Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis.

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported ß-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host-guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

Continuously Tunable MOFs Enable Precise Mass Transfer for High-Performance Isomer Separation.

Modulating mass transfer is crucial for optimizing the catalytic and separation performances of porous materials. Here, we systematically developed a series of continuously tunable MOFs (CTMOFs) that exhibit incessantly increased mass transfer. This was achieved through the strategic blending of ligands with different lengths and ratios in MOFs featuring the fcu topology. By employing a proportional mixture of two ligands in the synthesis of UiO-66, the micropores expanded, facilitating faster mass transfer. The mass transfer rate was evaluated by dye adsorption, dark-field microscopy, and gas chromatography (GC). The GC performance proved that both too-fast and too-slow mass transfer led to low separation performance. The optimized mass transfer in CTMOFs resulted in an exceptionally high separation resolution (5.96) in separating p-xylene and o-xylene. Moreover, this study represents the first successful use of MOFs for high-performance separation of propylene and propane by GC. This strategy provides new inspiration in regulating mass transfer in porous materials.

Polar alcohol guest molecules regulate the stacking modes of 2-D MOF nanosheets.

The modulation of two-dimensional metal-organic framework (2-D MOF) nanosheet stacking is an effective means to improve the properties and promote the application of nanosheets in various fields. Here, we employed a series of alcohol guest molecules (MeOH, EtOH and PrOH) to modulate Zr-BTB (BTB = benzene-1,3,5-tribenzoate) nanosheets and to generate untwisted stacking. The distribution of stacking angles was statistically analyzed from high-angle annular dark-field (HAADF) and fast Fourier transform (FFT) images. The ratios of untwisted stacking were calculated, such as 77.01% untwisted stacking for MeOH, 83.45% for EtOH, and 85.61% for PrOH. The obtained untwisted Zr-BTB showed good separation abilities for different substituted benzene isomers, superior para selectivity and excellent column stability and reusability. Control experiments of 2-D Zr-TCA (TCA = 4,4',4''-tricarboxytriphenylamine) and Zr-TATB (TATB = 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tribenzoic acid) nanosheets with similar pore sizes and stronger polarity regulated by the alcohol guests exhibited moderate separation performance. The electron microscopy images revealed that polar alcohol regulation dominantly generated the twisted stacking of Zr-TCA and Zr-TATB with various Moiré patterns. Polar guest molecules, such as alcohols, provide strong host-guest interactions during the regulation of MOF nanosheet stacking, providing an opportunity to design new porous Moiré materials with application prospects.

Increasing Mass Transfer Resistance of MOFs as a Reverse Tuning Strategy to Achieve High-Resolution Gas Chromatographic Separation.

In separation science, precise control and regulation of the MOF stationary phase are crucial for achieving a high separation performance. We supposed that increasing the mass transfer resistance of MOFs with excessive porosity to achieve a moderate mass transfer resistance of the analytes is the key to conducting the MOF stationary phase with a high resolution. Three-dimensional UiO-67 (UiO-67-3D) and two-dimensional UiO-67 (UiO-67-2D) were chosen to validate this strategy. Compared with UiO-67-3D with overfast mass transfer and low retention, the reduced porosity of UiO-67-2D increased the mass transfer resistance of analytes in reverse, resulting in improved separation performance. Kinetic diffusion experiments were conducted to verify the difference in mass transfer resistance of the analytes between UiO-67-3D and UiO-67-2D. In addition, the optimization of the UiO-67-2D thickness for separation revealed that a moderate diffusion length of the analytes is more advantageous in achieving the equilibrium of absorption and desorption.

Bipolar Molecular Torque Wrench Modulates the Stacking of Two-Dimensional Metal-Organic Framework Nanosheets.

The precise modulation of nanosheet stacking modes introduces unforeseen properties and creates momentous applications but remains a challenge. Herein, we proposed a strategy using bipolar molecules as torque wrenches to control the stacking modes of 2-D Zr-1,3,5-(4-carboxylphenyl)-benzene metal-organic framework (2-D Zr-BTB MOF) nanosheets. The bipolar phenyl-alkanes, phenylmethane (P-C1) and phenyl ethane (P-C2), predominantly instigated the rotational stacking of Zr-BTB-P-C1 and Zr-BTB-P-C2, displaying a wide angular distribution. This included Zr-BTB-P-C1 orientations at 0, 12, 18, and 24° and Zr-BTB-P-C2 orientations at 0, 6, 12, 15, 24, and 30°. With reduced polarity, phenyl propane (P-C3) and phenyl pentane (P-C5) introduced steric hindrance and facilitated alkyl hydrophobic interactions with the nanosheets, primarily resulting in the modulation of eclipsed stacking for Zr-BTB-P-C3 (64.8%) and Zr-BTB-P-C5 (93.3%) nanosheets. The precise angle distributions of four Zr-BTB-P species were in agreement with theoretical calculations. The alkyl induction mechanism was confirmed by the sequential guest replacement and 2-D 13C-1H heteronuclear correlation (HETCOR). In addition, at the single-particle level, we first observed that rotational stacked pores exhibited similar desorption rates for xylene isomers, while eclipsed stacked pores showed significant discrepancy for xylenes. Moreover, the eclipsed nanosheets as stationary phases exhibited high resolution, selectivity, repeatability, and durability for isomer separation. The universality was proven by another series of bipolar acetate-alkanes. This bipolar molecular torque wrench strategy provides an opportunity to precisely control the stacking modes of porous nanosheets.

Recognition of Oligonucleotide C by Polydopamine-Coated Solid-State Nanopores.

Selective recognition of short oligonucleotides at the single-molecule level is particularly important for early disease detection and treatment. In this work, polydopamine (PDA)-coated nanopores were prepared via self-polymerization as a solid-state nanopore sensing platform for the recognition of oligonucleotide C (PolyC). The PDA coating possesses abundant active sites, such as indole, amino, carboxyl, catechol, and quinone structures, which had interactions with short oligonucleotides to slow down the translocation rate. PDA-coated nanopores selectively interact with PolyC20 by virtue of differences in hydrogen bonding forces, generating a larger blocking current, while polyA and polyT demonstrated very small blockings. At the same time, PDA-coated nanopores can sensitively distinguish PolyC with different lengths, such as 20, 14, and 10 nt. The functionalization of PDA on the solid-state nanopore provides an opportunity for the rational design of the recognition surface for biomolecules.

Solid-State Nanopore Distinguishes Ferritin and Apo-Ferritin with Identical Exteriors through Amplified Flexibility at Single-Molecule Level.

Protein identification and discrimination at the single-molecule level are big challenges. Solid-state nanopores as a sensitive biosensor have been used for protein analysis, although it is difficult to discriminate proteins with similar structures in the traditional discrimination method based on the current blockage fraction. Here, we select ferritin and apo-ferritin as the model proteins that exhibit identical exterior and different interior structures and verify the practicability of their discrimination with flexibility features by the strategy of gradually decreasing the nanopore size. We show that the larger nanopore (relative to the protein size) has no obvious effect on discriminating two proteins. Then, the comparable-sized nanopore plays a key role in discriminating two proteins based on the dwell time and fraction distribution, and the conformational changes of both proteins are also studied with this nanopore. Finally, in the smaller nanopore, the protein molecules are trapped rather than translocated, where two proteins are obviously discriminated through the current fluctuation caused by the vibration of proteins. This strategy has potential in the discrimination of other important similar proteins.

Anisotropic flexibility and rigidification in a TPE-based Zr-MOFs with scu topology.

Tetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.

Sensitivity to thyroid hormone indices are associated with papillary thyroid carcinoma in Chinese patients with thyroid nodules.

BACKGROUND: The association between thyroid hormone sensitivity and thyroid cancer is unknown, and we aimed to investigate the association between sensitivity to thyroid hormone indices and papillary thyroid carcinoma (PTC) in Chinese patients with thyroid nodules (TNs). METHODS: A total of 1,998 patients undergoing thyroid surgery due to TNs from Nanjing Drum Tower Hospital were included in this study. We evaluated central sensitivity to thyroid hormones, such as thyroid stimulating hormone index (TSHI), TSH T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric thyroid feedback quantile-based Index (PTFQI). Peripheral sensitivity to thyroid hormone was evaluated by FT3 to FT4 ratio. Multivariate logistic regression analysis was performed to evaluate the association between sensitivity to thyroid hormone indices and PTC risk. RESULTS: The results showed that central indices of thyroid hormone sensitivity, including TSHI, TT4RI, TFQI, and PTFQI, were positively associated with PTC risk. For each SD increase in TSHI, TT4RI, TFQI, and PTFQI, the odds ratios (OR, 95% CI) of PTC were 1.31 (1.18-1.46), 1.01 (1.01-1.02), 1.94 (1.45-2.60), and 1.82 (1.41-2.34), respectively. On the other hand, the association between peripheral sensitivity to thyroid hormone and PTC was significantly negative. For each SD increase in FT3/FT4 ratio, the OR (95% CI) of PTC was 0.18 (0.03-0.96), and a negative correlation was found between FT3/FT4 ratio and TNM staging of PTC. CONCLUSIONS: Sensitivity to thyroid hormone indices could be used as new indicators for predicting PTC in Chinese patients with TNs. Future researches are still needed to confirm our findings.

Solid-State Quad-Nanopore Array for High-Resolution Single-Molecule Analysis and Discrimination.

The ability to detect and distinguish biomolecules at the single-molecule level is at the forefront of today's biomedicine and analytical chemistry research. Increasing the dwell time of individual biomolecules in the sensing spot can greatly enhance the sensitivity of single-molecule methods. This is particularly important in solid-state nanopore sensing, where the detection of small molecules is often limited by the transit dwell time and insufficient temporal resolution. Here, a quad-nanopore is introduced, a square array of four nanopores (with a space interval of 30-50 nm) to improve the detection sensitivity through electric field manipulation in the access region. It is shown that dwell times of short DNA strands (200 bp) are prolonged in quad-nanopores as compared to single nanopores of the same diameter. The dependence of dwell times on the quad-pore spacing is investigated and it is found that the "retarding effect" increases with decreasing space intervals. Furthermore, ultra-short DNA (50 bp) detection is demonstrated using a 10 nm diameter quad-nanopore array, which is hardly detected by a single nanopore. Finally, the general utility of quad-nanopores has been verified by successful discrimination of two kinds of small molecules, metal-organic cage and bovine serum albumin (BSA).

Asymmetric Low-Frequency Pulsed Strategy Enables Ultralong CO2 Reduction Stability and Controllable Product Selectivity.

Copper-based catalysts are widely explored in electrochemical CO2 reduction (CO2RR) because of their ability to convert CO2 into high-value-added multicarbon products. However, the poor stability and low selectivity limit the practical applications of these catalysts. Here, we proposed a simple and efficient asymmetric low-frequency pulsed strategy (ALPS) to significantly enhance the stability and the selectivity of the Cu-dimethylpyrazole complex Cu3(DMPz)3 catalyst in CO2RR. Under traditional potentiostatic conditions, Cu3(DMPz)3 exhibited poor CO2RR performance with the Faradaic efficiency (FE) of 34.5% for C2H4 and FE of 5.9% for CH4 as well as the low stability for less than 1 h. We optimized two distinguished ALPS methods toward CH4 and C2H4, correspondingly. The high selectivities of catalytic product CH4 (FECH4 = 80.3% and above 76.6% within 24 h) and C2H4 (FEC2H4 = 70.7% and above 66.8% within 24 h) can be obtained, respectively. The ultralong stability for 300 h (FECH4 > 60%) and 145 h (FEC2H4 > 50%) was also recorded with the ALPS method. Microscopy (HRTEM, SAED, and HAADF) measurements revealed that the ALPS method in situ generated and stabilized extremely dispersive and active Cu-based clusters (∼2.7 nm) from Cu3(DMPz)3. Meanwhile, ex situ spectroscopies (XPS, AES, and XANES) and in situ XANES indicated that this ALPS method modulated the Cu oxidation states, such as Cu(0 and I) with C2H4 selectivity and Cu(I and II) with CH4 selectivity. The mechanism under the ALPS methods was explored by in situ ATR-FTIR, in situ Raman, and DFT computation. The ALPS methods provide a new opportunity to boost the selectivity and stability of CO2RR.

Isomer recognition by dynamic guest-adaptive ligand rotation in a metal-organic framework with local flexibility.

Local flexibility in a metal-organic framework is intriguing for reconstructing a microenvironment to distinguish different guest molecules by emphasizing their differences. Herein, guest-adaptive flexibility is observed in a metal-organic framework for efficiently discriminating aromatic isomers. Microcrystal electron diffraction directly reveals that the anthracene rings can rotate around the single bond with the adsorption of guest molecules. Disorder transformation of the ligand enables the preferential adsorption of ethylbenzene over other xylene isomers. Especially, a coated capillary column combining single/multi-component adsorption confirms a unique separation order of ethylbenzene > p-xylene > m-xylene > o-xylene with excellent selectivities, which has not been reported in other materials. Density functional theory calculations and the calculated Hirshfeld surface of guest molecules in the framework demonstrate that a guest-induced splint-like confinement structure makes the main contribution to such separation performance. This finding will provide a rational strategy for molecular recognition utilizing the local flexibility of metal-organic frameworks.

Metal-Organic Cage as Single-Molecule Carrier for Solid-State Nanopore Analysis.

The ability to detect biomolecules at the single-molecule level is at the forefront of biological research, precision medicine, and early diagnosis. Recently, solid-state nanopore sensors have emerged as a promising technique for label-free and precise diagnosis assay. However, insufficient sensitivity and selectivity for small analytes are a great challenge for clinical diagnosis applications via solid-state nanopores. Here, for the first time, a metal-organic cage, PCC-57, is employed as a carrier to increase the sensitivity and selectivity of solid-state nanopores based on the intrinsic interaction of the nanocage with biomolecules. Firstly, it is found that the carrier itself is undetectable unless bound with the target analytes and used oligonucleotides as linkers to attach PCC-57 and target analytes. Secondly, two small analytes, oligonucleotide conjugated angiopep-2 and polyphosphoric acid, are successfully distinguished using the molecular carrier. Finally, selectivity of nanopore detection is achieved by attaching PCC-57 to oligonucleotide-tailed aptamers, and the human alpha-thrombin sample is successfully detected. It is believed that the highly designable metal-organic cage could serve as a rich carrier repository for a variety of biomolecules, facilitating single-molecule screening of clinically relevant biomolecules based on solid-state nanopores in the future.

Enhancing Separation Abilities of "Low-Performance" Metal-Organic Framework Stationary Phases through Size Control.

Peak broadening and peak tailing are common but rebarbative phenomena that always occur when using metal-organic frameworks (MOFs) as stationary phases. These phenomena result in diverse "low-performance" MOF stationary phases. Here, by adjusting the particle size of MOF stationary phases from microscale to nanoscale, we successfully enhance the separation abilities of these "low-performance" MOFs. Three zirconium-based MOFs (NU-1000, PCN-608, and PCN-222) with different organic ligands were synthesized with sizes of tens of micrometers and hundreds of nanometers, respectively. All the nanoscale MOFs exhibited exceedingly higher separation abilities than the respective microscale MOFs. The mechanism investigation proved that reducing the particle size can reduce the mass transfer resistance, thus enhancing the column efficiency by controlling the separation kinetics. Modulating the particle size of MOFs is an efficient way to enhance the separation capability of "low-performance" MOFs and to design high-performance MOF stationary phases.

Solid-state Nanopores: Chemical Modifications, Interactions, and Functionalities.

Nanopore technology is a burgeoning detection technology for single-molecular sensing and ion rectification. Solid-state nanopores have attracted more and more attention because of their higher stability and tunability than biological nanopores. However, solid-state nanopores still suffer the drawbacks of low signal-to-noise ratio and low resolution, which hinder their practical applications. Thus, developing operatical and useful methods to overcome the shortages of solid-state nanopores is urgently needed. Here, we summarize the recent research on nanopore modification to achieve this goal. Modifying solid-state nanopores with different coating molecules can improve the selectivity, sensitivity, and stability of nanopores. The modified molecules can introduce different functions into the nanopores, greatly expanding the applications of this novel detection technology. We hope that this review of nanopore modification will provide new ideas for this field.

Linker Scissoring Strategy Enables Precise Shaping of Metal-Organic Frameworks for Chromatographic Separation.

Precise shaping of metal-organic frameworks (MOFs) is significant in both fundamental coordination chemistry and practical applications, such as catalysis, separation, and biomedicine. Herein, we demonstrated a linker scissoring strategy for precisely shaping MOFs through surface conformational pairing. In this strategy, the bidentate linkers which were designed according to the original tetratopic ligands and the coordination environment of MOF surfaces, were utilized as the covering agents. The shape of these covering agents and the surface conformation of metals onto MOFs restricted them to coordinate on specific MOF facets thus precisely controlling the shape of the MOFs. Different shapes of PCN-608 from nanoplate (PCN-NP) to nanorod (PCN-NR) have been targeted by adding different bidentate linkers. The universality of this strategy was demonstrated by controlling the shapes of the NU-MOFs from nanoplate to nanorod. This strategy provides a new guiding principle to synthesize MOF nanocrystals with controlled shapes.

Homogeneously Mixing Different Metal-Organic Framework Structures in Single Nanocrystals through Forming Solid Solutions.

Pore engineering plays a significant role in the applications of porous materials, especially in the area of separation and catalysis. Here, we demonstrated a metal-organic framework (MOF) solid solution (MOSS) strategy to homogeneously and controllably mix NU-1000 and NU-901 structures inside single MOF nanocrystals. The key for the homogeneous mixing and forming of MOSS was the bidentate modulator, which was designed to have a slightly longer distance between two carboxylate groups than the original tetratopic ligand. All of the MOSS nanocrystals showed a uniform pore size distribution with a well-tuned ratio of mesopores to micropores. Because of the appropriate pore ratio, MOSS nanocrystals can balance the thermodynamic interactions and kinetic diffusion of the substrates, thus showing exceedingly higher separation abilities and a unique elution sequence. Our work proposes a rational strategy to design mixed-porous MOFs with controlled pore ratios and provides a new direction to design homogeneously mixed MOFs with a high separation ability and unique separation selectivity.

Precise Spatial-Designed Metal-Organic-Framework Nanosheets for Efficient Energy Transfer and Photocatalysis.

High-efficiency photocatalysis in metal-organic frameworks (MOF) and MOF nanosheets (NSs) are often limited by their short-lived charge separation as well as self-quenching. Here, we propose to use the energy-transfer process (EnT) to increase charge separation, thus enhancing the catalytic performance of a series of MOF NSs. With the use of NS, the photocatalyst can also be well isolated to reduce self-quenching. Tetrakis(4-carboxyphenyl) porphyrin (H4 TCPP) and 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4 TBAPy) linkers were chosen as the acceptor and donor moieties, respectively. Accounting for the precise spatial design afforded by the MOF NSs, the donor and acceptor moieties could be closely positioned on the NSs, allowing for an efficient EnT process as well as a high degree of site isolation. Two templates, donor-on-acceptor NS and acceptor-on-donor NS catalysts, were successfully synthesized, and the results show that the second one has much enhanced catalytic performances over the first one due to site-isolated active photocatalysts.

Two-dimensional materials as solid-state nanopores for chemical sensing.

Solid-state nanopores as a versatile alternative to biological nanopores have grown tremendously over the last two decades. They exhibit unique characteristics including mechanical robustness, thermal and chemical stability, easy modifications and so on. Moreover, the pore size of a solid-state nanopore could be accurately controlled from sub-nanometers to hundreds of nanometers based on the experimental requirements, presenting better adaptability than biological nanopores. Two-dimensional (2D) materials with single layer thicknesses and highly ordered structures have great potential as solid-state nanopores. In this perspective, we introduced three kinds of substrate-supported 2D material solid-state nanopores, including graphene, MoS2 and MOF nanosheets, which exhibited big advantages compared to traditional solid-state nanopores and other biological counterparts. Besides, we suggested the fabrication and modulation of 2D material solid-state nanopores. We also discussed the applications of 2D materials as solid-state nanopores for ion transportation, DNA sequencing and biomolecule detection.

Sn(101) Derived from Metal-Organic Frameworks for Efficient Electrocatalytic Reduction of CO2.

The synthesis of a specific Sn plane as an efficient electrocatalyst for CO2 electrochemical reduction to generate fuels and chemicals is still a huge challenge. Density functional theory (DFT) calculations first reveal that the Sn(101) crystal plane is more advantageous for CO2 electroreduction. A metal-organic framework (MOF) precursor Sn-MOF has been carbonized and then etched to successfully fabricate Sn(101)/SnO2/C composites with good control of the carbonization time and the concentration of hydrochloric acid. The Sn(101) crystal plane of the catalyst could enhance the faradaic efficiency of formate to as high as 93.3% and catalytic stability up to 20 h. The promotion of the selectivity and activity by Sn(101) advances new possibilities for the rational design of high-activity Sn catalysts derived from MOFs.