Studies of Intramolecular Cyclization of 4-Arylpyridines. II Syntheses of Condensed Tricyclic Pyridines

A convenient method for the synthesis of condensed tricyclic pyridines using intramolecular cyclization of 4-arylpyridines is reported. The tricyclic compounds, 2-azafluorenone (9), 2-azafluorenone (10), 2-azafluorenol (11), lactones 12 and 13, and anhydride 14 have been prepared.     

Determination of tricyclic antidepressants using silica gel with a reversed-phase eluent

Summary Five common tricyclic antidepressants are separated on a silica column using an aqueous eluent. The tricyclics are concentrated from serum using an adsorption procedure on a solid phase Sep Pak^TM C₁₈ cartridge. The method appears to be adequate for monitoring therapeutic levels of these drugs.Dedicated to Professor Dr. István Halász for his 60th birthday.     

The effect of 2-hydroxypropyl-β-cyclodextrin on the excited triplet state of promazine and chlorpromazine

Chlorpromazine hydrochloride (CPZ) is a widely used anti-psychotic drug that induces skin photosensitization and photoallergy response after systematic use or topical applications. The photoallergic mechanism is still unknown. However, it has been proposed that the triplet excited state (³CPZ*) could participate in the photodamaging effects. In this work, we report the photophysical properties of the triplet excited state of CPZ and its parent derivative promazine hydrochloride (PZ) in the presence of 2-hydroxypropyl-β-cyclodextrin (HPC). Absorption measurements indicate that PZ and CPZ form an inclusion complex with HPC through a 1:1 stoichiometry. The equilibrium constant at 25 °C is (2.55 ± 0.09) × 10³ M⁻¹ and (3.27 ± 0.07) × 10³ M⁻¹ for PZ and CPZ, respectively. The CPZ and PZ triplet excited state properties changed in the presence of HPC. The triplet lifetime increases with HPC concentration that is related to the amount of drug bound. In addition, the triplet intersystem crossing quantum yield was determined to be 0.45 and 0.17 for PZ and CPZ, respectively, when more than 95% of the drug molecules are bound to HPC. Altogether, these results suggest that the microenvironment plays a crucial role in the ³CPZ* and ³PZ* properties and thus it can modulate their photosensitizing effects.     

Is the Antidepressant Activity of Selective Serotonin Reuptake Inhibitors Mediated by Nicotinic Acetylcholine Receptors?

It is generally assumed that selective serotonin reuptake inhibitors (SSRIs) induce antidepressant activity by inhibiting serotonin (5-HT) reuptake transporters, thus elevating synaptic 5-HT levels and, finally, ameliorates depression symptoms. New evidence indicates that SSRIs may also modulate other neurotransmitter systems by inhibiting neuronal nicotinic acetylcholine receptors (nAChRs), which are recognized as important in mood regulation. There is a clear and strong association between major depression and smoking, where depressed patients smoke twice as much as the normal population. However, SSRIs are not efficient for smoking cessation therapy. In patients with major depressive disorder, there is a lower availability of functional nAChRs, although their amount is not altered, which is possibly caused by higher endogenous ACh levels, which consequently induce nAChR desensitization. Other neurotransmitter systems have also emerged as possible targets for SSRIs. Studies on dorsal raphe nucleus serotoninergic neurons support the concept that SSRI-induced nAChR inhibition decreases the glutamatergic hyperstimulation observed in stress conditions, which compensates the excessive 5-HT overflow in these neurons and, consequently, ameliorates depression symptoms. At the molecular level, SSRIs inhibit different nAChR subtypes by noncompetitive mechanisms, including ion channel blockade and induction of receptor desensitization, whereas α9α10 nAChRs, which are peripherally expressed and not directly involved in depression, are inhibited by competitive mechanisms. According to the functional and structural results, SSRIs bind within the nAChR ion channel at high-affinity sites that are spread out between serine and valine rings. In conclusion, SSRI-induced inhibition of a variety of nAChRs expressed in different neurotransmitter systems widens the complexity by which these antidepressants may act clinically.     

Two‐phase electromembrane extraction followed by gas chromatography‐mass spectrometry analysis

A two‐phase electromembrane extraction (EME) was developed and directly coupled with gas chromatography mass spectrometry (GC‐MS) analysis. The proposed method was successfully applied to the simultaneous determination of imipramine, desipramine, citalopram and sertraline. The model compounds were extracted from neutral aqueous sample solutions into the organic phase filled in the lumen of the hollow fiber. This method was accomplished with 1‐heptanol as organic phase, by means of 60 V applied voltage and with the extraction time of 15 min. Experiments reported recoveries in the range of 69–87% from 1.2 mL neutral sample solution. The compounds were quantified by GC‐MS instrument, with acceptable linearity ranging from 1 to 500 ng mL^?1 (R² in the range of 0.989 to 0.998), and repeatability (RSD) ranging between 7.5 and 11.5% (n = 5). The estimated detection limits (S/N ratio of 3:1) were less than 0.25 ng mL^?1. This novel approach based on two‐phase EME brought advantages such as simplicity, low‐costing, low detection limit and fast extraction with a total analysis time less than 25 min. These experimental findings were highly interesting and demonstrated the possibility of solving ionic species in the organic phase at the presence of electrical potential.     

Synthesis of Tricyclic Skeletons Mediated by (Diene)Fe(CO)3 Complexes

Sequential additions of carbon nucleophiles to the (η⁵-pentadienyl)Fe(CO)₃ cation afforded tricyclo[6.3.0.0^2.6]undecane, tricyclo[6.4.0.0^2.6]dodecane, tricyclo[7.3.0.0^2.7]dodecane and tricyclo[7.4.0.0^2.7]-tridecane derivatives. The same strategy can also be applied to construct heterotricyclic skeletons.     

(<Emphasis Type="Italic">S</Emphasis>)-(−)-α-Methylbenzylamine as chiral auxiliary in the synthesis of (+)-lortalamine

Abstract  (+)-Lortalamine was synthesised using (S)-(−)-α-methylbenzylamine as a chiral auxiliary. The stereochemistry of an intermediate compound was established on the basis of X-ray crystallography, allowing unambiguous assignment of the absolute configuration. Graphical abstract        

最大化小维数图的补的谱半径的统一方法

在树、单圈图、双圈图和三圈图的补图中,本文给出了统一的方法来刻画具有极大谱半径的图.     

Functionalized superparamagnetic nanoparticles with a polymer containing β‐cyclodextrin for the extraction of sertraline hydrochloride in biological samples

In this study, a novel magnetic nanoadsorbent was synthesized by grafting β‐cyclodextrin onto the modified surface of Fe₃O₄ nanoparticles for the sorption and extraction of sertraline hydrochloride from human biological fluids. The extracted sertraline hydrochloride was measured by high‐performance liquid chromatography. The grafted nanosorbent was confirmed by Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, and elemental analysis. The kinetic sorption of sertraline hydrochloride by magnetic nanosorbent was 1 h. The best temperature for sorption of sertraline hydrochloride was at 25°C at an optimum pH of 5. The adsorbed sertraline hydrochloride can be desorbed by using methanol solution containing acetic acid (5%) and trifluoroacetic acid (1%).     

Development of green sodium sulfate‐induced solidification of floating organic droplets–dispersive liquid phase microextraction method: Application to extraction of four antidepressants

Sodium sulfate‐induced deep eutectic solvent–based solidification of floating organic droplets–dispersive liquid phase microextraction was developed prior to gas chromatography–mass spectrometry. In this method, a mixture of Na₂SO₄ solution (as phase separation agent and disperser) containing menthol–decanoic acid was rapidly injected into an alkaline aqueous solution containing Na₂SO₄. The solution was placed in an ice bath and the menthol–decanoic acid solvent was solidified on the surface of the solution. Under the optimal conditions, the enrichment factors and extraction recoveries were 122–147 and 74–89%, respectively. Finally, an aliquot of the collected organic phase was removed and mixed with acetonitrile and injected into the separation system. The limits of detection and lower limits of quantification were obtained at the ranges of 13–25 and 24–41 ng L^?1, respectively. The relative standard deviations of the proposed method were ≤11% for intra‐ and inter‐day precisions at four concentrations.