Intrinsic Reaction Coordinate Research Articles

Insights into the variations of kinetic and potential energies in a multi-bond reaction: the reaction electronic flux perspective.

The debate over whether kinetic energy (KE) or potential energy (PE) are the fundamental energy components that contribute to forming covalent bonds has been enduring and stimulating over time. However, the supremacy of these energy components in reactions where multiple bonds are simultaneously formed or broken has yet to be explored. In this study, we use the reaction electronic flux (REF), an effective tool for investigating changes in driving electronic activity when bond formation or dissociation occurs in a chemical reaction, to examine the fluctuations in the KE and PE in a multi-bond reaction. To that end, the activation of CO by low-valent group 14 catalysts through a concerted -bond metathesis mechanism is analyzed. The findings of this preliminary study suggest that the REF can be utilized as a tool to rationalize alterations in the KE and PE in a multi-bond reaction. Specifically, analyses across the reaction coordinate reveal that changes in the KE and PE precede activation in the REF, stimulating the electronic activity where bond formation or dissociation processes dominate. The activation of CO by the low-valent LEH catalysts (L = N,N'-bis(2,6-diisopropyl phenyl)- -diketiminate; E = Si, Ge, Sn, and Pb) was studied along the reaction coordinate at the M06-2X/6-31G(d,p)-LANL2DZ(E) level of theory. The respective minimum energy path calculations were obtained using the intrinsic reaction coordinate (IRC) procedure. The reaction electronic flux (REF) was calculated through the computation of the electronic chemical potential using the frontier molecular orbital approximation. Mayer bond orders along the reaction coordinate have been determined using the NBO 3.1 program in Gaussian16. Most of the reaction coordinate quantities reported in this study (REF, KE, PE, among others) have been determined using the Kudi program and custom Python scripts.

Ab initio investigation on the mechanism of SO2 activation by P/B intermolecular frustrated Lewis pairs.

In silico study investigates the activation of sulfur dioxide by newly designed frustrated Lewis pairs, i.e., [P(tBu)3…B(C2NBSHF2)3], where the Lewis acid part is a super Lewis acid. The activation process involves the making of P-S and B-O bonds, leading to the formation of an FLP-SO2 adduct. The calculated results demonstrate that the activation of SO2 by the FLP is almost barrierless and exothermic. Exploration of the impact of the solvent environment on the feasibility and energetics of the reaction has been investigated. The exothermicity is increasing in nonpolar solvents. This study focuses on understanding the electronic activity of SO2 activation by FLP with the help of the Minnesota 06 functional, M06-2X (global hybrid functional with 54% HF exchange) along with Pople's basis set, 6-311G (d, p). Principal interacting orbital and extended transition state-natural orbitals for chemical valence studies, giving impactful insight into the favorable orbital interaction and electron transfer in this reaction. Furthermore, useful CDFT descriptors such as reaction force constant and reaction electronic flux profiles along the intrinsic reaction coordinate give insights into the synchronicity and total electronic activity of the reaction.

Thermal decomposition study of 1,3-dioxolane as a representative of battery solvent

As industrial compounds and organic solvent, 1,3-dioxolane (C3H6O2) is used in lithium-ion batteries arousing extensive interest. The pyrolysis of C3H6O2 at 150 torr pressure was conducted in the temperature range of 743-1013K. In order to quantify the major products, experimental measurements of the photoionization cross-section (PICS) and photoionization efficiency (PIE) for C3H6O2 were carried out by using synchrotron radiation photoionization mass spectrometry (SR-PIMS). Twenty-three intermediates were detected in pyrolysis of C3H6O2 including the newly observed ketene, acetaldehyde, ethenol, ethanol, dimethyl ether, diacetylene and 2-propen-1-ol which played important roles in developing mechanism. The H-abstraction of C3H6O2 by H, CH3 and OH radicals were studied via high level ab initio calculations. EStokTP code was used to find and calculate optimal geometries, vibration frequencies and intrinsic reaction coordinate (IRC) at the theory level of M06-2X/6-311+G(d,p). Conventional transition state theory (TST) was used and Rice-Ramsperger-Kassel-Marcus/Master Equation (RRKM/ME) was solved to obtain rate coefficients. For H-abstraction by H and CH3, the rates are increasing versus temperature, and rates of H-abstraction by OH show different tendency. These rate parameters were used to update the model of C3H6O2, which could well predict the ignition delay times (IDTs) in shock tube and oxidation data in jet stirred reactor (JSR) from literature. For the pyrolysis, H-abstraction reactions by H, CH3 and OH and unimolecular reactions contribute to solvent decay. Detailed pathways of C3H6O2 decomposition were also given and analyzed through this experiment and previous literature. The findings, including the experimental data and the calculations will assist to better understand pyrolysis characteristics of C3H6O2 as well.

Kinetic Isotope Effects and the Mechanism of CO2 Insertion into the Metal-Hydride Bond of fac-(bpy)Re(CO)3H.

The 1,2-insertion reaction of CO2 into metal-hydride bonds of d6-octahedral complexes to give κ1-O-metal-formate products is the key step in various CO2 reduction schemes and as a result has attracted extensive mechanistic investigations. For many octahedral catalysts, CO2 insertion follows an associative mechanism in which CO2 interacts directly with the coordinated hydride ligand instead of the more classical dissociative mechanism that opens an empty coordination site to bind the substrate to the metal prior to a hydride migration step. To better understand the associative mechanism, we conducted a systematic quantum chemical investigation on the reaction between CO2 and fac-(bpy)Re(CO)3H (1-Re-H; bpy = 2,2'-bipyridine) starting with the gas phase and then moving to THF and other solvents with increased dielectric constants. Detailed analyses of the potential energy surfaces (PESs) and intrinsic reaction coordinates (IRCs) reveal that the reaction is enabled in all media by an initial stage of making a 3c-2e bond between the carbon of CO2 and the metal-hydride bond that is most consistent with an organometallic bridging hydride Re-H-CO2 species. Once CO2 is bent and anchored to the metal-hydride bond, the reaction proceeds by a rotation motion via a cyclic transition state TS2 that interchanges Re-H-CO2 and Re-O-CHO coordination. The combined stages provide an asynchronous-concerted pathway for CO2 insertion on the Gibbs free energy surface with TS2 as the highest energy point. Consideration of TS2 as a rate-determining TS gives activation barriers, inverse KIEs, substituent effects, and solvent effects that agree with the experimental data available in this system. An important new insight revealed by the analyses of the results is that the initial stage of the reaction is not a hydride transfer step as has been assumed in some studies. In fact, the loose vibration of the TS that can be identified for the first stage of the reaction in solution (TS1) does not involve the Re-H stretching vibrational mode. Accordingly, the imaginary frequency of TS1 is insensitive to deuteration, and therefore, TS1 leads to no significant KIE.

Quantum chemical pathways for the formation of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) from 2,4,5-trichlorophenol: a mechanistic and thermo-kinetic study.

Dioxins, specifically 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD), are highly toxic dioxins known for their severe health impacts and persistent environmental pollutants. This study focuses on understanding the formation pathways of TCDD from its precursor molecule 2,4,5-trichlorophenol (2,4,5-TCP). In our exploration of reaction pathways from 2,4,5-trichlorophenol (TCP), we delve into three reaction mechanisms: free-radical, direct condensation, and anionic. Our findings highlight the significance of the radical mechanism, particularly propagated by H radicals, with a notable increase in dioxin formation around 900K. These results are consistent with experimental observations indicating an increase in the conversion of trichlorophenol from 600 to 900K in the non-catalytic gas phase reaction. Thermodynamic parameters (∆H, ∆S, and ∆G), reaction barriers, and rate constants (k) were calculated across a temperature range of 300-1200K to support the findings and provide insights into the optimal temperature range for controlling dioxins during the incineration process. In this study, quantum chemical calculations were conducted using density functional theory (DFT) with the B3LYP functional and the 6-311 + + G(d,p) basis set in Gaussian 16 software. Stationary points, including transition states (TS), were confirmed with frequency calculations. Intrinsic reaction coordinate (IRC) calculations ensured minimum energy paths between TS and products, visualized in GaussView 6.0 Program. Single-point energy calculations utilized a more precise basis set, 6-311 + + G(3df,2p), for enhanced energy accuracy, incorporating zero-point vibrational energy (ZPE) and other energy corrections. These calculations were repeated over a temperature range of 298.15-1200K at 1atm pressure. Finally, rate constant (k) expressions associated with TCDD formation were determined using transition state theory (TST).

Restriction on molecular fluxionality by substitution: A case study for the 1,10-dicyanobullvalene.

We show herein that 1,10-dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10-dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born-Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long-time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the "14 Cs → C7v" thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un-explored properties e.g. for the equilibration dynamics of C10H10.

Concerning for the solvent-polarity-dependent conformational equilibrium and ESIPT mechanism in Pz3HC system: A novel insight

In this report, we propose a new insight into the interaction between the solvent-polarity-dependent conformational equilibrium and excited state intramolecular proton transfer (ESIPT) behavior of Pz3HC system in four different polar solvents (polarity order: ACN > THF > TOL > CYC). Using quantum chemistry method, we first announce a coexistence mechanism between Pz3HC-1 and Pz3HC-3 in the ground state in four solvents based on the Boltzmann distribution. In particular, Pz3HC-1 is the principal configuration in non-polar solvent, but Pz3HC-3 is the principal configuration in polar solvent. In addition, the simulated fluorescence spectra interprets the negative solvatochromism effect of Pz3HC-1 and Pz3HC-3 in four solvents. The evidence from intramolecular hydrogen bonding (IHB) parameters and electronic perspective collectively confirms the light-induced IHB enhancement and intramolecular charge transfer (ICT) properties in Pz3HC-1 and Pz3HC-3, which raises the likelihood of the ESIPT process. Combining the calculation of potential energy curve (PEC) and intrinsic reaction coordinate (IRC), we demonstrate that the ESIPT ease of Pz3HC-1 in different polar solvents obeys the order of CYC > TOL > THF > ACN, while the order of ESIPT ease in Pz3HC-3 is opposite. Notably, the ESIPT process of Pz3HC-3 in CYC solvent is accompanied by the twisted intramolecular charge transfer (TICT) process. In addition, we also reveal that the enol* and keto* fluorescence peaks of Pz3HC-3 in CYC solvent are quenched by ISC and TICT process, respectively. Our work not only provides a satisfactory explanation of the novel dynamics mechanism for Pz3HC system, but also brings light to the design and application of new sensing molecules in the future.

Investigating the catalytic activity of Mgn (n = 4–8) clusters for the hydrogen evolution reaction using density functional theory

AbstractTo efficiently desorb H2, pure Mgn (n = 4–8) clusters were chosen for the hydrogen evolution reaction with H2O. At the PBE0/def2‐TZVP level and the PBE0‐D3/def2‐TZVP level, the lowest energy structures of Mgn (n = 4–8) clusters and the most stable structures of Mgn@H2O (n = 4–8) complexes were searched in the local region. The transition state was predicted, and then the hydrogen evolution reaction channel was obtained by using the intrinsic reaction coordinate (IRC) to confirm the transition state. To better analyze the hydrogen reaction mechanism, the character of Mgn@H2O (n = 4–8) complexes and MgnO (n = 4–8) clusters, as well as the atomic charge change trend, were investigated using interaction region indicator function analysis (IRI) and natural population analysis (NPA). The reaction effect of Mg4 cluster and H2O is the worst. The energy barrier does, however, progressively lower as the cluster atom count rises, improving the reaction effect.

Intermolecular interaction of azide, cyano and alkyne-N-phenethylacetamide dimers: Experimental and quantum chemical approach

In this study, we present the synthesis and structure characterization by single-crystal X-ray Diffraction (SC-XRD), Ultraviolet Spectroscopy (UV), Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and High-resolution Mass Spectrometry (HRMS) of 2-azido-N-phenethylacetamide (4) and 2-cyano-N-phenethylacetamide (6). Further, Density Functional Theory (DFT) was employed to get a better insight regarding the properties exhibited by the compounds. The computational chemistry has been used to explain and investigate the bimolecular nucleophilic substitution (SN2) and concerted acyl substitution mechanisms for the synthesis of compounds 4 and 6, respectively. Additionally, intrinsic reaction coordinate (IRC) calculations confirm the transition state for these reactions. The X-ray diffraction analysis showed that the compounds 4 and 6 crystallized as monoclinic systems, in space group P21/c and P21/n, respectively. The Hirshfeld Surface Analysis revealed that the main contributions in the crystal packing have H···H, H···N/N···H, H···C/C···H and H···O/O···H interactions. The frontier molecular orbital energies were calculated and the HOMO-LUMO energy gap of 4 and 6 were 10.011 and 10.278 eV, respectively. Theoretical values of electronic transitions, vibrational frequencies and NMR chemical shifts were calculated and compared with experimental results, they all showed good results.

Formic Acid-Ammonia Heterodimer: A New Δ-Machine Learning CCSD(T)-Level Potential Energy Surface Allows Investigation of the Double Proton Transfer.

The formic acid-ammonia dimer is an important example of a hydrogen-bonded complex in which a double proton transfer can occur. Its microwave spectrum has recently been reported and rotational constants and quadrupole coupling constants were determined. Calculated estimates of the double-well barrier and the internal barriers to rotation were also reported. Here, we report a full-dimensional potential energy surface (PES) for this complex, using two closely related Δ-machine learning methods to bring it to the CCSD(T) level of accuracy. The PES dissociates smoothly and accurately. Using a 2d quantum model the ground vibrational-state tunneling splitting is estimated to be less than 10-4 cm-1. The dipole moment along the intrinsic reaction coordinate is calculated along with a Mullikan charge analysis and supports the mildly ionic character of the minimum and strongly ionic character at the double-well barrier.

Synthesis, Characterization, Crystal Structure, and Theoretical Calculations of Novel 1,5-Benzodiazepine Derivatives Obtained via 1,3-Dipolar Cycloaddition Reactions

A series of triazolo-benzodiazepine derivatives were synthesized by the condensation of 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine (BZD) 1 with nitrilimine analogs (N-aryl-C-ethoxycarbonyl-nitrilimines and diarylnitrilimines). The newly synthesized cycloadducts were well-characterized by various spectroscopic techniques (1H, 13C NMR, and HRMS). The structure of single-crystal was characterized using a single-crystal X-ray technique. A theoretical study of the chemo and regioselectivity has been performed by density functional theory at the B3LYP/6-311G(d,p) level of theory. A comprehensive theoretical study of the reaction mechanism was performed. The geometry of the different reactants and products were analyzed, the transition states were located and the corresponding reaction paths were determined and characterized by the intrinsic reaction coordinate. Computational results show that the reactions were completely chemo and regioselective, the mechanism of reactions was non-concerted and explained the effect of aryl groups on the reaction yield.

Test of the orbital-based LI3 index as a predictor of the height of the [formula omitted]MLCT [formula omitted][formula omitted]MC transition-state barrier for gas-phase [Ru(N[formula omitted]N)[formula omitted]][formula omitted] polypyridine complexes

Ruthenium(II) polypyridine compounds often luminesce, with ligand-dependant lifetimes. This is the third in a series of papers devoted to finding orbital-based luminescence indices (LI) for predicting luminescence lifetimes. The third attempt (LI3) was based upon a frontier molecular orbital (FMO) like estimate of the height of the barrier to conversion from an initial phosophorescent triplet metal-ligand charge transfer (3MLCT) state to a nonluminescent triplet metal-centered (3MC) state which decays nonradiatively. A linear correlation was found between LI3 and extracted empirical average 3MLCT →3MC transition state (TS) barrier heights (Eaves) which were not believed to be quantitative but which were believed to capture the trends in the true barrier heights correctly. As it is known that Eave is a large underestimate of the true 3MLCT →3MC TS barrier height in the case of the trisbipyridine ruthenium(II) cation { [Ru(bpy)3]2+ }, but accurate TS barrier heights are difficult to obtain experimentally, it was judged useful to verify the ideas used to derive the LI3 index in the present work by calculating the energetics of the gas-phase 3MLCT →3MC reaction for a series of ruthenium(II) tris bipyridine complexes using the same density functional and basis sets used in calculating LI3. Specifically, four closely-related bipyridine complexes { [Ru(N∧N)3]2+ with N∧N = bpy (6), 4,4’-dm-bpy (70), 4,4’-dph-bpy (73), and 4,4’-DTB-bpy (74) } were used for these calculations. In the process, we examined the gas-phase trans dissociation mechanism in greater detail than has been previously done and uncovered a two part mechanism. In the first part, the electron is transferred to a single ligand rather than symmetrically to all three ligands. It is the two Ru-N bonds to this ligand which are equally elongated in the transition state. The intrinsic reaction coordinate then continues down a ridge in hyperspace and bifurcates into one of two symmetry-equivalent 3MC structures with elongated trans bonds. Interestingly, no significant difference is found for the TS barriers for the four complexes treated here. Instead, LI3 is linearly correlated with the energy difference ΔE=E(3MLCT)−E(3MC), different from what was originally intended but still consistent with the FMO arguments underlying the derivation of LI3.

Investigations of the reaction mechanism of sodium with hydrogen fluoride to form sodium fluoride and the adsorption of hydrogen fluoride on sodium fluoride monomer and tetramer.

The reaction between Na and HF is a typical harpooning reaction which is of great interest due to its significance in understanding the elementary chemical reaction kinetics. This work aims to investigate the detailed reaction mechanisms of sodium with hydrogen fluoride and the adsorption of HF on the resultant NaF as well as the (NaF)4 tetramer. The results suggest that the reaction between Na and HF leads to the formation of sodium fluoride salt NaF and hydrogen gas. Na interacts with HF to form a complex HF···Na, and then the approaching of F atom of HF to Na results in a transition state H···F···Na. Accompanied by the broken of H-F bond, the bond forms between F and Na atoms as NaF, then the product NaF is yielded due to the removal of H atom. The resultant NaF can further form (NaF)4 tetramer. The interaction of NaF with HF leads to the complex NaF···HF; the form I as well as II of (NaF)4 can interact with HF to produce two complexes (i.e., (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF), but the form III of (NaF)4 can interact with HF to produce only one complex (NaF)4(III)···HF. These complexes were explored in terms of noncovalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses. NCI analyses confirm the existences of attractive interactions in the complexes HF···Na, NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF. QTAIM analyses suggest that the F···Na interaction forms in the HF···Na complex while the F···H hydrogen bonds form in NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF complexes. Natural bond orbital (NBO) analyses were also applied to analyze the intermolecular donor-acceptor orbital interactions in these complexes. These results would provide valuable insight into the chemical reaction of Na and HF and the adsorption interaction between sodium fluoride salt and HF. The calculations were carried out at the M06-L/6-311++G(2d,2p) level of theory which were performed using the Gaussian16 program. Intrinsic reaction coordinate (IRC) calculations were carried out at the same level of theory to confirm that the obtained transition state was true. The molecular surface electrostatic potential (MSEP) was employed to understand how the complex forms. Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analysis was used to know the topology parameters at bond critical points (BCPs) and intermolecular interactions in the complex and intermediate. The topology parameters and the BCP plots were obtained by the Multiwfn software.

A 21st Century View of Allowed and Forbidden Electrocyclic Reactions.

In 1965, Woodward and Hoffmann proposed a theory to predict the stereochemistry of electrocyclic reactions, which, after expansion and generalization, became known as the Woodward-Hoffmann Rules. Subsequently, Longuet-Higgins and Abrahamson used correlation diagrams to propose that the stereoselectivity of electrocyclizations could be explained by the correlation of reactant and product orbitals with the same symmetry. Immediately thereafter, Hoffmann and Woodward applied correlation diagrams to explain the mechanism of cycloadditions. We describe these discoveries and their evolution. We now report an investigation of various electrocyclic reactions using DFT and CASSCF. We track the frontier molecular orbitals along the intrinsic reaction coordinate and modeled trajectories and examine the correlation between HOMO and LUMO for thermally forbidden systems. We also investigate the electrocyclizations of several highly polarized systems for which the Houk group had predicted that donor-acceptor substitution can induce zwitterionic character, thereby providing low-energy pathways for formally forbidden reactions. We conclude with perspectives on the field of pericyclic reactions, including a refinement as the meaning of Woodward and Hoffmann's "Violations. There are none!" Lastly, we comment on the burgeoning influence of computations on all fields of chemistry.

Experimental and kinetic study on 2-methoxyethanol part I: Molecular chemistry and pyrolysis investigation

Glycol ethers have been widely recognized as an alternative biofuels. 2-Methoxyethanol (ME2, HOCH2CH2OCH3) is the simplest and most representative glycol ether. Hence, the combustion chemistry of ME2 has aroused extensive interest. The ME2 pyrolysis has been investigated experimentally in a jet-stirred reactor (JSR) at atmospheric pressure within the temperature range of 650–1075 K for the first time. FTIR, GC–MS, and GC-FID were used to identify and quantify species profiles in ME2 pyrolysis. Sixteen intermediates were newly detected by the present work including acetaldehyde, hydroxyacetaldehyde, and methyl vinyl ether which are essential for mechanism development. The H abstraction reactions of ME2 by H, CH3, HO2, OH, O2, and the unimolecular reactions of four fuel-related radicals were first studied via high level ab initio calculations. The geometries optimization, vibrational frequencies, and intrinsic reaction coordinate (IRC) calculations were carried out at the M06–2X/6–311++G(d,p) level of theory. Conventional transition state theory (TST) and Rice-Ramsperger-Kassel-Marcus/Master Equation (RRKM/ME) were used to calculate the temperature- and pressure-dependent rate constants from 300 to 2000 K and 0.01 to 100 atm for the first time. It is found that the H abstraction reactions at the two middle carbon atoms are the most favored pathways, and b-scissions for fuel-related radicals have the lowest energy barriers. The thermochemical properties of ME2 and its derived radicals have been obtained via the combination of composite methods. A mechanism involving 596 species and 3123 reactions was developed for the first time to predict the ME2 pyrolysis characteristics based on experimental and calculated results obtained by the present work. Good agreements were achieved between the measured and simulated results. Rate of production (ROP), as well as sensitivity analysis, were performed to get a deeper insight into the ME2 pyrolysis. It has been revealed that the major ME2 decomposition channels are the H abstractions by H, CH3, and OH radicals, and unimolecular reactions have scarce contributions to fuel decay. The results, in terms of the measured data and of the calculated results, and the newly developed kinetic model as well as findings obtained within this study will assist and contribute to a better understanding of combustion characteristics of ME2 and of glycol ethers as well.

Insight into acrolein activation by P/B intramolecular frustrated Lewis pairs

AbstractThe study investigates the reactivity of a cyclic five‐membered intramolecular P/B frustrated Lewis pair towards acrolein through a cycloaddition reaction. Intrinsic reaction coordinate (IRC) calculations suggest the single‐step mechanism. It has been observed that the cycloaddition reaction occurs through a concerted mechanism in both the presence and absence of the catalyst. Analysis of reaction force and reaction electronic flux provides valuable information about the total work required and electronic activity along the IRC. Additionally, natural bonding orbital (NBO) analyses enrich the understanding of the mechanism in terms of the electron transfer process during the chemical reaction.

DFT mechanistic study of [4+2] cycloaddition reactions of 1-methyl-1H-pyrrole-2,5-dione with furoic acid, anticancer Activity, molecular modeling and ADMET properties of new products from the Norcantharimide family substituted by a carboxylic acid

The [4+2] cycloaddition reactions of 1-methyl-1H-pyrrole-2,5-dione, with furan-2-carboxylic acid, 5-methylfuran-2-carboxylic acid and 5 -(hydroxymethyl)-furan-2-Carboxylic acid have been studied using various theoretical approaches at the M06/6–311++G(d,p) level of theory. Conceptual DFT (CDFT) analysis shows that 1-methyl-1H-pyrrole-2,5-dione behaves as an electrophile and furan-2-carboxylic acid, 5-methylfuran-2-carboxylic acid and 5 -(hydroxymethyl)-furan-2-Carboxylic acid act as nucleophiles. Furthermore, the regioselectivity has been explored from the Parr functions and Houk's rule. The studied DA reactions followed a one-step mechanism presenting a polar character where the formation of the new bonds takes place according to an asynchronous process. The activation and reaction energy values, extracted from the energetic profile plots, allow us to determine the most favorable reaction pathway. Moreover, the topology of the electronic localization function (ELF) in specific points of the intrinsic reaction coordinate profile (IRC) associated with the most favorable reaction pathway makes it possible to highlight a non-concerted two stages one-step molecular mechanism. The valorization of the anticancer activity of six products from the Norcantharimide family substituted by carboxylic acids has been carried out using molecular docking calculations. It has been shown, for the first time, that these products are efficient against breast cancer. Finally, the physicochemical properties and medicinal potential of these products were evaluated using the SwissADME online tool, revealing that they lack toxicity and their potential as promising drug candidates.

The increased Diels–Alder reactivity of umpolung tropone: analysis of individual atoms and bonds using QTAIM and IQA along complete IRC paths

AbstractA fruitful debate took place recently in literature, discussing the enhanced Diels–Alder reactivity of tropone derivatives for which the carbonyl polarity was reversed by means of umpolung. Karas et al. sustained that the umpolung increases the antiaromatic character of the ring, affecting the highest occupied molecular orbital (HOMO)/least unoccupied molecular orbital (LUMO) energies, speeding up the reaction. Tiekink et al. challenged this interpretation by sustaining that the asynchronicity of the reaction mechanisms, rather than orbital energy perturbation, was the main responsible for the smaller reaction barriers. We shed light on this dispute by computing full interaction quantum atom (IQA) and quantum theory of atoms in molecules (QTAIM) analyses over complete intrinsic reaction coordinate (IRC) paths for the Diels–Alder reaction of tropone and its umpolung derivatives, using the same systems studied by Karas et al. and Tiekink et al. Our results confirm that the asynchronicity is indeed very high for those reactions with smaller reaction barriers and offer an atom‐by‐atom and bond‐by‐bond analysis of the entire IRC pathways. Even though asynchronicity and lower reactions barriers seem to be related, antiaromaticity and lower barriers are related as well, but discussing both these interpretations does not necessarily require arguments on HOMO/LUMO energies to be invoked.

A TD‐DFT/DFT study on the ESIPT and photophysical properties of symmetrical 2‐hydroxybenzilidene1,3‐diamines derivatives

AbstractDensity functional theory (DFT) and Time dependent density functional theory (TD‐DFT) methods are used to simulate the photoexcitation and emission of the symmetrical 2‐hydroxybenzilidene1,3‐diamine (HBDA) Schiff base and some of its derivatives in the gas phase and solution. Our aim here is to explore the details of Excited‐State Intramolecular Proton Transfer (ESIPT) which underlies the activity of HBDA molecules as fluorescent probes. The structures of HBDA in S0 and the S1 states are optimized utilizing the DFT and TD‐DFT methods, respectively. Geometric configurations, electronic spectra, frontier molecular orbitals, and potential energy surfaces have all been computed and analyzed for the purpose of interpreting the mechanism of ESIPT. The geometries and relative stabilities of 15 tautomeric forms and the corresponding isomers of the studied molecules have been identified and their relative stabilities are investigated. The potential energy profiles and intrinsic reaction coordinates (IRC) calculations along the proton transfer coordinates both in the ground and in the excited state are monitored as well. The impact of the donating (OMe) and withdrawing (NO2) groups on the single and double proton transfers are investigated both in the gas phase and solution.

Elucidating the Racemization Mechanism of Aliphatic and Aromatic Amino Acids by In Silico Tools.

The racemization of biomolecules in the active site can reduce the biological activity of drugs, and the mechanism involved in this process is still not fully comprehended. The present study investigates the impact of aromaticity on racemization using advanced theoretical techniques based on density functional theory. Calculations were performed at the ωb97xd/6-311++g(d,p) level of theory. A compelling explanation for the observed aromatic stabilization via resonance is put forward, involving a carbanion intermediate. The analysis, employing Hammett's parameters, convincingly supports the presence of a negative charge within the transition state of aromatic compounds. Moreover, the combined utilization of natural bond orbital (NBO) analysis and intrinsic reaction coordinate (IRC) calculations confirms the pronounced stabilization of electron distribution within the carbanion intermediate. To enhance our understanding of the racemization process, a thorough examination of the evolution of NBO charges and Wiberg bond indices (WBIs) at all points along the IRC profile is performed. This approach offers valuable insights into the synchronicity parameters governing the racemization reactions.