Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

The Synthesis, Bonding, and Transformation of a Ligand-Protected Gold Nanohydride Cluster.

Gold does not react with H2 to form bulk hydrides. Here we report the synthesis and characterization of a gold nanohydride protected by diphosphine ligands, [Au22 H4 (dppo)6 ]2+ [dppo=1,8-bis(diphenylphosphino)octane]. The Au22 core consists of two Au11 units bonded by eight Au atoms not coordinated by the diphosphine ligands. The four H atoms are found to bridge the eight uncoordinated Au atoms at the interface. Each Au11 unit can be viewed as a tetravalent superatom forming four delocalized Au-H-Au bonds, similar to the quadruple bond first discovered in the [Re2 Cl8 ]2- inorganic cluster. The [Au22 H4 (dppo)6 ]2+ nanohydride is found to lose H atoms over an extended time via H evolution (H2 ), proton (H+ ) and hydride (H- ) releases. This complete repertoire of H-related transformations suggests that the [Au22 H4 (dppo)6 ]2+ nanohydride is a versatile model catalyst for understanding the mechanisms of chemical reactions involving hydrogen on the surface of gold nanoparticles.

Nitrogen-containing flavonoid and their analogs with diverse B-ring in acetylcholinesterase and butyrylcholinesterase inhibition.

In this study, a series of new flavones (2-phenyl-chromone), 2-naphthyl chromone, 2-anthryl-chromone, or 2-biphenyl-chromone derivatives containing 6 or 7-substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2-naphthyl chromone, 2-anthryl-chromone derivatives against AChE significantly decreased, while that of 2-biphenyl chromone derivatives with 7-substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC50 = 1.29 ± 0.10 µmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed-type inhibitory effect against AChE.

Halogen effects on the electronic and optical properties of Au13 nanoclusters.

We report an experimental and theoretical investigation of the electronic and optical properties of a series of icosahedral Au13 nanoclusters, protected using different halogen ligands (Cl, Br, and I), as well as 1,2-bis(diphenylphosphino)ethane (dppe) ligands. All three clusters are comprised of the same Au13 kernel with two halogens coordinated to the poles of the icosahedral cluster along with five dppe ligands. UV-vis absorption spectra indicate a systematic red shift from Cl to Br to I, as well as a sudden enhancement of the second excitonic peak for the I-coordinated cluster. Density functional theory (DFT) calculations suggest that all clusters possess a wide HOMO-LUMO energy gap of ∼1.79 eV and are used to assign the first two excitonic bands. Frontier orbital analyses reveal several HOMO → LUMO transitions involving halogen-to-metal charge transfers. For the I-coordinated cluster, more complicated I-to-metal charge transfers give rise to different excitation features observed experimentally. The current findings show that halogen ligands play important roles in the electronic structures of gold clusters and can be utilized to tune the optical properties of the clusters.

Recyclable and superior selective CO2 adsorption of C4B32 and Ca@C4B32: a new category of perfect cubic heteroborospherenes.

The capture and separation of CO2 have attracted significant interest as a strategy to control the global emission of greenhouse gases. From the perspective of environmental protection, it is crucial to explore high-performance adsorbents that can efficiently capture CO2. Herein, we report a density functional theory study on the viability of the heteroborospherene C4B32 for the first time. C2v C4B32 was revealed to be a perfect cubic heteroborospherene with the HOMO-LUMO gap of 3.47 eV at the PBE0 level. Then, we evaluated the potential application of C4B32 in the capture and separation of CO2. Our results indicate that the cubic-like C4B32 can efficiently capture CO2 with a -1.34 eV adsorption energy via chemisorption at the most acidic and basic sites of the cage. The strong interaction between CO2 and C4B32 could be supported by an effective charge transfer and orbital overlap. C4B32 also displayed high selectivity for the separation of CO2 from NH3, N2, CH4, CO, and H2 mixtures. Furthermore, it was feasible to tune the CO2-capture ability of C4B32 by metal-doping, which regulated the Lewis acidity/basicity of the C4B32 surface. In particular, Ca-doping could significantly enhance the CO2-capture ability of C4B32. Our results show that as a highly symmetrical and stable heteroborospherene, C4B32 can be used as a building block for the design and synthesis of novel nanomaterials for the capture and separation of CO2.

Toward Solution Syntheses of the Tetrahedral Au20 Pyramid and Atomically Precise Gold Nanoclusters with Uncoordinated Sites.

A long-standing objective of cluster science is to discover highly stable clusters and to use them as models for catalysts and building blocks for cluster-assembled materials. The discovery of catalytic properties of gold nanoparticles (AuNPs) has stimulated wide interests in gaseous size-selected gold clusters. Ligand-protected AuNPs have also been extensively investigated to probe their size-dependent catalytic and optical properties. However, the need to remove ligands can introduce uncertainties in both the structures and sizes of ligand-protected AuNPs for catalytic applications. Ideal model catalysts should be atomically precise AuNPs with well-defined structures and uncoordinated surface sites as in situ active centers. The tetrahedral ( Td) Au20 pyramidal cluster, discovered to be highly stable in the gas phase, provided a unique opportunity for such an ideal model system. The Td-Au20 consists of four Au(111) faces with all its atoms on the surface. Bulk synthesis of Td-Au20 with appropriate ligands would allow its catalytic and optical properties to be investigated and harnessed. The different types of its surface atoms would allow site-specific chemistry to be exploited. It was hypothesized that if the four corner atoms of Td-Au20 were coordinated by ligands the cluster would still contain 16 uncoordinated surface sites as potential in situ catalytically active centers. Phosphine ligands were deemed to be suitable for the synthesis of Td-Au20 to maintain the integrity of its pyramidal structure. Triphenyl-phosphine-protected Td-Au20 was first observed in solution, and its stability was confirmed both experimentally and theoretically. To enhance the synthetic yield, bidentate diphosphine ligands [(Ph)2P(CH2) nP(Ph)2 or L n] with different chain lengths were explored. It was hypothesized that diphosphine ligands with the right chain length might preferentially coordinate to the Td-Au20. Promising evidence was initially obtained by the formation of the undecagold by the L3 ligand. When the L8 diphosphine ligand was used, a remarkable Au22 nanocluster with eight uncoordinated Au sites, Au22(L8)6, was synthesized. With a tetraphosphine-ligand (PP3), a new Au20 nanocluster, [Au20(PP3)4]Cl4, was isolated with high yield. The crystal structure of the new Au20 core did not reveal the expected pyramid but rather an intrinsically chiral gold core. The surface of the new chiral-Au20 was fully coordinated, and it was found to be highly stable chemically. The Au22(L8)6 nanocluster represents the first and only gold core with uncoordinated gold atoms, providing potentially eight in situ catalytically active sites. The Au22 nanoclusters dispersed on oxide supports were found to catalyze CO oxidation and activate H2 without ligand removal. With further understanding about the formation mechanisms of gold nanoclusters in solution, it is conceivable that Td-Au20 can be eventually synthesized, allowing its novel catalytic and optical properties to be explored. More excitingly, it is possible that a whole family of new atomically precise gold nanoclusters can be created with different phosphine ligands.

Probing the interaction between the encapsulated water molecule and the fullerene cages in H2O@C60- and H2O@C59N.

We report a high-resolution photoelectron imaging study of cryogenically-cooled H2O@C60- and H2O@C59N- endohedral fullerene anions. The electron affinity (EA) of H2O@C60 is measured to be 2.6923 ± 0.0008 eV, which is 0.0088 eV higher than the EA of C60, while the EA of H2O@C59N is measured to be 3.0058 eV ± 0.0007 eV, which is 0.0092 eV lower than the EA of C59N. The opposite shifts are found to be due to the different electrostatic interactions between the encapsulated water molecule and the fullerene cages in the two systems. There is a net coulombic attraction between the guest and host in H2O@C60-, but a repulsive interaction in H2O@C59N-. We have also observed low-frequency features in the photoelectron spectra tentatively attributed to the hindered rotational excitations of the encapsulated H2O molecule, providing further insights into the guest-host interactions in H2O@C60- and H2O@C59N-.

Elucidation of the Formation Mechanisms of the Octahydrotriborate Anion (B3H8-) through the Nucleophilicity of the B-H Bond.

Boron compounds are well-known electrophiles. Much less known are their nucleophilic properties. By recognition of the nucleophilicity of the B-H bond, the formation mechanism of octahydrotriborate (B3H8-) was elucidated on the bases of both experimental and computational investigations. Two possible routes from the reaction of BH4- and THF·BH3 to B3H8- were proposed, both involving the B2H6 and BH4- intermediates. The two pathways consist of a set of complicated intermediates, which can convert to each other reversibly at room temperature and can be represented by a reaction circle. Only under reflux can the B2H6 and BH4- intermediates be converted to B2H5- and BH3(H2) via a high energy barrier, from which H2 elimination occurs to yield the B3H8- final product. The formation of B2H6 from THF·BH3 by nucleophilic substitution of the B-H bond was captured and identified, and the reaction of B2H6 with BH4- to produce B3H8- was confirmed experimentally. On the bases of the formation mechanisms of B3H8-, we have developed a facile synthetic method for MB3H8 (M = Li and Na) in high yields by directly reacting the corresponding MBH4 salts with THF·BH3. In the new synthetic method for MB3H8, no electron carriers are needed, allowing convenient preparation of MB3H8 in large scales and paving the way for their wide applications.

[(Cp2M)2B9H11] (M = Zr or Hf): early transition metal 'guarded' heptaborane with strong covalent and electrostatic bonding.

Among the series of stable closo-borate dianions, [B n H n ]2-, the X-ray crystallographic structure of [B7H7]2- was determined only in 2011. To explore its chemistry and stability, we have isolated and structurally characterized two new transition metal complexes of the heptaborane, [(Cp2M)2B9H11] (Cp = η5-C5H5; M = Zr or Hf). The structures of [(Cp2M)2B9H11] contain a pentagonal bipyramidal B7 core, coordinated by two {Cp2M} and two {BH2} units equatorially. Structural and spectroscopic characterizations and DFT calculations show that [(Cp2M)2B9H11] complexes are substantially more stable than the parent dianion, in either [B7H7]2- or ( n Bu4N)2[B7H7]. Our theoretical study and chemical bonding analyses reveal that the surprising stability of the two new heptaborane metal complexes is due to multi-center covalent bonds related to the two exo-{Cp2M} units, as well as electrostatic interactions between the {Cp2M} units and the B7 core. The facile syntheses of the heptaborane metal-complexes will allow further exploration of their chemistry.

High-Resolution Photoelectron Imaging of Cryogenically-Cooled C59N- and (C59N)22- Azafullerene Anions.

We report a photoelectron imaging study of cryogenically cooled C59N- and (C59N)22- anions produced from electrospray ionization. High-resolution photoelectron spectra are obtained for C59N- for the first time, allowing seven vibrational frequencies of the C59N azafullerene to be measured. The electron affinity of C59N is determined accurately to be 3.0150 ± 0.0007 eV. The observed vibrational features are understood on the basis of calculated frequencies and compared with those of C60 and C59HN. The photoelectron image of (C59N)22-, which has the same mass/charge ratio as C59N-, is also observed, allowing the second electron affinity of the (C59N)2 azafullerene dimer to be measured as 1.20 ± 0.05 eV. The intramolecular Coulomb repulsion of the (C59N)22- dianion is estimated to be 1.96 eV and is investigated theoretically using the electron density difference between (C59N)22- and (C59N)2.

Diphosphine-Protected Au22 Nanoclusters on Oxide Supports Are Active for Gas-Phase Catalysis without Ligand Removal.

Investigation of atomically precise Au nanoclusters provides a route to understand the roles of coordination, size, and ligand effects on Au catalysis. Herein, we explored the catalytic behavior of a newly synthesized Au22(L8)6 nanocluster (L = 1,8-bis(diphenylphosphino) octane) with in situ uncoordinated Au sites supported on TiO2, CeO2, and Al2O3. Stability of the supported Au22 nanoclusters was probed structurally by in situ extended X-ray absorption fine structure (EXAFS) and high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), and their ability to adsorb and oxidize CO was investigated by IR absorption spectroscopy and a temperature-programmed flow reaction. Low-temperature CO oxidation activity was observed for the supported pristine Au22(L8)6 nanoclusters without ligand removal. Density functional theory (DFT) calculations confirmed that the eight uncoordinated Au sites in the intact Au22(L8)6 nanoclusters can chemisorb both CO and O2. Use of isotopically labeled O2 demonstrated that the reaction pathway occurs mainly through a redox mechanism, consistent with the observed support-dependent activity trend of CeO2 > TiO2 > Al2O3. We conclude that the uncoordinated Au sites in the intact Au22(L8)6 nanoclusters are capable of adsorbing CO, activating O2, and catalyzing CO oxidation reaction. This work is the first clear demonstration of a ligand-protected intact Au nanocluster that is active for gas-phase catalysis without the need of ligand removal.

Chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation of 3-trifluoromethylthioquinolines.

A chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation of 3-trifluoromethylthioquinolines has been successfully developed, providing direct and facile access to chiral 2,3-disubstituted 1,2,3,4-tetrahydroquinoline derivatives containing a stereogenic trifluoromethylthio group with up to 99% enantioselectivity.

Catalyst design based on agostic interactions: synthesis, characterization, and catalytic activity of bis(pyrazolyl)borate copper complexes.

Agostic interactions are often used to activate inert C-H bonds, and thus facilitate new reactions. We report the first example of designed catalysts based on the agostic interaction. Novel copper(i) complexes [BBN(pz(x))2]Cu(PPh3)n (BBN = 9-borabicyclo[3.3.1]nonane; pz(x) = 3-substituted pyrazole; x = H, n = 2; x = Me, n = 1) and {[BBN(pz(iPr))2]Cu}2 have been synthesized and characterized. Single crystal studies of the three compounds show weak intramolecular C-HCu interactions which can be assigned as agostic or anagostic interactions. Catalytic studies of these complexes toward carbenoid insertion into N-H bonds indicate these weak interactions act as a "switch" which will be turned "on" if interacting with the substrate and "off" if eliminating the product and regenerating the weak interaction. The process of the "switch" turning "on" or "off", which is related to the catalytic effect, is found to be influenced by both steric effects and the solvent: a less sterically hindered catalyst in non-coordinating benzene results in high yield, while a more sterically hindered catalyst in coordinating THF results in relatively low yield.

Polymorphism of Phosphine-Protected Gold Nanoclusters: Synthesis and Characterization of a New 22-Gold-Atom Cluster.

A new Au22 nanocluster, protected by bis(2-diphenyl-phosphino)ethyl ether (dppee or C28 H28 OP2 ) ligand, has been synthsized and purified with high yield. Electrospray mass spectrometry shows that the new cluster has a formula of Au22 (dppee)7 , containing 22 gold atoms and seven dppee ligands. The cluster is found to be stable as a solid, but metastable in solution. The new cluster has been characterized by UV-Vis-NIR absorption spectroscopy, collision-induced dissociation, and (31) P-NMR. The properties of the new cluster have been compared with the previous Au22 (dppo)6 nanocluster (dppo = 1,8-bis(diphenyl-phosphino)octane or C32 H36 P2 ), which contains two fused Au11 units. All the experimental data indicate that the new Au22 (dppee)7 cluster is different from the previously known Au22 (dppo)6 cluster and represents a new Au22 core, which contains most likely one Au11 motif with several Au2 (dppee) or Au(dppee) units. The Au22 (dppee)7 cluster provides a new example of the ligand effects on the nuclearity and structural polymorphism of phosphine-protected atom-precise gold nanoclusters.

Synthesis and structure determination of a new Au(20) nanocluster protected by tripodal tetraphosphine ligands.

We report the synthesis and structure determination of a new Au20 nanocluster coordinated by four tripodal tetraphosphine (PP3) ligands {PP3 = tris[2-(diphenylphosphino)ethyl]phosphine}. Single-crystal X-ray crystallography and electrospray ionization mass spectrometry show that the cluster assembly can be formulated as [Au20(PP3)4]Cl4. The Au20 cluster consists of an icosahedral Au13 core and a seven-Au-atom partial outer shell arranged in a local C3 symmetry. One PP3 ligand coordinates to four Au atoms in the outer shell, while the other three PP3 ligands coordinate to one Au atom from the outer shell and three Au atoms from the surface of the Au13 core, giving rise to an overall chiral 16-electron Au cluster core with C3 symmetry.

Controlling gold nanoclusters by diphospine ligands.

We report the synthesis and structure determination of a new Au22 nanocluster coordinated by six bidentate diphosphine ligands: 1,8-bis(diphenylphosphino) octane (L(8) for short). Single crystal X-ray crystallography and electrospray ionization mass spectrometry show that the cluster assembly is neutral and can be formulated as Au22(L(8))6. The Au22 core consists of two Au11 units clipped together by four L(8) ligands, while the additional two ligands coordinate to each Au11 unit in a bidentate fashion. Eight gold atoms at the interface of the two Au11 units are not coordinated by any ligands. Four short gold-gold distances (2.64-2.65 Å) are observed at the interface of the two Au11 clusters as a result of the clamping force of the four clipping ligands and strong electronic interactions. The eight uncoordinated surface gold atoms in the Au22(L(8))6 nanocluster are unprecedented in atom-precise gold nanoparticles and can be considered as potential in situ active sites for catalysis.