Local Electrophilicity Research Articles

Mechanical Stretching of Nature Inspired Linear and Branched Polysaccharide Motifs through Steered Molecular Dynamics.

A variety of 10 polysaccharide motifs comprising naturally inspired sequences of monosaccharide building blocks are studied to understand the inter-relation between their structural and mechanical behaviors. Equilibrium and steered molecular dynamics (SMD) simulations are employed to investigate the stress-strain relationships and the associated conformational flips of the pyranose moieties along the polysaccharide chains. The presence of a variety of glycosidic linkages connecting the diverse monosaccharide units along with chain-branching in some cases induce wide diversity in the carbohydrate-Ramachandran plots of the glycosidic dihedrals. Similar variations are observed in the Cremer-Pople ring puckering patterns across the polysaccharide variants. The work further provides a comparison between the experimentally obtained atomic force microscopic data of mechanical stretching for some polysaccharides with the stress-strain curves generated from our SMD simulations. Out of all the systems studied, pectin having an axial-axial orientation of the glycosidic linkage showed maximum stretching potential, while acetan-M, with an equatorial-equatorial disposition of the glycosidic bond, stretched the least. The experimental Young's modulus of the corresponding natural polysaccharides could be reasonably compared to the values obtained from our simulation models. Force distribution analysis is done to understand the propagation of punctual stress in the polysaccharides under SMD conditions. Changes in local electrophilicity or nucleophilicity of atomic centers in puckered pyranose rings are estimated through the condensed Fukui functions. All of this information can help understand the physical behavior and chemical reactivity of complex polysaccharides in a complicated milieu of electronic and steric effects experienced by them.

Valuable insights into the structural, electronic, and aromaticity aspects of azulene and its monophospha-derivatives

Azulene-based conjugated systems have garnered considerable interest owing to their atypical structures. The incorporation of a phosphorous atom into the azulene framework offers an enticing prospect for the creation of unique organophosphorous π-conjugated compounds. No such phosphaazulene skeleton however has been reported to date. Here, density functional theory calculations were employed to examine the physicochemical properties and aromaticity of azulene and its monophospha-derivatives. The electronic, magnetic, and structural properties were taken into consideration. The reactivity of azulene and its monophospha-analogs including 1-phospha (1p), 2-phospha (2p), 4-phospha (3p), 5-phospha (4p), and 6-phosphaazulene (5p), was examined through local electrophilicity and local nucleophilicity indices. The stability and aromaticity of these compounds were determined using DFT calculations with the B3LYP/6–311 + G(d,p) method. The stability of monophosphaazulene derivatives is significantly influenced by the position of the phosphorus atom, as indicated by the energy calculations. The order of stability was found to be 1p > 2p > 5p > 3p > 4p. Aromaticity studies based on HOMA, ΔBl, FLUπ, SA, and NICS indices indicated that the incorporation of a phosphorus atom into the 5-membered ring decreased its aromaticity while simultaneously increasing the aromaticity of the 7-membered ring. However, replacing the carbon atom with phosphorus atom in the 7-membered ring reduced the aromaticity of both rings. Additionally, the ability of π-stacking, as determined by the LOLIPOP criterion, was reduced in the monophosphaazulene derivatives compared to azulene, except for compound 5p. The order of π-stacking ability was 5p > azulene > 2p > 1p > 4p > 3p. Overall, there was a good agreement between the various aromaticity indices, providing consistent results for both rings in azulene and monophosphaazulenes.

Metal-free catalytic conversion of CO2into methanol: local electrophilicity as a tunable property in the design and performance of aniline-derived aminoborane-based FLPs

A deeper computational mechanistic study of an environmentally friendly metal-free CO2reduction process towards MeOH is presented, using a previously tested intramolecular frustrated Lewis pair (2-[bis(R)boryl]-N,N-dimethylaniline) as catalyst and H2as reducing agent.

New insights into H2 activation by intramolecular frustrated Lewis pairs based on aminoboranes: the local electrophilicity index of boron as a suitable indicator to tune the reversibility of the process.

A large set of intramolecular aminoborane-based FLPs was studied employing density functional theory in the H2 activation process to analyze how the acidity and basicity of boron and nitrogen atoms, respectively, affect the reversibility of the process. Three different linkers were employed, keeping the C-C nature in the connection between both Lewis centers: -CH2-CH2-, -CH[double bond, length as m-dash]CH-, and -C6H4-. The results show that significant differences in the Gibbs free energy of the process are found by considering all the combinations of substituents. Of the 75 systems studied, only 9 showed the ability to carry out the process reversibly (ΔGH2 in the range of -3.5 to 2.0 kcal mol-1), where combinations of alkyl/aryl or aryl/alkyl in boron/nitrogen generate systems capable of reaching reversibility. If the alkyl/alkyl or aryl/aryl combination is employed, highly exergonic (non-reversible H2 activation) and endergonic (unfeasible H2 activation) reactions are found, respectively. No appreciable differences in the linker were found, allowing us to continue the analysis with the most entropically favorable linker, the -C6H4- linker. From this, 25 different FLP systems of type 2-[bis(X)boryl]-(Y)aniline (X: H, CF3, C6F5, PFtB, FMes and Y: H, CH3, t-but, Ph, Mes) can be formed. By analyzing the electronic properties of each system, we have found that the condensed-to-boron electrophilicity index ωB+ is inversely related to the ΔGH2. Interestingly, two relationships were found; the first is for alkyl groups (Y: CH3 and t-but) and the second for aryl groups (Y: H, Ph, and Mes), which is intimately related to the proton affinity of each aniline. In addition, it is quite interesting when the frustration degree, given by B⋯N distance dB-N, is brought together with ωB+, since the quotient has unit energy/length corresponding to unit force; concomitantly, a measure of the FLP strength in H-H bond activation can be defined. With this finding, a rational design of this kind of FLP can be performed by analyzing the acidity of boron through condensed-to-boron electrophilicity and knowing the nature of the substituent of nitrogen according to whether the Y is alkyl or aryl, optimizing the H2 reversible activation in a rational way, which is crucial to improve the catalytic performance.

Introducing a new model based on electronegativity equalization principle for the analysis of the natural bond orbital reactivity in the c‐DFT background

AbstractPrevious studies presented two independent models based on the equalization of electronegativity and on an alternative operative formula for the Fukui function. The current paper presents modifications to these models to obtain a new model for calculating the local energy derivatives (electronic chemical potential, local electronic hardness and local hypersoftness) and density (Fukui and dual descriptor indices) in natural bond orbitals for the study of chemical reactivity from the perspective of these orbitals (local electrophilicity and local maximum charge variation have also been deduced). We have radically changed the way of partitioning the electron density because the atomic model cannot distinguish between bonding and non‐bonding electron pairs, or between electrons with different types of bonds, however, this is possible with the model based on bond orbitals. In this respect, this model is ideal for organic reactions because of their correspondence with Lewis structures, which are simple but very useful for representing reaction mechanisms.

Photoionization of stable mesoionic compounds

The electronic structures and valence ionizations of three mesoionic compounds: 3-methylsydnone, 3-phenylsydnone and 3-methyl-2-phenyl-1,3,4-thiadiazole-5-thione have been studied using high-level ab initio methods: electron-propagator theory (EPT) and coupled cluster method (IP-EOM-CCSD). We discuss the influence of valence electronic structure on chemical reactivity using global and local electrophilicity indices. We also discuss (non)aromatic character of the studied molecules using information pertaining to photoelectron spectra.

Spectroscopic, computational and mechanistic studies on regio- and stereoselectivity of the 1,3-dipolar cycloaddition reaction in the synthesis of dispiro[indoline-3,2′-pyrrolidine-3′,3"-indolines] festooned with pyrene moiety

• Novel polyheterocyclic pyrene-grafted dispiro-pyrrolidine oxindolines have synthesized. • 1D and 2D-NMR spectroscopy found to be excellent tool for confirmation of the regio- and stereochemistry of the cycloadducts. • The regioselectivity were studied by evaluating global and local electrophilicity and nucleophilicity descriptors. • local descriptors Parr functions proposed by Domingo is promising indices to explain the regioselectivity of cycloaddition processes. An efficient and catalyst-free multicomponent sequence for synthesizing fused new polyheterocyclic pyrene-grafted dispiro-pyrrolidine oxindolines through 1,3-dipolar cycloaddition reaction mediated by non-stabilized azomethine ylides is reported herein. The regio- and stereochemistry of the cycloadducts were determined on the basis of one-dimensional (1D) and two-dimensional (2D) homonuclear and heteronuclear correlation NMR spectroscopy. The mechanism of the cycloaddition reaction, as well as regioselectivity were discussed by evaluating global and local electrophilicity and nucleophilicity descriptors at B3LYP/6-31G level of theory. The findings suggested that the polarity and charge transfer flow between azomethine ylides (dipole) and 5-chloro-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-ones (dipolarophiles) was consistent with the global reactivity descriptors and substitutional pattern. These outcomes based on local descriptors Parr functions proposed by Domingo were found to be quite promising indices for the study of organic reactivity and to explain the regioselectivity of cycloaddition processes.

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol O -Nucleophiles

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol <i>O</i> -Nucleophiles

Mechanism and Selectivity of Cyclopropanation of 3-Alkenyl-oxindoles with Sulfoxonium Ylides Catalyzed by a Chiral N,N'-Dioxide-Mg(II) Complex.

The mechanism and stereoselectivity of an asymmetric cyclopropanation reaction between 3-alkenyl-oxindole and sulfoxonium ylide catalyzed by a chiral N,N'-dioxide-Mg(II) complex were explored using the B3LYP-D3(BJ) functional and the def2-TZVP basis set. The noncatalytic reaction occurred via a stepwise mechanism, with activation barriers of 21.6-23.5 kcal mol-1. The C2-Cα bond formed followed by the carbanion SN2 substitution, constructing a three-membered ring in spiro-cyclopropyl oxindoles, accompanied by the release of dimethylsulfoxide. The electron-withdrawing N-protecting t-butyloxy carbonyl (Boc) and acetyl (Ac) groups in isatin enhanced the local electrophilicity of the C2 atom and the repulsion between the two COPh groups in the reactants, contributing to high reactivity as well as good diastereoselectivity results. The N-Boc-3-phenacylideneoxindole coordinated to the chiral ligand (L-PiPr2) in a bidentate fashion, forming a hexacoordinate-Mg(II) complex as the reactive species. The origin of enantioselectivity was from the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the si-face of oxindole. The repulsion between the SO(CH3)2 and COPh groups in 3-alkenyl-oxindole and the neighboring ortho-iPr group in the ligand directed the re-face of ylide to attack the re-face of oxindole preferably, contributing to the high diastereoselectivity of the product. A metal-ion-ligand matching relationship was important for a good asymmetric induction effect of the chiral N,N'-dioxide-metal catalyst. A large chiral cavity in the Zn(II) catalyst weakened the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the prochiral face of oxindole, leading to inferior enantioselectivity observed in the experiment.

Aromaticity indices, electronic structural properties, and fuzzy atomic space investigations of naphthalene and its aza-derivatives

The aromaticity and CDFT properties of naphthalene and its aza-derivatives were theoretically investigated using density functional theory (DFT) electronic structure method. The reactivity and chemistry of Azanaphthalene (1-AN), 1, 2-diazanaphthalene (1, 2-DAN), 1, 3-diazanaphthalene (1, 3-DAN), 1, 4-diazanaphthalene (1,4-DAN), 1, 5-diazanaphthalene (1, 5-DAN), 1, 6-diazanaphthalene (1, 6-DAN), 1, 7-diazanaphthalene (1,7-DAN) and 1, 8-diazanaphthalene (1, 8-DAN) were thoroughly explored and predicted focusing more on the fuzzy atomic space analysis, quantum chemical descriptors (CDFT), natural bond orbital (NBO), and structural electronic properties. The CDFT is focused on predicting the condensed Fukui function and dual descriptors along with condensed local electrophilicity and nucleophilicity investigation. From the aromaticity computational study, 1,7-DAN gave PDI, FLU, FLU-π, PLR, HOMA, BIRD and LOLIPOP values of approximately one (1) was found to be the most aromatic in the group, and strongest π-stacking ability. The aromaticity follows the trend: 1, 7-DAN > 1, 8-DAN > 1, 5-DAN > 1, 6-DAN > 1, 4-DAN > 1, 2-DAN > 1-AN > naphthalene. The second order perturbation energy NBO analysis revealed that the 3 highest stabilization energies in the molecules are C6–Na to C3–C4(π∗−π∗ 236.90 kcal/mol) of 1, 6-DAN, C3–C4 to C1–C2 (π∗−π∗236.37 kcal/mol) of 1-AN and C7–N10 to C2–C4 (π∗−π∗235 kcal/mol) of 1, 3-DAN.

DFT Study and Synthesis of Novel Bioactive Bispyrazole using Mg/Al-LDH as a Solid Base Catalyst

Objective: To synthesize novel bispyrazole heterocyclic molecules may have important biological activities and thus can serve as good candidates for pharmaceutical applications. Methods: The bispyrazole derivatives 3a-m were prepared by the condensation reaction of substituted aromatic aldehydes with 1,3-diketo-N-phenylpyrazole by using Mg/Al-LDH as a heterogeneous catalyst under THF solvent at the refluxing temperature. Results: This protocol describes the synthesis of bioactive compounds under mild reaction conditions, with good yields, and easiness of the catalyst separation from the reaction mixture. Furthermore, a mechanistic study has been performed by using DFT calculations to explain the observed selectivity of the condensation reaction between aryl aldehyde and 1,3- diketo-N-phenylpyrazole via Knoevenagel reaction. The local electrophilicity/ nucleophilicity explains correctly the experimental finding. Conclusion: In summary, the pharmacologically interesting bis-pyrazole derivatives were synthesized through Mg/Al-LDH as a solid base catalyst, in THF as a solvent. The synthesized bioactive compounds containing the pyrazole ring may have important biological activities and thus can serve as good candidates for pharmaceutical applications. Therefore, the catalyst Mg/Al-LDH showed high catalytic activity. Besides, a series of bispyrazole molecules were synthesized with a good yield and easy separation of the catalyst by simple filtration. Moreover, DFT calculations and reactivity indexes were used to explain the selectivity of the condensation reaction between aryl benzaldehyde and 1,3-diketo-N-phenylpyrazole via Knoevenagel reaction, and the results were in good agreement with the experimental finding.

A theoretical study of the global and local electrophilicity, nucleophilicity, polarizability and QTAIM theory for calix[4]arene-gas interaction

The calix[4]arene molecule, abbreviated as CX[4], is known by the four phenolic groups and a hydrophobic cavity able to enclose small molecules. The interactions between CX[4] and NO3, NO2, CO2, and N2 gas molecules have been studied. These guest species are placed inside and outside the cavity of the host molecule CX[4]. The formation of H-bonding has been deeply discussed based on the infrared spectrum and the polarizability analysis. Global and local indices have been calculated for a series of gas (NO3, NO2, CO2 and N2) in interaction with the CX[4] molecule to explain the electrophilic or nucleophilic activations in endo-vs. exo-cavity interaction zone. As expected, there is a correlation between the proposed global electrophilicity and global nucleophilicity together for an explanation of the chemo-selectivity region. Finally, the topological parameter analyses of the host-guests interactions have been estimated by using DFT calculations.

Wave function and molecular reactivity study of char with different edges and the chemisorption properties of nitric oxide

Molecular reactivity of simplified char models with armchair and zigzag edges and chemisorption properties of nitric oxide were studied with wave function theory and density functional reactivity theory. By comparing the electronegativity, electrophilicity and nucleophilicity of different models, it was concluded that chemisorptions of nitric oxide onto carbon models were electrophilic reactions. Electrons transferred to nitric oxide during chemisorption processes. The lowest unoccupied molecular orbital (LUMO), the highest occupied molecular orbital (HOMO), value of electron localization function, electrostatic potential distribution on van der Waals surface and electron density difference of char models with armchair and zigzag edges were analyzed. Zigzag edges were packed with more lone pair electrons, making them more vulnerable to electrophilic attacks. Double descriptors of different models were analyzed to elucidate why NO was more inclined to be chemisorbed at edges rather than onto carbon plane. The specific adsorption sites at edges were predicted by comprehensive analyses of atomic charge, condensed local electrophilicity, condensed local softness and the contribution to HOMO/LUMO orbital of each atom. Energies released from NO chemisorptions in different modes were calculated with and without considering London dispersion interaction. The thermodynamic results were consistent with the predictions of wave function theory and density functional reactivity theory. The dispersion effect should be considered when simulating carbon-based material systems.

One pot synthesis of novel pregnane-sulphur prodrugs, spectroscopic investigation, conformational analysis, chemical reactivity, Fukui function and their mathematical model

Novel sulphur derivatives have been synthesized for the first time from 16-Dehydropregnenolone acetate (16-DPA) by adopting thia-Michael addition reaction yielding 2-[(3β-acetoxy) pregn–5-ene-20-one −16 –thio] propanoic acid, 2-[(3β-acetoxy) pregn–5-ene-20-one–16–thio] ethanoic acid, 3β-acetoxy 16α-(2-hydroxyethylthio)-pregn-5-ene-20-one and 3β-acetoxy-16β-(2-amino phenylthio)-pregn-5-ene-20-one. All the compounds were characterized with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. The molecular geometry and vibrational frequency of these compounds were calculated in ground state by density functional theory (DFT/B3LYP) using 6-31G (d, p) basis set. Conformational analysis of all the compounds was carried out to determine the most stable conformation. The electronic properties such as HOMO-LUMO energy were calculated by using time dependent density functional theory (TD-DFT). The topological parameters-electron density (ρBCP), Laplacian of electron density (∇2ρ(rBCP)), energy parameters-kinetic electron energy density (GBCP), potential electron density (VBCP) and the total electron energy density (HBCP) at the bond critical points (BCP) were analyzed by ‘Atoms in molecules’ AIM theory. Local reactivity descriptors like Fukui functions (fk+, fk−, fk0), local softness (sk+, Sk−, Sk0) and local electrophilicity indices (ωk+, ωk−, ωk0) analysis were performed to find out the reactive sites within the molecules. Molecular electrostatic potential of the synthesized compounds were also determined. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system was checked using theory of nonlinear ordinary differential equations.

Correlations between Fukui Indices and Reactivity Descriptors Based on Sanderson's Principle.

A previous study presented a very simple model mainly based on Sanderson's principle for estimating important reactivity descriptors, such as the local hardness and the local electrophilicity. In another study, a new way of calculating the Fukui function was obtained that resulted in a new operative formula for the function. We also obtained the second-order partial derivative of the electron density with regard to the number of electrons. The current study analyzes the relationships between the two models and justifies the origin of these relationships.

Quantum Reality in the Selective Reduction of a Benzofuran System.

Two 2,3-disubstituted benzofurans (1 and 2), analogs of gamma-aminobutyric acid (GABA), were synthesized to obtain their 2,3-dihydro derivatives from the Pd/C-driven catalytic reduction of the double bond in the furanoid ring. The synthesis produced surprising by-products. Therefore, theoretical calculations of global and local reactivity were performed based on Pearson’s hard and soft acids and bases (HSAB) principle to understand the regioselectivity that occurred in the reduction of the olefinic carbons of the compounds. Local electrophilicity (ωk) was the most useful parameter for explaining the selectivity of the polar reactions. This local parameter was defined with the condensed Fukui function and redefined with the electrophilic (Pk+) Parr function. The similar patterns of both resulting sets of values helped to demonstrate the electrophilic behavior (soft acid) of the olefinic carbons in these compounds. The theoretical calculations, nuclear magnetic resonance, and resonance hybrids showed the moieties in each compound that are most susceptible to reduction.

Microwave-assisted synthesis of novel 5-aminouracil-based compound with DFT calculations

In this investigation, microwave assisted synthesis of novel pyrazole ring formation via three reaction steps. In the beginning, nucleophilic acyl substitution reaction of the 5-aminouracil with ethyl cyanoacetate to afford 2-cyano-N-(2,4-dioxo-1,2,3,4-tetrahydropyridine-5-yl)acetamide (3). Knoevenagel Condensation of acetamide 3 with benzaldehyde afforded the corresponding acrylamide derivative 6 under microwave irradiation. Finally, Michael addition reaction of acrylamide with hydrazine hydrate to afford the novel 5-aminouracil-based compound 9. Computational studies for the three reactions have been carried out utilizing DFT/B3LYP/6-31 + G(d) theory level. The regioselectivity elucidated in terms of frontier molecular orbital (FMO), local electrophilicity, global electrophilicity and nucleophilicity indexes. The analysis of FMO showed the selectivity of these reactions was controlled through HOMO–LUMO interaction. Also, the molecular electrostatic potential (ESP) associated the hydrogen bonding interactions between electrophiles and nucleophiles. The IR of the optimized structures were examined by DFT/B3LYP/6 + 31G(d) and compared with experimental FT-IR. Furthermore, comparative study between experimental UV–Vis and calculated utilizing TD-DFT.

Synthesis, Antioxidant Activity and Theoretical Investigation of Isoxazolines Derivatives of Monoterpenoids

The 3+2 cycloaddition reactions are important to generate five-membered heterocyclic compounds as well as altering biological activity effects based on structure. In the study, we synthesized new isoxazoline derivatives of different monoterpenoids and examined the structure analysis using spectroscopical analysis methods, reveal changes in the theoretical analysis related to the biological activity. These new compounds exhibit antioxidant activities; DPPH radical scavenging, ferric reducing, metal chelating activities which are significantly higher than the related commercial monoterpenoids. Theoretical approaches on the compounds containing isoxazole moiety have been performed by the DFT/B3LYP/method, 6-31G(d,p) basis set in the ground state. The global and local chemical reactivity properties of the compounds were investigated by considering the values of electronegativity, global hardness-softness, electronic chemical potential, electrophilicity index and condensed Fukui functions, local softness and local electrophilicity index. Furthermore, total energy, FMOs energy values and the dipole moment (&amp;#181;), mean polarizability (&amp;#945;), and first order hyperpolarizability (&amp;#946;) values were analysed at the theoretical level to examine the polarizability characteristics of the compounds. The antioxidant activity values of the newly synthesized compounds were compared with a finding of the computational study. The results obtained exhibited good correlation on some parameters.

Unraveling the regioselectivity of odd electron halogen bond formation using electrophilicity index and chemical hardness parameters.

Odd electron halogen bonding of freons with five different free radicals have been investigated using M06-2X/6-311G++(d,p). Conceptual density functional theory parameters such as Fukui functions, electrophilicity index and chemical hardness have been utilised to examine the regioselectivity and strength of free radical induced halogen bonding. The strong electrophilic radical Cl˙ forms three-electron bonds upon interacting with the nucleophilic ring surrounding the sigma hole or fk- regions. This behavior is also observed for moderately electrophilic radicals OH˙ and OCl˙ for complexation with CHFCl2 only. In other complexes, these radicals along with least nucleophilic radicals ˙NO and ˙Ph form one-electron bond with sigma hole or fk+ regions of freons. This regioselectivity of radicals and the interaction energy upon complexation have been explained in terms of local electrophilicity index and chemical hardness. We hope that this finding will shed light on the understanding of non-covalent interactions in terms of conceptual density functional theory for halogen bonding as well as in pnictogen, chalcogen and tetrel bonding systems. This result may find applications in understanding the radical mediated reactions and ozone depletion in the stratosphere.

New insights in conceptual DFT: New model for the calculation of local reactivity indices based on the Sanderson's principle

AbstractIn the present study, a new model mainly based on the Sanderson's principle for estimating important reactivity descriptors, such as the local hardness and the local electrophilicity, is introduced. New approximations and corrections were taken into account, which led to a significantly different development, obtaining more realistic results than the previous ones used. The Fukui condensed‐to‐atom indices: f − and f + have been used in this model, but their role is clearly described in the development, reducing therefore, the ambiguity of previous developments where the indices could be arbitrarily used. It is important to underline that the proposed model is relatively simple, but leads to qualitatively correct results. It also makes it possible to interpret the hard‐soft acid base principle in local terms, as can be seen in the sample set of reactions (Diels‐Alder type) selected as an example in the present study, and which provides very coherent results with the expected experimental reactivity.