Exploring Tunable Properties, Solvent-Modulated Dynamics, and Novel C(sp3)-H Activation Mechanisms in Electron Donor-Acceptor Complexes.

Electron donor-acceptor (EDA) complex photochemistry has emerged as a vibrant area in visible-light-mediated synthetic radical chemistry. However, theoretical insights into the reaction mechanisms remain limited. Our study investigates the influence of solvent polarity and halogen atom types on radical reaction pathways in EDA complexes. We demonstrate that solvent polarity modulates the charge transfer and spatial arrangement within EDA complexes, thereby influencing their stability and reaction kinetics. Iodide ions play a crucial role in facilitating free radical generation and stabilizing reaction intermediates. Different halogen atom types exhibit distinct effects on radical reactions. Variations in radical concentration and solvent environment further affect the pathway selectivity. Additionally, light conditions influence the free radical generation and pathway selectivity. Our findings enhance the understanding of EDA complex photochemistry and radical reactions, offering insights for organic synthesis and photochemistry applications.

3D bioprinted tumor model: a prompt and convenient platform for overcoming immunotherapy resistance by recapitulating the tumor microenvironment.

BACKGROUND: Cancer immunotherapy is receiving worldwide attention for its induction of an anti-tumor response. However, it has had limited efficacy in some patients who acquired resistance. The dynamic and sophisticated complexity of the tumor microenvironment (TME) is the leading contributor to this clinical dilemma. Through recapitulating the physiological features of the TME, 3D bioprinting is a promising research tool for cancer immunotherapy, which preserves in vivo malignant aggressiveness, heterogeneity, and the cell-cell/matrix interactions. It has been reported that application of 3D bioprinting holds potential to address the challenges of immunotherapy resistance and facilitate personalized medication. CONCLUSIONS AND PERSPECTIVES: In this review, we briefly summarize the contributions of cellular and noncellular components of the TME in the development of immunotherapy resistance, and introduce recent advances in 3D bioprinted tumor models that served as platforms to study the interactions between tumor cells and the TME. By constructing multicellular 3D bioprinted tumor models, cellular and noncellular crosstalk is reproduced between tumor cells, immune cells, fibroblasts, adipocytes, and the extracellular matrix (ECM) within the TME. In the future, by quickly preparing 3D bioprinted tumor models with patient-derived components, information on tumor immunotherapy resistance can be obtained timely for clinical reference. The combined application with tumoroid or other 3D culture technologies will also help to better simulate the complexity and dynamics of tumor microenvironment in vitro. We aim to provide new perspectives for overcoming cancer immunotherapy resistance and inspire multidisciplinary research to improve the clinical application of 3D bioprinting technology.

Unveiling Mechanistic Insights and Photocatalytic Advancements in Intramolecular Photo-(3 + 2)-Cycloaddition: A Comparative Assessment of Two Paradigmatic Single-Electron-Transfer Models.

The synthesis of 1-aminonorbornane (1-aminoNB), a potential aniline bioisostere, through photochemistry or photoredox catalysis signifies a remarkable breakthrough with implications in organic chemistry, pharmaceutical chemistry, and sustainable chemistry. However, an understanding of the underlying mechanisms involved in these reactions remains limited and ambiguous. Herein, we employ high-precision CASPT2//CASSCF calculations to elucidate the intricate mechanisms regulating the intramolecular photo-(3 + 2)-cycloaddition reactions for the synthesis of 1-aminoNB in the presence or absence of the Ir-complex-based photocatalyst. Our investigations delve into radical cascades, stereoselectivity, particularly single-electron-transfer (SET) events, etc. Furthermore, we innovatively introduce and compare two SET models integrating Marcus electron-transfer theory and transition-state theory. These models combined with kinetic data contribute to recognizing the critical control factors in diverse photocatalysis, thereby guiding the design and manipulation of photoredox catalysis as well as the improvement and modification of photocatalysts.

Monitoring Hierarchical Assembly of Ring-in-Ring and Russian Doll Complexes Based on Carbon Nanoring by Förster Resonance Energy Transfer.

We presented the construction of the ring-in-ring and Russian doll complexes on the basis of triptycene-derived carbon nanoring (TP-[12]CPP), which not only acts as a host for pillar[5]arene (P5A) but also serves as an energy donor for building Förster resonance energy transfer (FRET) systems. We also demonstrated that their hierarchical assembly processes could be efficiently monitored in real time using FRET. NMR, UV-vis and fluorescence, and mass spectroscopy analyses confirmed the successful encapsulation of the guests P5A/P5A-An by TP-[12]CPP, facilitated by C-H···π and ···π interactions, resulting in the formation of a distinct ring-in-ring complex with a binding constant of Ka = 2.23 × 104 M-1. The encapsulated P5A/P5A-An can further reverse its role to be a host for binding energy acceptors to form Russian doll complexes, as evidenced by the occurrence of FRET and mass spectroscopy analyses. The apparent binding constant of the Russian doll complexes was up to 3.6 × 104 M-1, thereby suggesting an enhanced synergistic effect. Importantly, the Russian doll complexes exhibited both intriguing one-step and sequential FRET dependent on the subcomponent P5A/P5A-An during hierarchical assembly, reminiscent of the structure and energy transfer of the light-harvesting system presented in purple bacteria.

Probing Coordination Number of Single-Atom Catalysts by d-Band Center-Regulated Luminescence.

It is essential to probe the coordination number (CN) because it is a crucial factor to ensure the catalytic capability of single-atom catalysts (SACs). Currently, synchrotron X-ray absorption spectroscopy (XAS) is widely used to measure the CN. However, the scarcity of synchrotron X-ray source and complicated data analysis restrict its wide applications in determining the CN of SACs. In this contribution, we have developed a d-band center-regulated acetone cataluminescence (CTL) probe for a rapid screening of the CN of Pt-SACs. It is disclosed that the CN-triggered CTL is attributed to the fact that the increased CN could induce the downward shift of d-band center position, which assists the acetone adsorption and promotes the subsequent catalytic reaction. In addition, the universality of the proposed acetone-CTL probe is verified by determining the CN of Fe-SACs. This work has opened a new avenue for exploring an alternative to synchrotron XAS for the determination of CN of SACs and even conventional metal catalysts through d-band center-regulated CTL.

The nearby atomic environment effect on an Fe-N-C catalyst for the oxygen reduction reaction: a density functional theory-based study.

Fe-N-C materials have emerged as highly promising non-noble metal catalysts for oxygen reduction reactions (ORRs) in polymer electrolyte membrane fuel cells. However, they still encounter several challenges that need to be addressed. One of these challenges is establishing an atomic environment near the Fe-N4 site, which can significantly affect catalyst activity. To investigate this, herein, we employed density functional theory (DFT). According to our computational analysis of the Gibbs free energy of the reaction based on the computational hydrogen electrode (CHE) model, we successfully determined two C-O-C structures near the Fe-N4 site (referred to as str-11) with the highest limiting potential (0.813 V). Specifically, in the case of O-doped structures, the neighboring eight carbon (C) atoms around nitrogen (N) can be categorized into two distinct types: four C atoms (type A) exhibiting high sensitivity to the limiting potential and the remaining four C atoms (type B) displaying inert behavior. Electronic structure analysis further elucidated that a structure will have strong activity if the valence band maximum (VBM) around its gamma point is mainly contributed by dxz, dyz or dz2 orbitals of Fe atoms. Constant-potential calculations showed that str-11 is suitable for the ORR under both acidic and alkaline conditions with a limiting potential of 0.695 V at pH = 1 and 0.926 V at pH = 14, respectively. Additionally, microkinetic simulations indicated the possibility of str-11 as the active site for the ORR under working potential at pH = 14.

Structurally Diverse Pyrene-decorated Planar Chiral [2,2]Paracyclophanes with Tunable Circularly Polarized Luminescence between Monomer and Excimer.

We reported the synthesis of a series of structurally diverse CPL-active molecules, in which pyrene units were installed to chiral pm/po-[2,2]PCP scaffolds either with or without a triple bond spacer for pm/po-PCP-P1 and pm/po-PCP-P2, respectively. The X-ray crystallographic analyses revealed that these pyrene-based [2,2]PCP derivatives exhibited diverse structures and crystal packings in the solid phases. The pyrene-based [2,2]PCP derivatives exhibit various (chir)optical properties in organic solutions, depending on their respective structures. In a mixture of dioxane and water, pm/po-PCP-P1 emit green excimer fluorescence, whereas pm/po-PCP-P2 emit blue one. The chiroptical investigation demonstrated that Rp-pm-PCP-P1 and Rp-pm-PCP-P2 exhibited completely opposite CD and CPL signals even they possess the same chiral Rp-[2,2]PCP core. The same argument also holds for other chiral pyrene-based [2,2]PCP derivatives. The theoretical calculation revealed that these unusual phenomena were attributed to different orientation between transition electric dipole moments and the magnetic dipole moments originating from the presence or absence of a triple bond spacer. These pyrene-based [2,2]PCP derivatives display various colours and fluorescence emissions in the solid state and PMMA films, possibly due to the different packings as observed in the crystal structure. Moreover, these compounds also can interact with perylene diimide through π-π interactions, leading to near-white fluorescence.

Highly Luminescent Chiral Carbon Nanohoops via Symmetry Breaking with a Triptycene Unit: Bright Circularly Polarized Luminescence and Size-Dependent Properties.

Chiral carbon nanohoops with both high fluorescence quantum yield and large luminescence dissymmetry factor are essential to the development of circularly polarized luminescence (CPL) materials. Herein, the rational design and synthesis of a series of highly fluorescent chiral carbon nanohoops TP-[8-13]CPPs via symmetry breaking with a chiral triptycene motif is reported. Theoretical calculations revealed that breaking the symmetry of nanohoops causes a unique size-dependent localization in the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular obtitals (LUMOs) as the increasing of sizes, which is sharply different from those of [n]cycloparaphenylenes. Photophysical investigations demonstrated that TP-[n]CPPs display size-dependent emissions with high fluorescence quantum yields up to 92.9% for TP-[13]CPP, which is the highest value among the reported chiral conjugated carbon nanohoops. The high fluorescence quantum yields are presumably attributed to both the unique acyclic, and radial conjugations and high radiative transition rates, which are further supported by theoretical investigations. Chiroptical studies revealed that chiral TP-[n]CPPs exhibit bright CPL with CPL brightness up to 100.5 M-1 cm-1 for TP-[11]CPP due to the high fluorescence quantum yield. Importantly, the investigations revealed the intrigued size-dependent properties of TP-[n]CPPs with regards to (chir)optical properties, which follow a nice linear relationship versus 1/n. Such a nice linear relationship is not observed in other reported conjugated nanohoops including CPPs.

Preparation, Stimulus-Response Mechanisms and Applications of Micro/Nanorobots.

Micro- and nanorobots are highly intelligent and efficient. They can perform various complex tasks as per the external stimuli. These robots can adapt to the required functional form, depending on the different stimuli, thus being able to meet the requirements of various application scenarios. So far, microrobots have been widely used in the fields of targeted therapy, drug delivery, tissue engineering, environmental remediation and so on. Although microbots are promising in some fields, few reviews have yet focused on them. It is therefore necessary to outline the current status of these microbots' development to provide some new insights into the further evolution of this field. This paper critically assesses the research progress of microbots with respect to their preparation methods, stimulus-response mechanisms and applications. It highlights the suitability of different preparation methods and stimulus types, while outlining the challenges experienced by microbots. Viable solutions are also proposed for the promotion of their practical use.

Efficient manipulation of Förster resonance energy transfer through host-guest interaction enables tunable white-light emission and devices in heterotopic bisnanohoops.

In this study, we synthesized and reported the heterotopic bisnanohoops P5-[8,10]CPPs containing cycloparaphenylenes (CPPs) and a pillar[5]arene unit, which act not only as energy donors but also as a host for binding energy acceptors. We demonstrated that a series of elegant FRET systems could be constructed successfully through self-assembly between donors P5-[8,10]CPPs and acceptors with different emissions via host-guest interaction. These FRET systems further allow us to finely adjust the donors P5-[8,10]CPPs and acceptors (BODIPY-Br and Rh-Br) for achieving multiple color-tunable emissions, particularly white-light emission. More importantly, these host-guest complexes were successfully utilized in the fabrication of white-light fluorescent films and further integrated with a 365 nm LED lamp to create white LED devices. The findings highlight a new application of carbon nanorings in white-light emission materials, beyond the common recognition of π-conjugated molecules.

ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.

Shape-Persistent Triptycene-Derived Pillar[6]arenes: Synthesis, Host-Guest Complexation, and Enantioselective Recognitions of Chiral Ammonium Salts.

Construction of macrocyclic hosts with a novel structure and excellent property has emerged as an intriguing undertaking for the past few years. Here, we reported the synthesis of shape-persistent triptycene-derived pillar[6]arene (TP[6]). The single crystal structure analysis revealed that the macrocyclic molecule adopts a hexagonal structure, featuring a helical and electron-rich cavity capable of encapsulating electron-deficient guests. In order to obtain chiral TP[6] from an enantiomerically pure triptycene building block, an efficient resolution of chiral triptycene was successfully developed through introducing chiral auxiliaries into triptycene skeletons. The 1H NMR and isothermal titration calorimetry investigations demonstrated that chiral TP[6] exhibited enantioselectivity toward four pairs of chiral guests containing a trimethylamino group, implying a significant promising application in area of enantioselective recognition.

Co-function Mechanisms of Chlorine and Alkoxy Radicals in Cerium-Catalyzed C-H Functionalization of Alkane Mediated by Visible Light.

Identification of radical intermediates for the catalytic functionalization of alkanes offers a number of unique challenges and has recently raised a controversial issue concerning the subtle role of chlorine versus alkoxy radicals in cerium photocatalysis. This study is an attempt to settle the controversy within the theoretical frameworks of Marcus electron transfer and transition state theory. Co-function mechanisms were proposed together with a scheme of kinetic evaluations to account for ternary dynamic competition among photolysis, back electron transfer, and hydrogen atom transfer (HAT). Cl•-based HAT has been proven to initially control the early dynamics of the photocatalytic transformation on the picosecond to nanosecond time scale, which is subsequently taken over by a postnanosecond event of alkoxy radical-mediated HAT. The theoretical models developed herein provide a uniform understanding of the continuous time dynamics of photogenerated radicals to address some paradoxical arguments in lanthanide photocatalysis.

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer.

Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells' sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

Extended Single-Electron Transfer Model and Dynamically Associated Energy Transfer Event in a Dual-Functional Catalyst System.

Organic photocatalysis has been developed flourishingly to rely on bimolecular energy transfer (EnT) or oxidative/reductive electron transfer (ET), promoting a variety of synthetic transformations. However, there are rare examples to merge EnT and ET processes rationally within one chemical system, of which the mechanistic investigation still remains in its infancy. Herein, the first mechanistic illustration and kinetic assessments of the dynamically associated EnT and ET paths were conducted for realizing the C-H functionalization in a cascade photochemical transformation of isomerization and cyclization by using the dual-functional organic photocatalyst of riboflavin. An extended single-electron transfer model of transition-state-coupled dual-nonadiabatic crossings was explored to analyze the dynamic behaviors in the proton transfer-coupled cyclization. This can also be used to clarify the dynamic correlation with the EnT-driven E → Z photoisomerization that has been kinetically evaluated by using Fermi's golden rule with the Dexter model. The present computational results of electron structures and kinetic data contribute to a fundamental basis for understanding the photocatalytic mechanism of the combined operation of EnT and ET strategies, which will guide the design and manipulation for the implementation of multiple activation modes based on a single photosensitizer.

[2,2] Paracyclophanes-based double helicates for constructing artificial light-harvesting systems and white LED device.

The construction of efficient artificial light-harvesting systems (ALHSs) is of vital importance in utilizing solar energy. Herein, we report the non-covalent syntheses of double helicates PCP-TPy1/2 and Rp,Rp-PCP-TPy1/2 by metal-coordination interaction and their applications in ALHSs and white light-emitting diode (LED) device. All double helicates exhibit significant aggregation-induced emission in tetrahydrofuran/water (1:9, v/v) solvent. The aggregated double helicates can be used to construct one-step or sequential ALHSs with fluorescent dyes Eosin Y (EsY) and Nile red (NiR) with the energy transfer efficiency up to 89.3%. Impressively, the PMMA film of PCP-TPy1 shows white-light emission when doped 0.075% NiR, the solid of double helicates (Rp,Rp-) PCP-TPy2 can be used as the additive of a blue LED bulb to achieve white-light emission. In this work, we provided a general method for the preparation of novel double helicates and explored their applications in ALHSs and fluorescent materials, which will promote future construction and application of helicates as emissive devices.

Chiral Carbon Nanorings: Synthesis, Properties and Hierarchical Self-assembly of Chiral Ternary Complexes Featuring a Narcissistic Chiral Self-Recognition for Chiral Amines.

We report the synthesis and chiroptical properties of novel chiral carbon nanorings Sp-/Rp-[12]PCPP containing a planar chiral [2.2]PCP unit, and demonstrate that Sp-/Rp-[12]PCPP can not only host crown ether 18-Crown-6 to form ring-in-ring complexes with a binding constant 3.35×103  M-1 , but also accommodate the complexes of 18-Crown-6 and S/R-protonated amines to form homochiral S@Sp-/R@Rp- and heterochiral S@Rp-/R@Sp- ternary complexes, displaying significantly larger binding constants of up to 3.31×105  M-1 depending on the chiral guests. Importantly, homochiral S@Sp-/R@Rp- ternary complexes exhibit an enhanced CD signal, while the heterochiral S@Rp-/R@Sp- ones have a constant CD signal compared with the chiral carbon nanorings, respectively, which suggests that homochiral S@Sp-/R@Rp- ternary complexes display a highly narcissistic chiral self-recognition for S/R-protonated chiral amines, respectively. Finally, the chiral ternary complexes can be further applied to determine the ee values of chiral guests. The findings highlight a new application of carbon nanorings in supramolecular sensors, beyond the common recognition of π-conjugated molecules.

Mechanistic Understanding and Reactivity Analyses for the Photochemistry of Disubstituted Tetrazoles.

The photolysis of tetrazoles has undergone extensive research. However, there are still some problems to be solved in terms of mechanistic understanding and reactivity analyses, which leaves room for theoretical calculations. Herein, multiconfiguration perturbation theory at the CASPT2//CASSCF level was employed to account for electron correction effects involved in the photolysis of four disubstituted tetrazoles. Based on calculations of vertical excitation properties and evaluations of intersystem crossing (ISC) efficiencies in the Frank-Condon region, the combination of space and electronic effects is found in maximum-absorption excitation. Two types of ISC (1ππ* → 3nπ*, 1ππ* → 3ππ*) are determined in disubstituted tetrazoles, and the obtained rates follow the El-Sayed rule. Through mapping three representative types of minimum energy profiles for the photolysis of 1,5-, and 2,5-disubstituted tetrazoles, a conclusion can be drawn that the photolysis of tetrazoles exhibits reactivity characteristic of bond-breaking selectivity. Kinetic evaluations show that the photogeneration of singlet imidoylnitrene operates predominately over that in the triplet state, which can be confirmed by a double-well model in the triplet potential energy surface of 1,5-disubstituted tetrazole. Similar mechanistic explorations and reactivity analyses were also applied to the photolysis of 2,5-disubstituted tetrazole to unveil fragmentation patterns of nitrile imine generation. All computational efforts allow us to better understand the photoreactions of disubstituted tetrazoles and to provide useful strategies for regulating their unique reactivity.

Synergetic argentophilic and through space electronic interactions in a single-crystal-to-single-crystal photocycloaddition reaction: a mechanistic study.

Ag(I) is able to mediate single-crystal-to-single-crystal transformation through [2+2] photocycloaddition to prepare high-conductivity materials. However, the intrinsic mechanism of Ag(I) mediation, the detailed photophysical and photochemical processes as well as the origin of the enhanced conductivity of nanocrystals are still unclear. In this work, the comprehensive kinetic scheme and regulation mechanism are established by the accurate QM/MM calculations at the CASPT2//CASSCF/AMBER level of theory with consideration of the crystal environment. We find that the argentophilic interaction and through space electronic interaction are the key factors that promote Ag(I)-mediated [2+2] PCA reactions and may account for the enhancement of conductivity. These mechanistic insights into the Ag(I)-regulated photo-dimerization in the crystal surrounding are beneficial for the design of the structurally and electrically favorable skeletons of a metal-organic coordination polymer.