Publications

Abstract This is the first report of a computational study of the color tuning mechanism of firefly bioluminescence, using the oxidative conformation of luciferase. The results of these calculations demonstrated that the electrostatic field generated by luciferase is fundamental both for the emission shift and efficiency. Further calculations indicated that a shift in emission is achieved by modulating the energy, at different degrees, of the emissive and ground states. These differences in energy modulation will then lead to changes in the energy gap between the states.

Abstract Avobenzone is one of the most common UVA-filters in sunscreens, and is known to be photounstable. Some of the strategies used to stabilize this filter present some drawbacks like photosensitization reactions. Antioxidants are widely used as cosmetic ingredients that prevent photoageing and complement the photoprotection offered by the UV-filters preventing or reducing photogenerated reactive species. The purpose of this work was to study the effect of antioxidants in the photostabilization of avobenzone. The filter dissolved in dimethyl sulfoxide or incorporated in a sunscreen formulation was irradiated with simulated solar radiation (750 W/m(2)). The tested antioxidants were vitamin C, vitamin E, and ubiquinone. The area under the curve of the absorption spectrum for UVA range and the sun protection factor (SPF) were calculated. Vitamin E (1:2), vitamin C (1:0.5) and ubiquinone (1:0.5) were the more effective concentrations increasing the photostability of avobenzone. In sunscreen formulations, the most effective photostabilizer was ubiquinone which also promoted an increase in SPF. This knowledge is important to improve effectiveness of sunscreen formulation. Antioxidants can be valuable ingredients for sunscreens with a triple activity of filter stabilization, SPF boosting and photoageing prevention.

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.