A series of mono- and per-6-substituted cyclodextrin derivatives were synthesized as synthetic receptors (or host molecules) of rocuronium bromide, the most widely used neuromuscular blocker in anaesthesia. By forming host-guest complexes with rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced by rocuronium in vitro and in vivo and therefore can be used as reversal agents of the neuromuscular blocker to assist rapid recovery of patients after surgery. Because this supramolecular mechanism of action does not involve direct interaction with the cholinergic system, the reversal by these compounds, e.g., compound 14 (Org 25969), is not accompanied by cardiovascular side effects usually attendant with acetylcholinesterase inhibitors such as neostigmine. The structure-activity relationships are consistent with this supramolecular mechanism of action and are discussed herein. These include the effects of binding cavity size and hydrophobic and electrostatic interaction on the reversal activities of these compounds.
Cornering the 13th vertex: The first 13‐vertex carborane (see picture, B: brown, C: gray, H: white) has been prepared by a methodology that can in principle be applied repeatedly, leading to 14‐, 15‐, 16‐, …︁ vertex carboranes in the future. The 13‐vertex species has a henicosahedral geometry, not the docosahedral one expected, but the two forms are found to be very close in energy by DFT calculations.
1. General Methods All reagents were purchased from commercial suppliers (Aldrich or Fisher) and used without further purification. Cyclobis(paraquat-4,4′-biphenylene) tetrakis(hexafluorophosphate) S1 (1•4PF6), 4,4′(5′)-bis[2-(2-{2-(propargyl)ethoxy}ethoxy)ethoxy]tetrathiafulvalene S2 (7), the TTF/ DNP macrocycle S3 4, and 1,1ʹ′-[4,4ʹ′-biphenylenebis-(methylene)]bis(4,4ʹ′-bipyridinium) bis (hexafluorophosphate) S4 (5•2PF6) were prepared according to literature procedures. Thin layer chromatography (TLC) was performed on silica gel 60 F254 (E. Merck). Column chromatography was performed on silica gel 60F (Merck 9385, 0.040-0.063 nm). Nuclear magnetic resonance (NMR) spectra were recorded at 25 ˚C (unless otherwise noted) on Bruker Avance 500 and 600 spectrometers, with working frequencies of 500 and 600 MHz for 1 H, and 125 and 150 MHz for 13 C nuclei, respectively. Chemical shifts are reported in ppm relative to the signals corresponding to the residual non-deuterated solvents S5. All 13 C spectra were recorded with the simultaneous decoupling of proton nuclei. UV-Vis-NIR absorbance spectra
a b s t r a c tThe condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2-14). The copper(II) complexes (2a-14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, 1 H and 13 C NMR, AAS, UV-Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent antiCandida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2-8 and 2a-8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G 2 . Several derivatives were shown to be active comparable to that of cisplatin.
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