41009-92-1Relevant articles and documents
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.
Trifunctional phosphane ligands and their application in the synthesis of novel cage-structured platinacyclophanes and trinuclear chain-like platinacycles by self-assembly
Lindner, Ekkehard,Khanfar, Monther,Steimann, Manfred
, p. 2411 - 2419 (2007/10/03)
The synthesis of the 1,3,5-tris[(diphenylphosphoryl)alkyl]-benzenes 7-10 succeeds by reaction of the corresponding 1,3,5-tris(bromoalkyl)benzenes 3-6 with ethyl diphenylphosphinite in an Arbusov-type reaction. Reduction of these phosphane oxides leads to the trifunctional phosphane ligands 11-14. Their potency of self-assembly was examined by the employment of platinum(II) complex fragments. A five-component self-assembly consisting of 3 equiv, of the platinum complex Cl2Pt(NCPh)2 and 2 equiv, of the ligands 11-14 under high-dilution conditions led to the formation of the nanoscaled triplatinacyclophanes 1 and 15-17. Polymers were formed as by-products from the reactions between 11-13 and Cl2Pt(NCPh)2, whereas in the case of 14 three other platinacyles 18-20 with a chain-like structure were formed. The structures of the metallacycles 1 and 15-17 as well as 18-20 were elucidated by 31p{1H}, 13C{1H}, and 195Pt{1H} NMR spectroscopic investigations.
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.
