Abstract
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.
Highlights
Parkinson’s disease (PD) is known as idiopathic Parkinsonism or paralysis agitans [1]
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 similarity indexes are calculated using (1) for the Euclidean distances and (14) for the local Hodgkin-Richards index. This approach gives us information about the quantum similarity using shape function in the electron density of Gaussian type orbitals, taking into account the good correlation between the shape functions with the Hodgkin-Richards indexes demonstrated by Bultinck et al [16, 17]. Such analysis was developed on the series of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6pyridylpyrimidines as A2A Adenosine receptor antagonists for the PD treatment reported by Zhang and coworkers [8]
Summary
Parkinson’s disease (PD) is known as idiopathic Parkinsonism or paralysis agitans [1]. Bultinck and Carbo-Dorca have reported an analysis based on quantum similarity [16, 17], to define a link between quantum similarity and chemical reactivity Taking into account this background, in this study we suggest a methodology for quantifying the steric and electronic effects of a series of A2A adenosine receptor antagonists [8]. The similarity provided by the partition of molecular space in this study is used to rationalize and quantify steric and electrostatic effects, through the proposition of scales of quantitative convergence, allowing us to obtain insights into atoms in molecules, aromaticity, among others [26, 27] In this contribution all the molecular structures were optimized with the program Gaussian 03 [33] using DFT methods with the B3LYP exchange-correlation functional [34, 35], together with standard 6-31G∗ base set [36]. The quantum similarity field was introduced by Carbo-Dorca and coworkers [9,10,11,12,13,14,15]; they defined the quantum similarity measurements ZAB between molecules A and B with the electronic density ρA(r) and ρB(r) taking into account the minimization of the expression for the Euclidean distance as
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