Publications by authors named "Catherine Hemmert"

A series of seven novel iridium complexes were synthetized and characterized as potential photosensitizers for photodynamic therapy (PDT) applications. Among them, four complexes were evaluated in vitro for their anti-proliferative activity with and without irradiation on a panel of five cancer cell lines, namely PC-3 (prostate cancer), T24 (bladder cancer), MCF7 (breast cancer), A549 (lung cancer) and HeLa (cervix cancer), and two non-cancerous cell models (NIH-3T3 fibroblasts and MC3T3 osteoblasts). After irradiation at 458 nm, all tested complexes showed a strong selectivity against cancer cells, with a selectivity index (SI) ranging from 8 to 34 compared with non-cancerous cells.

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1,2,3-Triazolylidene MIC M-complexes (M = Au, Pd, Pt) having 2-azetidinones and penicillin G substituents at the triazole ring were prepared by CuAAC on 2-azetidinones having a terminal alkyne tethered at N1, followed by alkylation of the 1,2,3-triazole ring and transmetallation [Au(I), Pd(II) and Pt(II)]. The Au-MIC complexes efficiently catalyze the regioselective cycloisomerization of enynes, while the Pt-MIC complexes were efficient catalysts in hydrosilylation reactions.

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The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has called for an urgent need for dedicated antiviral therapeutics. Metal complexes are commonly underrepresented in compound libraries that are used for screening in drug discovery campaigns, however, there is growing evidence for their role in medicinal chemistry. Based on previous results, we have selected more than 100 structurally diverse metal complexes for profiling as inhibitors of two relevant SARS-CoV-2 replication mechanisms, namely the interaction of the spike (S) protein with the ACE2 receptor and the papain-like protease PL .

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The emergence of parasites, responsible for malaria disease, resistant to antiplasmodial drugs including the artemisinins, represents a major threat to public health. Therefore, the development of new antimalarial drugs or combinations is urgently required. In this context, several hybrid molecules combining a dihydroartemisinin derivative and gold(I) N-heterocyclic carbene (NHC) complexes have been synthesized based on the different modes of action of the two compounds.

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A family of hybrid complexes combining two biologically active motifs, an artemisinin derivative and a cationic bis(NHC)-gold(I) unit, has been synthesized. One of these complexes, 2 a, has been analyzed by single-crystal X-ray diffraction. 2 a shows strong anticancer activities on a large panel of human cancer cell models (prostate, breast, lung, liver, bladder, bone, acute and chronic myeloid leukemias) with GI values in the nm range, together with a high selectivity.

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Enantiopure bimetallic systems containing three different elements of chirality, namely a main-group-based chiral center (sulfur), a transition-metal chiral center (rhodium or iridium), and a planar chiral element (ferrocene or ruthenocene), have been prepared by a sequence of diastereoselective reactions. The chirality of the chiral sulfur center attached to C-5 of a 1,2,3-triazolylidene mesoionic carbene (MIC) ligand coordinated to a metal (Ir, Rh) was transferred through the formation of bimetallic complexes having a chiral-at-metal center and a planar chiral metallocene by C-H activation of the sandwich moiety (M=Fe, Ru). The sense of the planar chirality formed in this sequence of reactions depended on the nature of the ligands at the metal center of the starting complex.

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A series of four new mononuclear cationic gold(I) complexes containing nitrogen functionalized N-heterocyclic carbenes (NHCs) was synthesized and fully characterized by spectroscopic methods. The X-ray structures of three complexes are presented. These lipophilic gold(I) complexes originate from a pharmacomodulation of previously described gold(I)-NHC complexes, by replacing an aliphatic spacer with an aromatic one.

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A structurally diverse library of 14 gold(I) cationic bis(NHC) and neutral mono(NHC) complexes (NHC: N-heterocyclic carbene) was synthesized and characterized in this work. Four of them were new cationic gold(I) complexes containing functionalized NHCs, and their X-ray crystal structures are presented herein. All of the complexes were investigated for their anticancer activities in four cancer cell lines, including a cisplatin-resistant variant, and a noncancerous cell line.

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Article Synopsis
  • - A series of five new gold(I) complexes using N-heterocyclic carbenes was successfully created and analyzed using spectroscopy, with four of their structures determined through X-ray crystallography.
  • - These complexes, along with four previously studied ones, were tested for their effectiveness against Leishmania infantum parasites, and their toxicity was evaluated on murine macrophages.
  • - Most of the gold(I)-NHC-Cl complexes showed significant anti-parasitic activity, particularly lead-complex 11, which had a very low effective concentration and high selectivity, making it a promising candidate for further drug development.
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Mesoionic carbenes (MICs) derived from triazolium salts that contain chiral sulfoxide or sulfoximine functional groups were used to construct enantiopure chiral-at-metal Ir and Rh half-sandwich complexes through the synthetic sequence of MIC complexation/C-H aromatic activation. The process was efficient and diastereoselective for the formation of enantiopure five-membered metallacycles. The use of the enantiomers of the chiral sulfur groups allowed us to prepare complexes that had opposite configurations at the metal center.

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An unprecedented stereoselective domino reaction of 1,6-enynes with an aryl ring at C3-C4 in the presence of gold(I) catalysts at low temperature is described. This process involves a novel 5-exo-dig cycloisomerization-dimerization sequence to afford formal Diels-Alder adducts that undergo a smooth gold-catalyzed double bond migration at room temperature. In addition, the first examples of the gold mesoionic carbene mediated [2+2+2] cycloaddition of these enynes with benzaldehyde are reported.

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New and well-characterized Ag-bis(1,2,3-triazolylidene) complexes having enantiopure (S)-sulfoxides upon sequential treatment with alcohols and Au(I) form separable mixtures of regioisomeric C-unsubstituted Au-1,2,3-triazolylidene complexes. Mechanistic studies and DFT calculations support a desulfinylation process for in situ generated free triazolylidene salts.

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Gold mesoionic carbenes having a chiral sulfoxide group attached to the C4 position of the five membered ring have been prepared and tested as catalysts in the cycloisomerization of enynes. These new catalysts are very efficient, with the sulfoxide moiety playing a key role in their activity and the N1-substituent in control of the regioselectivity of these processes.

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A series of twenty five molecules, including imidazolium salts functionalized by N-, O- or S-containing groups and their corresponding cationic, neutral or anionic gold(I) complexes were evaluated on Plasmodium falciparum in vitro and then on Vero cells to determine their selectivity. Among them, eight new compounds were synthesized and fully characterized by spectroscopic methods. The X-ray structures of three gold(I) complexes are presented.

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Organometallic complexes are mostly used in catalytic applications and nowadays they are attracting more and more attention for biomedical applications. Until the last decade, research in the latter area was focused on screening of complexes against cancer cell lines, bacteria or parasites. For a couple of years mechanistic studies have helped in elucidating the mode of action of such complexes, one of the applied methods consists of studying cell uptake and intracellular distribution of luminescent bioactive complexes, in order to identify the main targets.

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A series of new mononuclear cationic or neutral gold(I) complexes containing quinoline functionalized N-heterocyclic carbene(s) (NHC(s)) were synthesized and fully characterized by spectroscopic methods. The X-ray structures of two key compounds are presented. Proligands and their corresponding gold(I) complexes together with previously described silver(I) and gold(I) bis(NHC-quinoline) and gold(I) bis(NHC-methylbipyridine) complexes were evaluated in vitro towards Leishmania infantum.

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The highly diastereoselective conjugate addition of alcohols and amines (RXH) to enantiopure 2-sulfinyl dienes renders transient allylic sulfoxides which undergo sulfoxide-sulfenate rearrangement and sulfenate cleavage providing 2-ene-1,4-diols and 2-ene-1,4-aminoalcohols with up to 99:1 dr. The method allows for the generation of two stereocenters in a single synthetic operation with remote chirality transfer of one center into the other.

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New gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands have been synthesized and characterized. The X-ray structures of two key compounds are presented. All complexes have been tested for their antiproliferative activities in prostate cancer cell line PC-3.

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A series of mono-and dinuclear silver(I) and mononuclear gold(I) complexes containing bis(N-heterocyclic carbene) (NHC) or N-functionalized NHC ligands were synthesized and fully characterized by spectroscopic methods and, in some cases, by single crystal X-ray diffraction. The in vitro antiplasmodial and antifungal activities of a previously described family of N-functionalized bis(imidazolium) proligands and their corresponding silver(I), gold(I) and gold(III) complexes but also the new here described compounds were investigated in a chloroquine-resistant strain of Plasmodium falciparum, and against two Candida strains, respectively. For the first family, interesting antiplasmodial and antifungal activities were found for the dinuclear silver(I) species but they also showed strong hemolytic properties.

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We report the synthesis of Au(I) and Au(III) complexes, involving alcohol functionalized bis(N-heterocyclic carbene) ligands. Two short reaction pathways lead to the diimidazolium precursors, namely 1,1'-(2,6-pyridinediyl)bis[3-(2-hydroxyethyl)-1H-imidazol-3-ium]diiodide (), 3,3'(methanediyl)bis[1-(2-hydroxy-2-methylpropyl)-1H-imidazol-3-ium]dibromide () and 3,3'-(1,3-propanediyl)bis[1-(2-hydroxy-2-methylpropyl)-1H-imidazol-3-ium]bis(4-methylbenzenesulfonate) (), in which the two azolium rings are bridged by a rigid pyridine unit or an aliphatic chain (C1 or C3). The Au(I) complexes [AuI(Lpy)]2(2+)[PF6-]2 () and [AuI(LC1)]2(2+)[PF6-]2 () were obtained by direct metallation of the salts and , respectively, in the presence of sodium acetate with Au(SMe(2))Cl, followed by an anionic metathesis in the presence of KPF6.

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We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III) salen complexes. The developed reaction pathway allows the modulation of the different key groups, namely, the chiral diimine, the bulky substituents in positions 3 and 3', and the linker used in the macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available structural variations.

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