Rodrigo Montecinos

Host–guest interaction of coumarin-derivative dyes and cucurbit[7]uril: leading to the formation of supramolecular ternary complexes with mercuric ions

We investigated the photophysical behavior of the complexes formed between cucurbit[7]uril (CB7) and coumarin-derivative dyes: 7-(diethylamino)-N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-oxo-2H-chromene-3-carboxamide (1) and N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-11-oxo-2,3,5,6,7,11-hexahydro-1H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carboxamide (2), in the absence or presence of mercuric ions (Hg2+). The maximum absorption of 1 shows a bathochromic shift with the addition of CB7 and the fluorescence intensity is highly increased. In contrast, addition of CB7 has no noticeable effect on the spectroscopic properties of 2. However, fluorescence quenching was observed in both cases after the addition of Hg2+. Interestingly, in the absence of it fluorescence lifetime measurements for the 1–CB7 complex suggest that the macrocycle is able to prevent the aggregation of 1. The stoichiometry for these complexes, determined from the fluorescence titration measurements and mass spectrometry, indicates that 1 : 1 complexes are formed and the binding constants (Kb) are estimated to be around 105 M−1. The NMR studies indicate that both dyes are included in the CB7 cavity but different moieties interact with it. Considering the hydrophobic effect of the cavity, and metal–ligand and ion–dipole interactions, it can be concluded that both compounds are able to form a novel supramolecular assembly that comprises CB7, 1 or 2 and Hg2+. The binding observed between them displays a positive cooperative effect relative to the dyes alone, 1–CB7 being the most efficient complex (Kb ≈ 107 M−1) in acidic conditions. Thus, the potential for these types of complexes to be used as multifaceted functional systems appears warranted.

Extended N-Arylsulfonylindoles as 5-HT6 Receptor Antagonists: Design, Synthesis & Biological Evaluation

Based on a known pharmacophore model for 5-HT6 receptor antagonists, a series of novel extended derivatives of the N-arylsulfonyindole scaffold were designed and identified as a new class of 5-HT6 receptor modulators. Eight of the compounds exhibited moderate to high binding affinities and displayed antagonist profile in 5-HT6 receptor functional assays. Compounds 2-(4-(2-methoxyphenyl)piperazin-1-yl)-1-(1-tosyl-1H-indol-3-yl)ethanol (4b), 1-(1-(4-iodophenylsulfonyl)-1H-indol-3-yl)-2-(4-(2-methoxyphenyl)piperazin-1-yl)ethanol (4g) and 2-(4-(2-methoxyphenyl)piperazin-1-yl)-1-(1-(naphthalen-1-ylsulfonyl)-1H-indol-3-yl)ethanol (4j) showed the best binding affinity (4b pKi = 7.87; 4g pKi = 7.73; 4j pKi = 7.83). Additionally, compound 4j was identified as a highly potent antagonist (IC50 = 32 nM) in calcium mobilisation functional assay.

Experimental and theoretical studies on the nucleofugality ratio in the aminolysis reactions of O-(4-cyanophenyl) O-(3-nitrophenyl) thionocarbonate with amines in aqueous ethanol

The reactions of O-(4-cyanophenyl) O-(3-nitrophenyl) thionocarbonate (1) with morpholine and aniline lead to the formation of 4-cyanophenol and 3-nitrophenol in a 1.5 : 1 ratio. This ratio corresponds to a δΔG± value of about 250 cal mol−1 for the expulsion of both nucleofuges. These reactions follow a mechanism through two tetrahedral intermediates: one zwitterionic (T±) and other anionic (T−). As a model, the reaction of 1 with morpholine was also theoretically examined using DFT methods. Theoretical calculations in the gas phase predict a distribution of 4-cyanophenol : 3-nitrophenol near 1 : 1.12, which differs from the experimental result. However, the microsolvation by two explicit water molecules predicts a product distribution of 1.34 : 1. Theoretical results show the dependency of the nucleofugality ratio when the reaction is assisted by water molecules. The results indicate that the energy barriers are mainly affected by kinetic variables more than the thermodynamic ones.

EFFECT OF LOW CONCENTRATION OF DHPC ON THE DPPC/SM BILAYER

ABSTRACT The organization of bilayers depends on the physicochemical and structural properties of the molecules that compose the membrane. The phospholipid molecular shape depends on the relative volumes of their polar headgroups and non-polar acyl chains. In this work, we study the effect of DHPC concentration over the bilayer of large unilamellar vesicles (LUV) prepared with different proportions of dipalmitoylphosphatidylcholine / sphingomyelin / dihexanoylphosphatidylcholine (DPPC/SM/DHPC) using fluorescence spectroscopy and molecular dynamics (MD) simulations. In this work, we use Laurdan´s generalized polarization (GP) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy to observe the effect of DHPC concentration on dynamic properties of both, the interface and hydrophobic region. Detailed information, at atomistic scale, was obtained by trajectory calculations of accessible solvent area (ASA), partial densities and order parameters using Molecular Dynamics (MD). The results indicate that DHPC induces global packing defects in the membrane, favoring the liquid crystalline state for the system with higher concentration of DHPC.