Local Reactivity Research Articles

In silico analysis of the action of saturated, monounsaturated, and polyunsaturated fatty acids against Echinococcus granulosus fatty-acid-binding protein 1

Background The zoonotic infection caused by tapeworms Echinococcus is a neglected tropical disease in poor regions with limited access to suitable sanitary conditions. Hydatid cysts produced by Echinococcus granulosus use fatty-acid-binding proteins (FABP) to obtain the fatty acids and cholesterol necessary for their survival from the host. In this work, we analyzed the behaviour of saturated, monounsaturated, and polyunsaturated fatty acids against EgFABP1. Methods We used computational biology and chemistry techniques and binding free energy estimations by molecular mechanics generalized Born surface area (MM/GBSA). Results This research has enabled us to clarify the EgFABP1 isoforms identified in the database, suggesting their potential involvement in diverse cellular activities of Echinococcus granulosus. Conversely, examining the global and local chemical reactivity of 14 fatty acids revealed that liposolubility is contingent upon the degree of unsaturation in the FAs. Additionally, FAs exhibited acceptable levels of oral absorption and bioavailability. The binding of EgFABP1 with FAs analyzed by molecular dynamics simulation showed us that these are highly stable, where the best affinity was with docosahexaenoic acid. Conclusions Our results suggest that the action of fatty acids could play an interesting role in detecting early Echinococcus granulosus.

Comprehensive study of Fenton reaction efficiency on textile wastewater treatment from dye solution to real effluent with emphasis on Fukui function analysis

This study investigated the continuous degradation monitoring of three reactive dyes, reactive yellow 176 (RY), reactive Blue 4 (RB) and reactive red 293 (RR), both in separate solutions and in a mixture, along with their corresponding dye bath and industrial dyeing effluent, using Fenton reaction. A kinetic study was conducted to compare the degradation efficiency of the studied solutions. This work provides important yield of dye degradation, where the results showed that RB, RY, and RR had 96.64 %, 92.47 %, and 73.27 % color removal, respectively, within a two-hour reaction time. The pseudo-second-order model fit well to describe the degradation of RR and RY, while the zero-pseudo-order model provided a better fit for RB. The dye mixture exhibited 57 % color removal, whereas the dyeing bath and real effluent showed 41 % and 36 % removal, respectively, over a two-hour reaction time. Moreover, significant reductions in chemical oxygen demand (COD) and biological oxygen demand over 5 days (BOD5) were observed, with the real effluent demonstrating a 73.91 % COD reduction and an 86.66 % reduction in BOD5. The COD and BOD5 reductions for the dye bath were 67.53 % and 95 %, respectively. Additionally, COD and BOD5 reductions of 72.96 % and 96.66 %, respectively, were observed for the dye bath. DFT calculations were employed to elucidate the regioselectivity of radical oxidation of the three reactive dyes by Fenton's reagent, providing insights into global and local reactivity descriptors. Toxicity studies further underscored the efficacy of the Fenton reaction in wastewater treatment. Additionally, UV–visible spectral analysis before and after 12 h of Fenton reaction revealed total discolouration and a reduction in UV and visible peaks across all reactions, indicating comprehensive dye degradation and reduction.

Mechanisms, regio- and stereoselectivities involved in NHC[sbnd]catalyzed dearomatizing annulation of ester with ylide: A computational study

The catalytic mechanism for dearomatizing annulation of ester with ylide by a chiral NHC catalyst is investigated by density functional theory (M06–2X) computations. After precatalyst activation giving active NHC, the transformation proceeds via five steps: (1) nucleophilic addition of the NHC to ester, (2) α−CH deprotonation to generate acylazolium intermediate, (3) coupling acylazolium intermediate with ylide to form a new C − C bond, (4) ring closure and (5) elimination of the NHC with formation of the annulation product tricyclic dihydroisoquinoline. The regio- and stereoselectivity controlling step is C − C bond formation. For regioselectivity, local reactivity index analysis indicates that the C1-addition is more favorable than either C3 or C4 addition. The stereoselectivity for the formation of SS-configurational product is ascribed to a number of noncovalent interactions (C–H·O, C–H·N and C–H·π). Electron localization function (ELF) analyses reveal the important role of the NHC in Ccarbonyl−Ocarbonyl bond breaking. These results enable both in-depth understanding of NHC catalysis and rational design of catalytic reactions.

Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks

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.

The Effect of Global and Local Chemical Reactivity Descriptors in the Determination of Properties of Transition Metal Clusters

Recently, research on material properties has got lots of attention because of their promising technological applications. In this paper, the author’s focus is on the global and local chemical reactivity descriptors of some transition metal clusters. In addition, the author also include findings of chemical properties with reactivity descriptors. Furthermore, according to Thomas–Fermi approximation and from the exact formulation of Density Functional Theory by Hohenberg and Kohn’s theorem, the author introduce electronegativity and the theory of hardness and softness for further investigation of chemical properties of the clusters. As a part of investigations, the author also introduce the Fukui functions with an emphasis for the determinations of chemical reactivity descriptors. All the results are obtained by theoretical investigation of electronegativity), Chemical potential (), chemical hardness (), and polarizability () of the given transition metal clusters (Cr and Mn). From the results, the author observed that the ionization potential of the clusters increases with decreasing cluster size as the clusters become more stable and tend towards chemical inertness. In conclusion, determination of the reactivity descriptors of the transition metal clusters show results that are in line with previous experimental and theoretical findings.

A theoretical approach to the corrosion inhibition of iron in acidic solution by a green formulation derived from Nigella sativa L seeds oil

A theoretical approach combining density functional theory (DFT) computation, Monte Carlo (MC) methods, and molecular dynamics (MD) simulations was used to investigate and validate the iron corrosion inhibition performances in the acidic medium of a green formulation based on the oil extracted from Nigella sativa L. DFT calculations allowed to determine the energetic, global, and local chemical reactivity parameters. The most stable adsorption configuration of the fatty acids components of the Nigella sativa L. formulation was determined by the Monte Carlo methods with the adsorption locator module and by molecular dynamics simulations. Results indicated that all the compounds are absorbed with a totally flat orientation on the first layer of the metal surface.The active sites of molecules were effectively established by using DFT through the analysis of frontier molecular orbitals (FMO), the Hirshfeld population analysis (HPA), the electrostatic potential (ESP), molecular electron density analysis (MED), and Fukui indices (FI). The solvent effect was investigated by using the conductor-like polarizable continuum model (CPCM). Protonation effects were also analysed through the protonation energy (PE), the proton affinity (PA), and the absolute gas phase basicity (GB). The formation of a coating on the iron surface validated the good protective action of the green formulation derived from Nigella sativa L.The computational and theoretical approaches substantiate our experimental electrochemical and spectroscopic studies [1].

Functional magnetic resonance imaging signal has sub-second temporal accuracy

Neuronal activation sequence information is essential for understanding brain functions. Extracting such timing information from blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI) signals is confounded by local cerebral vascular reactivity (CVR), which varies across brain locations. Thus, detecting neuronal synchrony as well as inferring inter-regional causal modulation using fMRI signals can be biased. Here we used fast fMRI measurements sampled at 10 Hz to measure the fMRI latency difference between visual and sensorimotor areas when participants engaged in a visuomotor task. The regional fMRI timing was calibrated by subtracting the CVR latency measured by a breath-holding task. After CVR calibration, the fMRI signal at the lateral geniculate nucleus (LGN) preceded that at the visual cortex by 496 ms, followed by the fMRI signal at the sensorimotor cortex with a latency of 464 ms. Sequential LGN, visual, and sensorimotor cortex activations were found in each participant after the CVR calibration. These inter-regional fMRI timing differences across and within participants were more closely related to the reaction time after the CVR calibration. Our results suggested the feasibility of mapping brain activity using fMRI with accuracy in hundreds of milliseconds.

Correction: Why are the local hyper-softness and the local softness more appropriate local reactivity descriptors than the dual descriptor and the Fukui function, respectively?

Correction: Why are the local hyper-softness and the local softness more appropriate local reactivity descriptors than the dual descriptor and the Fukui function, respectively?

Theoretical Study on the Regioselectivity of Leapfrog B18 and B30 Boron Sheets in Electrophilic and Nucleophilic Reactions Using DFT-Based Reactivity Indices.

A combined computational and interpretational DFT study is performed to investigate the regioselectivity of B18 and B30 leapfrog boron sheets upon reaction with XH3-type electrophiles and nucleophiles (X = N, P, As, B, Al). The M062X, B3LYP, and B3LYP-D3 functionals are used combined with the 6-31+G(d,p) basis. The molecular electrostatic potential (MEP), Fukui functions, and the dual descriptor are employed to predict the local reactivity of B18 and B30. Our results reveal that both clusters are hard and prefer to react with hard bases and acids, such as NH3 and BH3. Further, these leapfrog B6n clusters can play the role of catalysts as they break B-H and Al-H bonds of BH3 and AlH3 in s-BH3-B6n and s-AlH3-B6n complexes, respectively. Leapfrog B6n-XH3 complexes (X = B and Al) can be considered as an interaction between two electron-deficient systems. Therefore, the chemical reactivity between these systems cannot be interpreted in terms of the Hard-Soft-Acid-Base principle.

Toxicity of persistent organic pollutants: a theoretical study

ContextPolychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are two families of persistent organic pollutants that are dangerous as they remain in the atmosphere for long periods and are toxic for humans and animals. They are found all over the world, including the penguins of Antarctica. One of the mechanisms that explains the toxicity of these compounds is related to oxidative stress. The main idea of this theoretical research is to use conceptual density functional theory as a theory of chemical reactivity to analyze the oxidative stress that PCBs and PBDEs can produce. The electron transfer properties as well as the interaction with DNA nitrogenous bases of nine PCBs and ten PBDEs found in Antarctic penguins are investigated. From this study, it can be concluded that compounds with more chlorine or bromine atoms are more oxidizing and produce more oxidative stress. These molecules also interact directly with the nitrogenous bases of DNA, forming hydrogen bonds, and this may be an explanation for the toxicity. Since quinone-type metabolites of PCBs and PBDEs can cause neurotoxicity, examples of quinones are also investigated. Condensed Fukui functions are included to analyze local reactivity. These results are important as the reactivity of these compounds helps to explain the toxicity of PCBs and PBDEs.MethodsAll DFT computations were performed using Gaussian16 at M06-2x/6–311 + g(2d,p) level of theory without symmetry constraints. Electro-donating (ω-) and electro-accepting (ω +) powers were used as global response functions and condensed Fukui functions as local parameters of reactivity.

Shrimp shell waste-modified natural wood and its use as a reservoir of corrosion inhibitor (L-arginine) for brass in 3% NaCl medium: Experimental and theoretical studies

The primary objective of this study is to harness the valuable properties of natural wood waste (NWW) and a shrimp shell extract known as chitosan (Cs). In this context, and in order to prevent rapid consumption of the L-arginine inhibitor (Arg), it was encapsulated in NWW by means of a chitosan polymer. The resulting modification was verified using X-ray diffraction (XRD), which revealed the presence of chitosan and reflections corresponding to arginine in the modified wood. Additional techniques, including Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM) coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), were used for comprehensive characterization. The corrosion inhibition effect resulting from the application of NWW-Cs-Arg composite was investigated using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The obtained results revealed that, at an optimal concentration of 2 g/L and under ambient temperature conditions (298 K), this composite demonstrated a high level of corrosion inhibition, reaching up to 75 %, exhibiting cathodic behavior. Quantum chemical calculations were also carried out to predict the active sites in the used inhibitor. The methodology employed was based on the B3LYP/6-311G++(d,p) theory in an aqueous environment. Parameters such as frontier molecular orbitals (HOMO and LUMO), global reactivity descriptors, molecular electrostatic potential (MEP), and Mulliken population have been studied to assess local reactivity and identify reactive centers and potential nucleophilic and electrophilic attack sites. Weak interactions were analyzed using topological approaches (ELF, LOL, and NCI). It is noteworthy that the arginine molecule interacts through hydrogen bonds between its guanidine group and the hydroxyl groups present in the wood and chitosan residues. Meanwhile, the amine groups of chitosan promote charge transfer between arginine and copper atoms, particularly through the NH groups in the alpha position relative to the C = O group.

Green approach towards the corrosion suppression effect of carbon steel against an aggressive medium of 1 M HCl from peanut shells: Electrochemical examinations coupled with theoretical insights

The present work focuses on examining the corrosion inhibition activity of an aqueous green extract derived from peanut shell waste for carbon steel in 1 M HCl. The electrochemical tests evinced a notable inhibitory efficiency of the peanut shell extract (PSE). Total polyphenol and flavonoid content, as well as FT-IR analysis, were performed to explore the phytochemical abundance of the PSE, the results show the existence of polyphenol and flavonoid families in the aqueous extract of PSE. The electrochemical measurements PDP and EIS showed an optimum inhibition efficiency (IE) reaching 81% using 2 g/L of PSE at 293 K. The effect of temperature indicated that the mode of adsorption of PSE is physisorption. SEM-EDX analysis of the carbon steel surface texture was conducted to explore the PSE behavior at the surface. Based on Density Functional Theory (DFT) calculations at B3LYP/6-311 + G (d,p) level of theory, the anticorrosive effect of the main components of the aqueous green extract of peanut shells: Luteolin, (LTN) resveratrol (RVT) and p-hydroxybenzoic acid (HBA) was investigated, The HOMO and LUMO electron densities, as well as the molecular electrostatic potential maps, were used to identify the electron-rich and electron-poor regions. The most relevant global and local quantum chemical reactivity descriptors were also calculated and discussed. The results revealed that the inhibition efficiency of the investigated inhibitor molecules can be arranged as follows: RVT ≈ LTN ≫> HBA.

Biginelli dihydropyrimidines carrying azole rings: Synthesis, computational studies, and evaluation of alpha‐glucosidase inhibitory and antimicrobial activities

In the current study, we designed three novel compounds by merging two valuable nitrogen-containing pharmacophores, namely dihydropyrimidine (DHPM) and azole, within a single molecule. To obtain the target molecules, azole-linked benzaldehydes were initially synthesized via nucleophilic aromatic substitution reaction between 4-fluorobenzaldehyde and pyrazole, imidazole, or 1,2,4-triazole. Afterward, Biginelli reaction was applied to yield azole-carrying DHPMs. Following structural confirmation, the obtained compounds were tested for their alpha (α)-glucosidase inhibitory and antimicrobial activities. According to the biological data, DHPM-P and DHPM-T showed strong inhibition values whereas DHPM-I failed to effectively inhibit the α-glucosidase enzyme. This situation was explained by molecular docking studies of all compounds into the binding site of alpha-glucosidase. The title compounds also presented moderate antibacterial and antifungal activities. Computational methods based on density functional tight binding (DFTB) and density functional theory (DFT) calculations, along with molecular dynamics (MD) simulations were used to analyze the reactive properties of the compounds. A combination of DFTB and DFT calculations was applied to obtain the lowest energy conformations of the molecules. Further computational analysis included calculations of local reactivity descriptors, such as molecular electrostatic potential and average local ionization energy, by applying DFT calculations. DFT calculations were also used to study intramolecular non-covalent interactions. MD simulations were employed to understand how the title molecules behave in water and to obtain their solubility parameters.

The power of novel morpholinyl Mannich bases to protect N80 steel against corrosion in acidic environment: DFT and SAR investigations

In this research article, we investigate the corrosion inhibition properties of two novel morpholinyl mannich bases namely 3-morpholino-1-phenylpropan-1-one (MB1) and 3-morpholino-1-phenyl-3-(pyridin-4-yl) propan-1-one (MB2). To establish a link between their corrosion inhibition efficacy and molecular characteristics, we employ a comprehensive approach involving the calculation of DFT-derived global and local reactivity parameters, as well as structure-activity relationship (SAR) indices. The obtained values of the global reactivity indices including dipole moment, energy gap, hardness, and softness show a positive correlation with the experimental data earlier reported. Fukui functions give a comprehensive reactive scheme exhibiting the atoms responsible for the electronic transfer. SAR parameters such as molecular volume (V), surface area (SA), and the polarizability (α) were found to be in good accordance with the experimental inhibition effectiveness order.

In silico Exploration of Pharmacological and Molecular Descriptor Properties of Salacinol and Its Related Analogues

Salacinol and its related analogues have been known for their potent α-glucosidase inhibitor activity and making them interesting candidates for a new type of anti-diabetic agent. Therefore, it is essential to investigate the physicochemical properties, pharmacological parameters, and toxicity profile of these anti-diabetic agents. In this study, a comprehensive in-silico approach was used to explore the absorption, distribution, metabolism, excretion, and toxicity profiles of salacinol and its related analogues. In addition, to gain a better knowledge of structural and electrical characteristics, global and local reactivity descriptors, and molecular electrostatic potential were calculated and discussed by using DFT at the B3LYP/6–311++G (d, p) level of theory. The results explored that all the studied compounds have low GI absorption and are substrates for P-glycoprotein. None of the compounds can cross the BBB, and none of the compounds are inhibitors of cytochrome P450 isoenzymes. We also found that all compounds have various potential to interact with a wide range of biological targets, including GPCRs, enzymes, ion channels, kinases, and nuclear receptors. Additionally, all compounds have low toxicity and are unlikely to cause any major health hazards in terms of hepatotoxicity, mutagenicity, cardiotoxicity, cytotoxicity, and immunotoxicity. The molecular electrostatic potential map shows that the negative potential sites are in electronegative oxygen atoms, while the positive potential sites are around the hydrogen atoms. The present study concludes that salacinol and its analogues might be a promising safe and effective candidate for the development of therapeutic drugs derived from natural sources. However, some of their properties should be considered in the context of drug development and tissue protection strategies.

3D printed hybrid scaffolds do not induce adverse inflammation in mice and direct human BM-MSC chondrogenesis in vitro

Biomaterials that can improve the healing of articular cartilage lesions are needed. To address this unmet need, we developed novel 3D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) hybrid scaffolds. Our aim was to carry out essential studies to advance this medical device towards functional validation in pre-clinical trials. First, we show that the chemical composition, microarchitecture and mechanical properties of these scaffolds were not affected by sterilisation with gamma irradiation. To evaluate the systemic and local immunogenic reactivity of the sterilised 3D printed hybrid scaffolds, they were implanted subcutaneously into Balb/c mice. The scaffolds did not trigger a systemic inflammatory response over one week of implantation. The interaction between the host immune system and the implanted scaffold elicited a local physiological reaction with infiltration of mononuclear cells without any signs of a chronic inflammatory response.Then, we investigated how these 3D printed hybrid scaffolds direct chondrogenesis in vitro. Human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs) seeded within the 3D printed hybrid scaffolds were cultured under normoxic or hypoxic conditions, with or without chondrogenic supplements. Chondrogenic differentiation assessed by both gene expression and protein production analyses showed that 3D printed hybrid scaffolds support hBM-MSC chondrogenesis. Articular cartilage-specific extracellular matrix deposition within these scaffolds was enhanced under hypoxic conditions (1.7 or 3.7 fold increase in the median of aggrecan production in basal or chondrogenic differentiation media).Our findings show that 3D printed SiO2/PTHF/PCL-diCOOH hybrid scaffolds have the potential to support the regeneration of cartilage tissue.

Solvent effects on the structural, spectroscopic, electronic properties, NCI-RDG analysis, molecular docking and molecular dynamics studies of 1-benzyl-indole-3-carbinol

This investigation focuses on the 1-benzyl-indole-3-carbinol (1-benzyl-I3C) molecule and its capacity as a drug to combat breast cancer. The research employs different computational approaches including DFT simulations, molecular docking, and molecular dynamics calculations. The molecular configuration of 1-benzyl-I3C was optimized in the COSMO solvation model, using B3LYP/cc-pVTZ basis set. The modes of vibration of the compound were identified through Potential Energy Distribution (PED) simulations, and the results were found to be consistent with the available FT-IR and Raman data. The analysis of Natural Bond Orbitals (NBO) supports the idea that 1-benzyl-I3C has bioactive properties. The impact of solvents on the electronic characteristics of studied molecule is discussed. The reactive sites of 1-benzyl-I3C were confirmed by the local reactivity descriptors and the molecular electrostatic potential (MEP) surface analyses. Additionally, Non-covalent interaction (NCI) analysis confirms the existence of the Van der Waals interactions in the compound under investigation. Anti-breast cancer activities of the 1-benzyl-I3C molecule were examined based on molecular docking analysis, which reveals a good inhibitor nature of the studied molecule against the progesterone receptor (PR). The molecular dynamics analysis through the RMSD, RMSF, and Rg plots confirms the overall stability of the obtained 1-benzyl-I3C-PR complex.

Synthesis, Solvent effects, Chemical reactivity, Molecular Docking and Molecular Dynamic Studies of Triazole derivative

In the present study, (E)-3-(2-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)-2-bromo-6-methoxyphenol (AMTMP) is synthesized and characterized utilizing FT-IR, FT-Raman, NMR, Mass Spectra, and vibrational modes at DFT/B3LYP/6-31G (d, p) computational studies. The calculated properties were subsequently compared to the results of experiments. The absorption characteristics were assessed through the utilization of various kinds of solvents. The molecular properties of AMTMP, including the natural bond orbital (NBO), molecular electrostatic potential (MEP), and local and global reactivity descriptors, were utilized to ascertain the stability, reactivity, and reactive sites on the molecule. Using molecular docking, we have investigated the AMTMP's affinity for CA-2 as well as its potential binding mode. For the purpose of assessing the stability of AMTMP-CA-2 complexes over time, MD simulations were performed. The results suggest that AMTMP could act as CA-2 inhibitor for targeting GSC in GBM.

Elucidating the mechanism and origin of stereoselectivity in the activation/transformation of an acetic ester catalyzed by an N-heterocyclic carbene.

The activation of an ester by N-heterocyclic carbene (NHC) organocatalysis is an efficient and important approach for generating an NHC-bound enolate intermediate, an important active intermediate in the transformation of carbonyl compounds. Herein, we perform a theoretical study on the NHC-catalyzed activation and transformation reaction of an acetic ester in which the NHC-bound enolate intermediate is a key intermediate. Multiple activation and transformation pathways are proposed and analyzed to identify an energetically favorable pathway. The use of different substrates for the reaction is considered. When a chalcone substrate is used, [4+2] cycloaddition between the enolate intermediate and the chalcone is identified to be both the rate- and stereoselectivity-determining step for the reaction, with the R-configured product being generated as the major isomer. Noncovalent interaction (NCI) and atoms-in-molecules (AIM) analyses are performed to identify the origin of the stereoselectivity of the reaction, and a local reactivity analysis is conducted to explore substrate and catalyst effects on the reaction.

Structural parameters of amphetamine: A DFT approach

The structural parameters of Amphetamine, a significant psychoactive drug, are investigated experimentally and computationally using spectroscopic and DFT methods. The molecule is subjected to optimization using the B3LYP functional with both 6-311+G (2d,p) and augmented cc-pVTZ basis sets. Resulting values are then compared against published crystal data for validation. Analysis of the Fourier Transform Infrared and Raman spectra is carried out with PED assignments and after scaling, the calculated spectral frequency values are verified with experimental spectra, revealing a favorable match between them. The NMR spectrum of the molecule is obtained using TD-DFT techniques. The quantum theory of atoms in molecules is employed to analyze the electron density distributions. The reactivity of the molecule is predicted using various tools including analysis of the molecular electrostatic potential surface, electron localized function, molecular graph, non-covalent interaction (NCI), Hirshfeld charge, frontier orbital as well as local and global reactivity descriptors. Natural bonding orbital analysis identifies the hybridization, charge transfer and correlation effects. The results of this study could be utilized for the development of novel chemical sensors for drug detection and to predict the correlation between the structure and pharmacological activity of various amphetamine derivatives.