Assessing The Feasibility of Selective Piezoelectric Osteotomy in Transorbital Approach to The Middle Cranial Fossa: Anatomical and Quantitative Study and Surgical Implications.

OBJECTIVES: To verify the feasibility and to discuss advantages and disadvantages of a piezoelectric orbitotomy (PO) during Superior Eyelid Endoscopic Transorbital Approach (SETOA). METHODS: Five adult specimens underwent exoscopic/endoscopic SETOA to middle cranial fossa. The surgical corridor was created via piezoelectric orbitotomy by performing three selective and safe micrometric bone cuts providing a one-piece trapezoid bone flap which was repositioned and secured at the end of procedure. A 3D scan of the bone flap allowed us to reconstruct a 3D model and calculate its volume. An illustrative case demonstrating the application of this novel technique was also presented. RESULTS: Anatomical-morphometric quantitative analysis showed a mean bony-volume gain of 1,574.26 mm3 by using PO. PO yielded concrete surgical advantages and theoretical benefits in terms of functional and esthetic outcomes. All osteotomies were micrometric clear-cut and precise, resulting in a very thin bony gap; a complete sparing of soft tissues and neurovascular structures in- and around the orbit was observed. Lateral orbital wall reconstruction by replacing the bone flap aims to mitigate the risk of enophthalmos, proptosis, CSF leakage, pseudomeningocele and pulsatile headache, which represent significant challenges in the relevant literature. CONCLUSION: PO may offer a viable, selective, effective, safe alternative to high-speed drilling during SETOA, especially for patients affected by intra-axial pathologies in which a watertight closure is mandatory. This procedure could prevent/decrease the risk of some of the main postoperative complications associated to the standard SETOA, resulting potentially in better functional and esthetic outcome.

Modulating Decarboxylative Oxidation Photocatalysis by Ligand Engineering of Atomically Precise Copper Nanoclusters.

Copper nanoclusters (Cu NCs) characterized by their well-defined electronic and optical properties are an ideal platform for organic photocatalysis and exploring atomic-level behaviors. However, their potential as greener, efficient catalysts for challenging reactions like decarboxylative oxygenation under mild conditions remains unexplored. Herein, we present Cu13(Nap)3(PPh3)7H10 (hereafter Cu13Nap), protected by 1-naphthalene thiolate (Nap), which performs well in decarboxylative oxidation (90% yield) under photochemical conditions. In comparison, the isostructural Cu13(DCBT)3(PPh3)7H10 (hereafter Cu13DCBT), stabilized by 2,4-dichlorobenzenethiolate (DCBT), yields only 28%, and other previously reported Cu NCs (Cu28, Cu29, Cu45, Cu57, and Cu61) yield in the range of 6-18%. The introduction of naphthalene thiolate to the surface of Cu13 NCs influences their electronic structure and charge transfer in the ligand shell, enhancing visible light absorption and catalytic performance. Density functional theory (DFT) and experimental evidence suggest that the reaction proceeds primarily through an energy transfer mechanism. The energy transfer pathway is uncommon in the context of previous reports for decarboxylative oxidation reactions. Our findings suggest that strategically manipulating ligands holds significant potential for creating composite active sites on atomically precise copper NCs, resulting in enhanced catalytic efficacy and selectivity across various challenging reactions.

Fluorescence guidance in skull base surgery: Applications and limitations - A systematic review.

Introduction: Intraoperative fluorescence guidance is a well-established surgical adjunct in high-grade glioma surgery. In contrast, the clinical use of such dyes and technology has been scarcely reported in skull base surgery. Research question: We aimed to systematically review the clinical applications of different fluorophores in both open and endonasal skull base surgery. Material and methods: We performed a systematic review and discussed the current literature on fluorescence guidance in skull base surgery. Results: After a comprehensive literature search, 77 articles on skull base fluorescence guidance were evaluated. A qualitative analysis of the articles is presented, discussing clinical indications and current controversies. The use of intrathecal fluorescein was the most frequently reported in the literature. Beyond that, 5-ALA and ICG were two other fluorescent dyes most extensively discussed, with some experimental fluorophore applications in skull base surgery. Discussion and conclusion: Intraoperative fluorescence imaging can serve as an adjunct technology in skull base surgery. The scope of initial indications of these fluorophores has expanded beyond malignant glioma resection alone. We discuss current use and controversies and present an extensive overview of additional indications for fluorescence imaging in skull base pathologies. Further quantitative studies will be needed in the future, focusing on tissue selectivity and time-dependency of the different fluorophores currently commercially available, as well as the development of new compounds to expand applications and facilitate skull base surgeries.

High-Throughput Computational Screening of Metal Sulfides for the Chemical Looping Elemental Decomposition of H2S.

Hydrogen sulfide is a significant byproduct of oil and gas production and is typically recovered as elemental sulfur, a low-value commodity. In recent years, there have been efforts to upgrade H2S through elemental decomposition to S and H2, an essential energy carrier in a sustainable economy. Among the promising approaches is thermocatalytic looping, which involves a sulfide-based redox pair. Unfortunately, the search for sulfides capable of facilitating this conversion is progressing slowly, and primarily focusing on monometallic sulfides. With a few notable exceptions, the field of bimetallic sulfide remains largely unexplored. In this study, a machine learning framework is employed to explore the material space of mono and bimetallic sulfides. The workflow begins by mining sulfides from the Materials Project database, allowing the workflow to be benchmarked using formation enthalpies derived from established density functional theory calculations. Through the machine learning framework, the number of bimetallic sulfide redox pairs considered is expanded from 102 cases in the Materials Project database to 105 cases. This expansion allows for the identification trends that can serve as guidelines for future research and helps prioritize materials for experimental testing.

Endonasal Route for Tuberculum and Planum Meningiomas.

Tuberculum and planum meningiomas are challenging tumors per their critical location and neurovascular relationships. The standard treatment is usually represented by complete tumor removal, being the transcranial approaches the well-established routes. During the last decades, novel surgical routes have been experimented with emphasis on the concept of minimal invasive approaches. The peculiar perspective from below the endoscopic endonasal approach provides a short and direct access avoiding brain and neurovascular structures manipulation, featuring excellent outcomes and a reduced morbidity. Ideal indications are small or medium size midline meningiomas, with wide tuberculum sellae angle and deep sella at the sphenoid sinus, possibly with no optic nerve and/or vessels encasement. Adequate removal of paranasal structures and extended bony opening over the dural attachment provide a wide surgical corridor ensuring safe intradural exposure at the suprasellar area. The main advantage is related to early decompression of the optic apparatus and reduced manipulation of subchiasmatic perforating vessels, with improved visual outcomes. Direct exposure of the inferomedial aspect of the optic canals allows for maximal decompression in cases of tumor extending within. Transcranial approaches tend to be selected for larger tumors with lateral extension beyond optic nerves and supraclinoid carotid arteries, in inaccessible areas from an endonasal corridor.

KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary Study.

Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial-mesenchymal transition (EMT)-an underlying NF-PitNET pathogenic mechanism-were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67+ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14.

Selectivity descriptors of the catalytic n-hexane cracking process over 10-membered ring zeolites.

Zeolite-mediated catalytic cracking of alkanes is pivotal in the petrochemical and refining industry, breaking down heavier hydrocarbon feedstocks into fuels and chemicals. Its relevance also extends to emerging technologies such as biomass and plastic valorization. Zeolite catalysts, with shape selectivity and selective adsorption capabilities, enhance efficiency and sustainability due to their well-defined network of pores, dimensionality, cages/cavities, and channels. This study focuses on the alkane cracking over 10-membered ring (10-MR) zeolites under industrially relevant conditions. Through a series of characterizations, including operando UV-vis spectroscopy and solid-state NMR spectroscopy, we intend to address mechanistic debates about the alkane cracking mechanism, aiming to understand the dependence of product selectivity on zeolite topologies. The findings highlight topology-dependent mechanisms, particularly the role of intersectional void spaces in zeolite ZSM-5, influencing aromatic-based product selectivity. This work provides a unique understanding of zeolite-catalyzed hydrocarbon conversion, linking alkane activation steps to the traditional hydrocarbon pool mechanism, contributing to the fundamental knowledge of this crucial industrial process.

Highly Dispersed Pd@ZIF-8 for Photo-Assisted Cross-Couplings and CO2 to Methanol: Activity and Selectivity Insights.

Our study unveils a pioneering methodology that effectively distributes Pd species within a zeolitic imidazolate framework-8 (ZIF-8). We demonstrate that Pd can be encapsulated within ZIF-8 as atomically dispersed Pd species that function as an excited-state transition metal catalyst for promoting carbon-carbon (C-C) cross-couplings at room temperature using visible light as the driving force. Furthermore, the same material can be reduced at 250 °C, forming Pd metal nanoparticles encapsulated in ZIF-8. This catalyst shows high rates and selectivity for carbon dioxide hydrogenation to methanol under industrially relevant conditions (250 °C, 50 bar): 7.46 molmethanol molmetal-1 h-1 and >99%. Our results demonstrate the correlations of the catalyst structure with the performances at experimental and theoretical levels.

Thermodynamic and Kinetic Behaviors of Electrolytes Mediated by Intermolecular Interactions Enabling High-Performance Lithium-Ion Batteries.

Electrolyte solvation chemistry regulated by lithium salts, solvents, and additives has garnered significant attention since it is the most effective strategy for designing high-performance electrolytes in lithium-ion batteries (LIBs). However, achieving a delicate balance is a persistent challenge, given that excessively strong or weak Li+-solvent coordination markedly undermines electrolyte properties, including thermodynamic redox stability and Li+-desolvation kinetics, limiting the practical applications. Herein, we elucidate the crucial influence of solvent-solvent interactions in modulating the Li+-solvation structure to enhance electrolyte thermodynamic and kinetic properties. As a paradigm, by combining strongly coordinated propylene carbonate (PC) with weakly coordinated cyclopentylmethyl ether (CPME), we identified intermolecular interactions between PC and CPME using 1H-1H correlation spectroscopy. Experimental and computational findings underscore the crucial role of solvent-solvent interactions in regulating Li+-solvent/anion interactions, which can enhance both the thermodynamic (i.e., antireduction capability) and kinetic (i.e., Li+-desolvation process) aspects of electrolytes. Additionally, we introduced an interfacial model to reveal the intricate relationship between solvent-solvent interactions, electrolyte properties, and electrode interfacial behaviors at a molecular scale. This study provides valuable insights into the critical impact of solvent-solvent interactions on electrolyte properties, which are pivotal for guiding future efforts in functionalized electrolyte engineering for metal-ion batteries.

Electrocatalytic Hydrogen Generation by Ni-PN3P Pincer Complexes: Role of Phosphorus Substituents in Tuning the Reactivity.

Electrocatalytic hydrogen evolution reaction (eHER) is crucial in addressing the growing global energy demand. Although nickel-pincer-based molecular complexes, varying in donor atoms, were studied previously for eHER, the impact of variations in the substituents attached to the donor atoms was not investigated. Herein, three air-stable R1PN3PR2-based NiII-pincer complexes [R1=R2=Ph2 (7); R1=R2=tBu2 (9); R1= tBu2, R2=Ph2 (10)], varying solely in P-substituents, were studied in acetonitrile. While the redox potentials for NiII/I and NiI/0 couples underwent anodic shifts by ~100 mV upon progressively substituting tert-butyl by phenyl groups on each P-atom, the corresponding eHER reactivity with organic acids (acetic acid,  p-toluenesulfonic acid and trifluoromethanesulfonic acid) of different strengths followed different trends; likely influenced by the pKa of intermediate metal-hydride (M-H) species [pKa(M-H9) > pKa(M-H10) > pKa(M-H7)]. Depending on the acid strength, different oxidation states of the metal were activated to promote eHER. The catalytic rates for 9, 10, and 7 were calculated to be 85 s-1, 77 s-1 and 95 s-1 with Faradaic efficiencies of 88.5 ± 2%, 66.1 ± 1.4%, and 91.7 ± 1.5% respectively, in acetic acid. Electrochemical data supported by theoretical results reinforce a significant electronic influence of the anchoring P-substituents on the activity of these complexes.

Halogen Bonding Initiated Difunctionalization of [1.1.1]Propellane via Photoinduced Polarity Match Additions.

Bicyclo[1.1.1]pentane (BCP), recognized as a bioisostere for para-disubstituted benzene, has gained widespread interest in drug development due to its ability to enhance the physicochemical properties of pharmaceuticals. In this work, we introduce a photoinduced, halogen bonding-initiated, metal-free strategy for synthesizing various BCP derivatives. This method involves the generation of nucleophilic α-aminoalkyl radicals via halogen-bonding adducts. These undergo selective radical addition to [1.1.1]propellane, yielding electrophilic BCP radicals that subsequently participate in polarity-matched additions, culminating in the difunctionalization of bicyclopentane. The versatility and practicality of this metal-free approach are underscored by its broad substrate scope, which includes late-stage functionalization and a series of valuable transformations, all conducted under mild reaction conditions.

Transorbital Route to Intracranial Space.

The endoscopic superior eyelid transorbital approach has emerged as a notable and increasingly utilized surgical technique in recent years. This chapter presents an overview of the approach, tracing its historical development and highlighting its growing acceptance within the skull base community.Beginning with an introduction and historical perspective, the chapter outlines the evolution of the transorbital approach, shedding light on its origins and the factors driving its adoption. Subsequently, a comprehensive exploration of the anatomic bone pillars and intracranial spaces accessible via this approach is provided. Hence, five bone pillars of the transorbital approach were identified, namely the lesser sphenoid wing, the anterior clinoid, the sagittal crest, the middle cranial fossa, and the petrous apex. A detailed correlation of those bone targets with respective intracranial areas has been reported.Furthermore, the chapter delves into the practical application of the technique through a case example, offering insights into its clinical utility, indications, and limitations.

Temozolomide based treatment in glioblastoma: 6 vs. 12 months.

The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 ('6C' group) or 12 ('12C' group) cycles of temozolomide were collected between 2012 and 2022. A total of 45 patients were included in the 6C group and 42 patients were included in the 12C group. Data on isocitrate dehydrogenase mutation and methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also collected. The 12C group exhibited statistically significantly improved overall survival [OS; 22.8 vs. 17.5 months; hazard ratio (HR), 0.47; 95% CI, 0.30-0.73; P=0.001] and progression-free survival (15.3 vs. 9 months; HR, 0.39; 95% CI, 0.25-0.62; P=0.001). However, in the subgroup analysis according to MGMT status, OS in the 12C group was significantly superior to OS in the 6C group only in the MGMT unmethylated tumors. The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles.

From data to practice: brain meningioma treatment in elderly patients - a survey of the Italian Society of Neurosurgery (SINch®) and systematic review and meta-analysis.

The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature. A survey addressing the treatments options and management of meningioma in elderly was designed on behalf of SINch® (Società Italiana di Neurochirurgia) and sent via email to all Chiefs of Neurosurgical Departments. The survey remained open for responses from May 5th, 2022, until November 21st, 2022. A search of the literature published between January 2000 and March 2023, in accordance to PRISMA guidelines, was included. A total of 51 Neurosurgical centers participated in the survey. The caseload profile of each center influences the choice of treatment selection (Stereotactic Radiosurgery versus open surgery) (p = 0.01) and the consolidated practice of discussing cases within a multidisciplinary group (p = 0.02). The pooled meta-analysis demonstrated a significant increased risk in the elderly group for permanent deficits (p < 0.00001), postoperative infections (p = 0.0004) and hemorrhage (p = 0.0001), perioperative mortality (p < 0.00001), and medical complications (p < 0.00001) as compared to the young population. This study presents the initial comprehensive analysis of the existing trends in the surgical management of MEP in Italy. The significant variation in practices primarily stems from the absence of standardized guidelines. While most centers have adopted an integrated approach, there is a need to promote a multidisciplinary care model. Prospective studies are needed to gather robust evidence in this clinical setting.

Low-Temperature and Fast-Charging Lithium Metal Batteries Enabled by Solvent-Solvent Interaction Mediated Electrolyte.

Lithium metal batteries utilizing lithium metal as the anode can achieve a greater energy density. However, it remains challenging to improve low-temperature performance and fast-charging features. Herein, we introduce an electrolyte solvation chemistry strategy to regulate the properties of ethylene carbonate (EC)-based electrolytes through intermolecular interactions, utilizing weakly solvated fluoroethylene carbonate (FEC) to replace EC, and incorporating the low-melting-point solvent 1,2-difluorobenzene (2FB) as a diluent. We identified that the intermolecular interaction between 2FB and solvent can facilitate Li+ desolvation and lower the freezing point of the electrolyte effectively. The resulting electrolyte enables the LiNi0.8Co0.1Mn0.1O2||Li cell to operate at -30 °C for more than 100 cycles while delivering a high capacity of 154 mAh g-1 at 5.0C. We present a solvation structure and interfacial model to analyze the behavior of the formulated electrolyte composition, establishing a relationship with cell performance and also providing insights for the electrolyte design under extreme conditions.

Unveiling structural and energetic characterization of the emissive RNA alphabet anchored in the methylthieno[3,4-d]pyrimidine heterocycle core.

This study presents a comprehensive theoretical exploration of the fluorescent non-natural emissive nucleobases- mthA, mthG, mthC, and mthU derived from the methylthieno[3,4-d]pyrimidine heterocycle. Our calculations, aligning with experimental findings, reveal that these non-natural bases exert minimal influence on the geometry of classical Watson-Crick base pairs within an RNA duplex, maintaining H-bonding akin to natural bases. In terms of energy, the impact of the modified bases, but for mthG, is also found to be little significant. We delved into an in-depth analysis of the photophysical properties of these non-natural bases. This investigation unveiled a correlation between their absorption/emission peaks and the substantial impact of the modification on the energy levels of the highest unoccupied molecular orbitals (HOMO) and the lowest unoccupied molecular orbital (LUMO). Notably, this alteration in energy levels resulted in a significant reduction of the HOMO-LUMO gap, from approximately 5.4-5.5 eV in the natural bases, to roughly 3.9-4.7 eV in the modified bases. This shift led to a consequential change in absorption and emission spectra towards longer wavelengths, elucidating their bathochromic shift.

Open-door extended endoscopic transorbital technique to the paramedian anterior and middle cranial fossae: technical notes, anatomomorphometric quantitative analysis, and illustrative case.

OBJECTIVE: The superior eyelid endoscopic transorbital approach (SETOA) provides a direct and short minimally invasive route to the anterior and middle skull base. Nevertheless, it uses a narrow corridor that limits its angles of attack. The aim of this study was to evaluate the feasibility and potential benefits of an "extended" conservative variant of the "standard" endoscopic transorbital approach-termed "open-door"-to enhance the exposure of lesions affecting the paramedian aspect of the anterior and middle cranial fossae. METHODS: First, the authors described the technical nuances of the open-door extended transorbital approach (ODETA). Next, they documented its morphometric advantages over standard SETOA. Finally, they provided a clinical-anatomical application to demonstrate enhanced exposure and better angles of attack to treat lesions occupying the paramedian anterior and middle cranial fossae. Five adult cadaveric specimens (10 sides) initially underwent standard SETOA and then extended open-door SETOA (ODETA to the paramedian anterior and middle fossae). The adjunct of hinge-orbitotomy, through three surgical steps and straddling the frontozygomatic suture, converted conventional SETOA to its extended open-door variant. CT scans were performed before dissection and uploaded to the neuronavigation system for quantitative analysis. The angles of attack on the axial plane that addressed four key landmarks, namely the tip of the anterior clinoid process (ACP), foramen rotundum (FR), foramen ovale (FO), and trigeminal impression (TI), were calculated for both operative techniques and compared. RESULTS: Hinge-orbitotomy of the extended open-door SETOA resulted in several surgical, functional, and esthetic advantages: it provided wider axial angles of attack for each of the target points, with a gain angle of 26.68° ± 1.31° for addressing the ACP (p < 0.001), 29.50° ± 2.46° for addressing the FR (p < 0.001), 19.86° ± 1.98° for addressing the FO (p < 0.001), and 17.44° ± 2.21° for addressing the lateral aspect of the TI (p < 0.001), while hiding the skin scar, avoiding temporalis muscle dissection, preserving flap vascularization, and decreasing the rate of bone infection and degree of orbital content retraction. CONCLUSIONS: The extended open-door technique may be specifically suited for selected patients affected by paramedian anterior and middle fossae lesions, with prevalent anteromedial extension toward the anterior clinoid, the foremost compartment of the cavernous sinus and FR and not completely controlled with the pure endoscopic transorbital approach.

Correction: Simple synthetic access to [Au(IBiox)Cl] complexes.

Correction for 'Simple synthetic access to [Au(IBiox)Cl] complexes' by Ekaterina A. Martynova et al., Dalton Trans., 2023, 52, 7558-7563, https://doi.org/10.1039/D3DT01357J.

Detecting Hachimoji DNA: An Eight-Building-Block Genetic System with MoS2 and Janus MoSSe Monolayers.

In the pursuit of personalized medicine, the development of efficient, cost-effective, and reliable DNA sequencing technology is crucial. Nanotechnology, particularly the exploration of two-dimensional materials, has opened different avenues for DNA nucleobase detection, owing to their impressive surface-to-volume ratio. This study employs density functional theory with van der Waals corrections to methodically scrutinize the adsorption behavior and electronic band structure properties of a DNA system composed of eight hachimoji nucleotide letters adsorbed on both MoS2 and MoSSe monolayers. Through a comprehensive conformational search, we pinpoint the most favorable adsorption sites, quantifying their adsorption energies and charge transfer properties. The analysis of electronic band structure unveils the emergence of flat bands in close proximity to the Fermi level post-adsorption, a departure from the pristine MoS2 and MoSSe monolayers. Furthermore, leveraging the nonequilibrium Green's function approach, we compute the current-voltage characteristics, providing valuable insights into the electronic transport properties of the system. All hachimoji bases exhibit physisorption with a horizontal orientation on both monolayers. Notably, base G demonstrates high sensitivity on both substrates. The obtained current-voltage (I-V) characteristics, both without and with base adsorption on MoS2 and the Se side of MoSSe, affirm excellent sensing performance. This research significantly advances our understanding of potential DNA sensing platforms and their electronic characteristics, thereby propelling the endeavor for personalized medicine through enhanced DNA sequencing technologies.

Multiple neighboring active sites of an atomically precise copper nanocluster catalyst for efficient bond-forming reactions.

Atomically precise copper nanoclusters (NCs) are an emerging class of nanomaterials for catalysis. Their versatile core-shell architecture opens the possibility of tailoring their catalytically active sites. Here, we introduce a core-shell copper nanocluster (CuNC), [Cu29(StBu)13Cl5(PPh3)4H10]tBuSO3 (StBu: tert-butylthiol; PPh3: triphenylphosphine), Cu29NC, with multiple accessible active sites on its shell. We show that this nanocluster is a versatile catalyst for C-heteroatom bond formation (C-O, C-N, and C-S) with several advantages over previous Cu systems. When supported, the cluster can also be reused as a heterogeneous catalyst without losing its efficiency, making it a hybrid homogeneous and heterogeneous catalyst. We elucidated the atomic-level mechanism of the catalysis using density functional theory (DFT) calculations based on the single crystal structure. We found that the cooperative action of multiple neighboring active sites is essential for the catalyst's efficiency. The calculations also revealed that oxidative addition is the rate-limiting step that is facilitated by the neighboring active sites of the Cu29NC, which highlights a unique advantage of nanoclusters over traditional copper catalysts. Our results demonstrate the potential of nanoclusters for enabling the rational atomically precise design and investigation of multi-site catalysts.