Reactive Center Research Articles

Synthesis, crystal structure, DFT studies, and Hirshfeld surface analysis of a new Strontium Polyphosphate Form [formula omitted

The α-Sr(PO3)2 was synthesized at 273.15 K and P = 1.01325 bar and characterized by single crystal X-ray diffraction analysis, IR & Raman spectroscopy, and Computational simulation (ELF, HSA & DFT) studies. This compound crystallizes in the centrosymmetric triclinic space group P-1 (Z = 4) with a = 5.7938(3) (Å), b = 7.2039(4) (Å), c = 8.0673(4) (Å), α = 97.800(2)°, β = 104.590 (2)°, γ = 106.647(2)° & V = 304.25(3)Å3. The 3D structure contains Sr(PO3)2 chains, which form wavy layers between which exist layers of (PO3)- ions. In addition, theoretical calculations were performed using the DFT/B3LYP/LanL2DZ basis set for crystal molecular structure, Infrared and Raman spectra, and HOMO-LUMO properties of the title compound. 3D-MEPs and the α-Sr(PO3)2-(HOMO/LUMO) were used to assess the total electron density(Global reactivity) and the reactive centres(Local reactivity). Molecular orbital contributions are evaluated by DOS. A comparative study by the SD is in the range DFT/XRD; 0.06 in % for bond lengths and 0.016 in % for angles. The Intermolecular α-Sr(PO3)2 interactions were quantified by HAS. The ELF identifies (non-binding and binding) regions of space that can be associated with electron pairs for elaborated material. The IR spectrum confirms the existence of the functional groups in the elaborated material. The complete vibrational assignments and analysis of the observed fundamental bands of the molecule were carried out.

Targeted modification of furan-2-carboxaldehydes into Michael acceptor analogs yielded long-acting hemoglobin modulators with dual antisickling activities.

Sickle cell disease (SCD) is the most common genetic disorder, affecting millions of people worldwide. Aromatic aldehydes, which increase the oxygen affinity of human hemoglobin to prevent polymerization of sickle hemoglobin and inhibit red blood cell (RBC) sickling, have been the subject of keen interest for the development of effective treatment against SCD. However, the aldehyde functional group metabolic instability has severly hampered their development, except for voxelotor, which was approved in 2019 for SCD treatment. To improve the metabolic stability of aromatic aldehydes, we designed and synthesized novel molecules by incorporating Michael acceptor reactive centers into the previously clinically studied aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF). Eight such derivatives, referred to as MMA compounds were synthesized and studied for their functional and biological activities. Unlike 5-HMF, which forms Schiff-base interaction with αVal1 nitrogen of hemoglobin, the MMA compounds covalently interacted with βCys93, as evidenced by reverse-phase HPLC and disulfide exchange reaction, explaining their RBC sickling inhibitory activities, which at 2 mM and 5 mM, range from 0% to 21% and 9% to 64%, respectively. Additionally, the MMA compounds showed a second mechanism of sickling inhibition (12%-41% and 13%-62% at 2 mM and 5 mM, respectively) by directly destabilizing the sickle hemoglobin polymer. In vitro studies demonstrated sustained pharmacologic activities of the compounds compared to 5-HMF. These findings hold promise for advancing SCD therapeutics.

Molecular hybrids integrated with imidazole and hydrazone structural motifs: Design, synthesis, biological evaluation, and molecular docking studies

In the present work, a series of compounds containing imidazole and hydrazone structural frameworks were synthesized and characterized using various spectral techniques, including 1H NMR, 13C NMR, FTIR, and HRMS. Synthesized compounds were subjected to screening as antiproliferative agents as well as against two physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I and hCA II. Among them, some compounds exhibited remarkable antiproliferative activity with less cytotoxicity activity to healthy cells and significant CA inhibitory activities in contrast to a standard inhibitor with Ki values in the range of 0.49 ± 1.010–739.12 ± 111.35 nM for hCA I (Ki value for standard inhibitor = 271.15 ± 74.620 nM), 64.53 ± 19.44–314.37 ± 54.78 nM for hCA II (Ki value for standard inhibitor = 113.07 ± 20.980 nM). In addition, DFT calculations were performed to get insight into the distinctive reactive sites of all compounds, and subsequently, the reactive centers of the compounds were determined. Moreover, molecular docking studies of the most potent compounds were conducted, and results showed reasonable binding modes in the active sites of hCA I protein (PDB ID: 2CAB), hCA II protein (PDB ID: 3DC3), as well as colon cancer protein (PDB ID: 4UYA and 3DTC). Finally, in silico predictions of ADME and pharmacokinetic parameters indicated that these compounds should have good oral bioavailability.

CO2 Reduction to Methane and Ethylene on a Single-Atom Catalyst: A Grand Canonical Quantum Mechanics Study.

In recent years, two-dimensional metal-organic frameworks (2D MOF) have attracted great interest for their ease of synthesis and for their catalytic activities and semiconducting properties. The appeal of these materials is that they are layered and easily exfoliated to obtain a monolayer (or few layer) material with interesting optoelectronic properties. Moreover, they have great potential for CO2 reduction to obtain solar fuels with more than one carbon atom, such as ethylene and ethanol, in addition to methane and methanol. In this paper, we explore how a particular class of 2D MOF based on a phthalocyanine core provides the reactive center for the production of ethylene and ethanol. We examine the reaction mechanism using the new grand canonical potential kinetics (GCP-K) or grand canonical quantum mechanics (GC-QM) computational methodology, which obtains reaction rates at constant applied potential to compare directly with experimental results (rather than at constant electrons as in standard QM). We explain the reaction mechanism underlying the formation of methane and ethylene. Here, the key reaction step is direct coupling of CO into CHO, without the usual rate-determining CO-CO dimerization step observed on Cu metal surfaces. Indeed, the 2D MOF behaves like a single-atom catalyst.

Two-Component versus Three-Component Condensations in the Race between Hydrazide, Triketone, and Hydrogen Peroxide-How do All Six Reactive Centers Cooperate to Incorporate the Most Diverse Set of Heteroatomic Bridges in a Tricyclic Frame?

Relief of stereoelectronic frustration drives the acid-catalyzed three-component condensation of β,δ'-triketones with hydrazides and H2O2 to the direction where both nucleophiles and all three electrophilic carbons are involved in the formation of a tricyclic sp3-rich ring system that includes four heteroatoms. The otherwise inaccessible tricyclic N-substituted aminoperoxides are prepared rapidly and selectively from relatively simple substrates in good to high yields.

Phytocystatin 6 is a context-dependent, tight-binding inhibitor of Arabidopsis thaliana legumain isoform β.

Plant legumains are crucial for processing seed storage proteins and are critical regulators of plant programmed cell death. Although research on legumains boosted recently, little is known about their activity regulation. In our study, we used pull-down experiments to identify AtCYT6 as a natural inhibitor of legumain isoform β (AtLEGβ) in Arabidopsis thaliana. Biochemical analysis revealed that AtCYT6 inhibits both AtLEGβ and papain-like cysteine proteases through two separate cystatin domains. The N-terminal domain inhibits papain-like proteases, while the C-terminal domain inhibits AtLEGβ. Furthermore, we showed that AtCYT6 interacts with legumain in a substrate-like manner, facilitated by a conserved asparagine residue in its reactive center loop. Complex formation was additionally stabilized by charged exosite interactions, contributing to pH-dependent inhibition. Processing of AtCYT6 by AtLEGβ suggests a context-specific regulatory mechanism with implications for plant physiology, development, and programmed cell death. These findings enhance our understanding of AtLEGβ regulation and its broader physiological significance.

Unveiling the Structural Self-Reconstruction and Identifying the Reactive Center of a V, Fe Co-Doped Cobalt Precatalyst toward Enhanced Overall Water Splitting by Operando Raman Spectroscopy.

The development of efficient and stable bifunctional electrocatalysts based on non-noble metals for water electrolysis is both urgent and challenging. However, unresolved issues remain regarding the challenge of identifying the active phase and gaining a comprehensive understanding of its surface reconstruction and functionality throughout the reaction process. In this study, we have combined doping and heterostructure construction by a one-step electrodeposition and a subsequent activation treatment to synthesize Fe, V co-doped Co3O4/Co(OH)2 and Co/Co(OH)2 heterointerfaces (referred to as A-Co60Fe1.1V). These heterointerfaces, composed of Co/Co(OH)2 and Co3O4/Co(OH)2, are proposed to facilitate charge transfer process during catalysis. X-ray photoelectron spectroscopy (XPS) analysis demonstrates that the introduction of V and Fe dopants increases the valence state of Co centers in Co3O4 and Co(OH)2. Further operando Raman spectroscopy reveals that Co(OH)2 and Co3O4 with the high-valence Co centers remain stable during the hydrogen evolution reaction (HER) process. These high-valence Co centers are believed to promote the crucial water dissociation step and therefore enhance the overall HER catalysis. On the other hand, during the oxygen evolution reaction (OER), Fe, V co-doping leads to an earlier formation of the active CoOOH species, while Fe doping can further help stabilize the more reactive β-CoOOH species instead of the less reactive γ-CoOOH. As a result, the A-Co60Fe1.1V catalyst exhibits significantly improved catalytic activity for both HER and OER that it requires low overpotentials of 51 and 250 mV, respectively, to attain a current density of 10 mA cm-2. Moreover, when utilized as both the cathode and anode in alkaline water electrolysis, the A-Co60Fe1.1V catalyst can operate at a mere 1.54 V voltage while maintaining 10 mA cm-2, surpassing the majority of non-noble metal catalysts. Remarkably, it also exhibits stability for at least 40 h at ∼100 mA cm-2.

Competition between Elimination and Substitution for Ambident Nucleophiles CN- and Iodoethane Reactions in Gaseous and Aqueous Medium.

Nucleophilic substitution (SN2) and elimination (E2) reactions between ambident nucleophiles have long been considered as typical reactions in organic chemistry, and exploring the competition between the two reactions is of great importance in chemical synthesis. As a nucleophile, CN- can use its C and N atoms as the reactive centers to undergo E2 and SN2 reactions, but related research is currently limited. This study uses the CCSD(T)/pp/t//MP2/ECP/d electronic structure method to perform detailed investigations on the potential energy profiles for SN2 and E2 reactions between CN- and CH3CH2I in gaseous and aqueous media. The potential energy profiles reveal that the energy barriers for SN2 and E2 reactions with the C atom as the reactive center are consistently lower than those with the N atom, indicating that the C atom has a stronger nucleophilic ability and stronger basicity. Furthermore, the potential energy profiles in both gas and aqueous environments show that the barriers of SN2 reactions are lower than those for E2 reactions with both C and N as the attacking atom. By using the frontier molecular orbital and activation strain models to explain the interesting phenomenon, the transition from the gas phase to solution was investigated, specifically in the gas-microsolvation-water transition. The results show that water molecules reduce the nucleophilicity and basicity of CN-, while strain energy (ΔEstrain) causes a greater increase in the energy barrier for E2 reactions. This study provides new insights and perspectives on the understanding of CN- as a nucleophile in SN2 reactions and serves as theoretical guidance for organic synthesis.

Estimation of dipole moments by Solvatochromic shift method, spectroscopic analysis of UV–Visible, HOMO-LUMO, ESP map, Mulliken atomic charges, NBO and NLO properties of benzofuran derivative

Solvatochromic shift method has been used to estimate ground state (μg) and excited state (μe) dipole moments of benzofuran derivative (5NFMOT) at room temperature indifferent solvents. This method involves Lippert, Bakhshiev and Kawski-Chamma-Viallet equations. Reichardt microscopic solvent polarity parameter was used to calculate the change in dipole moment. Effect of solvents on absorption and fluorescence spectra was investigated using Kamlet and Catalan's MLR approach. Computational studies of benzofuran derivative were carried out using Gaussian 16. Geometry optimization was performed using DFT method at 6–311++G (d, p)/B3LYP basis set. UV–Visible spectra have been studied by using TD-DFT method for the same basis set. The μg was obtained from DFT method, whereas μe from TD-DFT method. It has been observed that both from experimentally and theoretically the ground state dipole moment is higher than the excited state dipole moment. HOMO-LUMO surfaces and Mulliken atomic charges have been studied in gas phase and solution. Furthermore, 3D plots of electrostatic potential map are used to identify reactive centers such as electrophilic and nucleophilic sites. NBO analysis is helpful to obtain stability and charge delocalization of the title molecule. Polarizablity, and hyper polarizability values were used to study the NLO properties.

Kinetic and Computational Studies of CO Oxidation and PROX on Cu/CeO2 Nanospheres

As supported CuO is well-known for low temperature activity, CuO/CeO2 nanosphere catalysts were synthesized and tested for CO oxidation and preferential oxidation of CO (PROX) in excess H2. For the first reaction, ignition was observed at 95 °C, whereas selective PROX occurred in a temperature window from 50 to 100 °C. The catalytic performance was independent of the initial oxidation state of the catalyst (CuO vs. Cu0), suggesting that the same active phase is formed under reaction conditions. Density functional modeling was applied to elucidate the intermediate steps of CO oxidation, as well as those of the comparably less feasible H2 transformation. In the simulations, various Cu and vacancy sites were probed as reactive centers enabling specific pathways.

Epoxy‐rich Fe Single Atom Sites Boost Oxygen Reduction Electrocatalysis

AbstractElectrocatalysts for highly efficient oxygen reduction reaction (ORR) are crucial for energy conversion and storage devices. Single‐atom catalysts with maximized metal utilization and altered electronic structure are the most promising alternatives to replace current benchmark precious metals. However, the atomic level understanding of the functional role for each species at the anchoring sites is still unclear and poorly elucidated. Herein, we report Fe single atom catalysts with the sulfur and oxygen functional groups near the atomically dispersed metal centers (Fe1/NSOC) for highly efficient ORR. The Fe1/NSOC delivers a half‐wave potential of 0.92 V vs. RHE, which is much better than those of commercial Pt/C (0.88 V), Fe single atoms on N‐doped carbon (Fe1/NC, 0.89 V) and most reported nonprecious metal catalysts. The spectroscopic measurements reveal that the presence of sulfur group induces the formation of epoxy groups near the FeN4S2 centers, which not only modulate the electronic structure of Fe single atoms but also participate the catalytic process to improve the kinetics. The density functional theory calculations demonstrate the existence of sulfur and epoxy group engineer the charges of Fe reactive center and facilitate the reductive release of OH* (rate‐limiting step), thus boosting the overall oxygen reduction efficiency.

Epoxy-rich Fe Single Atom Sites Boost Oxygen Reduction Electrocatalysis.

Electrocatalysts for highly efficient oxygen reduction reaction (ORR) are crucial for the energy conversion and storage devices. Single-atom catalysts with maximized metal utilization and altered electronic structure arethe most promising alternatives to replace current benchmark precious metals. However, the atomic level understanding of the functional role for each species at the anchoring sites is still unclear and poorly elucidated. Herein, we report Fe single atom catalysts with the sulfur and oxygen functional groups near the atomically dispersed metal centers (Fe1/NSOC) for highly efficient ORR. The Fe1/NSOC delivers a half-wave potential of 0.92 V vs. RHE, which is much better than those of commercial Pt/C (0.88 V), Fe single atoms on N-doped carbon (Fe1/NC, 0.89 V ) and most reported nonprecious metal catalysts. The spectroscopic measurements reveal that the presence of sulfur group induces the formation of epoxy groups near the FeN4S2 centers, which not only modulate the electronic structure of Fe single atoms but also participate the catalytic process to improve the kinetics. The density functional theory calculations demonstrate the existence of sulfur and epoxy group engineer the charges of Fe reactive center and facilitate the reductive release of OH* (rate-limiting step), thus boosting the overall oxygen reduction efficiency.

Synergistically Regulating the Electronic Structure of CoS by Cation and Anion Dual-Doping for Efficient Overall Water Splitting.

Precisely regulating the electronic construction of reactive center is an essential methodto increase the property of electrocatalysis, but achieving efficient multifunctional characteristics remains a challenge. Herein, CoS sample dual-doped by Cu and F atoms, as bifunctionalelectrocatalyst, is designed and synthesized for water electrolysis. According to the experimental results, Cu atom doping can perform primary electronic adjustment and obtain bifunctional properties, and then the electronic structure is adjusted for the second time to achieve an optimal state by introducing F atom. Meanwhile, this dual-doping strategy will result in lattice distortion and expose more active sites. As expected, dual-doped Cu-F-CoS show the brilliant electrocatalytic act, revealing ultralow overpotentials (59 mV for HER, 213 mV for OER) at 10 mA cm-2in alkaline electrolyte.Besides, it also exhibits distinguished water electrolysis activity withcell voltage is as low as 1.52 V at 10 mA cm-2.Our work can provide an atomic-level perception for adjusting the electronic construction of reactive sites by means of dual-doping engineering, and put forward a contributing path for the electrocatalysts with multifunctional designing.

Single‐atom Iron Catalyst with Biomimetic Active Center to Accelerate Proton Spillover for Medical‐level Electrosynthesis of H2O2Disinfectant

AbstractElectrosynthesis of H2O2has great potential for directly converting O2into disinfectant, yet it is still a big challenge to develop effective electrocatalysts for medical‐level H2O2production. Herein, we report the design and fabrication of electrocatalysts with biomimetic active centers, consisting of single atomic iron asymmetrically coordinated with both nitrogen and sulfur, dispersed on hierarchically porous carbon (FeSA‐NS/C). The newly‐developed FeSA‐NS/C catalyst exhibited a high catalytic activity and selectivity for oxygen reduction to produce H2O2at a high current of 100 mA cm−2with a record high H2O2selectivity of 90 %. An accumulated H2O2concentration of 5.8 wt.% is obtained for the electrocatalysis process, which is sufficient for medical disinfection. Combined theoretical calculations and experimental characterizations verified the rationally‐designed catalytic active center with the atomic Fe site stabilized by three‐coordinated nitrogen atoms and one‐sulfur atom (Fe‐N3S‐C). It was further found that the replacement of one N atom with S atom in the classical Fe‐N4‐C active center could induce an asymmetric charge distribution over N atoms surrounding the Fe reactive center to accelerate proton spillover for a rapid formation of the OOH* intermediate, thus speeding up the whole reaction kinetics of oxygen reduction for H2O2electrosynthesis.

Single-atom Iron Catalyst with Biomimetic Active Center to Accelerate Proton Spillover for Medical-level Electrosynthesis of H2 O2 Disinfectant.

Electrosynthesis of H2 O2 has great potential for directly converting O2 into disinfectant, yet it is still a big challenge to develop effective electrocatalysts for medical-level H2 O2 production. Herein, we report the design and fabrication of electrocatalysts with biomimetic active centers, consisting of single atomic iron asymmetrically coordinated with both nitrogen and sulfur, dispersed on hierarchically porous carbon (FeSA -NS/C). The newly-developed FeSA -NS/C catalyst exhibited a high catalytic activity and selectivity for oxygen reduction to produce H2 O2 at a high current of 100 mA cm-2 with a record high H2 O2 selectivity of 90 %. An accumulated H2 O2 concentration of 5.8 wt.% is obtained for the electrocatalysis process, which is sufficient for medical disinfection. Combined theoretical calculations and experimental characterizations verified the rationally-designed catalytic active center with the atomic Fe site stabilized by three-coordinated nitrogen atoms and one-sulfur atom (Fe-N3 S-C). It was further found that the replacement of one N atom with S atom in the classical Fe-N4 -C active center could induce an asymmetric charge distribution over N atoms surrounding the Fe reactive center to accelerate proton spillover for a rapid formation of the OOH* intermediate, thus speeding up the whole reaction kinetics of oxygen reduction for H2 O2 electrosynthesis.

Phosphine‐Triggered Structural Defects in Au44 Homologues Boost Electrocatalytic CO2 Reduction

AbstractThe systematic induction of structural defects at the atomic level is crucial to metal nanocluster research because it endows cluster‐based catalysts with highly reactive centers and allows for a comprehensive investigation of viable reaction pathways. Herein, by substituting neutral phosphine ligands for surface anionic thiolate ligands, we establish that one or two Au3 triangular units can be successfully introduced into the double‐stranded helical kernel of Au44(TBBT)28, where TBBT=4‐tert‐butylbenzenethiolate, resulting in the formation of two atomically precise defective Au44 nanoclusters. Along with the regular face‐centered‐cubic (fcc) nanocluster, the first series of mixed‐ligand cluster homologues is identified, with a unified formula of Au44(PPh3)n(TBBT)28−2n (n=0–2). The Au44(PPh3)(TBBT)26 nanocluster having major structural defects at the bottom of the fcc lattice demonstrates superior electrocatalytic performance in the CO2 reduction to CO. Density functional theory calculations indicate that the active site near the defects significantly lowers the free energy for the *COOH formation, the rate‐determining step in the whole catalytic process.

Phosphine-Triggered Structural Defects in Au44 Homologues Boost Electrocatalytic CO2 Reduction.

The systematic induction of structural defects at the atomic level is crucial to metal nanocluster research because it endows cluster-based catalysts with highly reactive centers and allows for a comprehensive investigation of viable reaction pathways. Herein, by substituting neutral phosphine ligands for surface anionic thiolate ligands, we establish that one or two Au3 triangular units can be successfully introduced into the double-stranded helical kernel of Au44 (TBBT)28 , where TBBT=4-tert-butylbenzenethiolate, resulting in the formation of two atomically precise defective Au44 nanoclusters. Along with the regular face-centered-cubic (fcc) nanocluster, the first series of mixed-ligand cluster homologues is identified, with a unified formula of Au44 (PPh3 )n (TBBT)28-2n (n=0-2). The Au44 (PPh3 )(TBBT)26 nanocluster having major structural defects at the bottom of the fcc lattice demonstrates superior electrocatalytic performance in the CO2 reduction to CO. Density functional theory calculations indicate that the active site near the defects significantly lowers the free energy for the *COOH formation, the rate-determining step in the whole catalytic process.

MetaSpot: A General Approach for Recognizing the Reactive Atoms Undergoing Metabolic Reactions Based on the MetaQSAR Database

The prediction of drug metabolism is attracting great interest for the possibility of discarding molecules with unfavorable ADME/Tox profile at the early stage of the drug discovery process. In this context, artificial intelligence methods can generate highly performing predictive models if they are trained by accurate metabolic data. MetaQSAR-based datasets were collected to predict the sites of metabolism for most metabolic reactions. The models were based on a set of structural, physicochemical, and stereo-electronic descriptors and were generated by the random forest algorithm. For each considered biotransformation, two types of models were developed: the first type involved all non-reactive atoms and included atom types among the descriptors, while the second type involved only non-reactive centers having the same atom type(s) of the reactive atoms. All the models of the first type revealed very high performances; the models of the second type show on average worst performances while being almost always able to recognize the reactive centers; only conjugations with glucuronic acid are unsatisfactorily predicted by the models of the second type. Feature evaluation confirms the major role of lipophilicity, self-polarizability, and H-bonding for almost all considered reactions. The obtained results emphasize the possibility of recognizing the sites of metabolism by classification models trained on MetaQSAR database. The two types of models can be synergistically combined since the first models identify which atoms can undergo a given metabolic reactions, while the second models detect the truly reactive centers. The generated models are available as scripts for the VEGA program.

Multistep Cascade Catalytic Reactions Employing Bifunctional Framework Compounds.

Multistep cascade reactions are important to achieve atom as well as step economy over conventional synthesis. This approach, however, is limited due to the incompatibility of the available reactive centers in a catalyst. In the present study, new MOF compounds, [Zn2(SDBA)(3-ATZ)2]·solvent, I and II, with tetrahedral Zn centers as good Lewis acidic sites and the free amino group of the 3-amino triazole ligand as a strong Lewis base center were shown to perform 4-step cascade/tandem reaction in a facile manner. Effective conversion of benzaldehyde dimethyl acetal in the presence of excess nitromethane at 100 °C in water to 1-(1,3-dinitropropan-2-yl) benzene was achieved in 10 h with yields of ∼95% (I) and ∼94% (II). This 4-step cascade reaction proceeds via deacetalization (Lewis acid), Henry (Lewis base), and Michael (Lewis base) reactions. The present work highlights the importance of spatially separated functional groups in multistep tandem catalysis─the examples of which are not common.

Insight into the Effects of Pd Single-atom Particles in the Activation of the Carbon-Chloride Bond

Palladium (Pd) shows high activity in a variety of catalysis reactions that refer to the activation of the carbon-halogenation bond, and single-atom Pd catalysts have received significant attention as new technology. Nevertheless, there is a huge knowledge gap regarding which Pd sites could form highly reactive centers. It is unclear whether single-atom Pd sites are active in this process or not. In this study, we synthesized Pd/TiO2 nanosheets with Pd loadings of 1%, 5%, and 10% and designed single atom Pd sites and Pd nanoparticles on similar substrates. A scanning transmission electron microscope was used to characterize the synthesized Pd catalysts. As a catalyst, Pd/TiO2 featuring Pd NPs showed high activity in activating the carbon-halogen bond in the activation of carbon-chloride bond, whereas Pd/TiO2 with single Pd atoms showed very low activity in this pros. Accordingly, our results demonstrate that the activation of carbon-halogen bonds cannot be catalyzed by the single-atom Pd sites and emphasize the significance of the ensemble effect in determining the activity of Pd sites.