Fukui Function Analysis Research Articles

New thiophene derivatives: chemoselective synthesis, antitumor effectiveness, structural characterization, DFT calculations, Hirshfeld surface, and Fukui function analysis.

In this study, the chemoselective synthesis of two new thiophene derivatives is presented. The structure of newly synthesized thiophenes derivatives; ethyl 4-acetyl-3-phenyl-5-(phenylamino)thiophene-2-carboxylate (5) and ethyl (E)-4-(3-(dimethylamino)acryloyl)-3-phenyl-5-(phenylamino)thiophene-2-carboxylate (8) were established using different FTIR and NMR spectral analyses. Compound 8 was isolated as single crystal and its 3D structure was determined using X-ray crystallographic analysis. Possible intermolecular interactions that control the molecular packing of 8 were elucidated using Hirshfeld topology analysis. The O…H (13.7%), H…H (55.3%) and C…C (2.3%) intermolecular interactions are the most significant. Fukui functions showed that C4 in thiophene 5 and C3 in thiophene 8 are the most reactive atoms for nucleophilic attack, while N9 in thiophene 5 and C1 in thiophene 8 are the most reactive atoms for electrophilic attack. Antitumor activity of thiophene 5 was assessed and the results showed higher activity against HepG-2 (7.46µg/mL) compared to the HCT 116 (12.60µg/mL) cell line.

Independent LUMO Reactivity in Mesoionic N‐Heterocyclic Thiones: Synthesis of a Stable Radical Anion

AbstractMesoionic compounds, with positive and negative charges, are expected to have dual‐site highest occupied molecular orbital (HOMO, donor) and lowest unoccupied molecular orbital (LUMO, acceptor) reactivity. Herein, we report a novel class of air‐stable mesoionic N‐heterocyclic thiones (mNHTs) synthesized from abnormal N‐heterocyclic carbenes (aNHCs). DFT studies revealed a highly polarized exocyclic thione moiety and computed Fukui function analysis suggests the dual‐site HOMO/LUMO reactivity of mNHTs predicting donor property at the negatively charged ‘S’ center while acceptor property at the cationic imidazole ring. The independent LUMO reactivity of the mNHT was realized by its chemical reduction to an elusive radical anion, which was characterized by a single crystal X‐raydiffraction study. Further, we explore the reactivity of radical anion for the activation of SO2 gas, C−Br bonds of aryl bromide and photocatalytic functionalization of C−X (X = F, Br) bonds. This work unlocks the independent LUMO reactivity of a mesoionic compound.

Copper‐Catalyzed Asymmetric Hydrogenation of Unsymmetrical ortho‐Br Substituted Benzophenones

AbstractThe asymmetric hydrogenation of benzophenones, catalyzed by low‐activity earth‐abundant metal copper, has hitherto remained a challenge due to the substrates equipped with two indistinguishably similar aryl groups. In this study, we demonstrated that the prochiral carbon of the ortho‐bromine substrate exhibits the highest electrophilicity and high reactivity among the ortho‐halogen substituted benzophenones, as determined by the Fukui function (f+) analysis and hydrogenation reaction. Considering that the enantiodirecting functional bromine group can be easily derivatized and removed in the products, we successfully achieved a green copper‐catalyzed asymmetric hydrogenation of ortho‐bromine substituted benzophenones. This method yielded a series of chiral benzhydrols with excellent results. The utility of this protocol has been validated through a gram‐scale reaction and subsequent product transformations. Independent gradient model based on Hirshfeld partition (IGMH) and energy decomposition analysis (EDA) indicate that the CH⋅⋅⋅HC multiple attractive dispersion interactions (MADI) effect between the catalyst and substrate enhances the catalyst's activity.

Independent LUMO Reactivity in Mesoionic N-Heterocyclic Thiones: Synthesis of a Stable Radical Anion.

Mesoionic compounds, with positive and negative charges, are expected to have dual-site highest occupied molecular orbital (HOMO, donor) and lowest unoccupied molecular orbital (LUMO, acceptor) reactivity. Herein, we reporta novel class of air-stable mesoionicN-heterocyclic thiones (mNHTs) synthesized from abnormalN-heterocyclic carbenes (aNHCs). DFT studies revealed a highly polarized exocyclic thione moiety and computed Fukui function analysis suggests the dual-site HOMO/LUMO reactivity of mNHTs predicting donor property at the negatively charged 'S' center while acceptor property at the cationic imidazole ring.The independent LUMO reactivity of the mNHT was realized by its chemical reduction to an elusive radical anion, which was characterized by a single crystal X-diffraction study.Further, we explore the reactivity of radical anion for the activation of SO2gas, C-Br bonds of aryl bromide and photocatalytic functionalization of C-X (X = F, Br) bonds.This work unlocks the independent LUMO reactivity of a mesoionic compound.

Synthesis of spiro[oxindole-2,3′-pyrrolidine] derivatives via exo-selective 1,3-dipolar cycloaddition reaction, characterization and DFT investigation

A series of spiro[oxindole-2,3′-pyrrolidine] derivatives (4a-q) were successfully synthesized via an exo-selective 1,3-dipolar cycloaddition reaction between a stabilized azomethine ylide and various (E)-3-arylidene-1-methylpyrrolidine-2,5-diones. The structures and stereochemistry of the cycloadducts were elucidated through 1D and 2D NMR spectroscopic techniques. The preferred reaction pathway was corroborated by DFT calculations using the B3LYP functional with the 6–31 G (d, p) basis set. The results revealed that the cycloaddition reaction follows a normal electron demand mechanism, where the azomethine ylide acts as the nucleophile and the dipolarophile as the electrophile. The Fukui function analysis favors the regio 2, contradicting the experimental observations while, transition state theory aligns perfectly with the experimental results.

DFT, Structure Activity Relationship, Fukui, Wave Function, NBO, NLO, Spectral and Hole-Electron Analyses of Dexmethylphenidate

Dexmethylphenidate (DMP) is used to treat attention deficit hyperactivity disorder (ADHD) and belongs to the central nervous system (CNS) stimulant group of medicines. The physical properties of DMP were analyzed under the DFT/B3LYP/6-311++G(d,p) basis set. The ESP study reveals the electrophilic attack is possible, while FMO analysis shows that the molecule is hard, stable and an electron donor. The non-covalent interaction (NCI) study explains that van der Waals and steric repulsion forces are observed. The HEI studies indicated that this molecule has CT excitation in the S0→S5 state. The shaded surface map analysis reveals the presence of electron depletion regions in this molecule. The UV-Vis spectral analysis was carried out in various solvents. The Fukui function analysis conveys that 7C is the best domain for electrophilic attack. Theoretical IR determinations and NLO properties were also performed. The structure-activity relationship findings were performed in order to improve the docking score.

Copper-Catalyzed Asymmetric Hydrogenation of Unsymmetrical ortho-Br Substituted Benzophenones.

The asymmetric hydrogenation of benzophenones, catalyzed by low-activity earth-abundant metal copper, has hitherto remained a challenge due to the substrates equipped with two indistinguishably similar aryl groups. In this study, we demonstrated that the prochiral carbon of the ortho-bromine substrate exhibits the highest electrophilicity and high reactivity among the ortho-halogen substituted benzophenones, as determined by the Fukui function (f+) analysis and hydrogenation reaction. Considering that the enantiodirecting functional bromine group can be easily derivatized and removed in the products, we successfully achieved a green copper-catalyzed asymmetric hydrogenation of ortho-bromine substituted benzophenones. This method yielded a series of chiral benzhydrols with excellent results. The utility of this protocol has been validated through a gram-scale reaction and subsequent product transformations. Hirshfeld partition (IGMH) and energy decomposition analysis (EDA) indicate that the CH···HC multiple attractive dispersion interactions (MADI) effect between the catalyst and substrate enhances the catalyst's activity.

Exploring boratrane's potential to enhance the thermal stability of phenol-formaldehyde resins by borate bridge as a crosslinker and the mechanistic formation of boron species in carbonaceous materials: A comprehensive study

In advanced material science, we explore the potential of boratrane, a promising agent for enhancing thermal stability. By combining rigorous Density Functional Theory (DFT) calculations with groundbreaking experimental analyses, we reveal the intricate interplay of radical intermediates and mechanisms underlying the thermal evolution of boratrane-infused materials. Our innovative approach illuminates dynamic structural transformations and elucidates boratrane's pivotal role in fortifying thermal resilience. The DFT calculations identify radical intermediates and mechanisms of thermal degradation, highlighting the role of borate bridges in delocalizing π-electrons in aromatic rings through Gibbs free energy (∆GRXN), Highest Occupied Molecular Orbital (HOMO), Lowest Unoccupied Molecular Orbital (LUMO), and electrostatic potential (ESP) analyses. Fukui function analysis provides insights into the reactivity of these structures towards free radical attacks. Our findings demonstrate that boratrane-modified resins exhibit a stable BO4- structure, which prevents self-condensation of boratrane to B2O3 and enhances the thermal stability of oxygenated resins. This improvement is due to the formation of intramolecular hydrogen bonds, contributing to helix-like structures that strengthen the resin. The mechanism by which the BO4- structure terminates radical agents and transforms into carbonaceous material is elucidated through thermodynamic values, revealing the plausible reactions and chemical structure of boron in the resulting material.

Design of molecular scale inhibitors for high temperature industrial cooling water systems based on group synergistic effects

In high-temperature industrial circulating cooling water systems, the pursuit of environmentally friendly and efficient scale inhibitors is crucial. This study introduced a novel series of monomers with exceptional scale inhibition properties, designed and optimized using Density Functional Theory (DFT). An in-depth analysis of ρ and ∇2ρ at critical points in the electrostatic potential distribution was conducted through the Atoms in Molecules (AIM) approach. Fukui Function analysis was also employed during the thorough screening of optimal molecular pairs. The result of this study is the development of a new ternary scale inhibitor, MA-IA-VS, which not only demonstrates a strong affinity and high binding energy but also exceptional dispersibility and biodegradability, aligning with the principles of green chemistry. Experimental data indicates that MA-IA-VS effectively inhibits over 99 % of CaCO3 and CaSO4 scales at minimal dosages (30 mg·L-1 and 7 mg·L-1, respectively), yielding substantial environmental and economic benefits. Furthermore, the interaction mechanism between MA-IA-VS and scaling crystals were elucidated through molecular dynamics simulations and mechanistic studies, revealing that MA-IA-VS forms a protective layer on the surface of Fe (110). Additionally, the adsorption of MA-IA-VS prevents calcium scale from adhering to the metal surface and alters its concentration distribution in solution, thus realizing scale inhibition effect. This contributes to a deeper understanding of scale inhibitor mechanisms and establishes a robust theoretical and practical foundation for the design of novel, eco-efficient scale inhibitors.

Fully Bio-Based 2,5-Furandicarboxylic Acid Polyester toward Plastics with Mechanically Robust, Excellent Gas Barrier and Fast Degradation.

Aliphatic-aromatic copolyesters offer a promising solution to mitigate plastic pollution, but high content of aliphatic units (>40 %) often suffer from diminished comprehensive performances. Poly(butylene oxalate-co-furandicarboxylate) (PBOF) copolyesters were synthesized by precisely controlling the oxalic acid content from 10 % to 60 %. Compared with commercial PBAT, the barrier properties of PBOF for H2O and O2 increased by more than 6 and 26 times, respectively. The introduction of the oxalic acid units allowed the water contact angle to be reduced from 82.5° to 62.9°. Superior hydrophilicity gave PBOF an excellent degradation performance within a 35-day hydrolysis. Interestingly, PBO20F and PBO30F also displayed obvious decrease of molecular weight during hydrolysis, with elastic modulus >1 GPa and tensile strength between 35-54 MPa. PBOF achieved the highest hydrolysis rates among the reported PBF-based copolyesters. The hydrolytic mechanism was further explored based on Fukui function analysis and density functional theory (DFT) calculation. Noncovalent analysis indicated that the water molecules formed hydrogen bonding interaction with adjacent ester groups and thus improved the reactivity of carbonyl carbon. PBOF not only meet the requirements of the high-performance packaging market but can quickly degrade after the end of their usage cycles, providing a new choice for green and environmental protection.

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.

Unveiling proton-responsive sites and reaction mechanisms in formic acid dehydrogenation catalyzed by Cp*Ir(III)-Pyridylpyrrole complexes: A DFT study

Transition metal catalysts based on proton-responsive ligands are crucial in the realm of chemical hydrogen storage. Nevertheless, the existence of multiple proton-responsive active sites on the ligand adds complexity to the mechanism, limiting our understanding of mechanistic preferences. In this study, density functional theory calculations are used to clarify the mechanistic preferences of iridium catalysts with multiple proton-responsive sites on the ligand for formic acid dehydrogenation. The calculated results show that, with the assistance of the α carbon atom (C2) of the pyrrole ligand site, the catalyst undergoes through an inner-sphere stepwise dehydrogenation mechanism. Moreover, the proton shuttle mechanism efficiently reduces the activation energy needed for H2 production, and solvent-assisted dehydrogenation shows lower energy barriers than substrate-assisted dehydrogenation. The reasons for mechanistic selectivity are further elucidated through Fukui function analysis, molecular plane parameter analysis, and the distortion-interaction model. These findings are anticipated to establish a theoretical foundation for the future design of high-performance catalysts for formic acid dehydrogenation.

Effects of chlorine and nitro groups on the crystal structure of novel 4-quinolinone derivatives from sulfonamide chalcone

This study explores the impact of introducing chlorine and nitro groups into two novel quinolone derivatives, (E)-3-(4-nitrobenzylidene)-2-(3-nitrophenyl)-2,3-dihydro-1-(phenylsulfonyl)-quinolin-4(1H)-one (NPQ) and (E)-3-(4-chlorobenzylidene)-2-(3-nitrophenyl)-2,3-dihydro-1-(phenylsulfonyl)-quinolin-4(1H)-one (CPQ), using experimental techniques and density functional theory (DFT). The research focuses on crystalline packing, conformational changes, and intermolecular interactions. The investigation reveals that weak non-classical hydrogen interactions, hydrophobic, and CH···π interactions, predominantly stabilize the crystal structures. These interactions, quantified through a Hirshfeld surface analysis. Additionally, the Fukui function analysis indicates antioxidant potential in the crystals. NPQ and CPQ exhibit a small energy gap, implying low kinetic stability, high reactivity, and reduced resistance to charge transfer when compared. These findings provide valuable insights into the structural and electronic properties of these quinolone derivatives, aiding the design of novel compounds with desired characteristics and applications. The DFT analysis utiliazsed the M062-X functional and the 6–311++G(d,p) basis set in the Gaussian 09 package, and the result was visualized using the GaussView software.

Microalgae derived honeycomb structured mesoporous diatom biosilica for adsorption of malachite green: Process optimization and modeling

The present study investigated the removal of malachite green dye from aquifers by means of microalgae-derived mesoporous diatom biosilica. The various process variables (dye concentration, pH, and adsorbent dose) influencing the removal of the dye were optimized and their interactive effects on the removal efficiency were explored by response surface methodology. The pH of the solution (pH = 5.26) was found to be the most dominating among other tested variables. The Langmuir isotherm (R2 = 0.995) best fitted the equilibrium adsorption data with an adsorption capacity of 40.7 mg/g at 323 K and pseudo-second-order model (R2 = 0.983) best elucidated the rate of dye removal (10.6 mg/g). The underlying mechanism of adsorption was investigated by Weber-Morris and Boyd models and results revealed that the film diffusion governed the overall adsorption process. The theoretical investigations on the dye structure using DFT-based chemical reactivity descriptors indicated that malachite green cations are electrophilic, reactive and possess the ability to accept electrons, and are strongly adsorbed on the surface of diatom biosilica. Also, the Fukui function analysis proposed the favorable adsorption sites available on the adsorbent surface.

New modifications of PBAT by a small amount of oxalic acid: Fast crystallization and enhanced degradation in all natural environments

Biodegradable plastics are often mistakenly thought to be capable of degrading in any environment, but their slow degradation rate in the natural environment is still unsatisfactory. We synthetized a novel series of poly(butylene oxalate-co-adipate-co-terephthalate) (PBOAT) with unchanged melting point (135 °C), high elastic modulus (140 - 219 MPa) and elongation at break (478 - 769%). Fast isothermal crystallization with a semi-crystallization time < 20 s was demonstrated by the PBOAT. In N2 and air atmospheres, the PBOAT maintained the Td,5% higher than 329 °C. They also had good thermal stability at melt processing temperature for more than 20 min. PBOAT exhibited faster hydrolysis and seawater degradation, even under natural soil burial without light, but still kept stable under low humidity conditions during the storage and the shelf-life. Moreover, the hydrolysis mechanisms were clarified based on Fukui function analysis and DFT calculation, indicating that the hydrolysis of PBOAT would be more straightforward. The mechanism of soil burial is also elucidated through detailed characterization of the structure changes. The PBOAT offered a fresh approach to the development of high-performing, naturally degradable materials.

Spectroscopic, computational, cytotoxicity, and docking studies of 6-bromobenzimidazole as anti-breast cancer agent.

6-Bromobenzimidazole (6BBZ) has been calculated in this study utilizing the 6-311++G(d,p) basis set and the Becke-3-Lee-Yang-Parr density functional approaches. The basic frequencies and geometric optimization are known. FTIR, FT-Raman, and UV-Vis spectra of the substance are compared between its computed and observed values. The energy gap between highest occupied molecular orbital-lowest unoccupied molecular orbital and molecule electrostatic potentials has been represented by charge density distributions that may be associated with the biological response. Time-dependent density functional theory calculations in the gas phase and dimethyl sulfoxide were carried out to ascertain the electronic properties and energy gap values using the same basis set. Molecular orbital contributions are investigated using the overlap population, partial, and total densities of states. Natural bond analysis was found to have strong electron delocalization by means of π(C4-C9) → π*(C5-C6), LP (N1) → π*(C7-C8), and LP(Br12) → π*(C5-C6) interactions. The Fukui function and Mulliken analysis have been explored on the atomic charges of the molecule. The nuclear magnetic resonance chemical shifts for 1 H and 13 C have been computed using the gauge-independent atomic orbital technique. With the highest binding affinity (-6.2 kcal mol-1 ) against estrogen sulfotransferase receptor (PDB ID: 1AQU) and low IC50 value of 17.23 μg/mL, 6BBZ demonstrated potent action against the MCF-7 breast cancer cell line. Studies on the antibacterial activity and ADMET prediction of the molecule have also been carried out.

Dark blue azo dye degradation by the electro-Fenton process and reaction mechanism prediction via theoretical Fukui function analysis

The electro-Fenton process, based on a new electrode combination, was investigated for the degradation of dark blue azo dye. Fukui function calculations were performed to propose a theoretical degradation mechanism.

Insight into properties and reutilization potential of spent polyaniline adsorbents containing transition metals through DFT calculations

Although adsorption technology is an efficient way for removing heavy metal pollutants from wastewater, its widespread application faces challenges related to the disposal and reutilization of hazardous spent adsorbents. Here, we employ density functional theory (DFT) calculations to investigate the properties and reutilization potential of spent PANI adsorbents containing transition metal ions. Bond strength analysis reveals the high stability of spent PANI adsorbents, which is crucial for their safe reutilization. The interaction region indicator (IRI), localized orbital locator (LOL), and decomposition analysis of Wiberg bond order were employed to understand the nature of the bonds between transition metals and imine N atoms. Fukui function analysis indicates that the presence of reducing groups and reductive metal ions in spent PANI adsorbents enhances their chemical stability. The atomic dipole moment corrected Hirshfeld (ADCH) charge and electron density difference (EDD) analysis reveals electron transfers between transition metals and PANI. Moreover, assessments of electrical conductivity, electronic density under electric fields, excited states, and surface charge demonstrate that spent PANI adsorbents hold significant potential for use in energy storage, electrocatalysis, photocatalysis, and environmental pollutant removal. This study provides a molecular-level understanding of the properties and reutilization potential of spent PANI adsorbents.

Structural elucidation and in-silico evaluation of 1,2,4-triazole derivative as potent Omicron variant of SARS-CoV-2 spike protein inhibitor with pharmacokinetics ADMET and drug-likeness predictions

One of the most significant issues in contemporary medicine and pharmacy is the search for powerful bioactive, efficient, low-toxic anti-COVID agents. In this contrast, present work involves the synthesis of triazole derivative 6-(4-Flurophenyl)-3-(pyridine-4yl)-7H-(1,2,4)triazolo(3,4-b) (1,3,4)thiadiazine (FPTT) and its characterizations using various spectroscopic techniques (LCMS, NMR, UV-vis, FTIR). The vibrational wavenumbers were evaluated and found to be in good agreement with theoretical values. The crystal structure is determined using single crystal X-ray diffraction study and the structure is reinforced by several intra-, intermolecular and π···π interactions. These interactions result in the formation of R12(7), R33(17), S(5) and S(6) synthons which significantly contribute towards the stability of the crystal structure. Further, these interactions are validated through Hirshfeld surface and 2D fingerprint plot analysis. The C-H···N and H···H contacts are the major contributors and are in consistency with the topology and natural bond orbital results. The optimized geometrical parameters through density functional theory (DFT) are in good agreement with the experimental data. Further, various electronic properties of the compound were evaluated using the optimized structure. The molecular electrostatic potential map (MEP) and Fukui function analysis revealed the most active sites. Analysis of non-covalent interactions based on a gradient of reduced density revealed the presence of van der Waals interactions. Intrigued, by the presence of large amounts of non-covalent interactions the pharmacokinetic profiles of the compound were evaluated through ADMET provides an insight into potential inhibitors and novel drug candidates. Further in-silico studies such as molecular docking was carried out against the Omicron variant of SARS-CoV-2 spike protein with an intention to assist towards the production of improved vaccines and therapeutics.

A pilot scale test study with theoretical justification of reaction mechanism for the recovery of chromium(VI) based on solvent extraction using novel centrifugal extractors

As a strategic resource and hazardous substance, the purification and recovery of chromium(VI) from the aqueous phase have attracted attention. In this study, the centrifugal extractor was used to treat the leach liquor of sodium roasting chromite on a pilot scale. The extraction performance and equilibrium distribution of chromium in countercurrent extraction were investigated. Meanwhile, the scrubbing effect of impurities was carefully studied, and the stripping and regeneration effects of the organic phase were tested. Under the selected process parameters, the pilot scale test results, including extraction efficiency of chromium, scrubbing efficiency of impurities, and regeneration performance of the organic phase, were excellent. The qualified (NH4)2Cr2O7 and Cr2O3 products were prepared using the strip liquor, and several physical properties of the products were tested. In addition, the molecular electrostatic potential surface maps, HOMO-LUMO orbitals, Fukui functions, and single point energy of the molecules involved were calculated by Quantum Chemistry. The molecular electrostatic potential analysis, frontiers molecular orbital analysis, Fukui function analysis and interaction energy analysis were applied to investigate the mechanism of separation of chromic acid from impurities in the extraction system.