect of enzymes. All of these suggest that Lyso-Pt-CH 3 might be a potential candidate as a simple and straightforward biomarker of lysosome-related Cys in vitro. Lyso-Pt-CH 3 can effectively identify tumor tissues with excessive levels of Cys. Lyso-Pt-CH 3 also showed excellent antitumor activity than cisplatin. This work provides a novel strategy for the rational design of controllably activated and Cys-targeted Pt­(II) anticancer prodrugs for clinical diagnosis and treatment.

Four-photon absorption (4PA) multimodal therapeutic agent applied to tumor ferroptosis process tracking is rarely reported. In this paper, two functionalized terpyridine iron complexes (TD-FeCl 3 , TD-Fe-TD) with four-photon absorption properties were designed and synthesized. The four-photon absorption cross sections of TD-FeCl 3 reached 6.87 × 10–74cm8·s3·photon–3. Due to its strong near-infrared absorption, TD-FeCl 3 has excellent photoacoustic imaging (PAI) capability for accurate PA imaging. TD-FeCl 3 has an efficient longitudinal electron relaxation rate (r 1 = 2.26 mM–1 s–1) and high spatial resolution, which can be applied as T1-weighted magnetic resonance imaging (MRI) contrast agent for tumor imaging in vivo. In addition, Fe3+ as a natural ferroptosis tracer, TD-FeCl 3 , is able to deplete glutathione (GSH) effectively, which can further enhance the ferroptosis process. We found that the series of cheap transition metal complexes has four-photon absorption activity and can be used as multimodal (MRI/PAI) diagnostic agents for tumor tracing processes.