Lianke Wang

Multiphoton fluorophores are typically based on extended π-conjugated architectures, resulting in structural complexity and limited tunability. Here, we report a chirality-guided strategy for constructing high-order multiphoton fluorophores from a minimalist single-aryl scaffold. Through solvent-assisted assembly, chirality and hydrogen-bonding interactions organize heteroatoms into ordered chiral heteroatom clusters (CHCs), enabling through-space conjugation and clusteroluminescence without direct aryl–aryl π–π stacking. Structural and chiroptical studies reveal that chirality is encoded into the emissive cluster states and governs clusteroluminescence. Donor–acceptor engineering further establishes CHC-mediated through-space charge transfer in which heteroatom clusters act as electronic bridges connecting spatially separated donor and acceptor units. The synergistic interplay between chirality-guided CHC organization and charge transfer enhances electronic delocalization and polarizability, leading to efficient two-, three-, and four-photon-excited fluorescence in an isolated aromatic framework. The enhanced nonlinear optical response enables deep imaging of three-dimensional tumor spheroids with penetration depths up to 160 μm. This work establishes chirality-guided heteroatom clustering as a general strategy for compact multiphoton fluorophores and nonlinear optical materials.

Homogeneous oxygen reduction reaction (ORR) studies rely on two predominant electron delivery modes, yet a critical solvent mismatch between electrochemically (aqueous) and chemically (nonaqueous) driven assays invalidates cross-system comparisons of catalytic activity and selectivity for Cu-based molecular catalysts. Herein, we compare ORR catalysis by two pyridinophane-copper(II) complexes, [Cu^tmpa-NH]²⁺ and [Cu^bmpa-NH]²⁺, under matched conditions to evaluate the intrinsic influence of electron delivery modes. Both follow an overall third-order rate law (first-order dependences on [catalyst], [O₂], [acid]) in acetonitrile. However, [Cu^tmpa-NH]²⁺ exhibits 40-fold higher activity and near-exclusive four-electron selectivity (96.42% H₂O), whereas [Cu^bmpa-NH]²⁺ displays mixed two-electron/four-electron behavior (58.22% H₂O₂). Critically, [Cu^tmpa-NH]²⁺ maintains consistent four-electron selectivity and activity across both electron delivery modes, confirming that its intrinsic ORR performance is independent of the electron delivery mode and governed solely by its coordination sphere. This work identifies an easily overlooked issue in chemical ORR assays: decamethylferrocene reacts with in situ formed H₂O₂ in acidic media, interfering with selectivity and kinetic analysis. Notably, a centrosymmetric bis(μ–OH)-bridged dinuclear Cu(II) intermediate generated from the reaction of [Cu^bmpa-NH]⁺ with O₂ has been successfully isolated and structurally characterized. Overall, this work establishes a structure–activity-selectivity relationship for pyridylamine-copper ORR catalysts and provides rational design guidance for their high-performance analogues.

A mononuclear Cu complex bearing a pentadentate polypyridylalkylamine ligand mediates four-electron O ₂ reduction in both organic and aqueous media, revealing the key role of ligand fine-tuning in catalytic performance.

The performance of chemotherapeutic agents has been largely restrained by the dose-dependent toxic side effects. In this work, cisplatin (CDDP) was endowed with the capability of photoactivated reactive oxygen species (ROS) generation and self-reporting cell uptake via coordination with a small organic molecule MSN. In the resultant MSN-Pt, the Pt-N coordination could obviously enhance the intermolecular charge transfer (ICT) process that allows the integration of fluorescence imaging, photogenerated ROS, and chemotherapeutic performance. The resultant MSN-Pt can recognize between normal and cancer cells and quickly penetrate the cancer cell membrane, self-reporting the cell uptake. Upon light illumination, mitochondria and nuclei were severely damaged. An in vivo mouse model demonstrated that MSN-Pt completely inhibited the tumor growth, exhibiting a higher efficacy compared with that of CDDP. This work provides a facile strategy to develop chemotherapy (CT) drugs for drug-resistant cancers.

Two-photon excited phototherapy has attracted considerable attention due to its advantages such as deeper penetration depth and higher spatial resolution. The lack of a high-performance photosensitizer with large two-photon absorption cross-sections and specific targeting ability makes the efficacy of phototherapy in the treatment of cancer unsatisfactory. Here, a new BODIPY-derived photosensitizer 6DBF₂ is designed with two-photon photosensitization for two-photon excited photodynamic therapy in vivo. 6DBF₂ possesses good two-photon absorption and efficient ¹O₂ generation upon near-infrared laser excitation. Excellent targeting specificities to lipid droplets of 6DBF₂ without any encapsulation or modification at a low working concentration of 0.1 μM is in favor of efficient photodynamic therapy. In vitro cancer cell ablation and in vivo tumor ablation inside mice models upon two-photon irradiation in NIR demonstrate the outstanding therapeutic performance of 6DBF₂ in two-photon excited photodynamic therapy. This work thus discusses a rare example of lipid droplets targeting two-photon excited photodynamic therapy for deep cancer tissue imaging and treatment under near-infrared light irradiation.

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-FeCl₃, TD-Fe-TD) with four-photon absorption properties were designed and synthesized. The four-photon absorption cross sections of TD-FeCl₃ reached 6.87 × 10^-74cm⁸·s³·photon^-3. Due to its strong near-infrared absorption, TD-FeCl₃ has excellent photoacoustic imaging (PAI) capability for accurate PA imaging. TD-FeCl₃ has an efficient longitudinal electron relaxation rate (r₁ = 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-FeCl₃, 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.

Owing to 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 have developed a series of carbazole terpyridine manganese(II) complexes (MD1–MD3) that are promising as aggregation-induced emission (AIE) photosensitizers (PSs). MD1–MD3 exhibit excellent three-photon AIE properties in DMSO/H₂O solution. We modulated the AIE properties of the Mn(II) complexes by introducing halogen atoms (Br/I). The three-photon fluorescence intensity of the complexes upon introducing halogen atoms is strong under the conditions of fw = 99% and 60%, respectively. Based on halogen-substituted carbazole ligands, MD3 can be applied as a multi-photon absorption photosensitizer which can produce ¹O₂ and O₂˙⁻. MD3 damages the mitochondrial morphology, leads to a decrease in mitochondrial membrane potential, and then triggers the apoptosis of cancer cells. Furthermore, MD3 is successfully applied as a photosensitizer in tumor theranostics in vivo. This work provides a new idea for ligand modulation of multiphoton AIE ground state transition metal complexes to make them multiphoton therapeutic agents.

Intracellular lipid storage and regulation occur in lipid droplets, which are of great significance to the physiological activities of cells. Herein, a lipid droplet-specific fluorescence probe (lip-YB) with a high quantum yield (QY_lip-YB = 73.28%), excellent photostability, and quickly polarity sensitivity was constructed successfully. Interestingly, lip-YB exhibited remarkable two-photon (TP) characteristics, which first realized real-time monitoring of the lipid droplet multidynamics process, diagnosing nonalcoholic fatty liver disease (NAFLD) and inflammation in living mice via TP fluorescence imaging. It is found that the as-prepared lip-YB provides a new avenue to design lipid droplet-specific imaging probes, clarifies its roles and mechanisms in cell metabolism, and can timely intervene in lipid droplet-related diseases during various physiological and pathological processes.