No abstract

The supramolecular interactions between Imipramine hydrochloride (IMI), a tricyclic antidepressant, and beta-cyclodextrin (betaCD) have been investigated by experimental techniques and theoretical calculations. The association between these molecules might be lead to a host/guest compound, in which the physical chemistry properties of the guest molecule, such as high solubility, can be decreased. These new properties acquired by the inclusion phenomena are important to develop a strategy for pharmaceutical formulation. Nuclear magnetic resonance and horizontal attenuated total reflectance provided relevant information on the complex stoichiometries and the sites of interactions between the host and guest molecules. Stoichiometries of 1:2, 1:1, and 2:1 betaCD/IMI have been detected in solution. Self-diffusion coefficient and dynamic light scattering analysis provided information on the self-aggregation of the complex. Also, isothermal titration calorimetry studies indicated the existence of equilibrium between different complexes in solution. In order to determine the preferred arrangement for the inclusion complex formed by the IMI molecule and betaCD, theoretical calculations were performed. Of all proposed supramolecular structures, the 2:1 betaCD/IMI complex was calculated to be the most energetically favorable, in both gas and aqueous phases. The calculations indicated that the intermolecular hydrogen bonds involving the hydroxyl groups of betaCD play a major role in stabilizing the supramolecular 2:1 structure, corroborating experimental findings.

An NMR study of 3α‐ and 3β‐friedelinol is described. In addition to conventional 1D NMR methods, 2D shift‐correlated NMR experiments HMQC [(1J(C,H)], HMBC [nJ(C,H); n=2 and 3] and 2D 1H,1H‐NOESY were used for 1H and 13C chemical shift assignments of these triterpenes. Copyright © 2000 John Wiley & Sons, Ltd.

Abstract. The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess amount of quercetin) on the complexation of quercetin with β-cyclodextrin using a 2 3 factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37°C/24 h/6 mM of quercetin. The stoichiometric ratio (1:1) and the apparent stability constant (Ks=230 M −1 ) of the quercetin/β-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production of a 1:1 quercetin/β-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited to 4.6-fold in the presence of 15 mM of β-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture of quercetin with β-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold, similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio of 1:1, i.e., 6 mM of quercetin and 6 mM of β-cyclodextrin).

Sertraline (SRT) is a widely used antidepressant whose poor solubility in water limits its oral applicability. Thus, the aim of this work was the evaluation of a multi-equilibrium system based on β-cyclodextrin (βCD) and SRT. The inclusion compounds (ICs) were investigated by infrared spectroscopy, isothermal titration calorimetry (ITC) and (1)H and 2D ROESY nuclear magnetic resonance experiments. SRT solubility was predicted in vitro in water and biomimetic fluids. The SRT in presence of βCD at 1:1 and 1:2 molar ratios was more soluble than free SRT in all biomimetics media investigated. The FTIR-HATR showed that βCD νC-O-C stretching band was reduced in presence of SRT, suggesting the interactions between them. Additionally, titration process and Job's plot provided information on the ICs stoichiometry and evidenced the multi-equilibrium coexistence in aqueous solution. According to the ITC, SRT:βCD interaction process was spontaneous and exothermic with a high affinity binding constant (K=14,726 M(-1)). Additionally, the stoichiometry coefficient (n) was 1.63, which was comparable to that found by FITR-HATR. The (1)H and 2D ROESY verified multiple SRT sites included into the host cavity. Theoretical calculations depicted the relative energy of different proposed ICs structures, in which the 1:2 IC was the most stable.

No abstract

Two simple and efficient procedures for the preparation of pentavalent antimony derivatives are described, using either antimony pentachloride (SbCl 5 ) or potassium hexahydroxoantimonate (KSb(OH) 6 ) as sources of antimony(V). These two new methods are evaluated for the synthesis of an important anti-leishmanial drug: meglumine antimonate. Using elemental (carbon, hydrogen, nitrogen) and thermal analysis, atomic absorption (antimony), proton NMR spectroscopy and highresolution positive-ion electrospray ionization mass spectrometry (ESI(+)-MS), products for the reaction with N-methyl-D-glucamine (NMG) using both the SbCl 5 and KSb(OH) 6 methods were characterized and found to be similar to a commercial sample of the drug. The only notable difference was observed for the ESI-MS spectrum of the KSb(OH) 6 product; it displays the same pattern of ESI-generated ions as those of both the SbCl 5 product and the commercial drug, but with significantly different abundance ratios. NMR data indicate that the NMG molecules coordinate antimony in two different fashions, which suggests either the coexistence of two different complexes or the existence of a single major complex in which two NMG molecules are coordinated with antimony in an asymmetrical geometry.

An NMR study of 15‐epiclusianone, 1‐benzoyl‐6‐hydroxy‐14,14‐dimethyl‐3,5,15‐tri(3‐methyl‐2‐butenyl)‐bicyclo[3.3.1]non‐1‐ene‐4,6‐dione (1), a novel tetraisoprenylated benzophenone isolated from pericarp of fruits of Rheedia gardneriana, is described. In addition to conventional 1D NMR techniques, 2D shift‐correlated NMR experiments [1H × 1H‐COSY, 1H × 13C‐HMQC‐1J(C,H), 1H × 13C‐HMBC‐nJ(C,H) (n = 2 and 3) and 1H × 1H‐NOESY] were used for 1H and 13C chemical shift assignments of this natural product. The 1D 13C NMR spectrum of 1 in the solid state was also obtained. Copyright © 2001 John Wiley & Sons, Ltd.