Prediction of blood-brain barrier penetrating peptides based on data augmentation with Augur.

BACKGROUND: The blood-brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain. In response to this challenge, many researchers have devoted themselves to developing drug delivery systems capable of breaching the blood-brain barrier. Among these, blood-brain barrier penetrating peptides have emerged as promising candidates. These peptides had the advantages of high biosafety, ease of synthesis, and exceptional penetration efficiency, making them an effective drug delivery solution. While previous studies have developed a few prediction models for blood-brain barrier penetrating peptides, their performance has often been hampered by issue of limited positive data. RESULTS: In this study, we present Augur, a novel prediction model using borderline-SMOTE-based data augmentation and machine learning. we extract highly interpretable physicochemical properties of blood-brain barrier penetrating peptides while solving the issues of small sample size and imbalance of positive and negative samples. Experimental results demonstrate the superior prediction performance of Augur with an AUC value of 0.932 on the training set and 0.931 on the independent test set. CONCLUSIONS: This newly developed Augur model demonstrates superior performance in predicting blood-brain barrier penetrating peptides, offering valuable insights for drug development targeting neurological disorders. This breakthrough may enhance the efficiency of peptide-based drug discovery and pave the way for innovative treatment strategies for central nervous system diseases.

Electro-Induced Phase Transformation of a Conductive Metal-Organic Framework Film for Nonlinear Optical Switching.

Achieving metal-organic frameworks (MOFs) with nonlinear optical (NLO) switching is profoundly important. Herein, the conductive MOFs Cu-TCNQ phase I (Ph-I) and phase II (Ph-II) films were prepared using the liquid-phase-epitaxial layer-by-layer spin-coating method and steam heating method, respectively. Electronic experiments showed that the Ph-II film could be changed into the Ph-I film under an applied electric field. The third-order NLO results revealed that the Ph-I film had a third-order nonlinear reverse saturation absorption (RSA) response and the Ph-II film displayed a third-order nonlinear saturation absorption (SA) response. With increases in the heating time and applied voltage, the third-order NLO response realized the reversible transition between SA and RSA. The theoretical calculations indicated that Ph-I possessed more interlayer charge transfer, resulting in a third-order nonlinear RSA response that was stronger than that of Ph-II. This work applies phase-transformed MOFs to third-order NLO switching and provides new insights into the nonlinear photoelectric applications of MOFs.

Topochemical Polymerization at Diacetylene Metal-Organic Framework Thin Films for Tuning Nonlinear Optics.

Developing the topochemical polymerization of metal-organic frameworks (MOFs) is of pronounced significance for expanding their functionalities but is still a challenge on third-order nonlinear optics (NLO). Here, we report diacetylene MOF (CAS-1-3) films prepared using a stepwise deposition method and film structural transformation approach, featuring dynamic structural diversity. The MOF structures were determined by the three-dimensional electron diffraction (3D ED) method from nanocrystals collected from the films, which provides a reliable strategy for determining the precise structure of unknown MOF films. We demonstrate the well-aligned diacetylene groups in the MOFs can promote topological polymerization to produce a highly conjugated system under thermal stimulation. As a result, the three MOF films have distinct NLO properties: the CAS-1 film exhibits saturable absorption (SA) while CAS-2 and CAS-3 films exhibit reverse saturable absorption (RSA). Interestingly, due to the topochemical polymerization of the MOF films, a transition from SA to RSA response was observed with increasing temperatures, and the optical limiting effect was significantly enhanced (∼46 times). This study provides a new strategy for preparing NLO materials and thermally regulation of nonlinear optics.

Chiral Liquid Crystalline Metal-Organic Framework Thin Films for Highly Circularly Polarized Luminescence.

Combining metal-organic frameworks (MOFs) with liquid crystals to construct liquid crystalline MOFs (LCMOF) offers the advantage of endowing and enhancing their functionality, yet it remains a challenging task. Herein, we report chiral liquid crystalline MOF (CLCMOF) thin films by cross-linking the chiral liquid crystals (CLC) with MOF thin films to realize highly circular polarization luminescence (CPL) performance with photo and thermal switching. By layer by layer cross-linking stilbene-containing CLC with stilbene-based MOF (CLC/MOF) thin film, the CLCMOF thin films were successfully obtained after UV irradiation due to the abundant [2 + 2] photocycloaddition. The resulted CLCMOF thin films have strong chirality, obvious photochromic fluorescent, and strong CPL performance (the asymmetry factor reaches to 0.4). Furthermore, due to the photochromic fluorescent MOF and thermotropic CLC, the CPL can be reversed and red-shifted after heating and UV irradiation treatment, showing photo- and thermal CPL switching. Such MOF-based CPL thin films with photo/thermal CPL switching were prepared to patterns and codes for the demonstration of potential application in advanced information anticounterfeit and encryption. This study not only opens a strategy for developing chiral thin films combining MOFs and liquid crystals but also offers a new route to achieve CPL switching in optical applications.

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.

1D Anionic Covalent Organic Frameworks With Directed Migration of Alkali Metal Ions for High Ionic Conductivity.

Rational construction of high-performance ionic conductors is a critical challenge in the field of energy storage. In this study, a series of 1D anionic titanium-based covalent organic frameworks (COFs) containing abundant alkali metal ion migration sites, namely, COF-M-R (M = Li, Na, K; R = H, Me, Et), is constructed. The integration of negative TiO6 2- sites on 1D anionic COFs allows alkali metal cations to migrate directly through the channels. Meanwhile, the π-π stacking of 1D chain-to-chain allows the distribution of ion-migration sites in 2D planes. In view of this, multidimensional ionic transport in COFs is realized to achieve high ionic conductivity. COF-M-Rs exhibit an increased ionic conductivity as the counterions change from Li+ to Na+ to K+. Notably, COF-Na-Et has an impressive ionic conductivity as high as 0.81 × 10-3 S cm-1. The different decorated groups (H, Me, and Et) on the skeleton influence the dissociation of the cation from the polyanion. This study offers deep insights into the design of COF-based solid-state electrolytes to achieve high ionic conductivity by increasing the ionic transport dimensions.

Double-Shelled Open Hollow Metal-Organic Frameworks for Efficient Aqueous Zn-Ion Batteries.

Multi-shelled hollow metal-organic frameworks (MH-MOFs) are highly promising as electrode materials due to their impressive surface area and efficient mass transfer capabilities. However, the fabrication of MH-MOFs has remained a formidable challenge. In this study, two types of double-shelled open hollow Prussian blue analogues, one with divalent iron (DHPBA-Fe(II)) and the other with trivalent iron (DHPBA-Fe(III)), through an innovative inner-outer growth strategy are successfully developed. The growth mechanism is found to involve lattice matching growth and ligand exchange processes. Subsequently, DHPBA-Fe(II) and DHPBA-Fe(III) are employed as cathodes in aqueous Zn-ion batteries. Significantly, DHPBA-Fe(II) demonstrated exceptional performance, exhibiting a capacity of 92.5 mAh g-1 at 1 A g-1, and maintaining remarkable stability over an astounding 10 000 cycles. This research is poised to catalyze further exploration into the fabrication techniques of MH-MOFs and offer fresh insights into the intricate interplay between electronic structure and battery performance.

Delocalization State-Stabilized Znδ+ Active Sites for Highly Selective and Durable CO2 Electroreduction.

Zinc (Zn)-based materials are cost-effective and promising single-metal catalysts for CO2 electroreduction to CO but is still challenged by low selectivity and long-term stability. Undercoordinated Zn (Znδ+) sites have been demonstrated to be powerful active centers with appropriate *COOH affinity for efficient CO production However, electrochemical reduction conditions generally cause the inevitable reduction of Znδ+, resulting in the decline of CO efficiency over prolonged operation. Herein, a Zn cyanamide (ZnNCN) catalyst is constructed for highly selective and durable CO2 electroreduction, wherein the delocalized Zn d-electrons and resonant structure of cyanamide ligand prevent the self-reduction of ZnNCN and maintain Znδ+ sites under cathodic conditions. The mechanism studies based on density functional theory and operando spectroscopies indicate that delocalized Znδ+ site can stabilize the key *COOH intermediate through hard-soft acid-base theory, therefore thermodynamically promoting CO2-to-CO conversion. Consequently, ZnNCN delivers a CO Faradaic efficiency (FE) of up to 93.9% and further exhibits a remarkable stability lifespan of 96 h, representing a significant advancement in developing robust Zn-based electrocatalysts. Beyond expanding the variety of CO2 reduction catalysts, this work also offers insights into understanding the structure-function sensitivity and controlling dynamic active sites.

Layer by Layer Spraying Fabrication of Aggregation-Induced Emission Metal-Organic Frameworks Thin Film.

The development of new metal-organic frameworks (MOFs) thin films is important for expanding their functions and applications. Herein, we first report a new kind of MOF thin film by using aggregation-induced emission (AIE) dicarboxyl ligand through a liquid-phase epitaxial (LPE) layer-by-layer (LBL) spraying method (named AIE surface-coordinated metal-organic frameworks thin film, AIE-SURMOF). The obtained AIE-SURMOF Zn4O(TPE)3 (ZnTPE) has highly growth orientation and homogeneous thin film, showing strong fluorescent property. Furthermore, by loading chiral guest in the MOF pore, the formed chiral encapsulated AIE-SURMOF can clearly indicate obvious circularly polarized luminescence performance with glum of 0.01. This study provides new MOF thin film and new strategy for expanding function and application of MOF materials.

Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

Bioorthogonal chemistry for prodrug activation in vivo.

Prodrugs have emerged as a major strategy for addressing clinical challenges by improving drug pharmacokinetics, reducing toxicity, and enhancing treatment efficacy. The emergence of new bioorthogonal chemistry has greatly facilitated the development of prodrug strategies, enabling their activation through chemical and physical stimuli. This "on-demand" activation using bioorthogonal chemistry has revolutionized the research and development of prodrugs. Consequently, prodrug activation has garnered significant attention and emerged as an exciting field of translational research. This review summarizes the latest advancements in prodrug activation by utilizing bioorthogonal chemistry and mainly focuses on the activation of small-molecule prodrugs and antibody-drug conjugates. In addition, this review also discusses the opportunities and challenges of translating these advancements into clinical practice.

Coordination-Induced Symmetry Breaking on Metal-Porphyrinic Framework Thin Films for Enhanced Nonlinear Optical Limiting.

Structural asymmetry affecting the nonlinear optics (NLO) of metal-organic frameworks (MOFs) is very important in fundamentals and applications but is still a challenge. Herein we develop a series of indium-porphyrinic framework (InTCPP) thin films and provide the first study on the coordination-induced symmetry breaking on their third-order NLO. The continuous and oriented InTCPP(H2) thin films were grown on quartz substrates and then postcoordinated with different cations (Fe2+ or Fe3+Cl-) in InTCPP(H2) (named InTCPP(Fe2+) and InTCPP(Fe3+Cl-)). The third-order NLO results reveal the Fe2+ and Fe3+Cl- coordinated InTCPP thin films have substantially enhanced NLO performance. Moreover, InTCPP(Fe3+Cl-) thin films cause symmetry breaking of microstructures, resulting in a 3-fold increase in the nonlinear absorption coefficient (up to 6.35 × 10-6 m/W) compared to InTCPP(Fe2+). This work not only develops a series of nonlinear optical MOF thin films but also provides new insight into symmetry breaking on MOFs for nonlinear optoelectronic applications.

Highly Efficient Light Helicity Detection of Enantiomers by Chiral Metal-Organic Framework Thin Films.

The potential of chiral metal-organic frameworks (MOFs) for circularly polarized (CP) optics has been largely unexplored. Herein, we have successfully deposited monolithic and highly oriented chiral MOF thin films prepared by a layer-by-layer method (referred to as surface-coordinated MOF thin films, SURMOF) to fabricate CP photodetection devices and distinguish enantiomers. The helicity-sensitive absorption induced by a pair of enantiopure oriented SURMOF was found to be excellent, with an anisotropy factor reaching 0.41. Moreover, the chiral SURMOFs exhibited a pronounced difference in the uptake of the l- and d-tryptophan enantiomers. To demonstrate the potential of these novel MOF thin films for chirality analysis, we fabricated a portable sensor device that allows for chiral recognition by monitoring the photocurrent signals. Our findings not only introduce a new concept of using chiral building blocks for realizing direct CP photodetectors but also provide a blueprint for novel devices in chiral optics.

Host-Guest Metal-Organic Frameworks-Based Long-Afterglow Luminescence Materials.

Long-afterglow materials have a broad of applications in optoelectronic devices, sensors, medicine and other fields due to their excellent luminescent properties. The host-guest long-afterglow MOFs material combines the advantages of multi-component characteristics and the stability of MOFs, which improves its luminous performance and expands its other properties. This review introduces the classification, synthesis and application of host-guest MOFs materials with long afterglow. Due to their rigid frames and multi-channel characteristics, MOFs can load common guest materials including rare earth metals, organic dyes, carbon dots, etc. The synthesis methods of loading guest materials into MOFs include solvothermal synthesis, post-encapsulation, post-modification, etc. Those long-afterglow host-guest MOFs have a wide range of applications in the fields of sensors, information security and biological imaging.

Successively Controlling Nanoscale Wrinkles of Ultrathin 2D Metal-Organic Frameworks Nanosheets.

The wrinkles are pervasive in ultrathin two-dimensional (2D) materials, but the regulation of wrinkles is rarely explored systematically. Here, we employed a series of carboxylic acids (from formic acid to octanoic acid) to control the wrinkles of Zr-BTB (BTB=1, 3, 5-(4-carboxylphenyl)-benzene) metal-organic framework (MOF) nanosheet. The wrinkles at the micrometer scale were observed with transmission electron microscopy. Furthermore, high-angle annular dark-field (HAADF) images showed lattice distortion in many nanoscale regions, which was precisely matched to the nano-wrinkles. With the changes of hydrophilicity/hydrophobicity, MOF-MOF and MOF-solvent interactions were possibly synergistically regulated and wrinkles with different sizes were obtained, which was supported by HAADF, molecular dynamics, and density functional theory calculation. Different wrinkle sizes resulted in different pore sizes between the Zr-BTB nanosheet interlayers, providing highly-oriented thin films and the successive optimization of kinetic diffusion pathways, proved by grazing-incidence wide-angle X-ray scattering and nitrogen adsorption. The most suitable wrinkle pore from Zr-BTB-C4 exhibited highly efficient chromatographic separation of the substituted benzene isomers. Our work provides a rational route for the modulation of nanoscale wrinkles and their stacked pores of MOF nanosheets and improves the separation abilities of MOFs.

Three-Dimensional Covalent Organic Frameworks Based on Linear and Trigonal Linkers for High-Performance H2O2 Photosynthesis.

The design of three-dimensional covalent organic frameworks (3D COFs) using linear and trigonal linkers remains challenging due to the difficulty in achieving a specific non-planar spatial arrangement with low-connectivity building units. Here, we report the novel 3D COFs with linear and trigonal linkers, termed TMB-COFs, exhibiting srs topology. The steric hindrance provides an additional force to alter the torsion angles of peripheral triangular units, guiding the linear unit to connect with the trigonal unit into 3D srs frameworks, rather than the more commonly observed two-dimensional (2D) hcb structures. Furthermore, we comprehensively examined the hydrogen peroxide photocatalytic production capacity of the TMB-COFs in comparison with analogous 2D COFs. The experimental results and DFT calculations demonstrate a significant enhancement in photocatalytic hydrogen peroxide production efficacy through framework regulation. This work emphasizes the steric configuration using low connectivity building units, offering a fresh perspective on the design and application of 3D COFs.

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.

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.

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.