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Reaction of [Ru(H) 2 (CO)(PPh 3 ) 3 ] 1 with an equimolar amount of pyrrole-2-carboxylic acid ( H 2 L 1 ) leads to the homoleptic chelate derivative k 2 (O,O)-[RuH(CO)(HL 1 )(PPh 3 ) 2 ] 2 . Prolonged acetonitrile refluxing promotes an unusual k 2 (O,O)- → k 2 (N,O)- dynamic chelate conversion, forming a neutral, stable, air- and moisture- insensitive, solvento-species k 2 (N,O)-[Ru(MeCN)(CO)(L 1 )(PPh 3 ) 2 ] 3 . Analogously, reaction of 1 with the pyrrole-2-carboxyaldehyde ( HL 2 ) affords k 2 (N,O)-[RuH(CO)(HL 2 )(PPh 3 ) 2 ] 4 , 5 , as a couple of functional isomers. Optimized reaction conditions such as temperature and solvent polarity allow the isolation of dominant configurations. Structure 5 is a pyrrolide Ru-carbaldehyde, obtained from cyclization of the pendant CHO function, whereas species 4 can be viewed as an ethanoyl-conjugated Ru-pyrrole. Derivatives 3 - 5 were characterized by single crystal X-ray diffraction, ESI-Ms, IR, and NMR spectroscopy, indicating distinct features for the Ru-bonded pyrrolyl groups. DFT computational results, coplanarity, bond equalization, and electron delocalization along the fused five-membered rings support aromatic features. In accordance with the antisymbiotic trans -influence, both the isolated isomers 4 and 5 disclose CO ligands opposite to N- or O-anionic groups. The quantitative Mayer bond order evidences a stabilizing backbonding effect. Antibacterial and antifungal trials on Gram-positive ( Staphylococcus aureus ), Gram-negative ( Escherichia coli ), and Candida albicans were further carried out., Competing Interests: The authors declare no conflicts of interest.

Breast implants are extensively employed for both reconstructive and esthetic purposes. However, the safety of breast implants with textured surfaces has been questioned, owing to a potential correlation with anaplastic large-cell lymphoma and the recurrence of breast cancer. This study investigates the immune response elicited by different prosthetic surfaces, focusing on the comparison between macrotextured and microtextured breast implants. Through the analysis of intraoperatively harvested periprosthetic fluids and cell culture experiments on surface replicas, we demonstrate that macrotextured surfaces elicit a more pronounced chronic-like activation of leucocytes and an increased release of inflammatory cytokines, in contrast to microtextured surfaces. In addition, in vitro fluorescent imaging of leucocytes revealed an accumulation of lymphocytes within the cavities of the macrotextured surfaces, indicating that the physical entrapment of these cells may contribute to their activation. These findings suggest that the topography of implant surfaces plays a significant role in promoting a chronic-like inflammatory environment, which could be a contributing factor in the development of lymphomas associated with a wide range of implantable devices., (© 2024 Vinci et al.)

The "self-adaptability" of galvanostatic electrolysis was shown to assist a multistage unprecedented chemo- and diastereoselective electrochemically promoted cyclodimerization of chalcones. The process, all involving the reductive events, delivered densely functionalized cyclopentanes featuring five contiguous stereocenters (25 examples, yields of up to 95%, dr values up to >20 : 1). Dedicated and combined experimental as well as electrochemical investigation revealed the key role of a dynamic kinetic resolution of the aldol intermediate for the reaction mechanism.

A carbonylation-carboxylation synthetic sequence, via double CO 2 fixation, is described. The productive merger of a Ni-catalyzed cross-electrophile coupling manifold, with the use of AlCl 3 , triggered a cascade reaction with the formation of three consecutive C-C bonds in a single operation. This strategy traces an unprecedented synthetic route to ketones under Lewis acid assisted carbon dioxide valorization. Computational insights revealed a unique double function of AlCl 3 , and labeling ( 13 CO 2 ) experiments validate the genuine incorporation of CO 2 in both functional groups.

Theranostic and personalized medicine are blooming strategies to improve oncologic patients' health care and facilitate early treatment. While 18 F-radiochemistry for theranostic application is attractive due to its imaging properties, combining diagnosis by positron emission tomography (PET) via aluminum-fluoride-18 and β - therapy with lutetium-177 is relevant. Nevertheless, it requires the use of two different chelating agents, which are NOTA and DOTA for aluminum-fluoride-18 and lutetium-177 radiolabeling, respectively. To overcome this issue, we propose herein the synthesis of a new hybrid chelating agent named NO2A-AHM, which can be labeled with different types of emitters (β + , β - and γ) using the mismatched Al 18 F/ 177 Lu pair. NO2A-AHM, is based on a hydrazine moiety functionalized by a NOTA cycle, a chelating arm, and a linker with a maleimide function. This design is chosen to increase the flexibility and allow the formation of 5 up to 7 coordination bonds with metal ions. Moreover, this agent can be coupled to targeting moieties containing a thiol function, such as peptides, to increase selectivity towards specific cancer cells. Experimental complexation and computational chemistry studies are performed to confirm the capacity of our chelating agent to label both aluminum-fluoride and lutetium using molecular modeling approaches at Density Functional Theory (DFT) level. The proof of concept of the ability of NO2A-AHM to complex both aluminum-fluoride-18, for PET imaging applications, and lutetium-177 for radiotherapy has shown encouraging results which is prominent for the development of a fully consistent theranostic approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H) 2 CO(PPh 3 ) 3 ] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29.

The reaction of mer -(Ru(H) 2 (CO)(PPh 3 ) 3 ) ( 1 ) with one equivalent of thymine acetic acid (THAcH) unexpectedly produces the macrocyclic dimer k 1 (O), k 2 (N,O)-(Ru(CO)(PPh 3 ) 2 THAc) 2 ( 4 ) and, concomitantly, the doubly coordinated species k 1 (O), k 2 (O,O)-(Ru(CO)(PPh 3 ) 2 THAc) ( 5 ). The reaction promptly forms a complicated mixture of Ru-coordinated mononuclear species. With the aim of shedding some light in this context, two plausible reaction paths were proposed by attributing the isolated or spectroscopically intercepted intermediates on the basis of DFT-calculated energetic considerations. The cleavage of the sterically demanding equatorial phosphine in the mer -species releases enough energy to enable self-aggregation, producing the stable, symmetric 14-membered binuclear macrocycle of 4 . The k 1 -acetate iminol (C=N-OH) unit of the mer -tautomer k 1 (O)-(Ru(CO)(PPh 3 ) 2 (THAc)) ( 2 ) likely exhibits a stronger nucleophilic aptitude than the prevalent N(H)-C(O) amido species, thus accomplishing extra stabilization through concomitant k 2 (N,O)-thymine heteroleptic side-chelation. Furthermore, both the ESI-Ms and IR simulation spectra validated the related dimeric arrangement in solution, in agreement with the X-ray determination of the structure. The latter showed tautomerization to the iminol form. The 1 H NMR spectra in chlorinated solvents of the kinetic mixture showed the simultaneous presence of 4 and the doubly coordinated 5 , in rather similar amounts. THAcH added in excess preferentially reacts with 2 or trans -k 2 (O,O)-(RuH(CO)(PPh 3 ) 2 THAc) ( 3 ) rather than attacking the starting Complex 1 , promptly forming the species of 5 . The proposed reaction paths were inferred by spectroscopically monitoring the intermediate species, for which the results were strongly dependent on the of conditions the reaction (stoichiometry, solvent polarity, time, and the concentration of the mixture). The selected mechanism proved to be more reliable, due to the final dimeric product stereochemistry.

Background: Understanding the causes of perinatal death can provide relevant information to couples, caregivers, and society. Classification systems play a crucial role in identifying the most relevant conditions suggesting preventive measures for decreasing stillbirth (SB). In 2016 the International Classification of Disease to Deaths during the Perinatal Period (ICD-PM) was released with the aim to suggest a universally accepted classification., Methods: This is a prospective cohort study that enrolled all SBs occurred in Emilia-Romagna, from 2014 to 2017. We prospectively applied ReCoDe classification and retrospectively used Simplified CODAC classification and ICD-PM. The aim of this study is to compare different classification systems on a cohort of SBs, undergoing a comprehensive workup, to establish what classification minimizes rates of unexplained SB., Results: We registered 443 SBs. According to ReCoDe the largest category of SB was "placental insufficiency/infarction" (16.9%), followed by "abruptio placentae" (14.2%). Unexplained cases are 16.7%. Gestational age <37 weeks is less frequent in the group of women with unclassified SB (OR 0.50, OR95%CI [0.3-0.8]) against women with classified SB. Considering CODAC the two largest categories are "infarctions or thrombi" (16.3%) and "abruption or retro-placental haematoma" (15.1%), instead only 17.2% of cases remained unexplained., Conclusions: Comparing ReCoDe and CODAC we found no real difference in any category. ReCoDe and CODAC better underlines the primary cause of death. ICD-PM reveals to be easily applicable to clinical practice. ICD-PM has the lowest rate of unexplained SBs (9.3%) due to the structure itself and not to a deeper comprehension of death.

A new [Au(I)] catalyzed intramolecular hydrocarboxylation of allenes is presented as a valuable synthetic route to oxazino-indolones. The use of 3,5-(CF 3 ) 2 -C 6 H 3 -ImPyAuSbF 6 as the optimal catalyst (5 mol%) was necessary to guarantee (i) wide tolerance of functional groups, (ii) mild reaction conditions (r.t., 16 h), and (iii) high yields (up to 90%). Preliminary attempts towards an enantioselective version (81 : 19 er) are also documented by means of a new family of chiral C 1 -symmetric ImPyAuCl complexes.

The enantioselective 1,3-dipolar cycloaddition of nitrones and arylpropionaldehydes to generate highly functionalized scaffolds for application in drug discovery was herein investigated. The use of a second-generation MacMillan catalyst as hydrochloride salt consistently accelerated the reaction speed, allowing a decrease in the reaction time up to >100 times, still affording 4-isoxazolines with good to excellent enantiomeric ratios at room temperature. As a proof of concept, further functionalization of the isoxazoline core through Pd-catalyzed cross-coupling was performed, generating differently functionalized chemical architectures in high yield., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A carboxylative Ni-catalyzed tandem C-C σ-bond activation of cyclobutanones followed by CO 2 -electrophilic trapping is documented as a direct route to synthetically valuable 3-indanone-1-acetic acids. The protocol shows an adequate functional group tolerance and useful chemical outcomes (yield up to 76%) when AlCl 3 is adopted as an additive. Manipulations of the targeted cyclic scaffolds and a mechanistic proposal based on experimental evidence complete the investigation.

A series of modular ImPy-carbene-Au(I) complexes are synthesized and fully characterized both in the solid state and in solution. The presence of oligoaryl units (phenyl and thienyl rings) at the C5-position of the ImPy core (in close proximity to the gold center) imprints on the organometallic species fine-tunable and predictable catalytic properties. A marked accelerating effect was recorded in several [Au(I)]-catalyzed electrophilic activations of unsaturated hydrocarbons when a CF 3 -containing aromatic ring was accommodated at the ImPy core., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)