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Kinetics and thermodynamics of the phenolic O−H and the C-ring C−H bond breaking in dihydrokaempferol, a natural flavonoid compound, was investigated using density functional based approach. The rate constants calculated using the variational transition state theory with multidimensional tunneling corrections indicate 4’-OH phenolic hydrogen as operative in inactivation of hydroperoxyl radical (•OOH). Proton coupled electron transfer (PCET) mechanism appears as preferred in O−H bond breaking by the •OOH, while hydrogen atom transfer (HAT) mechanism is involved in the C−H bond cleavage. Comparison of antioxidant potency of dihydrokaempferol vs kaempferol proves superiority of the latter and negligible role of the C-ring hydrogens of dihydrokaempferol in radical scavenging. Obtained results confirm the traditional view that O−H groups of polyphenols are responsible for radical inactivation contrary to recent proposals that the aliphatic C-ring hydrogens also contribute to this activity.

The main goal of this study was to examine some of the underlying mechanisms of protection by ferulic acid (FA) from damage caused by free radicals, mainly mechanisms involving enzymes to suppress formation of free radicals and the sequestration of transition metal ions that catalyse free radical production. Hence, potential of FA to act as antioxidant via suppressing •OH radical formation by sequestering the catalytic Fe2+ ion, and by inhibiting prooxidative lipoxygenase (LOX) enzyme, i.e., by suppressing formation of free radical precursors, was studied. The M06-2X functional and 6-311++G(d, p) basis set implemented in the Gaussian 09 program package [1] was used for geometry optimisations and frequency calculations. All calculations were performed in gas-phase at 298.15 K. The AutoDock 4.0 software package [2] was used to predict the binding mode between LOX and investigated compounds, FA and 5- hydroxyferulic acid (5-OHFA). The crystal structure of LOX was taken from Protein Data Bank. Discovery Studio 4.0 [3] was used to prepare protein structures and for analysis of the obtained results. Polar hydrogen atoms were added using the hydrogen module in AutoDockTools (ADT) graphical interface. Grid maps were determined using the AutoGrid module with grid box of dimension 60×60×60 with point separated by 0.375 Å. The Lamarckian Genetic Algorithm (LGA) was implemented for rigid-flexible docking simulation. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with LOX active site. Exergonicity of chelation reactions of catalytic Fe2+ ion with FA and 5OHFA indicate potency of these chelators to prevent the formation of •OH radicals via Fenton-like reactions. Based on obtained results, inhibition of LOX could be more relevant mechanisms of protection against oxidative stress than iron chelation.

We present a novel strategy to generate accurate 3D models of Al(iii)–Aβ complexes, which circumvents first principles simulations of metal binding to peptides of Aβ., Senile plaques are extracellular deposits found in patients with Alzheimer’s Disease (AD) and are mainly formed by insoluble fibrils of β-amyloid (Aβ) peptides. The mechanistic details about how AD develops are not fully understood yet, but metals such as Cu, Zn, or Fe are proposed to have a non-innocent role. Many studies have also linked the non biological metal aluminum with AD, a species whose concentration in the environment and food has been constantly increasing since the industrial revolution. Gaining a molecular picture of how Al(iii) interacts with an Aβ peptide is of fundamental interest to improve understanding of the many variables in the evolution of AD. So far, no consensus has been reached on how this metal interacts with Aβ, partially due to the experimental complexity of detecting and quantifying the resulting Al(iii)–Aβ complexes. Computational chemistry arises as a powerful alternative to investigate how Al(iii) can interact with Aβ peptides, as suitable strategies could shed light on the metal–peptide description at the molecular level. However, the absence of any reliable template that could be used for the modeling of the metallopeptide structure makes computational insight extremely difficult. Here, we present a novel strategy to generate accurate 3D models of the Al(iii)–Aβ complexes, which still circumvents first principles simulations of metal binding to peptides of Aβ. The key to this approach lies in the identification of experimental structures of the isolated peptide that are favourably pre-organized for the binding of a given metal in configurations of the first coordination sphere that were previously identified as the most stable with amino acid models. This approach solves the problem of the absence of clear structural templates for novel metallopeptide constructs. The posterior refinement of the structures via QM/MM and MD calculations allows us to provide, for the first time, physically sound models for Al(iii)–Aβ complexes with a 1 : 1 stoichiometry, where up to three carboxylic groups are involved in the metal binding, with a clear preference towards Glu3, Asp7, and Glu11.

ESIgen és una aplicació web que permet generar resums de càlculs en química computacional de forma totalment automàtica. A través de les seves múltiples plantilles es poden aconseguir documents de suport a la publicació científica (Supporting Information) o informes tècnics adequats per a comunicacions internes durant el procés de recerca. ESIgen es una aplicación web que permite generar resúmenes de cálculos en química computacional de forma totalmente automática. A través de sus múltiples plantillas se pueden conseguir documentos de apoyo a la publicación científica (Supporting Information) o informes técnicos adecuados para comunicaciones internas durante el proceso de investigación. ESIgen is a web application that allows to create computational chemistry job reports in an fully automated way. Through its multiple templates, Supporting Information documents can be automagically generated, as well as technical reports suitable for internal communication during the research process.

GaudiMM és un programa de disseny molecular desenvolupat pel departament de Química de la UAB, que fa servir algorismes inspirats en la pròpia selecció natural per optimitzar estructures químiques que satisfacin diversos criteris alhora. El programari està disponible de forma gratuïta i lliure en www.github.com/insilichem/gaudi. GaudiMM es un programa de diseño molecular desarrollado en el departamento de Química de la Universidad Autónoma de Barcelona. Usa algoritmos inspirados en la propia selección natural para optimizar estructuras químicas que satisfagan varios criterios a la vez. Está disponible de forma gratuita y libre en www.github.com/insilichem/gaudi. GaudiMM is a molecular design program developed in the department of Chemistry of the Universitat Autònoma de Barcelona. It relies on algorithms inspired by natural selection to optimize chemical structures that can satisfy several criteria at once. It is freely available at www.github.com/insilichem/gaudi.