Unraveling a Concerted Proton-Coupled Electron Transfer Pathway in Atomically Precise Gold Nanoclusters.

Metal nanoclusters (MNCs) represent a promising class of materials for catalytic carbon dioxide and proton reduction as well as dihydrogen oxidation. In such reactions, multiple proton-coupled electron transfer (PCET) processes are typically involved, and the current understanding of PCET mechanisms in MNCs has primarily focused on the sequential transfer mode. However, a concerted transfer pathway, i.e., concerted electron-proton transfer (CEPT), despite its potential for a higher catalytic rate and lower reaction barrier, still lacks comprehensive elucidation. Herein, we introduce an experimental paradigm to test the feasibility of the CEPT process in MNCs, by employing Au18(SR)14 (SR denotes thiolate ligand), Au22(SR)18, and Au25(SR)18- as model clusters. Detailed investigations indicate that the photoinduced PCET reactions in the designed system proceed via an CEPT pathway. Furthermore, the rate constants of gold nanoclusters (AuNCs) have been found to be correlated with both the size of the cluster and the flexibility of the Au-S framework. This newly identified PCET behavior in AuNCs is prominently different from that observed in semiconductor quantum dots and plasmonic metal nanoparticles. Our findings are of crucial importance for unveiling the catalytic mechanisms of quantum-confined metal nanomaterials and for the future rational design of more efficient catalysts.

Cyclometalated gold(III)-hydride under oriented external electric fields: a new strategy to modulate its reactivity?

Selected gold complexes have been regarded as promising anti-cancer agents because they can bind with protein targets containing thiol or selenol moieties, but their clinical applications were hindered by the unbiased binding towards off-target thiol-proteins. Recently, a novel gold(III)-hydride complex (abbreviated as 1) with visible light-induced thiol reactivity has been reported as potent photo-activated anticancer agents (Angew. Chem. Int. Ed., 2020, 132, 11139). To explore new strategies to stimuli this potential antitumor drug, the effect of oriented external electric fields (OEEFs) on its geometric structure, electronic properties, and chemical reactivity was systematically investigated. Results reveal that imposing external electric fields along the Au-H bond of 1 can effectively activate this bond, which is conducive to its dissociation and the binding of Au site to potential targets. Hence, this study provides a new OEEF-strategy to activate this reported gold(III)-hydride, revealing its potential application in electrochemical therapy. We anticipate this work could promote the development of more electric field-activated anticancer agents. However, further experimental research should be conducted to verify the conclusions obtained in this work.

Theoretical prediction of superatom WSi12-based catalysts for CO oxidation by N2O.

Catalytic conversion of N2O and CO into nonharmful gases is of great significance to reduce their adverse impact on the environment. The potential of the WSi12 superatom to serve as a new cluster catalyst for CO oxidation by N2O is examined for the first time. It is found that WSi12 prefers to adsorb the N2O molecule rather than the CO molecule, and the charge transfer from WSi12 to N2O results in the full activation of N2O into a physically absorbed N2 molecule and an activated oxygen atom that is attached to an edge of the hexagonal prism structure of WSi12. After the release of N2, the remaining oxygen atom can oxidize one CO molecule via overcoming a rate-limiting barrier of 28.19 kcal mol-1. By replacing the central W atom with Cr and Mo, the resulting MSi12 (M = Cr and Mo) superatoms exhibit catalytic performance for CO oxidation comparable to the parent WSi12. In particular, the catalytic ability of WSi12 for CO oxidation is well maintained when it is extended into tube-like WnSi6(n+1) (n = 2, 4, and 6) clusters with energy barriers of 25.63-29.50 kcal mol-1. Moreover, all these studied MSi12 (M = Cr, Mo, and W) and WnSi6(n+1) (n = 2, 4, and 6) species have high structural stability and can absorb sunlight to drive the catalytic process. This study not only opens a new door for the atomically precise design of new silicon-based nanoscale catalysts for various chemical reactions but also provides useful atomic-scale insights into the size effect of such catalysts in heterogeneous catalysis.

Computational screening of metalloporphyrin-based drug carriers for antitumor drug 5-fluorouracil.

Developing novel nanoscale carriers for drug delivery is of great significance for improving treatment efficiency and reducing side effects of antitumor drugs. In view of the good biocompatibility and special affinity of porphyrin (PP) molecule to cancer cells, it was used to construct a series of metal-doped M@PP (M = Ca âˆ¼ Zn) materials for the delivery of anticancer drug 5-fluorouracil (5-Fu) in this work. Our results reveal that 5-Fu is tightly adsorbed on M@PP (M = Ca âˆ¼ V, Mn âˆ¼ Co, and Zn) by chemisorption, but is physically adsorbed by M@PP (M = Cr, Ni, and Cu). The calculated electronic properties show that all these 5-Fu@[M@PP] (M = Ca âˆ¼ Zn) complexes have both high stability and solubility. Among these 5-Fu@[M@PP] complexes, the chemical bond formed between 5-Fu and Ti@PP has the strongest covalent characteristic, resulting in the largest adsorption energy of -19.93 kcal/mol for 5-Fu@[Ti@PP]. In particular, 5-Fu@[Ti@PP] has the proper recovery time under the near-infrared light at body temperature, which further suggests that Ti@PP is the best drug carrier for 5-Fu. This study not only reveals the interaction strength and nature between 5-Fu and M@PP, but also confirmed the intriguing potential of Ti@PP as nano-carrier for drug delivery. However, further experimental research should be conducted to verify the conclusion obtained in this work.

On the Catalytic Performance of (ZrO)n (n=1-4) Clusters for CO Oxidation: A DFT Study.

The unique characteristic of superatoms to show chemical properties like those of individual atoms opens a new avenue towards replacing noble metals as catalysts. Given the similar electronic structures of the ZrO superatom and the Pd atom, the CO oxidation mechanisms catalysed by (ZrO)n (n=1-4) clusters were investigated in detail to evaluate their catalytic performance. Our results reveal that a single ZrO superatom exhibits superior catalytic ability in CO oxidation than both larger (ZrO)n (n=2-4) clusters and a Pd atom, indicating the promising potential of ZrO as a "single-superatom catalyst". Moreover, the mechanism of CO oxidation catalysed by ZrO+/- suggests that depositing a ZrO superatom onto the electron-rich substrates is a better choice for practical catalysis application. Accordingly, a graphene nanosheet (coronene) was chosen as a representative substrate for ZrO and Pd to assess their catalytic performances in CO oxidation. Acting as an "electron sponge", this carbon substrate can both donate and accept charges in different reaction steps, enabling the supported ZrO to achieve enhanced catalytic performance in this process with a low energy barrier of 19.63 kcal/mol. This paper presents a new realization on the catalytic performance of Pd-like superatom in CO oxidation, which could increase the interests in exploring noble metal-like superatoms as efficient catalysts for various reactions.

On the possibility of using the Ti@Si16 superatom as a novel drug delivery carrier for different drugs: A DFT study.

The potential application of an experimentally synthesized superatom Ti@Si16 as a novel drug carrier for cisplatin (DDP), isoniazid (INH), acetylsalicylic acid (ASA), 5-fluorouracil (5-Fu), and favipiravir (FPV) has been explored by density functional theory. It is observed that the Pt atom of DDP can be effectively absorbed on Ti@Si16 via a "donation-back donation" electron transfer mechanism, resulting in a moderate adsorption energy of -19.95 kcal/mol for DDP@[Ti@Si16]. As for INH, it prefers to combine with Ti@Si16 via the N atom of pyridine ring by forming a strongly polar N-Si bond. Differently, the interaction between Ti@Si16 and the ASA, 5-Fu, and FPV drugs is dominated by the Van der Waals interaction. Our results reveal that DDP@[Ti@Si16] possesses a moderate recovery time under body temperature, which benefits the desorption of DDP from Ti@Si16. More importantly, the release of DDP drug from the Ti@Si16 surface can be effectively controlled by exerting small orientation external electric fields on the DDP@[Ti@Si16] complex. Therefore, this study demonstrates that Ti@Si16 can serve as a promising drug carrier for DDP, and thus will further expand its practical applications in the biomedical field.

Polymeric tungsten carbide nanoclusters as potential non-noble metal catalysts for CO oxidation.

The discovery of tungsten carbide (WC) as an analog of the noble metal Pt atom is of great significance toward designing novel highly-active catalysts from the viewpoint of the superatom concept. The potential of such a superatom to serve as building blocks of replacement catalysts for Pt has been evaluated in this work. The electronic properties, adsorption behaviors, and catalytic mechanisms towards the CO oxidation of (WC)n and Ptn (n = 1, 2, 4, and 6) were compared. Counterintuitively, these studied (WC)n clusters exhibit quite different electronic properties and adsorption behaviours from the corresponding Ptn species. For instance, (WC)n preferentially adsorbs O2, whereas Ptn tends to first combine with CO. Even so, it is interesting to find that the catalytic performances of (WC)n are always superior to the corresponding Ptn, and especially, the largest (WC)6 cluster exhibits the best catalytic ability towards CO oxidation. Therefore, assembling superatomic WC clusters into larger polymeric clusters can be regarded as a novel strategy to develop efficient superatom-assembled catalysts for CO oxidation. It is highly expected to see the realization of non-noble metal catalysts for various reactions in the near future experiments by using superatoms as building blocks.

The Evaluation Indexes Suitable for Nonhuman Primates can be Extracted from Clinical Consciousness Disorder Assessment Scales: A Hypothesis.

BACKGROUND: Currently, case studies or clinical trials in different patient populations remain the main resource underlying the understanding of disorder of consciousness (DoC). This provides a low efficacy for the derivation of data and the implementation of associated controlled experimental designs. Preclinical models provide precise controls, reduced variability, rich data output and limited ethical complexity. Nonhuman primates are suitable model animals for disorders of consciousness due to their brain structure being very similar to that of humans. Behavioral tests remain the primary standard for assessing the consciousness status of humans. However, there is currently no behavioral assessment scale available for evaluation of the state of consciousness disorder in nonhuman primates. This presents a significant challenge for the establishment of different models of consciousness disorder. Therefore, there is considerable motivation to focus on the development of a proper tool for assessment of the state of consciousness associated with nonhuman primate models that are based on clinically common consciousness assessment scales. METHODS: It is assumed that the Delphi and level analysis methods based on clinical consciousness disorder assessment scales may provide an effective way to select and include assessment indexes for levels of consciousness in nonhuman primates. RESULTS: 8 first-level indicators with 41 second-level indexes were selected preliminary as a pool of evaluation entries of state of consciousness of nonhuman primates. CONCLUSIONS: It may be practicable to extract appropriate indicators for non-human primates from the clinical consciousness disorder assessment scales. Besides, a combination of Delphi method, behavioral analysis, electroencephalography, neuroimaging (such as positron emission tomography-computed tomography) and functional magnetic resonance imaging is necessary to test the reliability and validity of the novel scale reported here.

Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats.

BACKGROUND: The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown. METHODS: Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior. RESULTS: The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats. CONCLUSIONS: These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.

Designing Special Nonmetallic Superalkalis Based on a Cage-like Adamanzane Complexant.

In this study, to examine the possibility of using cage-like complexants to design nonmetallic superalkalis, a series of X@36adz (X = H, B, C, N, O, F, and Si) complexes have been constructed and investigated by embedding nonmetallic atoms into the 36adamanzane (36adz) complexant. Although X atoms possess very high ionization energies, these resulting X@36adz complexes possess low adiabatic ionization energies (AIEs) of 0.78-5.28 eV. In particular, the adiabatic ionization energies (AIEs) of X@36adz (X = H, B, C, N, and Si) are even lower than the ionization energy (3.89 eV) of Cs atoms, and thus, can be classified as novel nonmetallic superalkalis. Moreover, due to the existence of diffuse excess electrons in B@36adz, this complex not only possesses pretty low AIE of 2.16 eV but also exhibits a remarkably large first hyperpolarizability (ß 0) of 1.35 × 106 au, indicating that it can also be considered as a new kind of nonlinear optical molecule. As a result, this study provides an effective approach to achieve new metal-free species with an excellent reducing capability by utilizing the cage-like organic complexants as building blocks.

A randomized controlled trial to explore the efficacy and safety of transcranial direct current stimulation on patients with post-stroke fatigue.

BACKGROUND: Post-stroke fatigue seriously affects the quality of life for stroke patients. There is no effective treatment at present. transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation which may have therapeutic effect on post-stroke fatigue. This study will explore about this. METHOD: A total of 60 patients with post-stroke fatigue were randomly divided into the control group and the treatment group with 30 patients each by minimization randomization. Both groups received basic treatment and conventional rehabilitation. In the treatment group, patients were treated with active tDCS, while in the control group, sham tDCS. Both active and sham tDCS were administered 6 times a week for 4 weeks. Before and after the trial, the Fatigue Severity Scale (FSS), Fugl-Meyer Assessment (FMA) and Modified Barthel Index (MBI) were evaluated and analyzed. And comparisons were made among groups. And there were an 8-week follow-up after the intervention. RESULT: Before the intervention, there were no significant differences in baseline data and assessment scores between the groups (P > 0.05). After 4 weeks of intervention, FSS scores in the treatment group were significantly lower than those in the control group (P = 0.012), and FMA and BMI scores were significantly higher than those in the control group (P < 0.05). There was no significant change in FSS scores after 8 months of follow-up (P > 0.05). DISCUSSION: TDCS is a safe treatment that can effectively reduce the degree of fatigue after stroke, improve the motor function and daily activity ability of patients after stroke, and the efficacy is better than only routine rehabilitation training. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2000031120. Registered on March 22, 2020.

Designing an alkali-metal-like superatom Ca3B for ambient nitrogen reduction to ammonia.

Converting earth-abundant nitrogen (N2) gas into ammonia (NH3) under mild conditions is one of the most important issues and a long-standing challenge in chemistry. Herein, a new superatom Ca3B was theoretically designed and characterized to reveal its catalytic performance in converting N2 into NH3 by means of density functional theory (DFT) computations. The alkali-metal-like identity of this cluster is verified by its lower vertical ionization energy (VIE, 4.29 eV) than that of potassium (4.34 eV), while its high stability was guaranteed by the large HOMO-LUMO gap and binding energy per atom (Eb). More importantly, this well-designed superatom possesses unique geometric and electronic features, which can fully activate N2via a "double-electron transfer" mechanism, and then convert the activated N2 into NH3 through a distal reaction pathway with a small energy barrier of 0.71 eV. It is optimistically hoped that this work could intrigue more endeavors to design specific superatoms as excellent catalysts for the chemical adsorption and reduction of N2 to NH3.

Reduction in post-spinal cord injury spasticity by combination of peripheral nerve grafting and acidic fibroblast growth factor infusion in monkeys.

OBJECTIVE: Spasticity is a frequent complication after spinal cord injury (SCI), but the existing therapies provide only limited relief and are associated with adverse reactions. Therefore, we aimed to develop a novel strategy to ameliorate the spasticity induced by SCI. METHODS: This nonrandomized controlled study used a repeated measurement design. The study involved four monkeys, two of which served as controls and only underwent spinal cord hemisection surgery at the T8 spine level. The other two monkeys underwent transplantation of sural nerve segments into the injured sites and long-term infusion of acidic fibroblast growth factor (aFGF). All monkeys received postoperative exercise training and therapy. RESULTS: The combined therapy substantially reduced the spasticity in leg muscle tone, patella tendon reflex, and fanning of toes. Although all monkeys showed spontaneous recovery of function over time, the recovery in the controls reached a plateau and started to decline after 11 weeks. CONCLUSIONS: The combination of peripheral nerve grafting and aFGF infusion may serve as a complementary approach to reduce the signs of spasticity in patients with SCI.

IL-33 as a Novel Serum Prognostic Marker of Intracerebral Hemorrhage.

OBJECTIVE: Interleukin 33 (IL-33) is a key cytokine involved in inflammation and oxidative stress. The significance of serum IL-33 levels on the prognosis of patients with intracerebral hemorrhage (ICH) has not been well studied. The purpose of this study is to determine whether there is a relationship between the serum IL-33 level and the prognosis of patients with ICH upon admission. METHODS: A total of 402 patients with confirmed ICH were included in this study. Their demographic data, medical history, laboratory data, imaging data, and clinical scores on admission were collected. At the same time, enzyme-linked immunoassay (ELISA) was used to detect the serum IL-33 levels of patients. The prognosis of patients was evaluated by mRS scale after 3 months, and mRS > 2 was defined as poor prognosis. RESULTS: Among 402 patients with ICH, the number of patients with good prognosis and poor prognosis after 3 months was 148 and 254, respectively. Compared with the ICH group with poor prognosis, the ICH group with good prognosis had lower baseline NHISS scores (p = 0.039) and hematoma volume (p = 0.025) and higher GCS scores (p < 0.001) and serum IL-33 levels (p < 0.001). The results of linear correlation analysis showed that serum IL-33 levels were significantly negatively correlated with baseline NHISS scores (r = -0.224, p = 0.033) and hematoma volume (r = -0.253, p = 0.046) but were significantly positively correlated with baseline GCS scores (r = 0.296, p = 0.020). The receiver operating characteristic curve (ROC) analysis showed that the sensitivity and specificity of serum IL-33 level in evaluating the prognosis of ICH were 72.1% and 74.3%, respectively. A cut-off value of serum IL-33 level < 109.3 pg/mL may indicate a poor prognosis for ICH. CONCLUSIONS: Serum IL-33 level on admission may be a prognostic indicator of ICH, and its underlying mechanism needs further study.

DFT study on the adsorption of 5-fluorouracil on B40, B39M, and M@B40 (M = Mg, Al, Si, Mn, Cu, Zn).

Based on density functional theory, the adsorption behavior of 5-fluorouracil (5-Fu) on B40 and its derivatives has been explored. It was observed that 5-Fu prefers to combine with the corner boron atom of the B40 cage via one of its oxygen atoms, forming a strong polar covalent B-O bond. The adsorption energy of 5-Fu on B40 was calculated to be -11.15 kcal mol-1, and thus, it can be duly released from B40 by protonation in the slightly acidic environment of tumor tissue, which makes for reducing the toxic and side effects of this drug. Additionally, the substituent and embedding effect of Mg, Al, Si, Mn, Cu, and Zn atoms on the drug delivery performance of B40 have been also considered. We hope this work could offer some implications for the potential application of boron-based nanomaterials, such as B40 in drug delivery.

On the Role of Alkali-Metal-Like Superatom Al12 P in Reduction and Conversion of Carbon Dioxide.

Developing efficient catalysts for the conversion of CO2 into fuels and value-added chemicals is of great significance to relieve the growing energy crisis and global warming. With the assistance of DFT calculations, it was found that, different from Al12 X (X=Be, Al, and C), the alkali-metal-like superatom Al12 P prefers to combine with CO2 via a bidentate double oxygen coordination, yielding a stable Al12 P(η2 -O2 C) complex containing an activated radical anion of CO2 (i.e., CO2 .- ). Thereby, this compound could not only participate in the subsequent cycloaddition reaction with propylene oxide but also initiate the radical reaction with hydrogen gas to form high-value chemicals, revealing that Al12 P can play an important role in catalyzing these conversion reactions. Considering that Al12 P has been produced in laboratory and is capable of absorbing visible light to drive the activation and transformation of CO2 , it is anticipated that this work could guide the discovery of additional superatom catalysts for CO2 transformation and open up a new research field of superatom catalysis.

Unveiling the potential of superalkali cation Li3+ for capturing nitrogen.

The potential of the superalkali cation Li3+ for capturing N2 and its behavior in gaseous nitrogen have been theoretically studied at the MP2/6-311+G(d) level. The evolution of structures and stability of the Li3+(N2)n (n = 1-7) complexes shows that the N2 molecules tend to bind to different vertices of the Li3+ core, and that Li3+ might have the capacity to capture up to twelve nitrogen molecules in the first coordination shell. Based on natural population and molecular orbital analyses, Li3+ keeps its superatom identity in the lowest-lying Li3+(N2)n (n = 1-4) complexes. The change in the Gibbs free energies of possible fragmentation channels also indicates the thermodynamic stability of Li3+ in the (N2)n clusters when n ≤ 4. Different from the case of Li3+(H2O)n, where the electrostatic interaction is dominant, the electrostatic and polarization components are found to make nearly equal contributions to Li3+(N2)n complex formation. In addition, it can be concluded that the superalkali cation Li3+ surpasses heavy alkali metal cations in capturing N2 molecules, since it has a larger binding energy with N2 than Na+ and K+ ions.

On the Interaction between Superatom Al12Be and DNA Nucleobases/Base Pairs: Bonding Nature and Potential Applications in O2 Activation and CO Oxidation.

The interaction between quasi-chalcogen superatom Al12Be and DNA nucleobases/base pairs has been explored by searching for the most stable Al12Be-X (X = DNA bases and base pairs) complexes. Our results reveal that Al12Be prefers to combine with guanine by two Al-O and Al-N bonds rather than the other DNA bases, no matter in free state or base pair. The formed Al-N and Al-O bonds between Al12Be and DNA bases proved to be strong polar covalent bonds by the Wiberg bond index, nature bond orbitals, atoms in molecules theory, localized molecular orbitals, and electron localization functions analyses. More importantly, it is found that the formed global minimum of Al12Be-G has the ability to activate an oxygen molecule into a peroxide dianion 1O2 2-, which can further catalyze the CO oxidation via the Eley-Rideal mechanism with a small energy barrier of 7.78 kcal/mol. We hope that this study could not only provide an in-depth understanding on the intermolecular interaction between metallic superatoms and DNA at the molecular level but also attract more interest in designing and synthesizing superatom-based heterogeneous catalysts with DNA/nucleobases as basic building blocks.