Publications

Abstract CompX is a natural analog of the unknown luciferin of the bioluminescence earthworm Fridericia heliota. Given the difficulties of characterizing luciferin, the objective of this work was the quantum chemistry based structural and electronic characterization of CompX. A main feature of this molecule is a strong partially covalent O-H center dot center dot center dot O ionic bond, with sigma bonding character, present in all CompX species. Atomic charge transfers involving this interaction determine the relative stability of all species. Moreover, this interaction is involved in an excited state intramolecular proton transfer leading to a phototautomerism reaction. Thus, the large Stokes shift observed for CompX is attributed to an enol -> keto photoconversion.

Abstract A study focused on the discovery of new chemical entities based on the 3-arylcoumarin scaffold was performed with the aim of finding new adenosine receptor (AR) ligands. Thirteen synthesized compounds were evaluated by radioligand binding (A(1), A(2A), and A(3)) and adenylyl cyclase activity (A(2B)) assays in order to study their affinity for the four human AR (hAR) subtypes. Seven of the studied compounds proved to be selective A(3)AR ligands, with 3-(4'-methylphenyl)-8-(2-oxopropoxy) coumarin (12) being the most potent (K-i=634 nm). None of the compounds showed affinity for the A2B receptor, while four compounds were found to be nonselective AR ligands for the other three subtypes. Docking simulations were carried out to identify the hypothetical binding mode and to rationalize the interaction of these types of coumarin derivatives with the binding site of the three ARs to which binding was observed. The results allowed us to conclude that the 3-arylcoumarin scaffold composes a novel and promising class of A(3)AR ligands. ADME properties were also calculated, with the results suggesting that these compounds are promising leads for the identification of new drug candidates.

Abstract The standard (p degrees = 0.1 MPa) molar enthalpy of formation for crystalline azulene was derived from the standard molar enthalpy of combustion, in oxygen, at T = 298.15 K, measured in a mini-bomb combustion calorimeter (aneroid isoperibol calorimeter) and the standard molar enthalpy of sublimation, at T = 298.15 K, measured by Calvet microcalorimetry. From these experiments, the standard molar enthalpy of formation of azulene in the gaseous phase at T = 298.15 K was calculated. In addition, very accurate quantum chemical calculations at the G3 and G4 composite levels of calculation were conducted in order to corroborate our experimental findings and further clarify and establish the definitive standard enthalpy of formation of this interesting non-benzenoid hydrocarbon. (C) 2013 Published by Elsevier Ltd.

Abstract The chromone scaffold has been found to be an important tool in the drug discovery process through its relevant pharmacological activities. Chromone carboxamide derivatives synthesized within our group have shown noteworthy results as inhibitors of monoamino oxidase-B and as ligands for adesonine receptors. Specifically, chromone-2-carboxamide has been shown to be a privileged structure for the development of selective A(3) adenosine receptor ligands. In this work two novel substituted 4-oxo-N-phenyl-4H-chromene-2-carboxamides have been synthesized and a complete structural characterization was performed using Fourier Transform Infrared Spectroscopy, one-dimensional and two-dimensional Nuclear Magnetic Resonance techniques and Mass Spectroscopy. Finally, the molecular and supramolecular structures were determined by X-ray analysis. The X-ray crystallographic analysis describes in detail the molecular conformation and supramolecular structure of a hemihydrate of 7-methoxy-4-oxo-N-phenyl-4H-chromene-2-carboxamide. The data acquired from this study add valuable information to our chromone database. The unambiguous identification of the compounds will support the understanding of the structure-activity relationships of these compounds.

Abstract Pesticides continue to play an important role in pest management. However, the intensive pesticide application has triggered several environment negative effects that cannot be disregarded. In this study, the inclusion complex of pyrimethanil with HP-beta-CD has been prepared and characterized by proton nuclear magnetic resonance spectroscopy. The formation of the pyrimethanil/HP-beta-CD inclusion complex increased the aqueous solubility of this fungicide around five times. To assess the influence of microencapsulation on the environmental photostability of the fungicide, the photochemical degradation of pyrimethanil and pyrimethanil/HP-beta-CD-inclusion complex has been investigated in different aqueous media such as ultrapure and river water under simulated solar irradiation. The studies allow concluding that pyrimethanil/HP-beta-CD inclusion complex increases significantly the photostability of the fungicide in aqueous solutions, especially in natural water. Actually, the half-life of pyrimethanil/HP-beta-CD inclusion complex was increased approximately by a factor of four when compared to the free fungicide. The overall results point out that pyrimethanil can be successfully encapsulated by HP-beta-CD, a process that can improve its solubility and photostability properties.

Abstract Alzheimer's disease (AD) is an incapacitating neurodegenerative disease that slowly destroys brain cells. This disease progressively compromises both memory and cognition, culminating in a state of full dependence and dementia. Currently, AD is the main cause of dementia in the elderly and its prevalence in the developed world is increasing rapidly. Classic drugs, such as acetylcholinesterase inhibitors (AChEIs), fail to decline disease progression and display several side effects that reduce patient's adhesion to pharmacotherapy. The past decade has witnessed an increasing focus on the search for novel AChEIs and new putative enzymatic targets for AD, like beta- and gamma-secretases, sirtuins, caspase proteins and glycogen synthase kinase-3 (GSK-3). In addition, new mechanistic rationales for drug discovery in AD that include autophagy and synaptogenesis have been discovered. Herein, we describe the state-of-the-art of the development of recent enzymatic inhibitors and enhancers with therapeutic potential on the treatment of AD.

Abstract Simple chromones, a group of heterocyclic compounds, have been studied as a fruitful approach in medicinal chemistry and consequently, with value as a privileged scaffold. The main classic routes for the obtention of simple chromones from ortho-hydroxyarylalkylketones enclose three synthetic approaches, synthesis via Claisen condensation (classic Claisen condensation, Baker-Venkatamaran, and Kostanecki-Robinson reaction), synthesis via benzopyrylium salts and via Vilsmeier-Haack reaction. Chromones can be obtained by the reaction of a phenol with acetylenic dicarboxylic acids or esters or with chlorofumaric acid, or other analogues, in basic conditions, such as metallic sodium. Heterocyclic-substituted chromones are probably one of the most representative derivatives as these types of entities are very important as ligands in the medicinal chemistry artwork. It is expected that the research performed with type of compounds will uncover further interesting aspects in the medicinal field.

Abstract The growing awareness of the harmful effects of ultraviolet (UV) solar radiation has increased the production and consumption of sunscreen products, which contain organic and inorganic molecules named UV filters that absorb, reflect, or scatter UV radiation, thus minimizing negative human health effects. 4-tert-Butyl-4'-methoxydibenzoylmethane (BMDBM) is one of the few organic UVA filters and the most commonly used. BMDBM exists in sunscreens in the end l form which absorbs strongly in the UVA range. However, under sunlight irradiation tautomerization occurs to the keto form, resulting in the loss of UV protection. In this study we have performed quantum chemical calculations to study the excited-state molecular structure and excitation spectra of the enol and keto tautomers of BMDBM. This knowledge is of the utmost importance as the starting point for studies aiming at the understanding of its activity when applied on human skin and also its fate once released into the aquatic environment. The efficiency of excitation transitions was rationalized based on the concept of molecular orbital superposition. The loss of UV protection was attributed to. the enol -> keto phototautomerism and subsequent photodegradation. Although this process is not energetically favorable in the singlet bright state, photodegradation is possible because of intersystem crossing to the first two triplet states.

Abstract The decomposition mechanism of vinyl azide (CH2CHN3) has been studied by calculations of the electronic structure. In addition, a study based on the topology of the electron charge density distribution and its Laplacian function, within the Quantum Theory of Atoms in Molecules (QTAIM), has been carried out with the aim of comprehending the electron redistribution mechanisms that take place in the formation of vinyl nitrenes. The electronic structure calculations reveal that the decomposition of the s-cis conformer of vinyl azide leads to the formation of ketenimine through a single-step conversion, s-cis-CH2CHN3 -> CH2CNH + N-2, while the conversion of the s-trans conformer to acetonitrile occurs in two steps, s-trans-CH2CHN3 -> cyc-CH2NCH + N-2 -> CH3CN + N-2. The topological analysis of the L(r) function reveals that triplet vinyl nitrene has one lone pair on the valence shell charge concentration (VSCC) of nitrogen and thus could act as a monodentate Lewis base, while singlet vinyl nitrene has two lone pairs on the VSCC of nitrogen and thus could act as a bidentate Lewis base.

Abstract When a pesticide is released into the environment, most of it is lost before it reaches its target. An effective way to reduce environmental losses of pesticides is by using controlled release technology. Microencapsulation becomes a promising technique for the production of controlled release agricultural formulations. In this work, the microencapsulation of chlorophenoxy herbicide MCPA with native beta-cyclodextrin and its methyl and hydroxypropyl derivatives was investigated. The phase solubility study showed that both native and beta-CD derivatives increased the water solubility of the herbicide and inclusion complexes are formed in a stoichiometric ratio of 1:1. The stability constants describing the extent of formation of the complexes have been determined by phase solubility studies. H-1 NMR experiments were also accomplished for the prepared solid systems and the data gathered confirm the formation of the inclusion complexes. H-1 NMR data obtained for the MCPA/CDs complexes disclosed noticeable proton shift displacements for OCH2 group and H6 aromatic proton of MCPA provided clear evidence of inclusion complexation process, suggesting that the phenyl moiety of the herbicide was included in the hydrophobic cavity of CDs. Free energy molecular mechanics calculations confirm all these findings. The gathered results can be regarded as an essential step to the development of controlled release agricultural formulations containing herbicide MCPA.