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- ItemSqualenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections(Weinheim : Wiley-VCH Verlag, 2020) Ho, D.-K.; Murgia, X.; De Rossi, C.; Christmann, R.; Hüfner de Mello Martins, A.G.; Koch, M.; Andreas, A.; Herrmann, J.; Müller, R.; Empting, M.; Hartmann, R.W.; Desmaele, D.; Loretz, B.; Couvreur, P.; Lehr, C.-M.Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared. These nanocarriers allowed for remarkably high loading capacities of hydrophilic antibiotic tobramycin (Tob) and a novel lipophilic QSI at 30 % and circa 10 %, respectively. The drug-loaded SqNPs showed improved biofilm penetration and enhanced efficacy in relevant biological barriers (mucin/human tracheal mucus, biofilm), leading to complete eradication of PA biofilms at circa 16-fold lower Tob concentration than Tob alone. This study offers a viable therapy optimization and invigorates the research and development of QSIs for clinical use.
- ItemDinuclear lanthanide complexes supported by a hybrid salicylaldiminato/calix[4]arene-ligand: Synthesis, structure, and magnetic and luminescence properties of (HNEt3)[Ln2(HL)(L)] (Ln = SmIII, EuIII, GdIII, TbIII)(London : Soc., 2019) Ullmann, Steve; Hahn, Peter; Blömer, Laura; Mehnert, Anne; Laube, Christian; Abel, Bernd; Kersting, BertholdThe synthesis, structures, and properties of a new calix[4]arene ligand with an appended salicylaldimine unit (H4L = 25-[2-((2-methylphenol)imino)ethoxy]-26,27,28-trihydroxy-calix[4]arene) and four lanthanide complexes (HNEt3)[Ln2(HL)(L)] (Ln = SmIII (4), EuIII (5), GdIII (6), and TbIII (7)) are reported. X-ray crystallographic analysis (for 4 and 6) reveals an isostructural series of dimeric complexes with a triply-bridged NO3Ln(μ-O)2(OH⋯O)LnO3N core and two seven coordinated lanthanide ions. According to UV-vis spectrometric titrations in MeCN and ESI-MS the dimeric nature is maintained in solution. The apparent stability constants range between logK = 5.8 and 6.3. The appended salicylaldimines sensitize EuIII and TbIII emission (λexc 311 nm) in the solid state or immersed in a polycarbonate glass at 77 K (for 5, 7) and at 295 K (for 7). © The Royal Society of Chemistry 2019.
- ItemMixed-ligand lanthanide complexes supported by ditopic bis(imino-methyl)-phenol/calix[4]arene macrocycles: synthesis, structures, and luminescence properties of [Ln2(L2)(MeOH)2] (Ln = La, Eu, Tb, Yb)(London : Soc., 2020) Ullmann, Steve; Hahn, Peter; Mini, Parvathy; Tuck, Kellie L.; Kahnt, Axel; Abel, Bernd; Gutierrez Suburu, Matias E.; Strassert, Cristian A.; Kersting, BertholdThe lanthanide binding ability of a macrocyclic ligand H6L2 comprising two bis(iminomethyl)phenol and two calix[4]arene units has been studied. H6L2 is a ditopic ligand which provides dinuclear neutral complexes of composition [Ln2(L2)(MeOH)2] (Ln = La (1), Eu (2), Tb (3), and Yb (4)) in very good yield. X-ray crystal structure analyses for 2 and 3 show that (L2)6- accommodates two seven coordinated lanthanide ions in a distorted monocapped trigonal prismatic/octahedral coordination environment. UV-vis spectroscopic titrations performed with La3+, Eu3+, Tb3+ and Yb3+ ions in mixed MeOH/CH2Cl2 solution (I = 0.01 M NBu4PF6) reveal that a 2 : 1 (metal : ligand) stoichiometry is present in solution, with log K11 and K21 values ranging from 5.25 to 6.64. The ratio α = K11/K21 of the stepwise formation constants for the mononuclear (L2 + M = ML2, log K11) and the dinuclear complexes (ML2 + M = M2L2, log K21) was found to be invariably smaller than unity indicating that the binding of the first Ln3+ ion augments the binding of the second Ln3+ ion. The present complexes are less luminescent than other seven-coordinated Eu and Tb complexes, which can be traced to vibrational relaxation of excited EuIII and TbIII states by the coligated MeOH and H2O molecules and/or low-lying ligand-to-metal charge-transfer (LMCT) states. © 2020 The Royal Society of Chemistry.
- ItemContinuous synthesis of diethyl carbonate from ethanol and CO2 over Ce–Zr–O catalysts(London : RSC Publ., 2015) Prymak, Iuliia; Kalevaru, Venkata Narayana; Wohlrab, Sebastian; Martin, AndreasCexZr1−xO2 (x = 0, 0.2, 0.5, 0.8 and 1.0) solids were prepared by a citrate method and characterized by various techniques such as N2-adsorption (BET-SA), XRD, XPS, TEM, H2-TPR, NH3- and CO2-TPD. The catalytic performance of these solids was evaluated for the direct synthesis of diethyl carbonate (DEC) from ethanol and CO2 in continuous mode using a plug-flow reactor (PFR). According to thermodynamic data, the reaction is favourable at low reaction temperatures and high reaction pressures. Thus, the catalytic experiments were carried out at reaction temperatures ranging from 80 to 180 °C and at reaction pressures from 80 to 180 bar. The CexZr1−xO2 catalysts exhibited significant differences in their performance mainly depending on (i) their Ce : Zr ratio and (ii) the different acid–base characteristics. Among the series Ce0.8Zr0.2O2 (C80Z) and Ce0.5Zr0.5O2 (C50Z) catalysts displayed the most efficient performance. Moreover, C80Z, pretreated at 700 °C, yielded DEC at the equilibrium conversion level of YDEC ~ 0.7% at 140 °C and 140 bar at a CO2 : ethanol ratio of 6 : 1 at a LHSV of 42 Lliq kgcat−1 h−1.
- ItemLigand electronic fine-tuning and its repercussion on the photocatalytic activity and mechanistic pathways of the copper-photocatalysed aza-Henry reaction(London : RSC Publ., 2020) Li, Chenfei; Dickson, Robert; Rockstroh, Nils; Rabeah, Jabor; Cordes, David B.; Slawin, Alexandra M.Z.; Hünemörder, Paul; Spannenberg, Anke; Bühl, Michael; MejÃa, Esteban; Zysman-Colman, Eli; Kamer, Paul C.J.A family of six structurally related heteroleptic copper(i) complexes of the form of [Cu(N^N)(P^P)]+ bearing a 2,9-dimethyl-1,10-phenanthroline diimine (N^N) ligand and a series of electronically tunable xantphos (P^P) ligands have been synthesized and their optoelectronic properties characterized. The reactivity of these complexes in the copper-photocatalyzed aza-Henry reaction of N-phenyltetrahydroisoquinoline was evaluated, while the related excited state kinetics were comprehensively studied. By subtlety changing the electron-donating properties of the P^P ligands with negligible structural differences, we could tailor the photoredox properties and relate them to the reactivity. Moreover, depending on the exited-state redox potential of the catalysts, the preferred mechanism can shift between reductive quenching, energy transfer and oxidative quenching pathways. A combined study of the structural modulation of copper(i) photocatalysts, optoelectronic properties and photocatalytic reactivity resulted in a clearer understanding of both the rational design of the photocatalyst and the complexity of competing photoinduced electron and energy transfer mechanisms. © The Royal Society of Chemistry.
- ItemUnprecedented selective homogeneous cobalt-catalysed reductive alkoxylation of cyclic imides under mild conditions(Cambridge : RSC, 2017) Cabrero-Antonino, Jose R.; Adam, Rosa; Papa, Veronica; Holsten, Mattes; Junge, Kathrin; Beller, MatthiasThe first general and efficient non-noble metal-catalysed reductive C2-alkoxylation of cyclic imides (phthalimides and succinimides) is presented. Crucial for the success is the use of [Co(BF4)2·6H2O/triphos (L1)] combination and no external additives are required. Using the optimal cobalt-system, the hydrogenation of the aromatic ring of the parent phthalimide is avoided and only one of the carbonyl groups is selectively functionalized. The resulting products, N- and aryl-ring substituted 3-alkoxy-2,3-dihydro-1H-isoindolin-1-one and N-substituted 3-alkoxy-pyrrolidin-2-one derivatives, are prepared under mild conditions in good to excellent isolated yields. Intramolecular reductive couplings can also be performed affording tricyclic compounds in a one-step process. The present protocol opens the way to the development of new base-metal processes for the straightforward synthesis of functionalized N-heterocyclic compounds of pharmaceutical and biological interest.
- ItemAzapeptide activity-based probes for the SARS-CoV-2 main protease enable visualization of inhibition in infected cells(Cambridge : RSC, 2023) Vanhoutte, Roeland; Barniol-Xicota, Marta; Chiu, Winston; Vangeel, Laura; Jochmans, Dirk; De Jonghe, Steven; Zidane, Hadeer; Barr, Haim M.; London, Nir; Neyts, Johan; Verhelst, Steven H. L.The COVID-19 pandemic has revealed the vulnerability of the modern, global society. With expected waves of future infections by SARS-CoV-2, treatment options for infected individuals will be crucial in order to decrease mortality and hospitalizations. The SARS-CoV-2 main protease is a validated drug target, for which the first inhibitor has been approved for use in patients. To facilitate future work on this drug target, we designed a solid-phase synthesis route towards azapeptide activity-based probes that are capped with a cysteine-reactive electrophile for covalent modification of the active site of Mpro. This design led to the most potent ABP for Mpro and one of the most potent inhibitors reported thus far. We demonstrate that this ABP can be used to visualize Mpro activity and target engagement by drugs in infected cells.
- ItemFacile synthesis of supported Ru-Triphos catalysts for continuous flow application in selective nitrile reduction(Cambridge : RSC, 2019) Konrath, Robert; Heutz, Frank J.L.; Steinfeldt, Norbert; Rockstroh, Nils; Kamer, Paul C.J.The selective catalytic hydrogenation of nitriles represents an important but challenging transformation for many homogeneous and heterogeneous catalysts. Herein, we report the efficient and modular solid-phase synthesis of immobilized Triphos-type ligands in very high yields, involving only minimal work-up procedures. The corresponding supported ruthenium-Triphos catalysts are tested in the hydrogenation of various nitriles. Under mild conditions and without the requirement of additives, the tunable supported catalyst library provides selective access to both primary amines and secondary imines. Moreover, the first application of a Triphos-type catalyst in a continuous flow process is presented demonstrating high catalyst life-time over at least 195 hours without significant activity loss. © 2019 The Royal Society of Chemistry.
- ItemGeneral and selective synthesis of primary amines using Ni-based homogeneous catalysts(Cambridge : RSC, 2020) Murugesan, Kathiravan; Wei, Zhihong; Chandrashekhar, Vishwas G.; Jiao, Haijun; Beller, Matthias; Jagadeesh, Rajenahally V.The development of base metal catalysts for industrially relevant amination and hydrogenation reactions by applying abundant and atom economical reagents continues to be important for the cost-effective and sustainable synthesis of amines which represent highly essential chemicals. In particular, the synthesis of primary amines is of central importance because these compounds serve as key precursors and central intermediates to produce value-added fine and bulk chemicals as well as pharmaceuticals, agrochemicals and materials. Here we report a Ni-triphos complex as the first Ni-based homogeneous catalyst for both reductive amination of carbonyl compounds with ammonia and hydrogenation of nitroarenes to prepare all kinds of primary amines. Remarkably, this Ni-complex enabled the synthesis of functionalized and structurally diverse benzylic, heterocyclic and aliphatic linear and branched primary amines as well as aromatic primary amines starting from inexpensive and easily accessible carbonyl compounds (aldehydes and ketones) and nitroarenes using ammonia and molecular hydrogen. This Ni-catalyzed reductive amination methodology has been applied for the amination of more complex pharmaceuticals and steroid derivatives. Detailed DFT computations have been performed for the Ni-triphos based reductive amination reaction, and they revealed that the overall reaction has an inner-sphere mechanism with H2metathesis as the rate-determining step. © The Royal Society of Chemistry 2020.
- ItemCobalt-based nanoparticles prepared from MOF-carbon templates as efficient hydrogenation catalysts(Cambridge : RSC, 2018) Murugesan, Kathiravan; Senthamarai, Thirusangumurugan; Sohail, Manzar; Alshammari, Ahmad S.; Pohl, Marga-Martina; Beller, Matthias; Jagadeesh, Rajenahally V.The development of efficient and selective nanostructured catalysts for industrially relevant hydrogenation reactions continues to be an actual goal of chemical research. In particular, the hydrogenation of nitriles and nitroarenes is of importance for the production of primary amines, which constitute essential feedstocks and key intermediates for advanced chemicals, life science molecules and materials. Herein, we report the preparation of graphene shell encapsulated Co3O4- and Co-nanoparticles supported on carbon by the template synthesis of cobalt-terephthalic acid MOF on carbon and subsequent pyrolysis. The resulting nanoparticles create stable and reusable catalysts for selective hydrogenation of functionalized and structurally diverse aromatic, heterocyclic and aliphatic nitriles, and as well as nitro compounds to primary amines (>65 examples). The synthetic and practical utility of this novel non-noble metal-based hydrogenation protocol is demonstrated by upscaling several reactions to multigram-scale and recycling of the catalyst.