Synthesis and biological activity of cymantrene and cyrhetrene 4-aminoquinoline conjugates against malaria, leishmaniasis, and trypanosomiasis

Organometallic analogues of chloroquine show promise as new antimalarial agents capable of overcoming resistance to the parent drug chloroquine. Here, the synthesis and characterization of three new cymantrene (CpMn(CO)(3)) and cyrhetrene (CpRe(CO)(3)) 4-aminoquinoline conjugates with either an amine or amide linker are reported. The antimalarial activity of the new organometallic conjugates N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cymantrenylbutanamide (3), N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cyrhetrenylbutanamide (4) and N-(7-chloroquinolin-4-yl)-N'-(cymantrenylmethyl)ethane-1,2-diamine (6) was evaluated against a chloroquine-sensitive (CQS) and a chloroquine-resistant strain (CQR) of the malaria parasite Plasmodium falciparum. The cymantrene complex with an amine linker (6) showed good activity against the CQS strain but was inactive against the CQR strain. In contrast, cymantrene and cyrhetrene compounds with an amide linker were active against both the CQS and the CQR strain. In addition, the antibacterial, anti-trypanosomal and anti-leishmanial activity of the compounds was evaluated. Compound 6 showed submicromolar activity against Trypanosoma brucei at a concentration where the toxicity to normal human cells is low. No significant effect was noticed on the exchange of manganese for rhenium in the CpM(CO)(3) moiety in any of the biological assays.     

Stable vesicles composed of monocarboxylic or dicarboxylic fatty acids and trimethylammonium amphiphiles

The self-assembly of cationic and anionic amphiphile mixtures into vesicles in aqueous media was studied using two different systems: (i) decanoic acid and trimethyldecylammonium bromide and (ii) hexadecanedioic acid (a simple bola-amphiphile) and trimethyldecylammonium bromide. The resulting vesicles with varying amphiphile ratios were characterized using parameters such as the critical vesicle concentration, pH sensitivity, and encapsulation efficiency. We also produced and observed giant vesicles from these mixtures using the electroformation method and confocal microscopy. The mixed catanionic vesicles were shown to be more stable than those formed by pure fatty acids. Those containing bola-amphiphile even showed the encapsulation of a small hydrophilic solute (8-hydroxypyrene-1,3,6-trisulfonic-acid), suggesting a denser packing of the amphiphiles. Compression and kinetics analysis of monolayers composed of these amphiphiles mixtures at the air/water interface suggests that the stabilization of the structures can be attributed to two main interactions between headgroups, predominantly the formation of hydrogen bonds between protonated and deprotonated acids and the additional electrostatic interactions between ammonium and acid headgroups.     

Enhancement of Dielectronic Recombination by External Electromagnetic Fields

The enhancement of the dielectronic recombination rate of lithiumlike Ne⁷⁺ and O⁵⁺ ions by external electromagnetic fields has been measured at the storage ring CRYRING. The energy range covered all 1s ²2pnl dielectronic recombination resonances attached to the 2s→2p core excitation. Electric fields up to 1436 V/cm were applied in the Ne⁷⁺ experiment and the saturation of the enhancement with increasing electric field could clearly be seen. In the O⁵⁺ experiment the enhancement was studied as a function of the Rydberg quantum number n.

     

Resonant soft X-ray fluorescence spectra of molecules

Accepted: 6 March 1997     

离子和冷却电子重组的高分辨谱研究(英文)

给出了在CRYRING重离子储存环上测量到的在很低能量下电子与离子重组的最新实验结果和有关速率系数增强的新的数据 .主要讨论类锂、类钠和类铜离子的共振双电子重组的新近测量结果 ,以及从这些共振谱中所导出的非常精确的离子能级劈裂值 ,从而将严格检验相对论效应、电子关联效应和量子电动力学效应 .其中 ,对类锂Kr3 3 + 离子 2s1/2 能级Lamb移位的确定精度达到了0 .1%. We present our latest results on recombination of electrons with ions at very low energies obtained at the CRYRING heavy-ion storage ring. New data on the enhanced rate coefficient are shown. Then we concentrate on recent measurements of dielectronic recombination resonances with Li-like, Na-like, and Cu-like ions, where from the spectra of resonances very accurate values for energy splittings are derived for crucial tests of relativistic, correlation, and QED effects.     

Loschmidt echo in a system of interacting electrons

We study the Loschmidt echo for a system of electrons interacting through mean-field Coulomb forces. The electron gas is modeled by a self-consistent set of hydrodynamic equations. It is observed that the quantum fidelity drops abruptly after a time that is proportional to the logarithm of the perturbation amplitude. The fidelity drop is related to the breakdown of the symmetry properties of the wave function.     

Fragmentation of highly excited small neutral carbon clusters

We present a combined experimental and theoretical study of fragmentation of small Cn clusters (n = 5,7,9) produced in charge transfer collisions of fast (nu = 2.6 a.u.) singly charged Cn+ clusters with He. Branching ratios for all possible fragmentation channels have been measured. Comparison with microcanonical Metropolis Monte Carlo simulations based on quantum chemistry calculations allows us to determine the energy distribution of the excited clusters just after the collision.     

QED effects in Cu-like Pb recombination resonances near threshold

In an electron-ion recombination study with Pb53+ dielectronic recombination resonances are found for as low as approximately 10(-3)-10(-4) eV relative energy. The resonances have been calculated by relativistic many-body perturbation theory and through comparison with experiment the Pb53+(4p(1/2)-4s(1/2)) energy splitting of approximately 118 eV is determined with an accuracy comparable to the position of the first few resonances, i.e., approximately 10(-3) eV. Such a precision provides a test of QED in a many-body environment at a level which can still not be reached in calculations.     

Synthesis and electrical properties of substituted paracyclophane polymers

We report the synthesis of three new substituted [6.2]paracyclophane-1,5-dienes and their conversion to medium molecular weight polymers by an intra/intermolecular cyclopolymerization. These materials can be oxidatively “doped” by exposure to iodine vapor to give semiconductor properties.     

Unoccupied electronic states in graphite oxides

Unoccupied electronic states of graphite oxides with different oxidation times have been investigated using X-ray absorption spectroscopy (XAS) in total electron yield (TEY) and total fluorescence yield (TFY) modes. The graphite oxides exhibit graphite-like sp² states with additional electronic states originating from functional groups. The intensity of the π^* state decreases as the atomic ratio O:C increases. The intensity ratio of carboxyl to π^* states in XAS TEY mode corresponds to the area ratio of carboxyl to sp² carbon in X-ray photoelectron spectroscopy. In addition, the two modes in XAS can identify electronic states of functional groups originating from surface or bulk regions.