Frontier Molecular Orbital Interactions Research Articles

In-situ formation of hydrophobic deep eutectic solvents to separate lactic acid: Lactam as hydrogen bond acceptor and lactic acid as hydrogen bond donor

Lactic acid (LA) is a typical high added-value chemical and platform molecule derived from renewable biomass. To realize high efficiency and green separation of LA is of both scientific and practical significance. In this work, we proposed a novel mechanism of in-situ formation of hydrophobic deep eutectic solvents (HDES) to couple the separation of LA and synthesis of HDES. Due to the high solubility of LA as hydrogen bond donor in water, three hydrophobic lactams (N-Octyl-2-pyrrolidone (NOP), N-Dodecyl-2-pyrrolidone (NDP) and 2-Octyl-4-isothiazolin-3-one (OIT)) were optioned as hydrogen bond acceptors. The effect of lactam molecular structure on separation efficiency was discussed and compared in detail. The compositions of HDES forming in-situ were found to be 1.50 for NOP and NDP to LA while 1.20 for OIT to LA using experiments of slope method and continuous variations method. The key evidence of formation of HDES was confirmed by FT-IR, frontier molecular orbital analysis and interaction region indicator analysis. The multistage counter-current extraction experiment results showed the in-situ formation of HDESs can transfer 99% of LA from fermentation broth to the HDES, and LA was separated completely from the impurities. This work provided a new perspective on lactic acid separation and its potential industrial applications.

Molecular structure, electronic properties, spectroscopic, quantum computational studies of 1-(4-hydroxy-3-methoxyphenyl)ethanone-effective anticancer medicine

The molecular structure of 1-(4-hydroxy-3-methoxyphenyl) ethenone has been optimized, and its various parameters were ascertained, using Density Functional Theory. The molecule’s Fourier Transform-Infra Red and Raman spectra are recorded and examined. By comparing the computational and experimental results, molecular structure, bond length, and vibrational band intensity were all interpreted. The Integral Equation Formalism polarizable continuum model’s depictions of electronic and Frontier Molecular Orbital solvent interaction investigations are sported to perceive the charge transfer among the atoms of the molecule in eco-green solvents such as water, acetone, and ethanol. The reactivity sites can be studied by locating and charting the electron density on the surface. The compound’s hardness, softness, electrophilicity, and ionization potential were all analyzed. The pharmacological effects and intra-molecular hyper conjugative interactions are liable for its molecular stability, as shown by Natural Bond Orbital research. Topological studies, including Electron Localized Function, Localized Orbital Locator, and Reduced density gradient analysis, were performed to locate the compound’s bonding area and Vander Waals interactions. Urea was used as a reference compound to examine the substance’s non-linear optical characteristics. Total Density of States has investigated the role of molecular orbitals. Drug-likeness, a Ramachandran plot, and molecular docking were also performed to further analyze 1-(4-hydroxy-3-methoxyphenyl) ethanone’s biological activity. The docking results lend credence to the idea that the title compound could function as a powerful cancer treatment.

Orthogonal Inverse-Electron-Demand Cycloaddition Reactions Controlled by Frontier Molecular Orbital Interactions.

Chemoselective pairs of bioorthogonal reactants enable the simultaneous labeling of several biomolecules. Here, we access orthogonal click reactions by exploiting differences in frontier molecular orbital interaction energies in transition states. We establish that five-membered cyclic dienes are inert to isonitriles but readily react with strained alkynes, while tetrazines with bulky substituents readily react with isonitriles. Strained alkynes show an opposite reactivity pattern. The approach was demonstrated by orthogonally labeling two proteins with different fluorophores.

Substituent Effects in Bioorthogonal Diels-Alder Reactions of 1,2,4,5-Tetrazines.

1,2,4,5-Tetrazines are increasingly used as reactants in bioorthogonal chemistry due to their high reactivity in Diels-Alder reactions with various dienophiles. Substituents in the 3- and 6-positions of the tetrazine scaffold are known to have a significant impact on the rate of cycloadditions; this is commonly explained on the basis of frontier molecular orbital theory. In contrast, we show that reactivity differences between commonly used classes of tetrazines are not controlled by frontier molecular orbital interactions. In particular, we demonstrate that mono-substituted tetrazines show high reactivity due to decreased Pauli repulsion, which leads to a more asynchronous approach associated with reduced distortion energy. This follows the recent Vermeeren-Hamlin-Bickelhaupt model of reactivity increase in asymmetric Diels-Alder reactions. In addition, we reveal that ethylene is not a good model compound for other alkenes in Diels-Alder reactions.

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations.

Nitrile imine cycloaddition to hydantoins containing an exocyclic C=C double bond has been previously described in a very limited number of examples. In this work, regioselective synthesis of spiro-pyrazoline-imidazolidine-2,4-diones based on a 1,3-dipolar cycloaddition reaction of nitrile imines to 5-methylidene-3-phenyl-hydantoin have been proposed. It was found that, regardless of the nature of the aryl substituents at the terminal C and N atoms of the C-N-N fragment of nitrile imine (electron donor or electron acceptor), cycloaddition to the 5-methylidenhydantoin exocyclic C=C bond proceeds regioselectively, and the terminal nitrogen atom of the nitrile imine connects to the more sterically hindered carbon atom of the double bond, which leads to the formation of a 5-disubstituted pyrazoline ring. The observed cycloaddition regioselectivity was rationalized using DFT calculations of frontier molecular orbital interactions, global CDFT reactivity indices, and minimum energy paths.

The study of Letrozole adsorption upon CCT nanotube: A DFT/TD-DFT and spectroscopic (excited states and UV/Vis)

In this research, the geometric structure of LTZ and CCT (5,0) was optimized with B3LYP/6-31G* method using the Gaussian 09W program package to investigate the weak interaction of Letrozole (LTZ) and carbon carbon nanotube (CCT). According to the calculation of the release energy, it was found that the drug delivery process is desirable. Also, the structural properties of the title compounds were assessed by thermodynamic and frontier molecular orbital (FMO) parameters. In this study, a series of measures have been performed to detect changes in drug loading properties and non-bonding interactions between the LTZ and CCT (5,0) nanotube. The non-bonding interaction effects of LTZ and CCT over the electronic properties were also evaluated and argued. The research is based on the fact that studies can help to understand the interaction between the LTZ drug and CCT (5,0) nanotube and the development of CCT-based drug release systems. This research aimed to determine variations in electronic properties of anticancer LTZ drug in presences CCT. Then, the reactivity and stability behavior of LTZ drug and on CCT to be examined by density functional theory (DFT). Then, frontier molecular orbital (FMO) and noncovalent interaction (NCI) analyses were performed, which decrease in reactivity described increase in the stability of LTZ drug.

3 + 2]-Cycloadditions with Porphyrin β,β'-Bonds: Theoretical Basis of the Counterintuitive meso-Aryl Group Influence on the Rates of Reaction.

Removal of a β,β'-bond from meso-tetraarylporphyrin using [3 + 2]-cycloadditions generates meso-tetraarylhydroporphyrins. Literature evidence indicates that meso-tetraphenylporphyrins react more sluggishly with 1,3-dipoles such as ylides and OsO4 (in the presence of pyridine) than meso-tetrakis(pentafluorophenyl)porphyrin. The trend is counterintuitive for the reaction with OsO4, as this formal oxidation reaction is expected to proceed more readily with more electron-rich substrates. This work presents a density functional theory-based computational study of the frontier molecular orbital (FMO) interactions and reaction profile thermodynamics involved in the reaction of archetypical cycloaddition reactions (a simple ylide, OsO4, OsO4·py, OsO4·(py)2, and ozone) with the β,β'-double bonds of variously fluorinated meso-arylporphyrins. The trend observed for the Type I cycloaddition of an ylide is straightforward, as lowering the LUMO of the porphyrin with increasing meso-phenyl-fluorination also lowers the reaction barrier. The corresponding simple FMO analyses of Type III cycloadditions do not correctly model the reaction energetics. This is because increasing fluorination leads to lowering of the porphyrin HOMO-2, thus increasing the reaction barrier. However, coordination of pyridine to OsO4 preorganizes the transition state complex; lowering of the energy barrier by the preorganization exceeds the increase in repulsive orbital interactions, overall accelerating the cycloaddition and rationalizing the counterintuitive experimental findings.

Multi-targeted fluorescent probes for detection of Zn(II) and Cu(II) ions based on ESIPT mechanism

With the rapid development of industry, it is pretty critical to detect the heavy metals. Recently, the 2-(2-hydroxyphenyl) benzothiazole derivatives with different numbers of rotatable phenyl m (m = 1,2,3) fluorescent probes HLm were synthesized. However, the theoretical analysis of the mechanism was still missing. In this work, we have systematically researched the mechanisms of excited state intramolecular proton transfer (ESIPT) and the detection of Cu(II), Zn(II) ions for the hydrogen-bond system HLm though quantum chemistry methods. By bond parameters and the minimum energy pathways analyses, the proton of this system was probed directly transfer without barrier. Bond parameters, real space function at bond critical point, the frontier molecular orbital, electron spectra and orbital interaction diagram were carried to elucidate response to Cu(II), Zn(II) ions. In addition, comparing the Gibbs free energy variation of the complexation reaction between fluorescent probes and ions, it can be proved that the number of rotatable benzene rings affects the response ability of the probe to target ions.

Atroposelective Access to 1,3‐Oxazepine‐Containing Bridged Biaryls via Carbene‐Catalyzed Desymmetrization of Imines

AbstractWe disclose herein an atroposelective synthesis of novel bridged biaryls containing medium‐sized rings via N‐heterocyclic carbene organocatalysis. The reaction starts with addition of the carbene catalyst to the aminophenol‐derived aldimine substrate. Subsequent oxidation and intramolecular desymmetrization lead to the formation of 1,3‐oxazepine‐containing bridged biaryls in good yields and excellent enantioselectivities. These novel bridged biaryl products can be readily transformed into chiral phosphite ligands. Preliminary density function theory calculations suggest that the origin of enantioselectivity arises from the more favorable frontier molecular orbital interactions in the transition state leading to the major product.

Atroposelective Access to 1,3-Oxazepine-Containing Bridged Biaryls via Carbene-Catalyzed Desymmetrization of Imines.

We disclose herein an atroposelective synthesis of novel bridged biaryls containing medium-sized rings via N-heterocyclic carbene organocatalysis. The reaction starts with addition of the carbene catalyst to the aminophenol-derived aldimine substrate. Subsequent oxidation and intramolecular desymmetrization lead to the formation of 1,3-oxazepine-containing bridged biaryls in good yields and excellent enantioselectivities. These novel bridged biaryl products can be readily transformed into chiral phosphite ligands. Preliminary density function theory calculations suggest that the origin of enantioselectivity arises from the more favorable frontier molecular orbital interactions in the transition state leading to the major product.

Cycloaddition Reactivities Analyzed by Energy Decomposition Analyses and the Frontier Molecular Orbital Model.

This Account describes our quest to understand and predict organic reactivity, a principal goal of physical and theoretical organic chemistry. The focus is on the development and testing of models for the prediction of cycloaddition reactivities and selectivities. We describe the involvement of the Houk group, and other groups, in the evolution of theoretical models that can achieve ever greater accuracy as well as provide practical heuristic models for understanding and prediction.Is the venerable frontier molecular orbital (FMO) model, the basis of Kenichi Fukui's 1981 Nobel Prize, still useful, or must it be replaced with more advanced models? In particular, models such as Conceptual Density Functional, the Pauli Exclusion Model, and the recent popularity of Electrostatic Potential Plots and Dispersion Energies have not only added to our understanding, but they have also created uncertainty about whether the simple FMO heuristic model has a place in 21st century discussions. This Account addresses this issue and asserts the value of the FMO model.Beginning with brief descriptions of selected models for cycloaddition reactivity starting with early donor-acceptor (nucleophile-electrophile) charge-transfer concepts, this Account reviews Fukui's frontier molecular orbital model, Salem and Klopman's orbital, electrostatic and Pauli repulsion model, the conceptual DFT model by Parr and later by Domingo and others, the recent Houk and Bickelhaupt Distortion/Interaction Activation Strain model, and the Bickelhaupt-Hamlin's Pauli-repulsion lowering model.Computations and analyses of four well-studied Diels-Alder cycloadditions, both normal and inverse electron-demand types, are presented. Most were studied earlier in our published work but are presented here with new insights from calculations with modern methods. Depending on the types of substrates (cycloaddends), the dominant factors controlling reactivity can be orbital interactions, electrostatics and polarization, or Pauli repulsion and dispersion effects, or a combination of all of these.By comparing orbital interactions, especially the frontier molecular orbital interactions, with the other factors that influence reactivity, we show why the FMO model is such a powerful─and theoretically meaningful─heuristic for understanding and predicting reactivity. We also present a method to understand Pauli repulsion effects on activation barriers, ρ(1.1). The use of a new reaction coordinate, the extent of Pauli repulsion along the reaction path, is advocated to emphasize the role of repulsive occupied orbital interactions on reactivity.Fukui's frontier molecular orbital model is effective because FMO interactions parallel all the quantities that influence reactivity. The FMO model continues to provide a practical model to understand and guide experiments.

A pair of carbazate derivatives as novel Schiff base ligands: DFT and POM theory supported spectroscopic and biological evaluation

Schiff bases are mentioned as strongly important molecular scaffolds of industrial and medicinal purposes. Due to wide range applications of carbazate derivatives herein synthesis and characterization of a new Schiff base ligand, (E)-ethyl 2-(4-methoxybenzylidene)hydrazinecarboxylate and 4-(nitrobenzaldehyde)ethylcarbazate are reported. The compound was characterized on the basis of experimental and density functional theory calculations (using the B3LYP and 6-31 G(d,p)formalism combination). Among characterization techniques elemental analysis, FT-IR, UV-Vis and NMR spectroscopic evaluations were mainly employed to carry out the formulation of the compound. In addition to computational validation of characterization other significant molecular parameters were also evaluated including geometry optimization, frontier molecular orbital analysis (FMO) and Columbic interaction of different constituent atoms of the title compound. A good agreement has been found between DFT and experimental outcomes confined to prove the structure of the compound. Moreover, molecular docking and antimicrobial studies have proven the Schiff base as an effective bioactive compound. Communicated by Ramaswamy H. Sarma

A Green Chemistry Approach toward the Stereospecific Synthesis of Densely Functionalized Cyclopropanes via the Solid-State Photodenitrogenation of Crystalline 1-Pyrazolines.

The cyclopropane ring features prominently in active pharmaceuticals, and this has spurred the development of synthetic methodologies that effectively incorporate this highly strained motif into such molecules. As such, elegant solutions to prepare densely functionalized cyclopropanes, particularly ones embedded within the core of complex structures, have become increasingly sought-after. Here we report the stereospecific synthesis of a set of cyclopropanes with vicinal quaternary stereocenters via the solvent-free solid-state photodenitrogenation of crystalline 1-pyrazolines. Density functional theory calculations at the M062X/6-31+G(d,p) level of theory were used to determine the origin of regioselectivity for the synthesis of the 1-pyrazolines; favorable in-phase frontier molecular orbital interactions are responsible for the observation of a single pyrazoline regioisomer. It was also shown that the loss of N2 may take place via a highly selective solid-state thermal reaction. Scalability of the solid-state photoreaction is enabled through aqueous nanocrystalline suspensions, making this method a "greener" alternative to effectively facilitate the construction of cyclopropane-containing molecular scaffolds.

Nickelocene as an Air- and Moisture-Tolerant Precatalyst in the Regioselective Synthesis of Multisubstituted Pyridines.

Ni(COD)2-catalyzed cycloaddition reactions to access pyridines have been extensively studied. However, this catalyst typically requires drying procedures and inert-atmosphere techniques for the reactions. Herein, we report operationally simple nickel(0) catalysis to access substituted pyridines from various nitriles and 1,6-diynes without the aid of air-free techniques. The Ni-Xantphos-based catalytic manifold is tolerant to air, moisture, and heat while promoting the [2 + 2 + 2] cycloaddition reactions with high reaction yields and broad substrate scope. In addition, we disclose that not only the steric effect but also the frontier molecular orbital interactions can play a critical role in determining the regiochemical outcome of nickel-catalyzed [2 + 2 + 2] cycloaddition for the synthesis of substituted pyridines.

Lewis Acidity of Carbon in Activated Carbonyl Group vs. B(C6 F5 )3 for Metal-Free Catalysis of Hydrogenation of Carbonyl Compounds.

In this work, using DFT calculations, we investigated Lewis acidities of carbon (in activated carbonyl group) in comparison to the B(C6 F5 )3 in combination with dioxane as the Lewis base (LB) for metal-free catalysis of heterolytic H2 splitting and hydrogenation of carbonyl compounds. We found that in case of carbon as the Lewis acid (LA) the reaction is controlled by frontier molecular orbital interactions between the H2 and LA-LB fragments at shorter distances. The steric effects can be reduced by electrophilic substitutions on the carbonyl carbon. Synergic combination between stronger orbital interactions and reduced steric effects can lower the barrier of the H2 splitting below 10 kcal/mol. With the B(C6 F5 )3 , the H2 splitting is controlled by electrostatic interactions, which cause to form an early transition state. An advantage of employing Lewis acidity of the activated carbonyl carbon for hydrogenation is that the hydride-type attack and hydrogenation of the C=O bond occur in a single step throughout H2 splitting. Hence, stronger Lewis acidity of the C(C=O) reinforces hydrogenation without prohibition of the hydride delivery.

Capture and Release of Singlet Oxygen in Coordination-Driven Self-Assembled Organoplatinum(II) Metallacycles.

Singlet oxygen (1O2), as an important active reagent, has found wide applications in photodynamic therapy (PDT), synthetic chemistry, and materials science. Organic conjugated aromatics serving as hosts to capture and release singlet oxygen have been systematically investigated over the last decades. Herein, we present a [6 + 6] organoplatinum(II) metallacycle by using ∼180° dipyridylanthracene donor and ∼120° Pt(II) acceptor as the building blocks, which enables the capture and release of singlet oxygen with relatively high photooxygenation and thermolysis rate constants. The photooxygenation of the metallacycle to the corresponding endoperoxide was performed by sensitized irradiation, and the resulting endoperoxide is stable at room temperature and can be stored under ambient condition over months. Upon simple heating of the neat endoperoxide under inert atmosphere at 120 °C for 4 h, the resulting endoperoxide can be reconverted to the corresponding parent form and singlet oxygen. The photooxygenation and thermolysis products were characterized by NMR spectroscopy and electrospray ionization time-of-flight mass spectrometric analysis. Density functional theory calculations were conducted in order to reveal the frontier molecular orbital interactions and reactivity. This work provides a new material platform for singlet oxygen related promising applications.

Use of quantum-chemical descriptors to analyse reaction rate constants between organic chemicals and superoxide/hydroperoxyl (O2•−/HO2•)

The reaction between superoxide (O2•−) and organic chemicals is of interest in many scientific disciplines including biology and synthetic chemistry, as well as for the evaluation of chemical fate in the environment. Due to limited data and lack of congeneric modelling, the involvement of superoxide in many complex processes cannot be adequately evaluated. In this study, we developed new quantitative structure–property relationship (QSPR) models for the prediction of the aqueous-phase rate constant for the reaction between superoxide and a wide variety of organic chemicals reacting via one-electron oxidation, reduction and hydrogen-transfer. It is shown that the relative importance of these pathways is related to frontier molecular orbital (FMO) interaction and to pH. The class-specific QSPRs developed have good statistics (0.84 ≤ R2 ≤ 0.92). For non-congeneric chemicals it is demonstrated that the reactivity toward superoxide can be described by applying explicit descriptions for competition kinetics and speciation. Therefore, the relationships developed in this study are useful as a starting point to evaluate more complex molecules having, for example, multiple reactive functional groups, labile H bonds, or delocalised cationic charges. However, additional kinetic data and more rigorous computation are needed to evaluate such molecules.

Theoretical investigation on the gas phase decomposition of ethyl acetate by Ni+

The density functional theory calculations were performed to systematically investigate the reaction of Ni+ with ethyl acetate in the gas phase. The reactive sites and reactivity were predicted by the average local ionization energy (ALIE). All possible reaction pathways were identified, which led to the formation of ketene or ethanol, two acetal units, and acetic acid or ethylene. The product distribution was discussed by means of the Curtin-Hammett principle. In addition, the properties of the chemical bonding evolution along the reaction pathway were studied using various analysis methods including atoms in molecules (AIM) and natural bond orbital (NBO). The frontier molecular orbital interactions were analyzed. The calculation results confirm that there are three reaction paths, in which the path B is the most favorable path, and acetic acid or ethylene is the main product.

Influence of the charge on the reactivity of azafullerenes.

The influence of the charge on the Diels-Alder reactivity of azafullerenes (C59N+ and C59N-) has been computationally explored by means of density functional theory calculations. In addition, the regioselectivity of the process has been investigated and compared to the analogous cycloaddition reaction involving the parent neutral azahydro[60]fullerene C59NH. It is found that the [4+2]-cycloaddition reaction between C59N+ and cyclopentadiene, which occurs concertedly through a synchronous transition state, proceeds with a lower activation barrier and is more exothermic than the analogous process involving C59NH. In contrast, the anionic C59N- counterpart is clearly less reactive. This reactivity trend is quantitatively analyzed in detail by means of the activation strain model of reactivity in combination with the energy decomposition analysis method. It is found that the frontier molecular orbital interactions are not responsible for the observed reactivity trend but the Pauli repulsion between closed-shells mainly governs the transformation.

A DFT investigation of Diels-Alder reaction of ethyl propiolate to the cage-annulated hexacyclo[7.5.2.01,6.06,13.08,12.010,14]hexadeca-2,4-diene-7,16-dione

The Diels?Alder (DA) reaction between the cage-annulated diene hexacyclo[7.5.2.01,6.06,13.08,12.010,14]hexadeca-2,4-diene-7,16-dione (HHDD) with a cyclohexa-1,3-diene moiety and ethyl propiolate (EP) dienophile was investigated by the DFT method at the B3LYP/6-31+G(d,p) level to elucidate the mechanism and regioselectivity features of the reaction. The geometrical and electronic structures of the caged diene HHDD and EP were studied at B3LYP/6-31+G(d,p) level. In order to identify facial- and regio-selectivity of the DA reaction of HHDD and EP, the frontier molecular orbital (FMO) interactions of the reactants according to the FMO theory, and the molecular electrostatic potential map of HHDD were examined. The potential energy surface (PES) of the related DA reaction was calculated, and optimizations of transition states and of products corresponding to critical points on the PES were performed at the B3LYP/6-31+G(d,p), and their configurations were determined. In addition, the thermodynamic and kinetic parameters of each possible cycloaddition reaction were calculated using the B3LYP/6-31+G(d,p) method to determine whether the reaction occurs under thermodynamic or kinetic control. The thermochemical results showed that the related DA cycloaddition proceeds under kinetic control, and the activation energies of syn cycloadditions are clearly lower than that of anti cycloadditions. The theoretical calculations are in good agreement with experimental results.