- Antibiotic Conjugates with an Artificial MECAM-Based Siderophore Are Potent Agents against Gram-Positive and Gram-Negative Bacterial Pathogens
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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.
- Br?nstrup, Mark,Grunenberg, J?rg,Hotop, Sven-Kevin,Karge, Bianka,Lai, Yi-Hui,Peukert, Carsten,Pinkert, Lukas,Schulze, Lara Marie
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p. 15440 - 15460
(2021/10/25)
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- Chemically Triggered Synthesis, Remodeling, and Degradation of Soft Materials
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Polymer topology dictates dynamic and mechanical properties of materials. For most polymers, topology is a static characteristic. In this article, we present a strategy to chemically trigger dynamic topology changes in polymers in response to a specific chemical stimulus. Starting with a dimerized PEG and hydrophobic linear materials, a lightly cross-linked polymer, and a cross-linked hydrogel, transformations into an amphiphilic linear polymer, lightly cross-linked and linear random copolymers, a cross-linked polymer, and three different hydrogel matrices were achieved via two controllable cross-linking reactions: reversible conjugate additions and thiol-disulfide exchange. Significantly, all the polymers, before or after topological changes, can be triggered to degrade into thiol- or amine-terminated small molecules. The controllable transformations of polymeric morphologies and their degradation herald a new generation of smart materials.
- Anslyn, Eric V.,Bachman, James L.,Chwatko, Malgorzata,Lee, Doo-Hee,Lynd, Nathaniel A.,Reuther, James F.,Sun, Xiaolong
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supporting information
p. 3913 - 3922
(2020/03/10)
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- Corresponding amine nitrile and method of manufacturing thereof
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The present invention relates to a nitrile manufacturing method, which has characteristics of significantly-reduced ammonia source consumption, low environmental pressure, low energy consumption, low production cost, high nitrile purity, high nitrile yield and the like compared with the method in the prior art, wherein nitrile having a complicated structure can be obtained through the method. The present invention further relates to a method for producing a corresponding amine from the nitrile.
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Paragraph 0146; 0151
(2018/05/24)
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- Corresponding amine nitrile and method of manufacturing thereof
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The invention relates to a preparation method of nitrile. Compared with the prior art, the preparation method has the characteristics of obvious reduction of the usage amount of ammonia sources, low environmental pressure, low energy consumption, low production cost, high purity and yields of nitrile products, and the like, and can be used for obtaining nitrile with a more complex structure. The invention also relates to a method for preparing corresponding amine with nitrile.
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Paragraph 0148
(2018/05/24)
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- Shape-Persistent [4+4] Imine Cages with a Truncated Tetrahedral Geometry
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The synthesis of shape-persistent organic cage compounds is often based on the usage of multiple dynamic covalent bond formation (such as imines) of readily available precursors. By careful choice of the precursors geometry, the geometry and size of the resulting cage can be accurately designed and indeed a number of different geometries and sizes have been realized to date. Despite of this fact, little is known about the precursors conformational rigidity and steric preorganization of reacting functional groups on the outcome of the reaction. Herein, the influence of conformational rigidity in the precursors on the formation of a [4+4] imine cage with truncated tetrahedral geometry is discussed.
- Lauer, Jochen C.,Zhang, Wen-Shan,Rominger, Frank,Schr?der, Rasmus R.,Mastalerz, Michael
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p. 1816 - 1820
(2018/01/22)
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- Corresponding amine nitrile and method of manufacturing thereof (by machine translation)
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The invention relates to a method of manufacturing one kind of nitrile, compared with the prior art, has significantly reduced the amount of ammonia, the environmental pressure of the small, low energy consumption, low production cost, nitrile product purity and yield and the like, and can obtain more complex structure of the nitriles. The invention also relates to the corresponding amine by the nitrile manufacture method. (by machine translation)
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Paragraph 0149
(2017/10/22)
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- Rationally designed cooperatively enhanced receptors to magnify host-guest binding in water
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When disengaged interactions within a receptor are turned on by its guest, these intrahost interactions will contribute to the overall binding energy. Although such receptors are common in biology, their synthetic mimics are rare and difficult to design. By engineering conflictory requirements between intrareceptor electrostatic and hydrophobic interactions, we enabled complementary guests to eliminate the "electrostatic frustration" within the host and turn on the intrahost interactions. The result was a binding constant of Ka >105 M-1 from ammonium-carboxylate salt bridges that typically function poorly in water. These cooperatively enhanced receptors displayed excellent selectivity in binding, despite a large degree of conformational flexibility in the structure.
- Gunasekara, Roshan W.,Zhao, Yan
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p. 843 - 849
(2015/01/30)
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- SUBSTITUTED AROMATIC COMPOUND, HYDROGELATION AGENT, HYDROGEL, AND METHOD FOR GELATING AQUEOUS SAMPLE
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According to the present invention, a substituted aromatic compound represented by the following general formula (I) is provided. In general formula (I), A1, A2, and A3 each independently represent an aryl group substituted by a hydrophilic group.
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Paragraph 0128; 0129; 0130; 0131
(2014/01/23)
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- Connection of metallamacrocycles via dynamic covalent chemistry: A versatile method for the synthesis of molecular cages
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A modular approach for the synthesis of cage structures is described. Reactions of [(arene)RuCl2]2 [arene = p-cymene, 1,3,5-C6H3Me3, 1,3,5-C6H 3(i-Pr)3] with formylsub
- Granzhan, Anton,Schouwey, Clement,Riis-Johannessen, Thomas,Scopelliti, Rosario,Severin, Kay
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p. 7106 - 7115
(2011/06/26)
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- Self-assembly of ball-shaped molecular complexes in water
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We present a simple and versatile access to spheroidal molecular assemblies with pronounced stability in highly polar solvents. These complexes are composed of doubly and triply charged complementary building blocks based on ammonium or amidinium cations
- Grawe, Thomas,Schrader, Thomas,Zadmard, Reza,Kraft, Arno
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p. 3755 - 3763
(2007/10/03)
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- "Flexiball" toolkit: A modular approach to self-assembling capsules
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We report the synthesis and characterization of new, self-assembling molecular capsules. The modular strategy makes use of glycoluril building blocks available in multigram amounts combined with aromatic spacer elements. The lengthy syntheses encountered with earlier generations of capsules are avoided, and several capsules of nanometer dimensions are now accessible. Single bond attachments between spacers and glycoluril modules result in monomers as dimeric capsules that are less rigid than their earlier counterparts. The host-guest properties of the homo- and heterodimeric capsules were studied using a combination of NMR and ESI-mass spectrometry. They show a less pronounced selectivity for guests of different sizes, and their increased flexibility prevents self-assembly when no rigidifying elements are present on the central spacer unit. Some of the new capsules bear inwardly directed, secondary amide N-H protons. These can be further functionalized, as shown by their methylation to give tertiary analogues. The structures hold broader implications for the placement of functional groups on concave molecular surfaces.
- O'Leary,Szabo,Svenstrup,Schalley,Luetzen,Schaefer,Rebek Jr.
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p. 11519 - 11533
(2007/10/03)
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- Cascade polymer bound chelating compounds, their chelates and conjugates, processes for their production, and pharmaceutical agents containing them
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Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.
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- Synthesis and characterization of macrobicyclic iron(III) sequestering agents
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This paper reports the template and high-dilution syntheses of a series of macrobicyclic iron(III) sequestering agents based on catechol as the ligating group. An X-ray structure of the salt denoted as Na3[Fe(bicappedTRENCAM)]·17.5H2O is the first for any ferric tricatechoyl amide and displays an unprecedented trigonal prismatic coordination (C3h symmetry) for the ferric ion. The compound crystallizes in space group P63/m with a = 13.785 (3) A?, c = 16.244 (5) A?, dobs = 1.45, dcalc = 1-51 g cm-3. The structure was refined to an R factor of 4.38, Rw = 5.16. The O-O atoms of the trigonal face are separated by 2.713 (3) A?, those related by the mirror plane by 2.526 (4) A?. The Fe-O distances are 2.012 (2) A?, and the bite angle is 77.75 (11)°. Solution thermodynamic studies on one of the ligands, bicappedTRENCAM, determine surprisingly low protonation constants (log K1K2 = 27.2 (1), log K1 = 8.3 (1), log K4K5 = 8.73 (1), log K6K7K8 = 9.75 (1)) containing a number of polyprotic steps. Aqueous electrochemical studies performed on the ferric complexes of these ligands show reversible reduction potentials of -0.89 to -0.97 V (vs NHE). While still highly selective for the ferric ion (ratios of the formation constants of ferric to ferrous complexes range from 28.1 to 29.5), these ligands have a slight stabilization of the ferrous complex relative to related tripodal compounds, one of which is the siderophore enterobactin. A slow protonation reaction is seen upon reduction of the ferric complexes. The protonation constant of the Fe(bicappedTRENCAM) complex proceeds in an unusual two-proton step with an equilibrium constant of (log K1K2) 10.65 (1). The complex formation constant (log K) is 43.1 (4), which shows no increase due to the macrobicyclic structure of the ligand relative to related hexadentate catechol ligands. The pM value is 30.7, where pM = -log [Fe] at pH 7.4 and [Fe]T- = 10-6 M, [L]T = 10-5 M.
- Garrett, Thomas M.,McMurry, Thomas J.,Hosseini, Mir Wais,Reyes, Zeliderh E.,Hahn, F. Ekkehardt,Raymond, Kenneth N.
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p. 2965 - 2977
(2007/10/02)
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- ANION COORDINATION CHEMISTRY - SYNTHESIS AND ANION BINDING FEATURES OF CYCLOPHANE TYPE MACROBICYCLIC ANION RECEPTOR MOLECULES
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Three triply bridged cyclophane type, macrobicyclic polyamines 1-3 have been synthesized; in their hexa-protonated form they strongly bind a variety of anionic substrates, thus acting as anion receptor molecules.
- Heyer, Dennis,Lehn, Jean-Marie
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p. 5869 - 5872
(2007/10/02)
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- Large Oligocyclic Cavities for Strong Cation Complexation
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The syntheses of oligocyclic large cavities containing two or three catechol subunits are described.The X-ray analysis of a heptacyclic molecule composed of three triply clamped dimethyl catechol ether units demonstrates the size and shape of the cavity formed by this skeleton.Properties of the Fe(3+)- and Ga(3+)-complexes are elucidated by (1)H-NMR, IR, UV/Vis spectra, and by competition experiments with an open-chained reference ligand.
- Kiggen, W.,Voegtle, F.,Franken, S.,Puff, H.
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p. 1859 - 1872
(2007/10/02)
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- Triisocyanates
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The present invention provides novel triisocyanate compounds of the formula: STR1 the production thereof and the use thereof for polyurethane resins, especially, for solvent-free or high solids polyurethane coatings.
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