Hydroamination of alkynes catalyzed by NHC-Gold(I) complexes: the non-monotonic effect of substituted arylamines on the catalyst activity

: Imines are valuable key compounds for synthesizing several nitrogen-containing molecules used in biological and industrial fields. They have been obtained, as highly regioselective Markovnikov products, by reacting several alkynes with arylamines in the presence of three new N-Heterocyclic carbene gold(I) complexes (3b, 4b, and 6b) together with the known 1-2b and 7b gold complexes as well as silver complexes 1-2a. Gold(I) complexes were investigated by means of NMR, mass spectroscopy, elemental analysis, and X-ray crystallographic studies. Accurate screening of co-catalysts and solvents led to identifying the best reaction conditions and the most active catalyst (2b) in the model hydroamination of phenylacetylene with aniline. Complex 2b was then tested in the hydroamination of alkynes with a wide variety of arylamines yielding a lower percentage of product when arylamines with both electron-withdrawing and electron-donating substituents were involved. Computational studies on the rate-determining step of hydroamination were conducted to shed light on the significantly different yields observed when reacting arylamines with different substituents

Clinical Psychology in School and Educational Settings: Emerging Trends

Background: First clinical services in psychology have been established for educational purposes when Witmer founded its Psychological Clinic. Over the years, the educational dimension played a significant role in the development of new evaluation methods and intervention strategies for the pursuit of positive mental health. The present review aims to capture developments that have been considered emerging applications of clinical psychology in school and educational settings. Methods: We conducted a search of the literature on Scopus, PubMed and Web of Science. The following search terms were used and combined: “clinical”, “psychology”, “educational”, and “school”. Results: A total of 18 research articles were included and analyzed in the current review. A number of studies showed that school-based positive psychology interventions were effective not only in reducing symptoms of psychological distress (somatization, depression, and anxiety) but also in increasing levels of positive mental health (a sense of individual growth, self-esteem, self-efficacy and optimism). As to studies on evaluation methods, the WHO-5 and the psychological well-being subscale from the Kellner Symptom Questionnaire were found to be clinically valid self-rating scales for the assessment of positive mental health in children and adolescents. Conclusion: Studies demonstrated that promoting positive mental health is more beneficial in the long term than simply treating symptoms of psychological distress. In clinical psychology, time has come to move from a traditional psychopathology-based perspective to a positive clinical approach to be used for innovative interventions and assessment strategies in school and educational settings

Reduction in liver fat by dietary MUFA in type 2 diabetes is helped by enhanced hepatic fat oxidation

The aim of this work was to investigate hepatic lipid metabolic processes possibly involved in the reduction of liver fat content (LF) observed in patients with type 2 diabetes after an isoenergetic diet enriched in monounsaturated fatty acids (MUFAs)

NHC-Ag(I) and NHC-Au(I) Complexes with N-Boc-Protected α-Amino Acidate Counterions Powerfully Affect the Growth of MDA-MB-231 Cells

N-Heterocyclic carbene (NHC) metal complexes are attracting scientists' interest as an alluring class of metallodrugs. Indeed, the versatile functionalization of NHC ligands makes them optimal scaffolds to be developed in medicinal chemistry. Besides, amino acids are great biological ligands for metals, such as silver and gold, even though their use is still under-investigated. Aiming to shed light on the anticancer properties of this kind of complex, we investigated a series of silver and gold complexes, stabilized by NHC ligands and bearing carboxylate salts of tert-butyloxy-carbonyl (Boc)-N-protected glycine and l-phenyl-alanine as anionic ligands. The most active complexes, AuM1Gly and AuM1Phe, powerfully affect the growth of MDA-MB-231 breast cancer cells, with IC50 values in the low nanomolar range. Further studies demonstrated the blockade of the human topoisomerase I activity and actin polymerization reaction at 0.001 mu M. These unique features make these complexes very interesting and worthy to be used for future in vivo studies

N-Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin

In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. In our study, we designed and synthesized a new series of silver N-heterocyclic carbene (NHC) complexes [(NHC)(2)Ag](+)[AgX2](-) (X=iodide or acetate). The new complexes were active against two human breast cancer cell lines, MCF-7 and MDA-MB-231. These compounds showed multiple target actions as anticancer, by inhibiting in vitro the activity of the human topoisomerases I and II and interfering with the cytoskeleton dynamic, as also confirmed by in silico studies. Moreover, the antimicrobial activity of these silver complexes was studied against Gram-positive/negative bacteria. These dual properties provide a two-tiered approach, making these compounds of interest to be further deepened for the development of new chemotherapeutic agents

Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins. Similarly to the natural depsipeptides, the synthetic oligolactam analogues show a correlation between ion transport abilities in artificial liposomes and cytotoxic activity on human cancer cell lines. The reported results demonstrate that the versatile cyclic peptoid scaffold, for its remarkable conformational and complexing properties, can morphologically mimic related natural products and elicit powerful biological activities

SARS-CoV-2 multi-variant rapid detector based on graphene transistor functionalized with an engineered dimeric ACE2 receptor

Reliable point-of-care (POC) rapid tests are crucial to detect infection and contain the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The emergence of several variants of concern (VOC) can reduce binding affinity to diagnostic antibodies, limiting the efficacy of the currently adopted tests, while showing unaltered or increased affinity for the host receptor, angiotensin converting enzyme 2 (ACE2). We present a graphene field-effect transistor (gFET) biosensor design, which exploits the Spike-ACE2 interaction, the crucial step for SARS-CoV-2 infection. Extensive computational analyses show that a chimeric ACE2-Fragment crystallizable (ACE2-Fc) construct mimics the native receptor dimeric conformation. ACE2-Fc functionalized gFET allows in vitro detection of the trimeric Spike protein, outperforming functionalization with a diagnostic antibody or with the soluble ACE2 portion, resulting in a sensitivity of 20 pg/mL. Our miniaturized POC biosensor successfully detects B.1.610 (pre-VOC), Alpha, Beta, Gamma, Delta, Omicron (i.e., BA.1, BA.2, BA.4, BA.5, BA.2.75 and BQ.1) variants in isolated viruses and patient's clinical nasopharyngeal swabs. The biosensor reached a Limit Of Detection (LOD) of 65 cps/mL in swab specimens of Omicron BA.5. Our approach paves the way for a new and reusable class of highly sensitive, rapid and variant-robust SARS-CoV-2 detection systems

Origin of Enantioselectivity in the Asymmetric Ru-Catalyzed Metathesis of Olefins.

The mechanism of enantioselectivity in the asymmetric Ru-catalyzed metathesis of olefins is investigated with a theoretical approach. The models are based on the chiral N-heterocyclic (NHC)-based catalysts developed by Grubbs. Our analysis indicates that the origin of enantioselectivity in the ring-closing metathesis of achiral trienes is correlated to the chiral folding of the N-bonded aromatic groups, which is imposed by the Ph groups in positions 4 and 5 of the imidazole ring of the NHC ligand. This chiral folding of the catalyst imposes a chiral orientation around the RudC bond, which, in turn, selects between the two enantiofaces of the substrate. In the ring-closing transition state, the geometry in which additional groups on the forming ring are in pseudoequatorial positions is favored over transition states in which this additional group is in a pseudoaxial position. These combined effects rationalize the enantiomeric excesses experimentally obtained

Mechanistic Insights in Alternating Ring-Opening Metathesis Copolymerization

Synthesis of alternating copolymers via ring-opening polymerization represents a challenging field, still object of development. Since N-Heterocyclic Carbene (NHC)-Ru based complexes bearing unsymmetrical substitution on the nitrogen atoms revealed as more selective and efficient catalysts than symmetrically substituted complexes in alternating polymerization, research efforts have been devoted to enhance the selectivity by modifying N-substituents.1,2 Recently, we have reported on ruthenium bearing uNHCs with syn phenyl groups on the backbone (Figure 1), highly selective toward alternating copolymerization of norbornene (NBE) with cyclooctene (COE) or cyclopentadiene (CPE).3 Although several complexes were reported in literature in recent past, searching for best catalyst architecture able to promote highly efficient and selective catalysts toward alternating copolymerization via ring-opening polymerization, extensive molecular modelling studies that rationalize the influence of NHC ligand on catalyst selectivity still lack. Herein, we report a DFT study relative to the copolymerization NBE-CPE in the presence of NHC-Ru based catalyst, to interpret how different NHC design can influence the reaction selectivity. (1) Vehlow, K.; Wang, D.; Buchmeiser, M.R.; Blechert, S. Alternating Copolymerizations Using a Grubbs- Type Initiator with an Unsymmetrical, Chiral N-Heterocyclic Carbene Ligand. Angew. Chem. Int. Ed. 2008, 47, 2615. (2) Paradiso, V.; Grisi, F. Ruthenium-Catalyzed Alternating Ring-Opening Metathesis Copolymerization of Norborn-2-ene with Cyclic Olefins. Adv. Synth. Catal. 2019, 361, 4133. (3) Troiano, R.; Costabile, C.; Grisi, F. Alternating Ring-Opening Metathesis Polymerization Promoted by Ruthenium Catalysts Bearing Unsymmetrical NHC Ligands. Catalysts 2023, 13, 34