Catalytic Pathway Research Articles

Bioactive molecules from lignin via homogeneous and heterogeneous catalytic pathways

Valorization of lignin to valuable chemicals via catalytic pathways is recognized as one of the most practical approaches to explore its value and replace nonrenewable petroleum resources. This forum highlights remarkable progress and emerging strategies in the synthesis of valuable bioactive molecules from lignin via both homogeneous and heterogeneous catalytic pathways.

Mn-doped carbon-Al2SiO5 fibers enable catalytic ozonation for wastewater treatment: Interface modulation and mass transfer enhancement

Heterogeneous catalytic ozonation is an efficient approach to remove hazardous and refractory organic contaminants in wastewater. It is crucial to design an ozone catalyst with high catalytic activity, high mass transfer and facile separation properties. Herein, easily separable aluminosilicate (Al2SiO5) fibers were developed as carriers and after interface modulation, Mn-doped carbon-Al2SiO5 (Mn-CAS) fibrous catalysts were proposed for catalytic ozonation. The growth of carbon shells on Al2SiO5 fiber surface and the introduction of metal Mn provided abundant Lewis acid sites to catalyze ozone. The Mn-CAS fiber/O3 system exhibited superior reactivity to degrade oxalic acid with a rate constant of 0.034 min−1, which was about 19 times as high as Al2SiO5/O3. For coal gasification wastewater treatment, Mn-CAS fibers also demonstrated high catalytic activity and stability and the COD removal was over 56%. Computational fluid dynamic simulations proved the high mass transfer properties of fibrous catalysts. Hydroxyl radicals (•OH) were identified as the predominant active species for organic degradation. Particularly, the catalytic pathways of O3 to •OH on Mn-O4 sites were revealed by theoretical calculations. This work provides a novel fibrous catalyst with high reactivity and mass transfer as well as easy separation characteristics for catalytic ozonation and wastewater purification.

Catalytic absorption pathway with kinetically favorable dissolution of nitric oxide in aqueous absorbents

AbstractNitrogen capture is a crucial strategy for coping with the environmental crisis arising from continually industrial NO emissions, while it suffers from the generally inefficient aquatic absorbent. This work developed a novel absorbent with favorable gas affinity via using sterically hindered imidazole to regulate the gas–liquid interface of typical K2S2O8 solution, initially achieving an efficiently catalytic absorption of poorly soluble NO. The best catalytic absorption efficiencies increased from 17.83% to 91.90% as compared to traditional one. Moreover, an established absorption kinetic model indicated that both capacity and rate of NO dissolution were increased. The imidazole molecules spontaneously migrated to gas–liquid interface of solution and imparted an additional dissolution impetus to NO. This catalytic absorption method overcoming the conventional NO dissolution limitation in water not only improves commercial NO capture, but also provides a new design of aquatic absorbent for heterogeneous reactions requiring transporting poorly soluble gases in aqueous solvents.

Photocatalysis of Metallic Nanoparticles: Interband vs Intraband Induced Mechanisms.

Photocatalysis induced by localized surface plasmon resonance of metallic nanoparticles has been studied for more than a decade, but photocatalysis originating from direct interband excitations is still under-explored. The spectral overlap and the coupling of these two optical regimes also complicate the determination of hot carriers' energy states and eventually hinder the accurate assignment of their catalytic role in studied reactions. In this Featured Article, after reviewing previous studies, we suggest classifying the photoexcitation via intra- and interband transitions where the physical states of hot carriers are well-defined. Intraband transitions are featured by creating hot electrons above the Fermi level and suitable for reductive catalytic pathways, whereas interband transitions are featured by generating hot d-band holes below the Fermi level and better for oxidative catalytic pathways. Since the contribution of intra- and interband transitions are different in the spectral regions of localized surface plasmon resonance and direct interband excitations, the wavelength dependence of the photocatalytic activities is very helpful in assigning which transitions and carriers contribute to the observed catalysis.

Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia

The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

Dendritic alloy shell Au@AgPt yolk sensor with excellent dual SERS enhancement and catalytic performance for in-situ SERS monitoring reaction

In situ monitoring of the changes of reactants on the metal catalyst surface/interface, capture, and identification of intermediate species and products are very important for revealing catalytic pathways, mechanisms, and designing high-performance catalysts. A novel Au@AgPt yolk structure with ternary metallic composition and dendritic alloy shell was synthesized, which had dual catalytic and surface-enhanced Raman spectroscopy (SERS) performance to meet the demand of in-situ SERS monitoring reaction. The key factors for the formation of this special structure are the Ag-Pt mole ratio (nAg: Pt) and surfactant types. The yolk structure with the most optimal catalytic and SERS performance (nAg: Pt=1:1) was screened out for in-situ SERS monitoring. The classic 4-NTP reduction to 4-ATP model was first used to verify the excellent SERS and catalytic dual-functional properties of the Au@AgPt yolk structure. Importantly, this yolk structure was further used to detect plasmon-induced halogenated benzene dehalogenated coupling reaction, and the results show that the hot electrons generated by Au@AgPt NPs could trigger C-X (X = Cl, Br) bond fracture to form the C-C bond under continuous laser irradiation, which provided an effective way for C-X bond activation in organic synthesis.

Filling the Gap: Atomically Precise Metal Nanoclusters‐Induced Z‐Scheme Photosystem toward Robust and Stable Solar Hydrogen Generation

AbstractAtomically precise metal nanoclusters (NCs) represent a promising generation of metal nanomaterial because of characteristic atomic stacking mode, abundant catalytic active sites, and molecular‐like discrete energy band structure. However, crafting metal NCs‐dominated photocatalytic systems with mediated charge transport pathways for photoredox catalysis is in the infant stage and their photocatalytic mechanisms remain elusive, which is largely hampered by the ultra‐short charge lifetime, generic instability, and complicated electronic structure of metal NCs. In this study, the smart construction of all‐solid‐state metal NCs‐transition metal chalcogenides quantum dots (TMCs QDs) Z‐scheme artificial photosystems for robust and stable solar‐to‐hydrogen conversion is demonstrated. The concurrent favorable photosensitization efficiency of metal NCs and TMCs QDs synergistically stimulate the unexpected Z‐scheme charge transport pathway, which significantly boosts the anisotropic spatial vectorial charge transport/separation, giving rise to considerably enhanced visible‐light‐responsive photocatalytic hydrogen generation performances along with favorable stability. This study would push forward the prosperity of exploring metal NCs‐based photosystems for solar‐to‐hydrogen conversion.

Insights into SnO2 Nanoparticles Supported on Fibrous Mesoporous Silica for CO Catalytic Oxidation

A large surface area dendritic mesoporous silica material (KCC-1) was successfully synthesized and used as a support to confine SnO2 nanoparticles (NPs). Owing to the large specific surface area and abundant mesoporous structure of dendritic KCC-1, the SnO2 NPs were highly dispersed, resulting in significantly improved CO catalytic oxidation activity. The obtained Snx/KCC-1 catalysts (x represents the mass fraction of SnO2 loading) exhibited excellent CO catalytic activity, with the Sn7@KCC-1 catalyst achieving 90% CO conversion at about 175 °C. The SnO2 NPs on the KCC-1 surface in a highly dispersed amorphous form, as well as the excellent interaction between SnO2 NPs and KCC-1, positively contributed to the catalytic removal process of CO on the catalyst surface. The CO catalytic removal pathway was established through a combination of in situ diffuse reflectance infrared transform spectroscopy and density-functional theory calculations, revealing the sequential steps: ① CO → CO32−ads, ② CO32−ads → CO2free+SnOx−1, ③ SnOx−1+O2 → SnOx+1. This study provides valuable insights into the design of high-efficiency non-precious metal catalysts for CO catalytic oxidation catalysts with high efficiency.

Ultrahigh-flux 2D CoO@MoS2 composite membrane activated peroxymonosulfate through enhanced electron transfer for rapid degradation of refractory benzotriazole

The application of heterogeneous advanced oxidation processes (AOPs) in the removal of refractory pollutants has been hindered by several drawbacks, such as difficult recovery of the powder catalyst, the low yields and inefficient utilization of reactive oxygen species (ROS). We developed a novel catalytic membrane named 2D CoO@MoS2 membrane, its catalytic active layer was a composite material formed by MoS2 nanosheets wrapped and intercalated between 2D CoO porous nanoplates, providing abundant active sites and oxygen vacancies (Ov). 2D CoO@MoS2 membrane was applied to activate peroxymonosulfate (PMS) for benzotriazole (BTA) degradation. DFT calculations and series characterizations demonstrated that electron transfer occurred at the contact interface between 2D CoO and MoS2 phase, while the 2D CoO@MoS2 composite could act as an effective electron donor for PMS. The redox cycles of Mo(IV)/Mo(VI) and Ov/O2− could synergistically enhance the regeneration of Co(II), thereby maintaining the cycle of catalytic active center, which facilitated the spontaneous dissociation of PMS to generate various ROS, including SO4− (30.2 μM), 1O2 (8.6 μM) and OH (5.8 μM). These ROS rapidly degraded 99.7% of BTA (20 mg/L) through the nanoconfined layer of hydrophilic membrane with an ultra-high flux of 2172 L m−2h−1 in a super-fast time (∼195 ms). Surprisingly, the degradation rate constant k exhibited 3 to 5 orders of magnitude higher compared to conventional heterogeneous AOPs. Furthermore, the catalytic stability, degradation pathways and biological toxicity of BTA degradation were also evaluated. This membrane-based AOPs technique provides a new approach to overcome the limitations of conventional heterogeneous catalysis.

Tailoring a local acid-like microenvironment for efficient neutral hydrogen evolution

Electrochemical hydrogen evolution reaction in neutral media is listed as the most difficult challenges of energy catalysis due to the sluggish kinetics. Herein, the Ir-HxWO3 catalyst is readily synthesized and exhibits enhanced performance for neutral hydrogen evolution reaction. HxWO3 support is functioned as proton sponge to create a local acid-like microenvironment around Ir metal sites by spontaneous injection of protons to WO3, as evidenced by spectroscopy and electrochemical analysis. Rationalize revitalized lattice-hydrogen species located in the interface are coupled with Had atoms on metallic Ir surfaces via thermodynamically favorable Volmer-Tafel steps, and thereby a fast kinetics. Elaborated Ir-HxWO3 demonstrates acid-like activity with a low overpotential of 20 mV at 10 mA cm−2 and low Tafel slope of 28 mV dec−1, which are even comparable to those in acidic environment. The concept exemplified in this work offer the possibilities for tailoring local reaction microenvironment to regulate catalytic activity and pathway.

Identifying And Unveiling the Role of Multivalent Metal States for Bidirectional UOR and HER Over Ni, Mo-Trithiocyanuric Based Coordination Polymer.

Urea oxidation reaction (UOR), an ideal alternative to oxygen evolution reaction (OER), has received increasing attention for realizing energy-saving H2 production and relieving pollutant degradation. Normally, most studied Ni-based UOR catalysts pre-oxidate to NiOOH and then act as active sites. However, the unpredictable transformation of the catalyst's structure and its dissolution and leaching, may complicate the accuracy of mechanism studies and limit its further applications. Herein, a novel self-supported bimetallic Mo-Ni-C3 N3 S3 coordination polymers (Mo-NT@NF) with strong metal-ligand interactions and different H2 O/urea adsorption energy are prepared, which realize a bidirectional UOR/hydrogen evolution reaction (HER) reaction pathway. A series of Mo-NT@NF is prepared through a one-step mild solvothermal method and their multivalent metal states and HER/UOR performance relationship is evaluated. Combining catalytic kinetics, in situ electrochemical spectroscopic characterization, and density-functional theory (DFT) calculations, a bidirectional catalytic pathway is proposed by N, S-anchored Mo5+ and reconstruction-free Ni3+ sites for catalytic active center of HER and UOR, respectively. The effective anchoring of the metal sites and the fast transfer of the intermediate H* by N and S in the ligand C3 N3 S3 H3 further contribute to the fast kinetic catalysis. Ultimately, the coupled HER||UOR system with Mo-NT@NF as the electrodes can achieve energy-efficient overall-urea electrolysis for H2 production.

Thermochemical processes for CO[formula omitted] hydrogenation to fuels and chemicals: Challenges and opportunities

This manuscript discusses the potential use of CO2 as a carbon and oxygen carrier to return it to the carbon life cycle in the form of fuels or chemicals via thermochemical catalytic pathways. Theoretically, CO2 hydrogenation can form a variety of fuels and chemicals. Practically, however, the selectivity, conversion, operating range, and kinetic limitations and operational cost determine the end product. Because of their high value and versatility as a chemical or fuel, small olefins (i.e., C2H4) and methanol are often considered as target species. Whether alcohol or olefin formation, CH4 and CO are the nature’s primary choices of CO2 conversion. They can be formed over a wide operating temperature, pressure, and CO2:H2 ratios. They are often competitive carbon species in olefin or methanol formation steps. Although they are less valuable as end products, they can be used as intermediate species. Secondary processes of CO and CH4 to form chemicals and fuels can increase the overall CO2 hydrogenation yield. Independent of the choice of end product, CO2 hydrogenation requires hydrogen. Pure hydrogen derived mostly from fossil fuels adds to the overall process cost and also increases the CO2 emissions. Hydrogen produced from water electrolysis is a renewable green pathway but is limited by the process efficiency and cost. As an alternative to pure hydrogen, low-value, small chain paraffins are suggested as the hydrogen carriers. Carbon dioxide–assisted oxidative dehydrogenation of paraffins to olefins process is a direct pathway to olefin formation. The paper discusses these potential pathways for CO2 utilization based on theoretical analysis and recent advances in academia and industry.

Borane‐Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio‐ and Diastereoselective Construction of trans‐2,3‐Disubstituted‐1,2,3,4‐Tetrahydroquinoxalines

AbstractRecent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4‐tetrahydroquinoxalines. However, enantio‐ and diastereoselective access to trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair‐based catalyst generated via in situ hydroboration of 2‐vinylnaphthalene with HB(C6F5)2 allows for the one‐pot tandem cyclization/hydrosilylation of 1,2‐diaminobenzenes and 1,2‐diketones with commercially available PhSiH3 to exclusively afford trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane‐based catalyst derived from HB(C6F5)2 and a binaphthyl‐based chiral diene to give rise to enantioenriched trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines in high yields with almost complete diastereo‐ and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20‐gram scale production are demonstrated. The enantio‐ and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.

Borane-Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio- and Diastereoselective Construction of trans-2,3-Disubstituted-1,2,3,4-Tetrahydroquinoxalines.

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4-tetrahydroquinoxalines. However, enantio- and diastereoselective access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair-based catalyst generated via in situ hydroboration of 2-vinylnaphthalene with HB(C6 F5 )2 allows for the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones with commercially available PhSiH3 to exclusively afford trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst derived from HB(C6 F5 )2 and a binaphthyl-based chiral diene to give rise to enantioenriched trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with almost complete diastereo- and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20-gram scale production are demonstrated. The enantio- and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.

Catalytic pyrolysis of fatty acids and oils into liquid biofuels and chemicals over supported Ni catalysts on biomass-derived carbon

Herein, biomass-derived activated carbon (bio-AC) was synthesized using rice husk as a biotemplate and natural carbon source. After immobilization of Ni, the supported Ni/bio-AC showed excellent catalytic activity in the pyrolysis of fatty acids to paraffin-based biodiesel in H2-free and solvent-free conditions, corresponding to the conversion of 99.6% and a total alkane yield of 95.1%, including 88.9% heptadecane. Based on comprehensive characterizations, the calculated turnover frequency of Ni/bio-AC was 3.9 times that of conventional Ni/AC. Significantly enhanced olefin selectivity was further obtained by N-doping of Ni/bio-AC, which was attributed to the inhibition of -COO* dissociation by the Ni-N sites. The possible catalytic reaction pathways from stearic acid to heptadecane via aliphatic alcohol as a reaction intermediate were investigated. Besides, efficient conversions of saturated and unsaturated plant oils were also achieved over Ni/bio-NAC catalysts in Py-GC/MS through pulsed catalytic pyrolysis manner, showing a promising prospect for sustainable biofuels and chemical production.

Structural evidence of the conversion of nitric oxide (NO) to nitrite ion (NO2−) by lactoperoxidase (LPO): Structure of the complex of LPO with NO2− at 1.89 Å resolution

Lactoperoxidase (LPO) is a heme containing mammalian enzyme which uses hydrogen peroxide (H2O2) to catalyze the conversion of substrates into oxidized products. LPO is found in body fluids and tissues such as milk, saliva, tears, mucosa and other body secretions. The previous structural studies have shown that LPO converts substrates, thiocyanate (SCN−) and iodide (I−) ions into oxidized products, hypothiocyanite (OSCN−) and hypoiodite (IO−) ions respectively. We report here a new structure of the complex of LPO with an oxidized product, nitrite (NO2−). This product was generated from NO using the two step reaction of LPO by adding hydrogen peroxide (H2O2) in the solution of LPO in 0.1 M phosphate buffer at pH 6.8 as the first step. In the second step, NO gas was added to the above mixture. This was crystallized using 20% (w/v) PEG-3350 and 0.2 M ammonium iodide at pH 6.8. The structure determination showed the presence of NO2− ion in the distal heme cavity of the substrate binding site of LPO. The structure also showed that the propionate group which is linked to pyrrole ring D of the heme moiety was disordered. Similarly, the side chain of Asp108, which is covalently linked to heme moiety, was also split into two components. As a result of these changes, the conformation of the side chain of Arg255 was altered allowing it to form new interactions with the disordered carboxylic group of propionate moiety. These structural changes are indicative of an intermediate state in the catalytic reaction pathway of LPO.

Molecular self-assembled synthesis of highly dispersed Co single-atom coordinated 2-methylimidazole modified carbon nitride for peroxymonosulfate activation

Although single-atom catalysts are pioneers in peroxymonosulfate (PMS) activation, selection of substrates and enhanced binding remains ambiguous. Here, a novel highly dispersed cobalt single-atom loaded 2-methylimidazole (MeIm) ligand-modified carbon nitride catalyst (Co-MCAMeIm) was prepared by a molecular self-assembly strategy. The densely distributed SA-Co with Co-N sites were corroborated by HAADF-STEM and XAFS analysis. The strong chelation of pre-dispersed ligands and triazine ring of g-C3N4 confers higher stability to the catalyst, reducing Co leaching. Meanwhile, the g-C3N4 substrate offers additional adsorption sites to shorten the reaction distance. The embedded Co-N functions as an electron donor capable of bridging N-rich carbon networks, hence accelerating the electron transport. Experimental findings demonstrated that sulfamethoxazole (SMX) could be effectively cleared through Co-MCAMeIm/PMS process (99.1%, 0.13 min−1). Several key influencing factors like Co to MeIm molar ratio, PMS concentration, Co-MCAMeIm dosage, pH value, anions, and humic acid were examined. The catalytic pathway is dominated by the activation of PMS with SA-Co-N as active sites to form 1O2. Meanwhile, a multi-ROS process with occurrence of SO4•-, O2•- and •OH was confirmed. Additionally, the SMX degradation routes and toxicity variations were derived and analyzed. Herein, the research may provide new insights for stable single-atom catalyst towards water treatment.

Nitrogen–doped titanium dioxide/schwertmannite nanocomposites as heterogeneous photo–Fenton catalysts with enhanced efficiency for the degradation of bisphenol A

Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen–doped titanium dioxide/schwertmannite nanocomposites (N–TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo–Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as–prepared N–TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N–TiO2 (ca. 10.8%). In this photo–Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (•OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo–Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral–based materials in wastewater treatment.

F-enhanced anti-bonding activation effect of FeO on catalytic degradation of chloramphenicol by dielectric barrier discharge plasma

In this study, dielectric barrier discharge (DBD) plasma and F/FeO catalyst were utilized to degrade chloramphenicol (CAP) in water. The operation conditions, catalyst properties and catalytic mechanisms were systematically studied, and the anti-bonding activation effect was highlighted as the key for the catalytic effect. The results show that CAP was 100% degraded by DBD and F/FeO after 8 min treatment under optimal operating conditions, and F/FeO catalyst increased the degradation efficiency of CAP by 34.1%. FeO transferred electrons into the π* anti-bonding orbital of O3 and the σ* anti-bonding orbitals of H2O2 and O2, leading to an anti-bonding activation effect and weakening their bonding. Additionally, F facilitated the electron transfer of FeO and changed the stable adsorption of O3 and H2O2 on FeO to dissociated adsorption on F/FeO. The –OH groups generated by the H2O2 dissociation could induce a non-Fenton catalytic pathway. The intensive electron transfer of F/FeO converted O2 into ·O2−. The ant-bonding activation of O3, H2O2 and O2 on F/FeO facilitated the production of ·OH. A degradation pathway for CAP was proposed based on the findings of experiments and simulation. The developmental toxicity of CAP was weakened after F/FeO/DBD treatment. This study proposes an efficient plasma catalyst for purifying antibiotic wastewater, and provides a new insight into the mechanism of the plasma/catalysis process.

Unlocking Cu(I)-Mediated Catalytic Pathways for Efficient ROS Generation by Incorporating an Oxazole-Based Histidine Surrogate into Cu(II)-ATCUN Complexes.

The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (pKa 7.0) of Gly-Gly-His-NH2 (GGHa, a canonical ATCUN peptide) with thiazole (pKa 2.7) and oxazole (pKa 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest pKa among known analogues. Despite similar square-planar Cu(II)-N4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.