Georges Dahm
@lns.lu/departement/laboratoires-protection-de-la-sante
Laboratoire National de Santé
RESEARCH INTERESTS
Analytical chemistry
Analytical toxicology
Drug testing
Mass spectrometry/Chromatography
Scopus Publications
Scopus Publications
Georges Dahm, Karin Roschel, Claude Marson, Adèle Bourmaud, Jennifer Macedo, Mauro Lupo, Lionel Fauchet, Claudia Allar, Raoul Schaaf, and Serge Schneider
Springer Science and Business Media LLC
Abstract 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.
Luc Schuler, Danny Zust, Georges Dahm, and Fabienne Clabots
Informa UK Limited
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.
Alba Iglesias-González, Charline Schaeffer, Georges Dahm, Emilie M. Hardy, Achilleas Pexaras, Paul Palazzi, and Brice M. R. Appenzeller
Springer Science and Business Media LLC
AbstractAwareness of the adverse effects of exposure to pollutant mixtures, possibly much more severe than individual chemicals, has drawn attention towards the necessity of using multi-residue methods to obtain the most possible comprehensive information on exposome. Among the different biological matrices used for exposure assessment, hair enables to detect the largest number of chemicals, including many classes such as persistent pollutants, hydrophilic metabolites and metals. Most biomonitoring studies are however focused on a limited number of pollutants and only give a partial information on exposure. Combining several multi-residue methods, the present study aimed at assessing the exposure of a population to an extensive variety of chemicals by hair analysis. One hair sample was collected from each participant (55 children and 134 adults). Samples were analysed with three different multi-residue methods, targeting, respectively, 152 organic pollutants (pesticides, PCBs, bisphenols, PBDEs), 62 polycyclic aromatic hydrocarbons (PAHs) and metabolites, nicotine and cotinine and 36 metals. From 33 to 70 organic chemicals were detected in each child’s hair sample, and from 34 up to 74 in adults. From 7 to 26 PAH were detected per child, and 7 to 21 in adults. Twenty-three to 27 metals were detected per child and 21 to 28 per adult. The highest median concentration were observed for zinc (143 μg /mg in children; 164 μg /mg in adults), bisphenol A (95.9 pg/mg in children; 64.7 pg/mg in adults) and nicotine (66.4 pg/mg in children; 51.9 pg/mg in adults). The present study provides the most comprehensive exposure assessment ever and highlights the simultaneous exposure to multiple classes of pollutants in the general population. The results support the use of multi-residue methods for future studies on exposure-associated effects, to document exposome and better consider the effect of chemical mixtures.
Adèle Bourmaud, Georges Dahm, François Meys, Nicolas Gengler, Alain Origer, and Serge Schneider
Springer Science and Business Media LLC
Abstract 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.
Georges Dahm, Claudia Allar, Raoul Schaaf, Adèle Bourmaud, and Serge Schneider
Springer Science and Business Media LLC
Abstract 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.
Elsa Charignon, Mathilde Bouché, Caroline Clave-Darcissac, Georges Dahm, Gabriel Ichim, Anthony Clotagatide, Hichem C. Mertani, Philippe Telouk, Julie Caramel, Jean-Jacques Diaz,et al.
MDPI AG
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).
Georges Dahm, Mathilde Bouché, Corinne Bailly, Lydia Karmazin, and Stéphane Bellemin-Laponnaz
Elsevier BV
Abstract A series of platinum (II) complexes bearing N-heterocyclic carbene NHC ligands functionalized by various benzyl moieties were synthesized and characterized. The molecular structure of two complexes has been confirmed by X-ray diffraction studies on single crystals. Investigation of in vitro cytotoxic activities against various cancer cell lines revealed a strong substituent effect: IC50 as low as 0.005 μM were obtained depending on the substituent on the benzyl moiety.
Sébastien Harlepp, Edith Chardon, Mathilde Bouché, Georges Dahm, Mounir Maaloum, and Stéphane Bellemin-Laponnaz
MDPI AG
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.
May Wantz, Mathilde Bouché, Georges Dahm, Neïla Chekkat, Sylvie Fournel, and Stéphane Bellemin-Laponnaz
MDPI AG
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.
Edith Chardon, Georges Dahm, Gilles Guichard, and Stéphane Bellemin-Laponnaz
Elsevier BV
Abstract A series of novel ruthenium(II), palladium(II) and rhodium(I) complexes bearing N-heterocyclic carbene ligand functionalized by an alkyne-protected functional group ( C C SiMe3) were synthesized by transmetalation from the silver-NHC intermediate or by deprotonation of the azolium salt using an external base. The complexes were fully characterized and X-ray diffraction was used for the structure determination. The donating properties of the NHC ligand were evaluated through the synthesis of the rhodium carbonyl complex. The reactivity of the functional group has been studied: deprotection of the alkyne on the ruthenium and rhodium species gave instable products whereas deprotection of the palladium compound was quantitative. However the resulting alkyne-functionalized species was incompatible with conditions for further post-functionalization such as metal-catalyzed 1,3-dipolar cycloaddition.
Neila Chekkat, Georges Dahm, Edith Chardon, May Wantz, Justine Sitz, Marion Decossas, Olivier Lambert, Benoit Frisch, Riccardo Rubbiani, Gilles Gasser,et al.
American Chemical Society (ACS)
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.
Mathilde Bouché, Georges Dahm, Aline Maisse-François, Thierry Achard, and Stéphane Bellemin-Laponnaz
Wiley
A series of heterotopic platinum complexes combining N-heterocyclic carbene (NHC) and pnictogen-based ligands [Pn = P(nBu)3, PPh3, AsPh3 and SbPh3] has been synthesized and fully characterized. Use of an excess of Pn ligand led to the formation of cationic bis-Pn platinum-NHC complexes in high yield, with both Pn ligands being arranged trans to each other. Several representative complexes could be characterized by X-ray crystallographic studies thus confirming the ligand arrangement around the metal. This simple approach allows the generation of diversity in metallodrug candidates. Biological activities on various human cancer cells have been studied and compared with those of cisplatin. The results confirmed the high cytotoxicity of these NHC-platinum complexes bearing pnictogen ligands.
Etienne Borré, Georges Dahm, Gilles Guichard, and Stéphane Bellemin-Laponnaz
Royal Society of Chemistry (RSC)
Carbonyl condensation reactions have been used for accessing N-heterocyclic carbene (NHC) platinum bioconjugate complexes.
M. Bouché, G. Dahm, M. Wantz, S. Fournel, T. Achard, and S. Bellemin-Laponnaz
Royal Society of Chemistry (RSC)
We report the synthesis and cytotoxic activity of novel platinum(iv) N-heterocyclic carbene complexes of the general formula [(NHC)PtX4(L)], X = Br, Cl; L = nitrogen-containing ligand.
Georges Dahm, Etienne Borré, Changkan Fu, Stéphane Bellemin-Laponnaz, and Matteo Mauro
Wiley
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.
Georges Dahm, Corinne Bailly, Lydia Karmazin, and Stéphane Bellemin-Laponnaz
Elsevier BV
Abstract A series of platinum(II) and palladium(II) complexes bearing N-heterocyclic carbene ligands functionalized by specific functionalities such as alcohol, nitrile or ester were synthesized. The novel complexes were fully characterized and X-ray diffraction was used for the structure determination of eight derivatives. The reactivity of the functional groups has been studied; for example, Pt and Pd NHC complexes containing tBu ester functions were easily hydrolyzed giving water-soluble NHC complexes. The palladium complex 21 containing dangling COOH group was evaluated in copper-free Sonogashira coupling reaction. In addition, platinum NHC complexes are attractive metal-based systems for the development of anticancer drugs. Preliminary results of the biological effects on various human cancer and non-cancer cells are also reported.
Vincent César, Valentina Mallardo, Adela Nano, Georges Dahm, Noël Lugan, Guy Lavigne, and Stéphane Bellemin-Laponnaz
Royal Society of Chemistry (RSC)
A new anionic N-heterocyclic carbene composed of a diaminocarbene unit fused with an acetylacetonate backbone is described.
Georges Dahm, Etienne Borré, Gilles Guichard, and Stéphane Bellemin-Laponnaz
Wiley
We report oxime ligation in combination with metal ligand exchange as a novel orthogonal and practical approach to the multifunctionalization of NHC–platinum complexes. This strategy, which enables strong diversity enhancement of metallodrug candidates, could also be applied to selective bioconjugation.
Etienne Borré, Georges Dahm, Alessandro Aliprandi, Matteo Mauro, Samuel Dagorne, and Stéphane Bellemin-Laponnaz
American Chemical Society (ACS)
A series of group 10 complexes featuring chelating tridentate bis-aryloxide N-heterocyclic carbenes were synthesized and characterized by using different techniques. Ni(II), Pd(II), and Pt(II) complexes were isolated in good yields by straightforward direct metalation of the corresponding benzimidazolium or imidazolium precursors in a one-pot procedure. All of the compounds were fully characterized, including single-crystal X-ray diffractometric determination for three of the derivatives. In the solid state, the complexes adopt a typical square-planar coordination geometry around the platinum atom, sizably distorted in order to comply with the geometrical constraints imposed by the bis-aryloxide N-heterocyclic carbene ligand. For platinum and palladium derivatives, a joint experimental and theoretical characterization was performed in order to study the optical properties of the newly prepared complexes by means of electronic absorption and steady-state and time-resolved photophysical techniques as well a...
Edith Chardon, Georges Dahm, Gilles Guichard, and Stéphane Bellemin-Laponnaz
Wiley
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.
Edith Chardon, Georges Dahm, Gilles Guichard, and Stéphane Bellemin-Laponnaz
American Chemical Society (ACS)
A simple procedure for the preparation of N-heterocyclic carbene platinum complexes with a nitrogen-based neutral ligand in trans geometry is presented. The lability of a trans pyridine ligand in an N-heterocyclic carbene–Pt(II)–pyridine complex, namely, (3-benzyl-1-methylimidazolylidene)PtI2(pyridine), 2, was probed by a displacement reaction with various nitrogen-based ligands (e.g., amines, hydrazine, amino esters, and peptides) to yield the corresponding complexes, which could be easily isolated by column chromatography. Two representative complexes could be characterized by X-ray crystallographic studies. This strategy allows generating diversity in metallodrug candidates. Preliminary results of the biological effects on various human cancer cells and comparison wih cisplatin are reported.
Edith Chardon, Gian Luigi Puleo, Georges Dahm, Sylvie Fournel, Gilles Guichard, and Stéphane Bellemin-Laponnaz
Wiley
In the search for novel metal-based pharmaceuticals, ruthenium-catalysed 1,3-dipolar cycloaddition is used to functionalise a series of palladium and platinum N-heterocyclic carbene complexes. This strategy was applied to the conjugation of amino acid, polyethylene glycol and oestradiol derivatives with the aim of enhancing chemical diversity and introducing specific features (e.g., water solubility, cell targeting). Antiproliferative activities of the different complexes were assayed against several cancer cell lines (KB, MCF7, HCT116, PC3, SKOV3, OVCAR8, HL60) and healthy cell lines (MRC5, VERO, EPC), which established their efficiency. The ease of the structural derivatisation thus renders these complexes attractive metal-based systems for the development of selective targeted metal-hybrid anticancer drugs.
Edith Chardon, Gian Luigi Puleo, Georges Dahm, Gilles Guichard, and Stéphane Bellemin-Laponnaz
Royal Society of Chemistry (RSC)
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.