41009-91-0Relevant academic research and scientific papers
Antibiotic Conjugates with an Artificial MECAM-Based Siderophore Are Potent Agents against Gram-Positive and Gram-Negative Bacterial Pathogens
Br?nstrup, Mark,Grunenberg, J?rg,Hotop, Sven-Kevin,Karge, Bianka,Lai, Yi-Hui,Peukert, Carsten,Pinkert, Lukas,Schulze, Lara Marie
, p. 15440 - 15460 (2021/10/25)
The development of novel drugs against Gram-negative bacteria represents an urgent medical need. To overcome their outer cell membrane, we synthesized conjugates of antibiotics and artificial siderophores based on the MECAM core, which are imported by bacterial iron uptake systems. Structures, spin states, and iron binding properties were predicted in silico using density functional theory. The capability of MECAM to function as an effective artificial siderophore in Escherichia coli was proven in microbiological growth recovery and bioanalytical assays. Following a linker optimization focused on transport efficiency, five β-lactam and one daptomycin conjugates were prepared. The most potent conjugate 27 showed growth inhibition of Gram-positive and Gram-negative multidrug-resistant pathogens at nanomolar concentrations. The uptake pathway of MECAMs was deciphered by knockout mutants and highlighted the relevance of FepA, CirA, and Fiu. Resistance against 27 was mediated by a mutation in the gene encoding ExbB, which is involved in siderophore transport.
Flexibility of C3h-Symmetrical Linkers in Tris-oligonucleotide-Based Tetrahedral Scaffolds
Panagiotidis, Christos,Kath-Schorr, Stephanie,Von Kiedrowski, Günter
, p. 254 - 259 (2016/02/12)
Flexibility of tris-oligonucleotides is determined by the length of their connecting hydrocarbon chains. Tris-oligonucleotides are branched DNA building blocks with three oligonucleotide arms attached to a C3h-symmetrical linker core at these chains. Four tris-oligonucleotides hybridise into a tetrahedral nanocage by sequence-determined self-assembly. The influence of methylene, ethylene and propylene chains was studied by synthesising sets of tris-oligonucleotides and analysing the relative stability of the hybridisation products against digestion by mung bean nuclease by using gel electrophoresis. Linkers with ethylene chains showed sufficient flexibility, whereas methylene-chain linkers were too rigid. Tris-oligonucleotides based on the latter still formed tetrahedral scaffolds in intermixing experiments with linkers of higher flexibility. Thus, a new generation of versatile isocyanurate-based linkers was established.
Preparation, properties, and reactions of metal-containing heterocycles, 99. - Cage-structured triplatinacyclophanes
Lindner, Ekkehard,Hermann, Christian,Baum, Gerhard,Fenske, Dieter
, p. 679 - 685 (2007/10/03)
The synthesis of the tris(triflate) 4 (Scheme 1) has been achieved by means of a straightforward three-step reaction sequence. After initial lithiation of mesitylene, treatment of the obtained trilithium compound C6H3(CH2Li)3 (2) with oxirane results in the formation of 1,3,5-tris(3- hydroxypropyl)benzene (3), which is then transformed to 4 by reaction with (CF3SO2)2O in the presence of pyridine. Whereas 4 reacts with Na2[Os(CO)4] in a somewhat complicated manner, similar reactions with Na[Re(CO)5] and LiPPh2 give the hydrocarbon-bridged tris(rhenium) complex C6H3[(CH2)3Re(CO)5]3 (5) and the tris(phosphane) C6H3[(CH2)3PPh2]3 (6), respectively. Employing the high-dilution method, from 6 and Cl2Pt(NCPh)2 the nanoscaled tri- and hexaplatinacyclophanes 7 and 9 are available. Owing to the optimal geometry and flexibility of the cage in 7, 1,2-dichloroethane can be reversibly encapsulated. The molecular structure of 7 · 7 1,2-Cl2C2H4 was determined by an X-ray structure analysis. The utility of the reactive metal centers in 7 has been demonstrated by replacing the chloro ligands by acetonitrile to give the cationic platinacyclophane 8, in which, according to NMR studies, the cage-like structure is preserved.
Synthesis of Imidazole-Containing Ligands and Studies on Metal Complexes
Yamagiwa, Yoshiro,Koreishi, Yoshiro,Kiyozumi, Satoshi,Kobayashi, Masanori,Kamikawa, Tadao,Tsukino, Mitsuji,Goi, Hironori,Yamamoto, Mikiko,Munakata, Megumu
, p. 3317 - 3323 (2007/10/03)
1,5-Di(imidazol-l-yl)-3-(2-(imidazol-l-yl)ethyl]pentane, 1,7-di(imidazol-l-yl)-4-[3-(imidazol-l-yl)propyl]heptane, N,N′,N″ -tris[2-(imidazol-4-yl)ethyl]benzene-1,3,5-tricarboxamide, and 1,3,5-tris[3-(imidazol-l-yl)propyl]benzene (TIPB) have been synthesized for a study of the formation and characteristics of zinc complexes. TIPB forms a crystalline zinc complex, not a tetrahedral complex but an octahedral complex. Other ligands form either microcrystalline complexes or polymer complexes with zinc.
