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Background The primary goal of this research is to underscore the significance of molecular docking in the context of malaria drug discovery. Molecular docking plays a crucial role in comprehending the interactions between prospective drugs and the target proteins found in Plasmodium parasites. The study delves into the docking interactions of various compounds, emphasizing the necessity of stabilizing the active site to formulate potent and selective drugs. Methods The research focuses on highlighting compound-specific interactions with residues, stressing the importance of stabilizing the active site to design drugs tailored to specific target proteins. Inhibiting the function of these target proteins disrupts the life cycle of the malaria parasite. Quantum Similarity Analysis, utilizing Overlap and Coulomb operators, is employed to identify electronic similarities. The resulting quantum similarity values guide subsequent chemical reactivity analysis. Global reactivity indices such as chemical potential, hardness, softness, and electrophilicity contribute to drug design by showcasing compound-specific indices that underscore the significance of stability and electrophilicity. Fukui functions are utilized to visualize regions for stabilization, providing insights crucial for potential malaria treatment. Results The enhancement of drug-target binding affinity is observed through stabilizing interactions in the active site. Understanding electrophilicity at the active site emerges as a critical factor in drug design and selectivity. The rational manipulation of electrophilic interactions holds promise for developing potent and selective drugs against malaria. Consequently, the integration of molecular docking, quantum similarity analysis, and chemical reactivity indices offers a comprehensive approach to malaria drug discovery. Conclusions The study identifies potential lead compounds, emphasizing the crucial role of stabilizing the active site. Additionally, it sheds light on electronic considerations vital for the design of effective and resistance-resistant drugs. The insights provided by Fukui functions into regions susceptible to -H bond formation make these compounds promising candidates for malaria treatment.

The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic.

Background A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: Darunavir (Daru), Dexamethasona (Dexame), Dolutegravir (Dolu), Fosamprenavir (Fosam), Ganciclovir (Gan), Insoine (Inso), Lopinavir (Lop), Ritonavir (Rito) and Tipranavir (Tipra). Methods These ligands were analyzed using molecular docking, molecular quantum similarity using four similarity indices like overlap, Coulomb and their Euclidean distances. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LYS621, ARG555 and ASP623, CYS622, ASP760, among others. In the molecular quantum similarity, the highest indices have been obtained in the electronic similarity in comparison with the structural similarity. Conclusions These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Background The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, molecular quantum similarity, and chemical reactivity indices defined within a conceptual density functional theory framework. Results The analysis of molecular quantum similarity indices on inhibitors showed a high number of differences from a structural point of view. However, they are quite similar in their electronic density, obtaining the highest values in the electronic similarity index. Global and local chemical reactivity indices were analyzed. Conclusions These studies allowed for the identification of the main stabilizing interactions using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical reactivity descriptors provide novel insights into these ligands that can be used in the design of new COVID-19 treatments.

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods: In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, molecular quantum similarity, and chemical reactivity indices defined within a conceptual density functional theory framework. Results: The analysis of molecular quantum similarity indices on inhibitors showed a high number of differences from a structural point of view. However, they are quite similar in their electronic density, obtaining the highest values in the electronic similarity index. Global and local chemical reactivity indices were analyzed. Conclusions: These studies allowed for the identification of the main stabilizing interactions using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical reactivity descriptors provide novel insights into these ligands that can be used in the design of new COVID-19 treatments.

Background: A coronavirus identified in 2019, SARS- CoV- 2, has caused a pandemic of respiratory illness, called COVID- 19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: the Zidovudine, Tromantadine, Pyramidine, Oseltamivir, Hydroxychoroquine, Cobicistat, Doravirine (Pifeltro), Dolutegravir, Boceprevir, Indinavir, Truvada, Trizivir, Trifluridine, Sofosbuvir and Zalcitabine. Methods: These ligands were analyzed using molecular docking, Receptor-Based Pharmacophore Modelling. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LEU141, GLN189, GLU166 and GLY143, HIE41, among others. Also was development an electrostatic potential comparison using the global and local reactivity indices. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Background: A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: Darunavir (Daru), Dexamethasona (Dexame), Dolutegravir (Dolu), Fosamprenavir (Fosam), Ganciclovir (Gan), Insoine (Inso), Lopinavir (Lop), Ritonavir (Rito) and Tipranavir (Tipra). Methods: These ligands were analyzed using molecular docking, molecular quantum similarity using four similarity indices like overlap, Coulomb and their Euclidean distances. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LYS621, ARG555 and ASP623, CYS622, ASP760, among others. In the molecular quantum similarity, the highest indices have been obtained in the electronic similarity in comparison with the structural similarity. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Background: A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: the Zidovudine, Tromantadine, Pyramidine, Oseltamivir, Hydroxychoroquine, Cobicistat, Doravirine (Pifeltro), Dolutegravir, Boceprevir, Indinavir, Truvada, Trizivir, Trifluridine, Sofosbuvir and Zalcitabine. Methods: These ligands were analyzed using molecular docking, Receptor-Based Pharmacophore Modelling. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LEU141, GLN189, GLU166 and GLY143, HIE41, among others. Also was development an electrostatic potential comparison using the global and local reactivity indices. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

In this work, we have studied the torquoselectivity of a set of unusual ring‐opening electrocyclic reactions that have not been successfully rationalized using models based on orbital symmetry nor have they been explained by steric hindrance. Firstly, the corresponding transition states have been obtained, and it has been verified that the intrinsic reaction coordinates associated with these transition states are consistent with the reactants and products of the reactions studied. This has allowed us to theoretically calculate the reaction barriers (with their corresponding thermal corrections) and compare them with the corresponding experimental values. In a second step, we have analyzed the electronic bonding structure using the methodologies of Natural Bond Orbital Analysis and Quantum Theory of Atoms in Molecules, searching for interactions that may significantly stabilize the transition states. Finally, we have analyzed the reactivity using a recent model that has allowed us to calculate the corresponding bond reactivity descriptors. [ABSTRACT FROM AUTHOR]

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods: In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, molecular quantum similarity, and chemical reactivity indices defined within a conceptual density functional theory framework. Results: The analysis of molecular quantum similarity indices on inhibitors showed a high number of differences from a structural point of view. However, they are quite similar in their electronic density, obtaining the highest values in the electronic similarity index. Global and local chemical reactivity indices were analyzed. Conclusions: These studies allowed for the identification of the main stabilizing interactions using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical reactivity descriptors provide novel insights into these ligands that can be used in the design of new COVID-19 treatments.

Background : The protein kinases present in the human body have received a lot of attention because of the interest in their use as therapeutic targets. However, little is known about the protein kinases associated with tuberculosis. For these reasons, this research investigates a new point of view regarding the crystallized serine/threonine protein kinases Pkn A, B and G of Mycobacterium tuberculosis. Methods : The conformational analysis shows a DFG-in motif in Pkn B and G and a DFG-out motif in Pkn A. For all the protein kinases that have been studied, the gatekeeper residue is methionine. A study of the protein kinases with their ligands was also conducted to find new insights on the binding site with a series of ligands associated to protein kinases Pkn A, B and G through molecular docking. The residues with hydrogen bonds on the hinge zone of Pkn A are GLU96 and VAL 98, of Pkn B are GLU 93 and VAL 95 and of Pkn G are GLU233 and VAL235. Results : The results show the H-bond acceptor and H-bond donor sites on the hinge zone to all ligands, establishing a structural model of the ligands on the active site with two or three interactions in this zone. This interaction model was validated using density functional theory calculations (by means of net charges and images of the electrostatic potential) and molecular quantum similarity analysis, showing a high correlation between the electronic and steric effects in each ATP complex studied. Conclusions: In this work we can see that the interactions of the hinge zone are characterized by the key factor of one or two H-bonds acceptors and one H-bond donor in the ligands of this zone. The quantum similarity analysis shows good correlation between the steric and electronic effects in each ATP complex.

This work presents the study of a series of electrocyclic reactions with the main aim of obtaining new insights into the reaction process along IRCs. The energy variation of the different reaction paths as well as the different transition states have been calculated. These trends are according to the experimental data. The natural bond orbitals have been obtained and the second order perturbational theory analysis has been carried out to determine the main charge transfers due to delocalization. Bond reactivity indexes have been used to describe the reactivity mechanism in a local way. These reactivity indexes are also based on NBOs and this has made it possible to connect the results of the indexes with the previous analysis. To determine quantitatively the bond structure, we used the quantum theory of atoms in molecules and we have hereby completed the information obtained from the NBO analysis. Finally, we used the Hirshfeld population analysis as an approximation to understand how the load density changes in the different reaction pathways, and we have connected these variations with the information obtained from the bond structure.The results has found that the reaction path with the lowest energy barrier Transition State Inward Conrotatory (TSIC) or Transition State Outward Conrotatory (TSOC) is determined by two magnitudes: the charge donations by delocalisation of the substituents (which we obtained from the Second Order Perturbational Theory Analysis of the NBOs) and in the case that these donations were very similar, the non-covalent interactions dominated (which we studied by means of the interaction energies of the Hirshfeld charges). Additionality, the most important factor influencing the lower energy reaction path was the interaction of lone pairs of the substituents with the σ∗(C–C) bond that is broken at the opening of the cycle. The alignment of these lone pairs with the C–C bond favours charge donation between them and, as can be seen in the discussion, this alignment varies depending on whether the structure is TSIC and TSOC.

Background: Heat shock protein (Hsp90KDa) is a molecular chaperone involved in the process of cellular oncogenesis, hence its importance as a therapeutic target. Geldanamycin is an inhibitor of Hsp90 chaperone activity, which binds to the ATP binding site in the N-terminal domain of Hsp90. However, geldanamycin has shown hepatotoxic damage in clinical trials; for this reason, its use is not recommended. Taking advantage that geldanamycin binds successfully to Hsp90, many efforts have focused on the search for similar analogues, which have the same or better biological response and reduce the side effects of its predecessor; 17-AAG and 17-DMAG are examples of these analogues. Methods: In order to know the chemical factors influencing the growth or decay of the biological activity of geldanamycin analogues, different computational techniques such as docking, 3DQSAR and quantum similarity were used. Moreover, the study quantified the interaction energy between amino acids residues of active side and geldanamycin analogues, through hybrid methodology (Autodock-PM6) and DFT indexes. Results: The evaluation of interaction energies showed that the interaction with Lys58 residue is essential for the union of the analogues to the active site of Hsp90, and improves its biological activity. This union is formed through a substituent on C-11 of the geldanamycin macrocycle. A small and attractor group was found as the main steric and electrostatic characteristic that substituents on C11 need in order to interact with Lys 58; behavior was observed with hydroxy and methoxy series of geldanamycin analogues, under study. Conclusion: This study contributes with new hybrid methodology (Autodock-PM6) for the generation of 3DQSAR models, which to consider the interactions between compounds and amino acids residues of Hsp90´s active site in the alignment generation. Additionally, quantum similarity and reactivity indices calculations using DFT were performed to know the non-covalent stabilization in the active site of these compounds.

Background: Heat shock protein (Hsp90KDa) is a molecular chaperone involved in the process of cellular oncogenesis, hence its importance as a therapeutic target in clinical trials. Geldanamycin is an inhibitor of Hsp90 chaperone activity, which binds to the ATP binding site in the N-terminal domain of Hsp90. However, geldanamycin has shown hepatotoxic damage in clinical trials; for this reason, its use is not recommended. Taking advantage that geldanamycin binds successfully to Hsp90, many efforts have focused on the search for similar analogues, which have the same or better biological response and reduce the side effects of its predecessor; 17-AAG and 17-DMAG are examples of these analogues. Methods: In order to know the chemical factors influencing the growth or decay of the biological activity of geldanamycin analogues, different computational techniques such as docking, 3DQSAR and quantum similarity were used. Moreover, the study quantified the interaction energy between amino acids residues of active side and geldanamycin analogues, through hybrid methodologies and density functional theory (DFT) indexes. Results: The evaluation of interaction energies showed that the interaction with Lys58 residue is essential for the union of the analogues to the active site of Hsp90, and improves its biological activity. This union is formed through a substituent on C-11 of the geldanamycin macrocycle. A small and attractor group was found as the main steric and electrostatic characteristic that substituents on C11 need in order to interact with Lys 58; behavior was observed with hydroxy and methoxy series of geldanamycin analogues, under study. Conclusion: These outcomes were supported with quantum similarity and reactivity indices calculations using DFT in order to understand the non-covalent stabilization in the active site of these compounds.

In this study the thermal cyclotrimerization reactions of fluoro- and chloroacetylenes involving regioselectively stepwise {2 + 2} and stepwise {4 + 2} cycloadditions were studied using the topological analysis of the electron localization function (ELF), the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses. These methodologies have shown that the electronic reorganization in the regioselectively stepwise {2 + 2} and stepwise {4 + 2} cycloadditions may be considered as {2n+2n} and {2π+2n} pseudodiradical process, respectively. Finally, the last phase of this thermal reaction can be understood as an electronic migration process under the pseudodiradical character in the thermal ring-opening reaction, with the subsequent formation of reaction products. In this sense, new insights are reported on the electronic behavior in the bond formation in the thermal cyclotrimerization of fluoroacetylene.

Inhibitor of kappa B kinase subunit β (IKKβ) is a main regulator of nuclear factor kappa B (NF-κB) and has received considerable attention as an attractive therapeutic target for the treatment of lung cancer or other inflammatory disease. A group of diversified thienopyridine derivatives exhibited a wide range of biological activity was used to investigate its structural requirements by using DFT and 3D-Quantitative structure activity relationship. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established using the experimental activity of thienopyridine derivatives. The cross-validation coefficient (q2) values for CoMFA and CoMSIA are 0.671 and 0.647 respectively, were achieved, demonstrating high predictive capability of the model. The contour analysis indicate that presence of hydrophobic and electrostatic field is highly desirable for biological activity. The results indicate that substitution of hydrophobic group with electron withdrawing effect at R4 and R6 position have more possibility to increase the biological activity of thienopyridine derivatives. Subsequently molecular docking and DFT calculation were performed to assess the potency of the compounds.

This work delves into the study presented by Caramella and co‐workers (J. Am. Chem. Soc. 2002, 124, 7) on the cyclopentadiene dimerization. We have reperformed the calculations of this work using updated methodologies, obtaining the structures of the reactants and transition states, as well as new energy profiles. Additionally, we have obtained new insights that were not included in the previous work, such as bond structures from NBO analysis, QTAIM theory, and spin density. Reactivity indices of the principal NBOs responsible for the reaction have also been obtained using a recently developed model based on conceptual DFT and Sanderson's principle of electronegativity equalization and the new results obtained have allowed us to propose reaction mechanisms that satisfactorily justify all reaction stages. This work is a study of the mechanism of the cyclopentadiene dimerization reaction, but it is also an example of applying the new model for calculating reactivity indices for NBOs. Additionally, it demonstrates the combined use of these descriptors with other types of analyses that also employ NBOs or provide a description of the molecular bonding structure. As shown in this work, the collective use of all these methodologies generally provides an adequate description of the chemical reactivity of the studied processes. [ABSTRACT FROM AUTHOR]

This study aims to investigate the phenomenon of torquoselectivity through three thermal cyclobutene ring-opening reactions (N1–N3). This research focuses on the nature of the chemical bond, electronic reorganization, predicting non-competitive or competitive reactions, and torquoselectivity preference within Quantum Theory of Atoms in Molecules (QTAIM) and stress tensor frameworks. Various theoretical analyses for these reactions, such as metallicity ξ(rb), ellipticity ε, total local energy density H(rb), stress tensor polarizability ℙσ, stress tensor eigenvalue λ3σ, and bond-path length, display differently for non-competitive and competitive reactions as well as for the conrotatory preferences either it is the transition state outward conrotatory (TSout) or transition state inward conrotatory (TSin) directions by presenting degeneracy or non-degeneracy in their results. The ellipticity profile provides the motion of the bond critical point locations due to the different substituents of cyclobutene. In agreement with experimental results, examinations demonstrated that N1 is a competitive reaction and N2–N3 are non-competitive reactions with TSout and TSin preference directions, respectively. The concordant results of QTAIM and stress tensor scalar and vectors with experimental results provide a better understanding of reaction mechanisms. [ABSTRACT FROM AUTHOR]

New N-propargyl tetrahydroquinolines 6a-g have been synthesized efficiently through the cationic Povarov reaction (a domino Mannich/Friedel-Crafts reaction), catalyzed by Indium (III) chloride (InCl3), from the corresponding N-propargylanilines preformed, formaldehyde and N-vinylformamide, with good to moderate yields. All tetrahydroquinoline derivatives obtained were evaluated in vitro as free radical scavengers. Results showed that compound 6c presents a potent antioxidant effect compared with ascorbic acid, used as a reference compound. ADME predictions also revealed favorable pharmacokinetic parameters for the synthesized compounds, which warrant their suitability as potentials antioxidant. Additionally, a theoretical study using Molecular Quantum Similarity and reactivity indices were developed to discriminate different reactive sites in the new molecules in which the oxidative process occurs.

Chelotropic reactions are widely used in organic synthesis. These reactions are of the pericyclic type where a π bond and a lone pair are transformed into a pair of sigma bonds; with both sigma bonds added to the same atom. This work presents an analysis of several representative chelotropic reactions. To study the reaction path, we have divided it into two parts, from the reactants to the transition state and from the transition state to the products which has allowed us to compare the behavior of the reactants in these two ranges of the path. To perform the analysis, global reactivity descriptors based on the conceptual‐density functional theory (DFT), such as electrophilicity and global softness, have been calculated. To analyze these descriptors, the corresponding local descriptors have been used. A model based on Sanderson's principle (electronegativity equalization principle), developed previously, has been used to calculate the local reactivity descriptors (atomic). The statistical methodology of multiple regression analysis has been used to determine which local variables are the most relevant for the global parameter under study (softness, and electrophilicity), also the principal component analysis has been used as a guide to estimate the number of variables to take into account in the analysis, finally this has led us to important correlations between global and local parameters which has allowed us to analyze the reactions of the study. Transition states of the reactions are aromatic as obtained from the nucleus independent chemical shift (NICS) and gauge including magnetically induced ring current (GIMIC) analysis. [ABSTRACT FROM AUTHOR]