Highly enantioselective “inherently chiral” electroactive materials based on a 2,2' -biindole atropisomeric scaffold

Chiral oligothiophene monomers with C2 symmetry, based on 3,30 -bithiophene atropisomeric cores with high racemization barriers, have recently been shown to provide excellent chiral starting materials with high electroactivity for the easy preparation of enantiopure electroactive films endowed with powerful chirality manifestations. We now introduce an inherently chiral monomer based on a 2,20 -biindole core, as the prototype of a new inherently chiral monomer family, whose properties could be modulable through functionalization of the pyrrolic N atoms. By fast, regular electrooligomerization the new monomer yields inherently chiral films with high, reversible electroactivity and, above all, impressive enantioselectivity towards very different chiral probes, some of pharmaceutical interest, as generalscope electrode surfaces. Such results, while opening the way to a new, attractive inherently chiral selector class, nicely confirm the general validity of the inherent chirality strategy for chiral electrochemistry. Furthermore, the enantioselectivity of the new selectors not only holds with electroactive chiral probes, but also with circularly polarized light components as well as electron spins, resulting in good chiroptical and spin filter performances, which suggests fascinating correlations between the three contexts

Medicamentos, consumos de performance e culturas terapêuticas em mudança

This work is licensed under a CC BY Creative Commons Attribution 3.0 License. Please visit http://creativecommons.org/licenses/by/3.0/"O uso de fármacos e produtos naturais para a gestão do desempenho pessoal, aqui designado consumos de performance, constitui o foco deste artigo e dá suporte a uma reflexão analítica sobre a mudança nas culturas terapêuticas. Tendo por referência a atual problemática da farmacologização, bem como o lugar do natural na expansão do uso do medicamento, demonstra-se que a farmacologização do quotidiano está a emergir noutros campos, que não exclusivamente o da saúde, dando lugar a novas lógicas de relação com estes recursos. A sustentação empírica desta abordagem tem por base os resultados de um estudo nacional sobre os consumos de performance na população jovem em Portugal.

Mercury clathration-driven phase transition in a luminescent bipyrazolate metal-organic framework: a multitechnique investigation

Mercury is one of the most toxic heavy metals. By virtue of its triple bond, the novel ligand 1,2-bis(1H-pyrazol-4-yl)ethyne (H2BPE) was expressly designed and synthesized to devise metal-organic frameworks (MOFs) exhibiting high chemical affinity for mercury. Two MOFs, Zn(BPE) and Zn(BPE)·nDMF [interpenetrated i-Zn and noninterpenetrated ni-Zn·S, respectively; DMF = dimethylformamide], were isolated as microcrystalline powders. While i-Zn is stable in water for at least 15 days, its suspension in HgCl2 aqueous solutions prompts its conversion into HgCl2@ni-Zn. A multitechnique approach allowed us to shed light onto the observed HgCl2-triggered i-Zn-to-HgCl2@ni-Zn transformation at the molecular level. Density functional theory calculations on model systems suggested that HgCl2 interacts via the mercury atom with the carbon-carbon triple bond exclusively in ni-Zn. Powder X-ray diffraction enabled us to quantify the extent of the i-Zn-to-HgCl2@ni-Zn transition in 100-5000 ppm HgCl2 (aq) solutions, while X-ray fluorescence and inductively coupled plasma-mass spectrometry allowed us to demonstrate that HgCl2 is quantitatively sequestered from the aqueous phase. Irradiating at 365 nm, an intense fluorescence is observed at 470 nm for ni-Zn·S, which is partially quenched for i-Zn. This spectral benchmark was exploited to monitor in real time the i-Zn-to-HgCl2@ni-Zn conversion kinetics at different HgCl2 (aq) concentrations. A sizeable fluorescence increase was observed, within a 1 h time lapse, even at a concentration of 5 ppb. Overall, this comprehensive investigation unraveled an intriguing molecular mechanism, featuring the disaggregation of a water-stable MOF in the presence of HgCl2 and the self-assembly of a different crystalline phase around the pollutant, which is sequestered and simultaneously quantified by means of a luminescence change. Such a case study might open the way to new-conception strategies to achieve real-time sensing of mercury-containing pollutants in wastewaters and, eventually, pursue their straightforward and cost-effective purification

Electrochemistry of inherently chiral molecular materials with bisindole atropisomeric cores: interacting equivalent redox sites, configurational stability, and enantioselection ability for different chiral probes

In "inherently chiral" molecules chirality and key functional properties originate from the same structural element, and are thus strictly linked together. In the case of poly(hetero)aromatic electroactive molecules, this can be achieved by inserting in the main conjugated backbone a tailored torsion with an energy barrier too high to be overcome at room temperature, while not entirely hampering conjugation. This strategy results in outstanding chirality manifestations. including e.g. circularly polarized luminescence as well as outstanding enantiorecognition ability in CV experiments. For instance, large peak potential differences were observed for the enantiomers of different chiral probes on electroactive surfaces obtained by electrooligomerization of inherently chiral monomers having atropisomeric (= with hindered rotation between two moieties) bibenzothiophene (Fig 1A) or bithiophene cores. [1-4]. An interesting option is also to change the thiophene-based atropisomeric cores with 2,2'-bisindole and 3,3'-bisindole ones (Fig 1B and 1C), on account of the easy functionalization of the core e.g. with long alkyl chains, modulating solubility and processability. A B C Figure 1 R = H or C1-C6 alkyl chains; Spacer = phenyl or nothing (oligothiophene wing attached to core) The change also leads to quite interesting modifications in the electrochemical activity. Since indole is electron richer than thiophene, the first two oxidations take place at significantly less positive potentials than in the former cases, and are localized on the two interacting moieties of the bisindole core rather than on the terminal wings; thus, they are chemically reversible (oligomerization can be achieved cycling around the third oxidation peak). A peculiar attractive feature concerns the interaction between the two equivalent redox centers in the biindole core, which can be evaluated from the potential difference between the corresponding oxidation peak: it can be shown that it can account for the atropisomeric energy barrier (depending on the 2,2' or 3,3' connectivity and on the N-alkyl substituents), and is also modulated by temperature and the solvent polarity. Thus electrochemistry can provide information on the torsional energy barrier and on the enantiomer stability, as confirmed by other approaches. Besides the intrinsic interest of these inherently chiral families, they are also quite attractive from the applicative point of view, since enantioselectivity test on films obtained by electrooligomerization of the more stable 2,2' monomers yield large potential differences for the antipodes of very different chiral probes, also of pharmaceutical interest. The current support of Fondazione Cariplo/Regione Lombardia "Avviso congiunto per l\u2019incremento dell\u2019attrattivit\ue0 del sistema di ricerca lombardo e della competitivit\ue0 dei ricercatori candidati su strumenti ERC - edizione 2016\u201d (Project 2016-0923) to our inherently chiral research is gratefully acknowledged. References: 1. Angew. Chem. Int. Ed. 2014, 53, 2623. 2. Chem. Eur. J. 2014, 20, 15298. 3. Chem. Sci. 2015, 6,1706. 4. Chem. Eur.2016 , 22,10839. 5. Anal. Bioanal. Chem. 2016, 408, 7243

Osteonecrosis of the jaws in patients under osteoporosis treatment: a nine-year experience report

ABSTRACT Objective: This study aimed to report the experience of medication-related osteonecrosis of the jaws (MRONJ) in osteoporotic patients for nine years, and their associated initiating factors. Materials and methods: The numbers of invasive oral procedures (IOP) (tooth extraction, dental implant placement, and periodontal procedures) and removable prostheses performed from January 2012 to January 2021 were obtained from the digital records of a large public dental center. There were an estimated 6,742 procedures performed in patients under osteoporosis treatment. Results: Two cases (0.03%) of MRONJ were registered in nine years amongst patients with osteoporosis who had dental treatment at the center. From the 1,568 tooth extractions, one patient (0.06%) developed MRONJ. There was also one case from the 2,139 removable prostheses delivered (0.05%). Conclusions: The prevalence of MRONJ associated with osteoporosis treatment was very low. The protocols adopted seem to be adequate for the prevention of this complication. The findings of this study reinforce the rare frequency of MRONJ associated with dental procedures in patients submitted to the pharmacological management of osteoporosis. An integral analysis of systemic risk factors and oral preventive strategies may be considered regularly in the dental treatment of these patients

Qualidade óssea de ratas wistar em crescimento alimentadas com ração hiperlipídica

A relação entre a obesidade e o tecido ósseopermanece contraditória, mesmo após anos deinvestigações. Os resultados são inespecíficos,sobretudo, quando é avaliado o efeito de dietas ricas emgordura em modelos experimentais. O objetivo desseestudo foi avaliar a qualidade óssea de ratas wistar emcrescimento alimentadas com ração hiperlipídica. Foramutilizadas 20 ratas pós-desmame. Elas foram divididasigualmente em dois grupos, sendo PAD: ratasalimentadas com ração padrão AIN-93 e HIP: ratasalimentadas com ração AIN-93 modificada de modo aconter 60% da energia em forma de gordura. O períodode tratamento foi de 5 semanas. As ratas foramsubmetidas à eutanásia por doses excessivas deanestesia e, após necropsia e dissecação, as tíbias foramanalisadas quando à Densidade Mineral Óssea (DMO),Resistência Mecânica e Análise microestrutural atravésda Microscopia Eletrônica de Varredura. A DMO foiestatisticamente maior no grupo HIP em relação aogrupo PAD, entretanto, a resistência mecânica foiestatisticamente igual entre os dois grupos. Amicroarquitetura permaneceu similar entre os doisgrupos após análise quantitativa. Foi possível concluir,portanto, que embora a DMO tenha sido maior no grupoalimentado com ração hiperlipídica, a resistênciamecânica e microarquitetura óssea permaneceu intactaapós 5 semanas de tratamento.The relationship between obesity and bonetissue remains contradictory, even after years ofinvestigation. The results are non-specific, particularlywhen it assessed the effect of high-fat diets inexperimental models. The aim of this study was toevaluate bone quality of wistar growing rats fed withhigh-fat diet. 20 post-weaning wistars rats were used inthis study. They were equally divided into two groups,PAD: rats fed with standard diet AIN-93 and HIP: ratsfed with a modified AIN-93 diet to contain 60% ofenergy as fat. The exposure period was 5 weeks. Therats were euthanized by overdose of anesthesia and,after autopsy and dissection, tibiae were analyzed whenthe Bone Mineral Density, Mechanical Strength andMicrostructural Analysis by Scanning ElectronMicroscopy. BMD was statistically higher in the HIPgroup compared to the PAD group. However, themechanical strength was statistically similar betweenthe two groups. Microarchitecture remained similarbetween the two groups observed by quantitativeanalysis. It was concluded, therefore, that althoughBMD was higher in the group fed high-fat diet, themechanical strength and bone microarchitectureremained intact after 5 weeks of exposure

The thiophene-based inherently chiral monomer family grows: molecular design and electrochemical properties

Our group has recently presented electroactive thiophenebased polyconjugated films of unprecedented chirality manifestations and enantiorecognition ability,[1] based on the "inherent chirality" concept, implying that the whole electroactive backbone coincides with the stereogenic element, consisting in a tailored torsion induced by an atropisomeric bi-benzothiophene scaffold. Such films are easily prepared as enantiopure electrode surfaces by electrooligomerization of (R) and (S) enantiopure monomer 1. Now, concurrently with the exploration of the applicative potentialities of this "parent" molecular material, both racemic and enantiopure, we are widening the class of available monomers designed according the same strategy, but with different atropisomeric heteroaromatic scaffolds, different side chains, and/or with the addition of a further stereogenic element. The electrochemical properties of a selection of the new inherently chiral monomers now available will be presented in detail and rationalized as a function of their molecular structure, also in the perspective of potential applications. With the contribution of Fondazione Cariplo, grant no. 2011-0417. [1] F. Sannicol\uf2, S. Arnaboldi, T. Benincori, V. Bonometti, R. Cirilli, L. Dunsch, W. Kutner, G. Longhi, P.R. Mussini, M. Panigati, M. Pierini, S. Rizzo, Angew. Chemie 2014, 53, 2623-2627