Accounts of Chemical Research最新文献

Upconversion nanoparticles (UCNPs) have become one of the most frequently used nanomaterials for optical biosensing and imaging. UCNPs unique properties include high photostability, low toxicity, large anti-Stokes shifts, and negligible sample background fluorescence under near-infrared (NIR) excitation. Combining these advantages with Förster resonance energy transfer (FRET) for the investigation of biomolecular interactions seems to be an obvious choice. However, UCNPs are rather large and have low absorption cross sections, which makes the development of UCNP-based FRET systems challenging. Nevertheless, various UCNP-FRET approaches have been developed over the last 20 years, and, in particular, the development of smaller UCNPs and new UCNP architectures has significantly advanced UCNP-FRET.

Donor–acceptor distance is extremely important in FRET because its efficiency decreases with the sixth power of that distance. In UCNPs, the donors are the emitting lanthanide ions (activators), which can be placed all over the UCNP volume, resulting in some being close to and others far from the UCNP surface. The “far ones” may be bright because they are well protected from the environment, but they can only provide very low FRET efficiencies to an outside acceptor. The “close ones” can generate high FRET efficiencies but are also exposed to efficient quenching from the surrounding environment on the UCNP surface. This twisted tongue requires an ideal compromise between bright donor ions and a close surface distance for high FRET efficiency.

The combination of different core–shell UCNP architectures with the ability to dope cores and shells with different amounts of sensitizers and activators, smaller UCNP sizes, reduced water absorption by changing the excitation wavelength from 980 to 808 nm, functional surface coatings and bioconjugation, as well as optimized FRET acceptor concepts are important parameters to overcome the limits of UCNP-FRET. Careful photophysical characterization, with spatial resolution throughout the entire UCNP volume and on its surface, and advanced modeling to better interpret the experimental results and understand the underlying mechanisms are key to translating UCNP-FRET into the application space.

This Account discusses the recent advances of UCNP-FRET, including advanced UCNP core–shell architectures, UCNP surface chemistry and bioconjugation, versatility in acceptor selection, a better understanding of the UCNP-FRET mechanisms, UCNP-FRET modeling approaches, and applications in biosensing, bioimaging, and theranostics. We highlight the challenges of combining UCNPs and FRET and share our vision concerning future developments toward a complete understanding of UCNP-FRET, optimization of nanobiohybrid materials, multiplexed biosensing, and translation of UCNP-FRET technology into broadly usable applications in bioanalysis and biomedicine.

Monocoordinate main-group-element compounds have been postulated as key intermediates in diverse chemical transformations and continue to attract significant interest due to their unique bonding and high reactivity. Among them, neutral one-coordinate species stabilized by monoanionic ligands, such as carbynes, nitrenes, and their heavier congeners, exhibit intriguing electronic structures and potential utility as reactive platforms in synthetic chemistry. However, the isolation of such species under ambient conditions remains a formidable task.

In this Account, we summarize our recent efforts in the synthesis and characterization of neutral pseudo-monocoordinate group 14–16 compounds, stabilized by sterically encumbered hydrindacenyl ligands. Dehalogenation of hydrindacenyl-tetrelene halides with potassium graphite yielded isolable germylyne, stannylyne, and plumbylyne compounds, representing the first structurally authenticated one-coordinate tetrel radicals. These species possess one unpaired electron populating two nearly degenerate np orbitals and thereby exhibit unquenched orbital angular moment, leading to significant g-factor anisotropy, evidenced by electron paramagnetic resonance (EPR) spectroscopic and wave function based ab initio multireference computational analyses.

Photolysis of an azide precursor generated a stable nitrene, and its triplet ground state was conclusively characterized by EPR and superconducting quantum interference device (SQUID) magnetometry to feature a well-defined axial zero-field splitting (ZFS) of D = 0.92 cm^–1 and a nearly vanishing rhombicity E/D ratio. Heavier congeners, including a stibinidene and two bismuthinidenes, were accessed via the reduction of dihalide precursors. Despite possessing triplet ground states, these species are silent in conventional EPR measurements due to extremely large, positive ZFS values (D = 960 cm^–1 for stibinidene; D > 4300 cm^–1 for bismuthinidene), as predicted by ab initio calculations and confirmed by SQUID measurements for stibinidene. Notably, triplet bismuthinidenes are even nonmagnetic at room temperature, due to their gigantic ZFSs that completely depopulate the excited magnetic sublevels. Attempts to synthesize a free phosphinidene led to the isolation of a phosphanorcaradiene containing a strained three-membered PC₂ heterocycle, which could behave as a phosphinidene source in activating a variety of small molecules. Hydrogen abstraction of a tellurol with PbO₂ gave rise to a rare, isolable telluryl radical with an almost orbitally degenerate ground state and field-induced slow magnetic relaxation. This collection of pseudo-one-coordinate species expands the landscape of low-valent main-group chemistry and highlights their potential as functional open-shell platforms for fundamental studies and molecular design.

Propylene oxide manufacturing has experienced one of the fastest growth rates of commodity chemicals in recent years (ca. 21% from 2020 to 2023) and is expected to reach a market size of 36 billion US $ by 2031. Newly installed production facilities frequently use Ti-zeotype catalysts, most notably, titanium silicalite-1 (TS-1). Owing to their industrial relevance, these catalysts have been studied intensively. However, to date, many aspects of this catalytic process remain unclear, in particular, regarding the nature of the active sites. Most commonly, the active sites have been described as framework-incorporated isolated metal sites. Yet, an increasing number of reports has highlighted the role of defect sites and/or the presence of di- (or multi) nuclear sites. Many of the assignments have, however, remained tentative due to limited structural resolution or the lack of suitable molecular references, where so far UV/vis, IR, Raman, and K-edge XAS spectroscopy have predominately been utilized. In this Account, we show how the combination of advanced solid-state nuclear magnetic resonance spectroscopy (ssNMR) and/or X-ray absorption spectroscopy (XAS) augmented by computational modeling and classical characterization approaches can yield molecular-level understanding of active sites in titanosilicate zeotype catalysts. Specifically, we focus on understanding their structure and dynamics, with the ultimate goal of extracting guideline principles to develop optimal catalysts. We also highlight how developing new methods for low-γ, quadrupolar, and metal-centered NMR spectroscopy has allowed us to gain unprecedented insights into their electronic structure and how related detailed information can be obtained from X-ray absorption-based methods. This account discusses the following challenges and associated learning opportunities: (i) how key peroxo intermediates can be identified based on ¹⁷O ssNMR, how their stability can be quantified, and how it relates to the presence of TiO₂ domains and the overall catalyst performance; (ii) how novel approaches based on direct metal characterization, in particular ^47/49Ti ssNMR, yield information on Ti-site symmetry and help to assign T-site (distribution); (iii) how soft X-rays (Ti L_2,3-edge NEXAFS) can help detecting octahedral Ti sites and can be used to measure, track the conversion, and distinguish mono- and dinuclear Ti-peroxo species; and (iv) how ambient conditions affect the active-site structure and how water-induced structural rearrangement gives rise to Brønsted acidity in TS-1. Finally, we provide an outlook on ongoing developments that are needed to further expand the scope of the methodology discussed herein, in particular, with a focus on characterizing reactive intermediates and translating the methodology to other Ti-based catalysts.

Chiral materials are anticipated to play a significant role in next-generation technologies such as displays, information storage, optical/quantum communications, and polarization imaging due to their ability to selectively absorb and emit circularly polarized light (CPL) through chirality-dependent light-matter interactions.

Highly efficient conversion of the unique optical signals generated by chiroptical responses into electrical signals─and vice versa─is crucial for advanced chiroptical applications. However, molecularly chiral materials often suffer from low chiroptical activities and low-efficiency conversion. To address this limitation, researchers have been actively developing not only novel chiral molecules but also chiral plasmonic structures (CPSs) that can effectively interact with CPL. Furthermore, efforts are underway to boost chiroptical performance of hybrid systems comprising chiral molecules and CPSs by optimizing their synergistic interactions.

CPSs have emerged as promising candidates for practical applications in CPL sensors, emitters, and various photonic devices due to their preferential and strong interactions with CPL. In contrast to the chiroptical responses of molecularly chiral materials, which typically exhibit weak interactions with CPL, CPSs demonstrate strong, tunable, and even reconfigurable chiroptical responses across a broad range of wavelengths (or frequencies) from the ultraviolet to the terahertz regimes originating from the coupling of chirality with plasmonic effects, enabling localized electromagnetic field enhancements.

This Account focuses on the mechanisms of chirality transfer, chirality induction, and the methodological fabrication strategies of CPSs, with a specific emphasis on the role of macroscopic deformations including twisting, rotating, stretching, bending, folding, pushing, and pulling. By employing these macroscale mechanical deformations, novel CPSs with unprecedented functionality can be readily fabricated, thereby encoding macroscopic chirality onto the micro- and nanoscale. The plasmonic chirality induction can be achieved by introducing symmetry breaking into the achiral plasmonic structures, transforming them into systems that exhibit strong chiroptical responses such as circular dichroism (CD) and optical rotatory dispersion (ORD). These responses can be dynamically tuned by modulating the applied macroscopic deformations.

In addition to discussing current advancements, this Account also outlines potential future research directions in this emerging field, including the exploration of hybrid methods that combine top-down and bottom-up approaches with macroscopic deformation-based techniques, as well as the investigation of other approaches for macroscopic deformation, which has not yet been used in the field of chiral plasmonics.

The nano-bio interface, where nanomaterials and biological systems converge, represents a critical frontier in modern science, bridging materials chemistry with biotechnology. A deep understanding of the physicochemical processes at this interface is essential for both assessing the environmental impact of nanomaterials and for designing new bioinspired technologies. While much of this field has focused on bacteria and eukaryotes, the domain of Archaea, pivotal to global biogeochemical cycles and a promising resource for bioenergy, remains a comparatively underexplored territory. The unique cellular architecture of archaea, particularly their distinct membrane lipids and crystalline surface layers (S-layers), presents a unique set of rules for nano-bio interactions, making the study of the nano-archaea interfaces a grand challenge of fundamental importance.

In this Account, we summarize the biophysical tools and bioengineering strategies developed in our laboratory to probe and program the nano-archaea interaction. We first developed a single-cell anaerobic atomic force microscopy (AFM) technique to overcome the primary technical barrier of measuring these sensitive, strictly anaerobic organisms in situ, which provided an unprecedented window into the archaeal nanomechanical world. This platform enabled us to reveal the critical role of the archaeal S-layer in maintaining the cellular stability and mediating hydrophobic interactions. We then deciphered the complex chemical dialogue between nanoparticles and archaea, discovering the dominant influence of nanoparticle surface chemistry on the nature of the interaction and the ultimate biological response. Building upon this foundation of fundamental understanding, we have rationally designed and constructed several functional nano-archaeal biohybrid systems. These breakthroughs, progressing from tool development to fundamental discovery and finally to functional engineering, not only help fill a theoretical gap in nanointerface science but also provide new strategies and insights for developing next-generation biotechnologies.

Chronic, non-healing wounds pose a serious public health issue and the need for new treatment methods is paramount. Dehydrated human amnion/chorion membrane has potential wound healing properties, due to the enrichment of growth factors and anti-inflammatory properties. However, its auxiliary advantage on diabetic wounds with demonstrated safety and efficacy in animal models has not been extensively documented. This study aimed at evincing the wound-healing property of dehydrated human amnion chorion membrane in diabetic and non-diabetic rats. An excisional wound model was developed in 36 male Sprague-Dawley rats that were randomly classified into six groups for two experiments. The non-diabetic rat group included non-diabetic control (G1), dHACM treatment (G2), and dHACM dressing + saline-treatment (G3); (n = 6). Similarly, the diabetic group included diabetic control (G4), dHACM treatment (G5), and dHACM dressing + saline-treatment (G6); (n = 6). The results of wound contractility rate, re-epithelialization, grading of granulation tissue, and collagen deposition from histopathological observation demonstrated that in comparison with the other groups (G1, G2, G4, and G5), the animal groups treated with dHACM dressing + saline-treatment (G3 and G6) had superior regenerative effects in excisional wound model. Also, in the animals of G5 and G6 of the diabetic group, there was no statistically significant difference (P > 0.05) in the levels of glucose, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP), when compared to G4 animals during the experiment. It is evident from this study that dHACM could be applied as a potential wound healing biomaterial, especially in diabetic conditions.

The general anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. This study was aimed to compare the analgesic effectiveness and safety of systemic analgesics alone or plus at-home topical sevoflurane for the management of patients with painful nonrevascularizable leg ulcers who were referred to a Pain Clinic by their attending vascular surgeons. We reviewed charts of patients treated in a single Pain Clinic with analgesic Standard of Care either alone (group SoC) or plus at-home topical sevoflurane (group SoC + Sevo), according to safety criteria. The area under the curve of pain over a year (AUC-Pain) was the primary outcome for analgesic effectiveness. Opioids were converted into Oral Morphine Milligram Equivalents. Groups SoC (n = 26) and SoC + Sevo (n = 38) were similar in baseline characteristics. Compared to SoC, median values [interquartile range] of area under the curve of pain for one-year follow-up were markedly lower for SoC + Sevo (54 [35-65] vs. 15 [11-23]; p < 0.000001, U Mann-Whitney test). Oral Morphine Milligram Equivalents were similar at baseline (SoC: 78.5 [22.5-135] vs. SoC + Sevo: 101.3 [30-160]; p = 0.753), but significantly lower for SoC + Sevo at three (120 [22.5-202.5] vs. 30 [0-80]; p = 0.005), six (120 [11.3-160] vs. 20 [0-67.5]; p = 0.004), nine (114.4 [0-154] vs. 0 [0-37]; p = 0.018), and 12 months (114.4 [0-154] vs. 0 [0-20]; p = 0.001). Multiple linear regression analysis revealed the addition of sevoflurane to be the most likely variable to explain this difference in outcome (ß:-33.408; p < 0.000001). Nine patients (24%) in SoC + Sevo had adverse effects attributed to sevoflurane, but only one patient needed to stop using sevoflurane due severe dermatitis. In conclusion, the addition of topical sevoflurane to the analgesic standard of care in patients with painful nonrevascularizable leg ulcers was a well-tolerated therapy that significantly improved pain control and allowed for a significant reduction in opioid consumption.

Pyoderma gangrenosum (PG) is a rare inflammatory skin disease that is difficult to diagnose. PG may be an extra-intestinal manifestation of ulcerative colitis (UC). In recent times, coronavirus disease (COVID-19) vaccines have caused various adverse cutaneous reactions. However, to the best our knowledge, combinations thereof have not been reported. We encountered a case of PG triggered by COVID-19 vaccination in a patient with UC. A 40-year-old woman developed severe pain and an abscess in the dorsum of the left foot after receiving the first dose of the messenger RNA (mRNA)-based Pfizer/BioNTech BNT162b2 COVID-19 vaccine. Severe painful ulcers with purulent necrosis and gaseous gangrene progressed rapidly along the extensor tendons and muscles to the toes and ankle. Although surgical debridement can worsen PG by triggering pathergy, we nonetheless performed wide debridement including partial extensor tenotomy with abscess drainage to prevent progression to pyogenic ankle arthritis and to rescue the toes. Antibiotics, corticosteroids, and anticoagulants were prescribed during surgical wound management via negative pressure therapy. After the lesion improved, the skin and soft tissue defect were covered using a superficial circumflex iliac artery perforator free flap and a split-thickness skin graft. The patient was satisfied with the foot salvage, and could walk unaided (without a brace or cane) from 8 weeks after the final surgery. PG may be rare even in UC patients, but mRNA-based COVID-19 vaccines may find an immunosuppressive niche. A high level of caution and suspicion of skin manifestations after vaccination is essential.

Chronic ulcers are a major public health problem, due to their chronic nature, their poor response to treatment, the high frequency of recurrences, and their affection to the patient's quality of life. Even with the development of new therapies in the field of chronic wound care, chronic ulcers remain a clinical problem. As a novel branch of research, Catalytic Nanomedicine has offered promising results in disinfection and treatment of chronic wounds through the use of bionanocatalysts, organically functionalized mesoporous nanostructured materials with catalytic properties. Particularly, Cu/TiO₂-SiO₂ mixed oxide bionanocatalysts have shown favorable results for chronic ulcer healing. In this work, we present the treatment of 15 patients (8 females and 7 males, mean age of 69.59 ± 12.07 years old) affected with chronic ulcers (wound age ranging from 4 months to 10 years old, mean size of 12.94 ± 18.20 cm²) by the administration of Cu/TiO₂-SiO₂ bionanocatalysts embedded in a nanoemulsion matrix. In all cases, complete epithelialization and healing of the lesions was achieved (healing time from 3 to 35 weeks), without the appearance of side effects. Wound healing time was analyzed in the context of initial wound size, wound's age, patient's age, and concomitant conditions, being wound size and patient's age the main factor affecting the duration of the treatment with the bionanocatalysts.