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This study introduces a sustainable and pioneering cascade synthesis of 1,3-thiazolidine derivatives under eco-friendly conditions. The methodology transcends traditional approaches yielding complex novel compounds with unique N,S-heterocyclic structures. By operating at room temperature, utilizing green solvents, and minimizing excess of reactants, this procedure offers an innovative pathway for sustainable chemical development. Notably, this method not only prioritizes sustainability but also delivers high-purity products with exceptional yields. The simplicity of the process, requiring only a simple filtration and featuring short reaction times, underscores its efficiency and utility.
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Gold catalysis has emerged as a groundbreaking field in synthetic chemistry, revolutionizing numerous organic transformations. Despite the significant achieved advancements, the mechanistic understanding behind many gold-catalyzed reactions remains elusive. This Concept article covers the so-called "self-activating" Au(I) complexes, sorting out their pivotal role in gold catalysis. We comment on how Au(I) complexes can undergo self-activation, triggering diverse catalytic transformations without the need for external additives. The most important examples reported so far that underlie the catalytic activity of these species are discussed. This intrinsic reactivity represents a paradigm shift in gold catalysis, offering new avenues for the design of efficient and sustainable catalytic systems. Furthermore, we explore the factors influencing the stability, reactivity, and selectivity of these Au(I) complexes, providing insights into their synthetic utility and potential applications. This area of research not only advances our fundamental understanding of gold catalysis but also paves the way for the development of novel catalytic strategies with broad implications in organic synthesis and the chemical industry.
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The first chiral and luminescent cyclic trinuclear gold(I) complex, [{AuCH(PPh2Me)(Ph2P)}3]3+, has been isolated with metalated phosphorus ylides (PY). This complex was initially obtained through the reaction of either mononuclear [C6F5SAuCH(PPh2Me)(Ph2P)]OTf or dinuclear [C6F5S{AuCH(PPh2Me)(Ph2P)}2](OTf)2 thiolate-gold-phosphane complexes in the presence of NaH, followed by the abstraction of the thiopyridine moiety employing either AgOTf or [Cu(CH3CN)4]PF6. Our quest for a more efficient synthesis route led to the development of a streamlined one-pot synthesis method, employing Ag(acac) as both a halogen abstractor and a base, offering a quicker and more direct path to this intriguing trimer. Comprehensive computational studies have unveiled the luminescent characteristics of this complex, which can be attributed to phosphorescence. These emissions originate from ligand-to-metal (LMCT) and metal-centered (MC) charge transfer excited states. Furthermore, the structural analysis via X-ray crystallography corroborated the formation of a trimeric species, featuring three monomers with the [AuCH(PPh2Me)(Ph2P)] motif. Each monomer exhibits a single chiral center, leading to four possible absolute configurations (RRR, RRS, RSR, and SRR). NMR and X-ray spectroscopy have provided valuable insights, establishing that the former configuration (RRR) is disfavored due to steric hindrance, while the three remaining configurations can interconvert, arising from the structural arrangement of the metallacycle and inherent symmetry operations.
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Terpyridine-based complexes with groupâ 11 metals emerge as potent metallodrugs in cancer therapy. This comprehensive review focuses on the current landscape of anticancer examples, particularly highlighting the mechanisms of action. While Cu(II) complexes, featuring diverse ancillary ligands, dominate the field, exploration of silver and gold species remains limited. These complexes exhibit significant cytotoxicity against various cancer cell lines with a commendable selectivity for non-tumorigenic cells. DNA interactions, employing intercalation and groove binding, are pivotal and finely tuned through terpyridine ligand functionalization. In addition, copper complexes showcase nuclease activity, triggering apoptosis through ROS generation. Despite silver's high affinity for nitrogen donor atoms, its exploration is relatively sparse, with indications of acting as intercalating agents causing DNA hydrolytic cleavage. Gold(III) compounds, overshadowing gold(I) due to stability concerns, not only intercalate but also induce apoptosis and disrupt the mitochondrial membrane. Further investigations are needed to fully understand the mechanism of action of these compounds, highlighting the necessity of exploring additional biological targets for these promising metallodrugs.
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Antineoplásicos , Complexos de Coordenação , Neoplasias , Piridinas , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Piridinas/química , Piridinas/farmacologia , Piridinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Apoptose/efeitos dos fármacos , Relação Estrutura-Atividade , AnimaisRESUMO
Twelve (N^N^N)platinum pyridyl complexes, (N^N^N)Pt(pyF), were synthesised and investigated for their singlet oxygen generation and potential biological activities. They exhibited 1IL and 1MLCT absorption transitions at approximately 325 and 360 nm, identified through TD-DFT calculations. Luminescence was observed only in the L1-derived compounds in solution, with a dual emission with the main contribution of phosphorescence under deaerated conditions. Room temperature phosphorescence was detected in all solid-state cases. Electron-withdrawing substituents at specific positions (R1 and X) and the number of fluorine atoms in R2 were found to enhance the photosensitizing capabilities of these compounds. Biological assessments, including cytotoxicity and photocytotoxicity, were conducted to evaluate their potential as chemotherapeutic agents and photosensitizers. Complexes with chloro substitution in the N^N^N tridentate ligand of the central pyridine ring exhibited promising chemotherapeutic properties. Ancillary pyridine ring substitution became significant under irradiation conditions, with fluoromethylated substituents enhancing cytotoxicity. Complex 2-CF3 was the most efficient singlet oxygen producer and a highly effective photosensitizer. CHF2-substituted complexes also showed improved photosensitizing activity. DNA binding studies indicated moderate interactions with DNA, offering insights into potential biological applications.
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Fármacos Fotossensibilizantes , Oxigênio Singlete , DNA , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Platina/química , Piridinas/farmacologia , Piridinas/química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologiaRESUMO
Invited for the cover of this issue are the groups of Raquelâ P. Herrera and M.â Concepción Gimeno at the Instituto de Síntesis Química y Catálisis Homogénea (University of Zaragoza-CSIC). The image depicts the light of the full moon illuminating a bridge between the gold(I) metal centers. Two dragons, symbolizing the use of bridging ligands, confront each other to determine the ultimate victor. Read the full text of the article at 10.1002/chem.202303585.
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The combination of the ferrocene moiety with gold(I) catalysis remains a relatively unexplored field. In this article, we delve into the synthesis, characterization, and potential catalytic activity of four complexes utilizing both monodentate and bidentate ferrocenyl diphenylphosphane ligands (ppf and dppf), coordinated with two gold(I) metal centers, linked by either chloride or pentafluorophenylthiolate bridging ligands. This leads to the formation of cationic "self-activated" precatalysts capable of initiating the catalytic cycle without the need for external additives. The catalytic activity of these complexes was assessed through a model reaction in gold(I) catalysis, specifically the cyclization of a N-propargylbenzamide to produce an oxazole. In addition, we studied and compared the influence exerted by both the phosphane and the bridging ligand on the performance of these catalysts.
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Gold(II) complexes, unlike their gold(I) and gold(III) counterparts, have been sparsely employed in the field of catalysis. This is primarily due to the challenges associated with isolating and characterising these open-shell species. However, these complexes offer a wide range of possibilities. On one hand, this intermediate oxidation state has proven to be more easily accessible through reduction and oxidation processes compared to the gold(I)/gold(III) redox couple, thereby facilitating potential homo-coupling and cross-coupling reactions. On the other hand, gold(II) exhibits Lewis acid behaviour, bridging the characteristics of the soft acid gold(I) and the hard acid gold(III). In this review, we focus on mono- and dinuclear gold(II) complexes, whether they are isolated and well-studied or proposed as intermediates in cross-coupling reactions induced by the action of oxidants or light. We delve into the unique reactivity and potential applications of these gold(II) species, shedding light on their role in this field. This comprehensive exploration aims to underscore the latent promise of gold(II) complexes in catalysis, offering insights into their structural and mechanistic aspects while highlighting their relevance in contemporary chemical transformations.
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Geologically "saline" zones with scarce pluviometry, which are already susceptible to the salinization of natural drainage, can experience the acceleration of the salinization of the receiving water systems with the implementation of irrigation. The main objective of this paper is to analyze the geochemical processes that control the variations of the hydrosaline balance due to the implementation of irrigation of the Lerma basin (Spain) from the beginning of its transformation into irrigation land (2004) until the consolidation of irrigation (2020). The results of this study evidence the dissolution of some mineral phases, such as halite, gypsum, and dolomite, and the precipitation of others, such as calcite. Additionally, the final composition of the irrigation return flows cannot be explained without consideration of the NaCa exchange. Part of the dissolved Ca2+ is deposited in the soil, which, in turn, contributes with Na+ to the solution. These natural processes are accelerated with irrigation but progressively slow down as the soil salts are washed with time. Although less evident, there is an additional negative agroenvironmental effect associated with the precipitation of calcite and the possible formation of petrocalcic horizons in the soil. The results obtained herein indicate that studies focusing on the salinity of irrigated zones should go a step further and include the geochemical processes in quantifying the global mass of exported salts.
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Geologically saline zones with scarce pluviometry are areas susceptible to salinization of their natural drainage. However, the salinization of the receiving water systems can be accelerated with the implementation of irrigation. This work aims to analyze the effects of irrigation on some zones transformed into irrigation land, from the beginning of the process until its complete consolidation. To this end, salt balances are evaluated as a whole and for each significant chemical element. The study zone is the irrigable area of the Lerma basin (Spain), where hydrosaline balances have been carried out since the hydrological year 2004 (before the implementation of irrigation) until 2020 (after the consolidation of irrigation). The implementation of irrigation in the area has doubled the mass of exported salts up to an average of 3177 kg/ha irrigable·year, for the entire study period. 55 % of that amount results from a global mineral dissolution, although this process seems to decrease with time as these minerals are being flushed from the soil. Before irrigation was implemented, the general global dissolution pattern produced more concentration of most ions (SO42-, Cl-, Mg2+, Na+, and K+) in the water outputs than in the water inputs. After the implementation of irrigation, there were more water inputs than outputs in the balance and that was shown by the decrease in the dissolved HCO3- and Ca2+.These results indicate that the consolidation of irrigation progressively decreases the induced salinization in the water systems that receive the irrigation return flows. Further studies are required to expand the general understanding of the process and its effects, quantify the different geochemical processes involved, and identify possible additional environmental issues induced by irrigation.
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A 2-year-old Standardbred gelding was referred for a mass on the palmaromedial right front pastern which was accompanied by progressively worsening lameness. The mass was firm to palpation and covered by normal skin. Ultrasonographically, a smooth encapsulated mass was present, medial to the flexor tendons and palmar to the neurovascular bundle. Because of a poor prognosis for future athletic performance without surgical or chemotherapeutic intervention and economic constraints preventing further diagnostics and treatment, the horse was euthanised. Post-mortem magnetic resonance imaging, histopathology and immunohistochemistry revealed the mass to be a perivascular wall tumour, the first record of such a neoplasia in the horse.
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Doenças dos Cavalos , Cavalos , Animais , Masculino , Doenças dos Cavalos/diagnóstico por imagem , Doenças dos Cavalos/tratamento farmacológico , Imageamento por Ressonância Magnética/veterinária , Tendões/patologia , Coxeadura Animal/etiologiaRESUMO
Cationic [Cu(P^P)(Htbz)]PF6 [P^P = xantphos, dpephos; Htbz = 2-(4-thiazolyl)benzimidazole] and the corresponding neutral complexes [Cu(P^P)(tbz)], obtained through deprotonation of the diimine ligand, have been synthesized with the aim of analyzing the role of the diphosphane and Htbz deprotonation in the emissive properties of these complexes. For the study of the diphosphane effect, the luminescence properties of these compounds have been compared with those of the reported analogous derivatives with Htbz and carborane diphosphanes. Complexes [Cu(P^P)(Htbz)]PF6 (P^P = xantphos, dpephos) and [Cu(dpephos)(tbz)] display thermally activated delayed fluorescence, which has been studied, revealing a ΔE(S1-T1) between 658 and 455 cm-1. Theoretical calculations indicate different origins for the absorptions, leading to the observed emissions.
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Silver complexes bearing substituted terpyridine or tetra-2-pyridinylpyrazine ligands have been prepared and structurally characterised. The study of the anticancer properties of silver complexes with this type of ligands is scarce, despite the possibilities of combining the properties of the metal and the ability of the ligands for DNA binding. Here, the antiproliferative activity, stability, CT-DNA binding, and mechanism of cell death of these types of derivatives are studied. High cytotoxicity against different tumour cells was observed, and, more important, a great selectivity index has been detected between tumour cells and healthy lymphocytes T for some of these compounds. The CT-DNA interaction study has shown that these derivatives are able to interact with CT-DNA by moderate intercalation. Furthermore, cell death studies indicate that these derivatives promote the apoptosis by a mitochondrial pathway.
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Antineoplásicos , Complexos de Coordenação , Neoplasias , Humanos , Relação Estrutura-Atividade , Prata , Ligantes , Ensaios de Seleção de Medicamentos Antitumorais , DNA/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Linhagem Celular TumoralRESUMO
INTRODUCTION: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with Covid-19. OBJECTIVE: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with Acute Respiratory Distress Syndrome and clinical trial of Covid-19 treated in intensive care units. METHODOLOGY: A systematized bibliographic review was carried out in the Pubmed, Cuiden, Lilacs, Medline, Cinahl and Google Scholar databases, using MeSH terms (Adult Respiratory Distress Syndrome, Mechanical Ventilation, Prone Position, Nitric Oxide, Extracorporeal Membrane Oxygenation, Nursing Care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. RESULTS: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and 1 cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is ECMO, with the care provided by qualified and trained nursing staff being very important. CONCLUSION: Mortality from Covid-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.
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COVID-19 , Síndrome do Desconforto Respiratório , Adulto , Humanos , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , COVID-19/etiologia , Estudos de Coortes , Estudos Transversais , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapiaRESUMO
The reaction of propargylamines with isothiocyanates results in the selective formation of iminothiazolidines, aminothiazolines or mixed thiazolidine-thiourea compounds under mild conditions. It has been observed that secondary propargylamines lead to the selective formation of cyclic 2-amino-2-thiazoline derivatives, while primary propargylamines form iminothiazoline species. In addition, these cyclic thiazoline derivatives can further react with an excess of isothiocyanate to give rise to thiazolidine-thiourea compounds. These species can also be achieved by reaction of propargylamines with isothiocynates in a molar ratio of 1 : 2. Coordination studies of these heterocyclic species towards silver and gold with different stoichiometries have been carried out and complexes of the type [ML(PPh3)]OTf, [ML2]OTf (M = Ag, Au) or [Au(C6F5)L] have been synthesised. Preliminary studies of the cytotoxic activity in lung cancer cells have also been performed in both ligands and complexes, showing that although the ligands do not exhibit anticancer activity, their coordination to metals, especially silver, greatly enhances the cytotoxic activity.
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PURPOSE: The Spanish Incisional Hernia Surgery Registry (EVEREG) was promoted by the Abdominal Wall Section of the Spanish Association of Surgeons, starting data collection in July 2012 and currently has more than 14,000 cases. The objective of this study was to validate the data collected through a pilot audit process. METHODS: A sample of hospitals participating in the EVEREG registry since the beginning was selected. Patients registered in these centers in the 2012-2020 period were included. A stratified random sampling was carried out, with the inclusion of 10% of registered cases per center with a minimum of 20 cases per center. At each participating center, two researchers not belonging to the center undergoing the audit checked (on site or telematically) the concordance between the data in the registry and the data contained in the case history of each patient. RESULTS: 330 patients have been analyzed, out of a total of 2673 registered, in 9 participating centers. The average accuracy has been 95.7%. Incorrect data 1.5% and missing data 2.3% CONCLUSION: The group of pilot hospitals from this EVERG incisional hernia surgery registry shows a very high precision of 95.7%. The confirmation of these findings in all the centers participating in the registry will make it possible to guarantee the quality of the studies made and their comparability with other similar national registries. TRIAL REGISTRATION: nnTrial registration number: ClinicalTrials.gov ID:NCT03899012.
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Hérnia Incisional , Humanos , Hérnia Incisional/cirurgia , Projetos Piloto , Confiabilidade dos Dados , Herniorrafia , Sistema de RegistrosRESUMO
Laforin and Malin are two proteins that are encoded by the genes EPM2A and EPM2B, respectively. Laforin is a glucan phosphatase and Malin is an E3-ubiquitin ligase, and these two proteins function as a complex. Mutations occurring at the level of one of the two genes lead to the accumulation of an aberrant form of glycogen meant to cluster in polyglucosans that go under the name of Lafora bodies. Individuals affected by the appearance of these polyglucosans, especially at the cerebral level, experience progressive neurodegeneration and several episodes of epilepsy leading to the manifestation of a fatal form of a rare disease called Lafora disease (LD), for which, to date, no treatment is available. Despite the different dysfunctions described for this disease, many molecular aspects still demand elucidation. An effective way to unknot some of the nodes that prevent the achievement of better knowledge of LD is to focus on the substrates that are ubiquitinated by the E3-ubiquitin ligase Malin. Some substrates have already been provided by previous studies based on protein-protein interaction techniques and have been associated with some alterations that mark the disease. In this work, we have used an unbiased alternative approach based on the activity of Malin as an E3-ubiquitin ligase. We report the discovery of novel bonafide substrates of Malin and have characterized one of them more deeply, namely PIP3-dependent Rac exchanger 1 (P-Rex1). The analysis conducted upon this substrate sets the genesis of the delineation of a molecular pathway that leads to altered glucose uptake, which could be one of the origin of the accumulation of the polyglucosans present in the disease.
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Doença de Lafora , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Doença de Lafora/genética , Doença de Lafora/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Glicogênio , UbiquitinasRESUMO
OBJECTIVE: Oropharyngeal dysphagia is caused by difficulty in bolus preparation and transport from the mouth to the oesophagus; this may result in malnutrition and aspiration pneumonia. It has a high prevalence in head and neck cancer patients. The objective of this study is to reduce these complications using a new protocol of diagnosis and evaluation of oropharyngeal dysphagia. METHOD: This is a prospective study developed in a secondary hospital. All patients diagnosed with head and neck cancer in 2021 and 2022 are subjected to this protocol: an oropharyngeal dysphagia screening test, a swallowing-related quality of life questionnaire and a flexible endoscopic evaluation of swallow. RESULTS: A total of 72 evaluations are reported using this protocol, before and after cancer treatment, and only 1 presents with aspiration pneumonia. CONCLUSION: Using this protocol, the incidence of aspiration pneumonia can be reduced, and diet recommendations can be given earlier in order to maintain a patient's nutritional requirements.
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Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Pneumonia Aspirativa , Humanos , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Estudos Prospectivos , Qualidade de Vida , Neoplasias de Cabeça e Pescoço/complicações , Deglutição , Pneumonia Aspirativa/etiologia , Pneumonia Aspirativa/prevenção & controle , Pneumonia Aspirativa/epidemiologiaRESUMO
Introduction: This bibliographic review is carried out in order to obtain answers about aspects related to techniques and treatments, as well as care associated with the critically ill patient diagnosed with COVID-19. Objective: To analyze the available scientific evidence on the effectiveness of the use of invasive mechanical ventilation together with other adjuvant techniques, in reducing the mortality rate in patients with acute respiratory distress syndrome and clinical trial of COVID-19 treated in intensive care units. Methodology: A systematized bibliographic review was carried out in the PubMed, CUIDEN, LILACS, Medline, CINAHL and Google Scholar databases, using MeSH terms (adult respiratory distress syndrome, mechanical ventilation, prone position, nitric oxide, extracorporeal membrane oxygenation, nursing care) and the corresponding Boolean operators. The selected studies underwent a critical reading carried out between December 6, 2020 and March 27, 2021 using the Critical Appraisal Skills Program tool in Spanish and a cross-sectional epidemiological studies evaluation instrument. Results: A total of 85 articles were selected. After performing the critical reading, a total of 7 articles were included in the review, 6 being descriptive studies and one a cohort study. After analyzing these studies, it appears that the technique that has obtained the best results is extracorporeal membrane oxygenation, with the care provided by qualified and trained nursing staff being very important. Conclusion: Mortality from COVID-19 increases in patients treated with invasive mechanical ventilation compared to patients treated with extracorporeal membrane oxygenation. Nursing care and specialization can have an impact on improving patient outcomes.
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A series of neutral acridine-based gold(III)-NHC complexes containing the pentafluorophenyl (-C6F5) group were synthesized. All of the complexes were fully characterized by analytical techniques. The square planar geometry around the gold center was confirmed by X-ray diffraction analysis for complexes 1 (Trichloro [1-methyl-3-(9-acridine)imidazol-2-ylidene]gold(III)) and 2 (Chloro-bis(pentafluorophenyl)[1-methyl-3-(9-acridine)imidazol-2-ylidene]gold(III)). In both cases, the acridine rings play a key role in the crystal packing of the solid structures by mean of π-π stacking interactions, with centroid-centroid and interplanar distances being similar to those found in other previously reported acridine-based Au(I)-NHC complexes. A different reactivity when using a bulkier N-heterocyclic carbene ligand such as 1,3-bis-(2,6-diisopropylphenyl)-2-imidazolidinylidene (SIPr) was observed. While the use of the acridine-based NHC ligand led to the expected organometallic gold(III) species, the steric hindrance of the bulky SIPr ligand led to the formation of the corresponding imidazolinium cation stabilized by the tetrakis(pentafluorophenyl)aurate(III) [Au(C6F5)4]- anion. Computational experiments were carried out in order to figure out the ground state electronic structure and the binding formation energy of the complexes and, therefore, to explain the observed reactivity.