Introduction: It has been suggested that nicotinic acetylcholine receptors (nAchRs) expressed in the ventral tegmental area (VTA) and the nucleus accumbens (nAcc) modulate the effects of drug abuse. This research assessed the effects of intra-accumbal administration of the nAchR antagonist (mecamylamine) and agonist (cytisine) on the operant oral self-administration of ethanol (EtOH) in rats. Methods: Male Wistar rats were water-deprived for 24 h and then trained to lever-press for EtOH reinforcement on a fixed-ratio 1 (FR1) schedule for three sessions. After that, the number of responses in the FR schedule increased to 3 until the response rate remained stable at 80%. After this training, the rats received an intra-accumbal injection of the nAchR antagonist, mecamylamine (0.0, 1.25, 2.5, and 5.0 mu g), then nAchR agonist, cytisine (0.0, 0.8, 1.6, and 3.2 mu g) or the combination of mecamylamine (0.0, 1.25, 2.5, and 5.0 mu g) and cytisine (3.2 mu g) before being provided access to EtOH on a FR3 schedule. Results: The data showed that intra-accumbal administration of mecamylamine reduced operant oral self-administration of EtOH, whereas cytisine increased operant oral self- administration of EtOH. This effect was reversed by mecamylamine. Conclusion: These findings suggest that nAchRs in the nAcc may modulate the operant oral self-administration of EtOH in rats.

The formation of a host-guest complex between the ionic resorcinarene, C-methylresorcin[4]arene tetraminomethylated hydrochloride (TAM) and sodium sulfamerazine (SMR) has been studied using experimental and computational techniques. The host-guest complex has been characterized using spectroscopic, spectrometric, and calorimetric experiments. The computational studies have shown the favor ability, in terms of Gibbs free energy, of the different orientations of SMR forming host-guest complexes with TAM. Calculations have also enabled us to estimate the solvation free energies and the origin of the absorption bands, in agreement with the experimental findings. The results have also shown that SMR is stabilized in a lateral posture on the upper amino rim of TAM. TAM-SMR complex has shown a greater association constant than those reported for beta-CD, presumably due to the anion-cation electrostatic interactions, being TAM more selective towards SMR in the complex formation.(c) 2022 Elsevier B.V. All rights reserved.

The catalytic activity of Cu(i) confined within a phenanthroline-containing calix[8]arene derivative was tested in C-S cross-coupling reactions. The substrate selectivity, solvent dependence, and catalyst loading differ significantly from those reported for bimetallic molecular systems. The putative monomeric complex represents the first calix[8]arene functionalised for endo-oriented metal chelation used as a nanoreactor.

An extension of the method for the regioselective introduction of nitrogen-containing heterocycles at the 1,5-phenolic positions of p-tert-butylcalix[8]arene previously described for 2,6-bis(chloromethyl)pyridine allowed the use of 2,9-bis(bromomethyl)-1,10-phenanthroline as a selective 1,5-dialkylating agent. The 1,5-dimethylpyridine derivative was previously characterized as a relatively rigid dicesium complex [1(4H)2−·2Cs+], its metal-free counterpart 1(6H) is herein described as a fluxional species in solution, as evidenced by VT–NMR and theoretical studies. The 1,5-[2,9-bis(methylene)-1,10-phenanthroline]-p-tert-butylcalix[8]arene analogue 2(6H) was characterized spectroscopically in solution as a relatively rigid cone conformer at 390K. The identity of both metal-free 1(6H) and the monocesium complex [2(5H)−·Cs+] was established in the solid state by X-ray crystallography, confirming the 1,5-substitution of the latter. The conformational behavior of 1(6H) and 2(6H) in solution is described in terms of the enthalpic and entropic contributions by semiempirical methods.

The molecular interactions of 5,6-dichloro-2-(trifluoromethyl)-1H-benzimidazole (G2), an antiprotozoa with poor aqueous solubility, with 2-hydroxypropyl-α-cyclodextrin (HPαCD), methyl-β-cyclodextrin (MβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were examined. The aqueous solubility enhancement by cyclodextrins (CDs) was evidenced in phase-solubility diagrams, and the stoichiometry of G2/CD systems was determined by Job's plots. Two-dimensional NMR spectroscopic data revealed that a different mode of interaction took place between G2 and CDs in solution. With HPαCD, a non-inclusion complex was generated. In the case of MβCD, a typical host-guest system was obtained and with HPβCD a partial inclusion complex through the narrow side of the macrocycle was formed. ESI-mass spectrometric data confirmed the stoichiometry and mode of interaction of these systems in solution. Solid-state characterization (scanning calorimetry and powder X-ray diffraction) supported the inclusion complex formation. The leishmanicidal activity, trypanocidal activity and non-toxic profile of G2/MβCD showed the advantages of using this inclusion complex to promote the biological assays extension of G2.

Plasmodium, the parasite which causes malaria in humans multiplies in the liver and then infects circulating erythrocytes. Thus, the role of the erythrocyte cell membrane in antimalarial drug activity and resistance has key importance. The effects of the antiplasmodial N6-(4-methoxybenzyl)quinazoline-2,4,6-triamine (M4), and its inclusion complex (M4/HPβCD) with 2-hydroxypropyl-β-cyclodextrin (HPβCD) on human erythrocytes and on cell membrane molecular models are herein reported. This work evidences that M4/HPβCD interacts with red cells as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a 10μM concentration; b) in isolated unsealed human erythrocyte membranes (IUM) a concentration as low as 1μM induced sharp DPH fluorescence anisotropy decrease whereas increasing concentrations produced a monotonically decrease of DPH fluorescence lifetime at 37°C; c) X-ray diffraction studies showed that 200μM induced a complete structural perturbation of dimyristoylphosphatidylcholine (DMPC) bilayers whereas no significant effects were detected in dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of lipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively; d) fluorescence spectroscopy data showed that increasing concentrations of the complex interacted with the deep hydrophobic core of DMPC large unilamellar vesicles (LUV) at 18°C. All these experiments are consistent with the insertion of M4/HPβCD in the outer monolayer of the human erythrocyte membrane; thus, it can be considered a promising and novel antimalarial agent.

The macrocycles known as calix[n]arenes, where n represents the number of phenolic units bridged by methylene groups, represent ideal building blocks in supramolecular chemistry for the development of scaffolds with a preorganized structure, a well-defined cavity size, and modifiable positions for the introduction of a variety of functional groups, as shown in Fig. 1 (Bohmer, 1995; Asfari et al., 2001). The development of novel calixarene derivatives with the capability to act as receptors, sensors, catalysts, or ion transporters designed for specific purposes has been exploited to a great extent with the smaller member of the family calix[4]arene, and to a lesser degree with calix[6]arene. In the particular case of calix[4]arenes, the ease of modification by introduction of several types of functional groups at the phenolic rim has led to the development of numerous examples of versatile compounds (Baklouti et al., 2006; Baldini et al., 2007). The variety of derivatives reported to date is related to the well established synthetic protocols, which allow the preparation of calix[4]arenes with regioand atropisomeric control by deprotonation of the phenolic OH groups with specific alkali-metal bases. These synthetic methods have been extended to the more recently developed thiacalix[4]arenes, which feature sulfur atoms as bridging groups between the phenolic components. The development of systems based on the larger members of the calixarene and thiacalixarene families, namely calix[8]arene and thiacalix[8]arene (from now on referred to indiscriminately as calix[8]arenes), has been slow relative to its smaller analogues. This is likely due to the number of phenolic OH and aromatic positions available for functionalization, for which the regioselective introduction of substituents remains a challenging synthetic task. As a consequence, reports on crystallographically characterized calix[8]arene derivatives are relatively sparse. While the solution structures can be determined by a variety of methods, notably NMR spectroscopy, crystallographic characterization still represents the most reliable proof of the spatial arrangement of the macrocycles, particularly when the mobility of the large calix[8]arene is concerned. The limited availability of structural data is likely related to the large number of degrees of freedom present in the larger macrocycles, which does not allow the long-range ordering required for single-crystal formation. A search of the Cambridge Structural Database affords 89 structures of methylene-bridged calix[8]arenes, compared to the numbers of the fourand six-member macrocycles (Table 1).

Reaction of p-tert-butylcalix[8]arene 1 with 2,6-bis(chloromethyl)pyridine results in the regioselective introduction of the nitrogen-containing heterocycle to the 1 and 5 phenolic positions. The deprotonated form of the 1,5-bridged compound 2 acts as a dianionic ligand toward Cs+. The dicesium complex [2 center dot CS2O(H2O)], which has water molecules as additional ligands for the cesium cations, was characterized by X-ray crystallography. (C) 2009 Elsevier Ltd. All rights reserved.

Surface tension of aqueous solutions of 1,2-hexanediol (1,2HD), 1,5-hexanediol (1,5HD), 1,6-hexanediol (1,6HD), and 2,5-hexanediol (2,5HD) was measured as a function of composition using the method of capillary rise at 283.15, 288.15, 293.15, 298.15, 303.15 and 308.15K with emphasis in the very dilute region.