Nickel in foodstuffs available on the Luxembourgish market and dietary intake.

Nickel is a food contaminant of natural or anthropogenic origin. Monitoring of contaminants in food in general allows obtaining an overview on the presence of substances that are undesirable to health. The aim of this study was to analyse nickel content in food of non-animal origin and beverages sold in Luxembourg to determine the exposure of the population to this contaminant. In total, 660 samples were analysed in the timeframe from 2017 to 2021. The results demonstrate high concentrations of nickel in cashew nuts, walnuts, hemp and sunflower seeds, dried peas, oregano, and cocoa powder. Surveillance of contaminants in food allows identifying contributors to the chronic and acute exposure of nickel in order to potentially set official maximum levels in European legislation in the future, allowing for better enforcement actions in case of contaminated products and increasing consumer protection.

Consumer expectations, drug effects, price and purity of heroin and cocaine purchased at drug consumption rooms.

BACKGROUND: Drug consumption rooms offer heroin and cocaine consumers a secure and hygienic environment including medical and social guidance. Despite the support and mentoring, only sparse information is available about how drug quality, drug prices and user expectations match at these locations. The present study reports analysis of these three parameters in two drug consumption rooms in Luxembourg. METHODS: Drug users were invited to participate in the project by handing in a few milligrams of the product they planned to consume for chemical analysis and filling out a short questionnaire about the price and their expectations. After consumption, they were asked to report the experienced effects. Drug quality was accessed using LC-Q-ToF and HPLC-UV, and a statistical analysis was carried out of the questionnaires that were correctly filled out. RESULTS: A total of 513 drug samples have been analyzed. Most consumers were looking for the relaxing/calming effects of heroin and the stimulating effects of cocaine, but they generally overestimated heroin potency and underestimated cocaine potency. No strong correlation based on Spearman's ρ between drug user estimations, drug prices and drug quality was found. CONCLUSION: To the best of our knowledge, this study is the first to combine drug analysis with heroin and cocaine user feedback about expectation, drug prices and drug effects. The analytical results were of great interest for users and the staff working at the drug consumption rooms. They may be a strong supplementary communication tool for health care workers when discussing effects and risks of highly toxic substance consumption.

Investigation on heroin and cocaine quality in Luxembourg.

BACKGROUND: Heroin and cocaine are among the most dangerous illicit drugs available and their presence on the market is increasing. These facts have led to the investigation of the quality of heroin and cocaine samples seized in Luxembourg by police and customs but also collected at the national supervised drug consumption facilities. METHODS: Samples obtained from 2019 to 2020 were analyzed to determine their composition and content using GC-MS, HPLC-UV and LC-Q-ToF. The statistical evaluation of concentration changes depending on the source of collection is based on an ANOVA single factor test and a two-tailed t test. RESULTS: Results showed important differences between seizure and collection sources. For both drugs, customs samples had significantly higher concentrations than police samples and the latter had significantly higher concentrations than samples from drug consumption facilities, whereas for heroin two cutting steps were identified, for cocaine samples only one appears to occur on the local market. Indeed, cocaine samples seized by police consisted of a mixture of low and high concentration samples. CONCLUSION: The results show that extensive adulteration with pharmacological active and inactive compounds takes place at local levels, which, however, are different for heroin and cocaine. This knowledge on variability of quality of drugs should be considered in the elaboration of drug and harm prevention strategies.

Cooking heroin the Turkish way: chemical investigation on an unusual heroin preparation method.

BACKGROUND: Reports from experienced heroin users about an alternative and appreciated but harmful so-called "Turkish" heroin preparation technic led to the chemical investigation of the compounds produced during this process and investigation of the presence of other psychoactive contaminants. METHODS: Comparison of diacetylmorphine, 6-monoacetylmorphine, morphine, paracetamol and caffeine concentrations were performed in the non-processed material, after processing according to the standard and to the alternative preparation methods using liquid chromatography coupled to quadrupole time of flight mass spectrometry followed by statistical evaluation of the results. RESULTS: The two preparation methods had in common a diminution of diacetylmorphine as compared to the starting material but significantly more 6-monoacetylmorphine was produced using the "Turkish" preparation method as compared to the standard method. CONCLUSION: The high amount of psychoactive 6-monoacetylmorphine may have an impact on the reported effects of heroin using the "Turkish" preparation procedure.

In Cellulo Evaluation of the Therapeutic Potential of NHC Platinum Compounds in Metastatic Cutaneous Melanoma.

We describe here the evaluation of the cytotoxic efficacy of two platinum (II) complexes bearing an N-heterocyclic carbene (NHC) ligand, a pyridine ligand and bromide or iodide ligands on a panel of human metastatic cutaneous melanoma cell lines representing different genetic subsets including BRAF-inhibitor-resistant cell lines, namely A375, SK-MEL-28, MeWo, HMCB, A375-R, SK-MEL-5-R and 501MEL-R. Cisplatin and dacarbazine were also studied for comparison purposes. Remarkably, the iodine-labelled Pt-NHC complex strongly inhibited proliferation of all tested melanoma cells after 1-h exposure, likely due to its rapid uptake by melanoma cells. The mechanism of this inhibitory activity involves the formation of DNA double-strand breaks and apoptosis. Considering the intrinsic chemoresistance of metastatic melanoma cells of current systemic treatments, these findings are promising and could give research opportunities in the future to improve the prognosis of patients suffering from unresectable metastatic melanoma that are not eligible or that do not respond to the most effective drugs available to date, namely BRAF inhibitors and the anti-PD-1 monoclonal antibody (mAb).

N-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety: Anti-Cancer Activity and DNA Interaction.

A platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the N-heterocyclic carbene (NHC) Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase atomic force microscopy (AFM). The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behavior was quantified from the different experiments due to contour length variations. At 24 h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands.

N-Heterocyclic Carbene-Polyethyleneimine (PEI) Platinum Complexes Inducing Human Cancer Cell Death: Polymer Carrier Impact.

The high interest in N-Heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed on 8 different types of cells that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. Using HCT116 cells, the conjugates displayed an effective activity after only 45 min of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.

N-Heterocyclic Carbene-Polyethylenimine Platinum Complexes with Potent in Vitro and in Vivo Antitumor Efficacy.

The current interest for platinum N-heterocyclic carbene complexes in cancer research stems from their impressive toxicity reported against a range of different human cancer cells. To date, the demonstration of their in vivo efficacy relative to that of established platinum-based drugs has not been specifically addressed. Here, we introduce an innovative approach to increase the NHC-Pt complex potency whereby multiple NHC-Pt(II) complexes are coordinated along a polyethylenimine polymer (PEI) chain. We show that such NHC-Pt(II)-PEI conjugates induce human cancer cell death in vitro and in vivo in a xenograft mouse model with no observable side effects in contrast to oxaliplatin. Additional studies indicate nucleus and mitochondria targeting and suggest various mechanisms of action compared to classical platinum-based anticancer drugs.

Tridentate Complexes of Palladium(II) and Platinum(II) Bearing bis-Aryloxide Triazole Ligands: A Joint Experimental and Theoretical Investigation.

A novel class of palladium(II) and platinum(II) complexes bearing tridentate bis-aryloxide triazole ligands was prepared by using straightforward and high-yielding synthetic routes. The complexes were fully characterized and the molecular structures of four derivatives were unambigously determined by single-crystal X-ray diffractometric analyses. For the most promising luminescent Pt(II) derivatives, further experimental investigations were carried out to characterize their photophysical features and to ascertain the nature of the emitting excited state by means of electronic absorption, steady-state, and time-resolved emission techniques in different conditions. In degassed fluid solution the complexes displayed broad and featureless photoluminescence with λ(em) =522-585 nm, excited-state lifetime up to few microseconds and quantum yield (PLQY) up to 17%, depending on the nature of both ancillary ligand and substituent on the tridentate ligand. Computational investigation using density functional theory and time-dependent DFT were performed to gain insight into the electronic processes responsible for optical transitions and structure-photoluminescence relationship. Jointly, experimental and theoretical characterization indicated that the radiative transition arises from an excited state with admixed triplet-manifold metal-to-ligand charge transfer and ligand-centered ((3)MLCT/(3)LC) character. We elucidated the modulation of the photophysical properties upon variation of substituents for this new family of complexes.

IMes-acac: hybrid combination of diaminocarbene and acetylacetonato sub-units into a new anionic ambidentate NHC ligand.

The mesoionic 5-acetylimidazolium-4-olate serves as precursor for an anionic, hybrid NHC, "IMes-acac", consisting of fused diaminocarbene and acetylacetonato units, whose respective coordination abilities are evaluated by the formation of a series of representative copper(I) complexes illustrating the ambidentate character of the ligand.

Exploring nitrogen ligand diversity in trans-N-heterocyclic carbene-amine platinum complexes: synthesis, characterization, and application to fluorescence.

Expand and diversify your Ptfolio: N-Heterocyclic carbene-Pt-pyridine complexes have been used to generate an expanded and diversified set of trans NHC-Pt complexes with various amines, polyamines, hydroxylamines, or hydrazine as ligands. Attachment of a fluorophore moiety has also been successfully achieved.

Direct functionalisation of group 10 N-heterocyclic carbene complexes for diversity enhancement.

The synthesis of alkyne-substituted N-heterocyclic carbene complexes of Pd(II) and Pt(II) is reported. Catalyzed 1,3-dipolar cycloaddition with azides has been applied as a modular way of functionalisation of group 10 transition metal NHC complexes to generate potentially new metallodrugs.