Adenosine Derivates as Antioxidant Agents: Synthesis, Characterization, in Vitro Activity, and Theoretical Insights

In this work, we present results about the synthesis and the antioxidant properties of seven adenosine derivatives. Four of these compounds were synthesized by substituting the N6-position of adenosine with aliphatic amines, and three were obtained by modification of the ribose ring. All compounds were obtained in pure form using column chromatography, and their structures were elucidated by infrared spectroscopy (IR) and Nuclear Magnetic Resonance (NMR). All adenosine derivatives were further evaluated in vitro as free radical scavengers. Our results show that compounds 1c, 3, and 5 display a potent antioxidant effect compared with the reference compound ascorbic acid. In addition, the absorption, distribution, metabolism and excretion (ADME) calculations show favorable pharmacokinetic parameters for the set of compounds analyzed, which guarantees their suitability as potential antioxidant drugs. Furthermore, theoretical analyses using Molecular Quantum Similarity and reactivity indices were performed in order to discriminate the different reactive sites involved in oxidative processes.

Understanding the Polar Character Trend in a Series of Diels-Alder Reactions Using Molecular Quantum Similarity and Chemical Reactivity Descriptors

In molecular similarity there is a premise “similar molecules tend to behave similarly”; however in the actual quantum similarity field there is no clear methodology to describe the similarity in chemical reactivity, and with this end an analysis of charge-transfer (CT) processes in a series of Diels-Alder (DA) reactions between cyclopentadiene (Cp) and cyano substitutions on ethylene has been studied. The CT analysis is performed in the reagent assuming a grand canonical ensemble and the considerations for an electrophilic system using B3LYP/6-31G(d) and M06-2X/6-311 + G(d,p) methods. An analysis for CT was performed in agreement with the experimental results with a good statistical correlation (R2=0.9118) relating the polar character to the bond force constants in DA reactions. The quantum distortion analysis on the transition states (TS) was performed using molecular quantum similarity indexes of overlap and coulomb showing good correlation (R2=0.8330) between the rate constants and quantum similarity indexes. In this sense, an electronic reorganization based on molecular polarization in terms of CT is proposed; therefore, new interpretations on the electronic systematization of the DA reactions are presented, taking into account that today such electronic systematization is an open problem in organic physical chemistry. Additionally, one way to quantify the similarity in chemical reactivity was shown, taking into account the dependence of the molecular alignment on properties when their position changes; in this sense a possible way to quantify the similarity of the CT in systematic form on these DA cycloadditions was shown.

Mathematical Analysis of a Series of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines: A Simple Way to Relate Quantum Similarity to Local Chemical Reactivity Using the Gaussian Orbitals Localized Theory

Molecular Quantum Similarity (MQS) descriptors and Density Functional Theory (DFT) based reactivity descriptors were studied for a series of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines compounds used for Parkinson’s disease (PD) treatment. The quantification of the steric and electronic effects was shown through scales of quantitative convergence; such scales allow us to establish a methodology to quantify the similarity from the local chemical reactivity (Fukui Functions) point of view. This procedure provides new considerations in the local reactivity of the A2A Adenosine receptor antagonists in a disease of difficult control as PD. In addition, we present new considerations to the localized bonding theory and show a new methodology for quantum similarity on the Fukui Functions. Considering that the Fukui functions under a condensation scheme may have ambiguities in the (DFT) context.

Theoretical Calculations and Modeling for the Molecular Polarization of Furan and Thiophene under the Action of an Electric Field Using Quantum Similarity

A theoretical study on the molecular polarization of thiophene and furan under the action of an electric field using Local Quantum Similarity Indexes (LQSI) was performed. This model is based on Hirshfeld partitioning of electron density within the framework of Density Functional Theory (DFT). Six local similarity indexes were used: overlap, overlap-interaction, coulomb, coulomb-interaction, Euclidian distances of overlap, and Euclidean distances of coulomb. In addition Topo-Geometrical Superposition Algorithm (TGSA) was used as a method of alignment. This method provides a straightforward procedure to solve the problem of molecular relative orientation. It provides a tool to evaluate molecular quantum similarity, enabling the study of structural systems, which differ in only one atom such as thiophene and furan (point group C2v) and cyclopentadienyl molecule (point group D5h). Additionally, this model can contribute to the interpretation of chemical bonds, and molecular interactions in the framework of the solvent effect theory.

Scale Alpha and Beta of Quantitative Convergence and Chemical Reactivity Analysis in Dual Cholinesterase/Monoamine Oxidase Inhibitors for the Alzheimer Disease Treatment Using Density Functional Theory (DFT)

Molecular quantum similarity descriptors and Density Functional Theory (DFT) based reactivity descriptors were studied for a series of cholinesterase/monoamine oxidase inhibitors used for the Alzheimer's disease treatment (AD). This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these molecules with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamine oxidase (MAO) A and B. The Topogeometrical Superposition Algorithm to handle flexible molecules (TGSA-Flex) alignment method was used to solve the problem of the relative orientation in the quantum similarity (QS) field. Using the molecular quantum similarity (MQS) field and reactivity descriptors supported in the DFT was possible the quantification of the steric and electrostatic effects through of the Coulomb and Overlap quantitative convergence scales (alpha and beta). In addition, an analysis of reactivity indexes is development, using global and local descriptors, identifying the binding sites and selectivity in the (cholinesterase/monoamine oxidase) inhibitors, understanding the retrodonor process, and showing new insight for drugs design in a disease of difficult control as Alzheimer.