Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics.

In this work, the pKa values of 69 polar alkanes (YH2) in acetonitrile were computed using the method developed by Luo and Zhang in 2020, and representative 69 thermodynamic network cards on 22 elementary steps of YH2 and related polar alkenes (Y) releasing or accepting H2 were naturally established. Potential electron reductants (YH-), hydride reductants (YH-), antioxidants (YH2 and YH-), and hydrogen molecule reductants (YH2) are unexpectedly discovered according to thermodynamic network cards. It is also found that there are great differences between YH2 and common hydrogen molecule reductants (XH2), such as Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydro-phenanthridine (PH2), releasing two hydrogen ions to unsaturated compounds. During the hydrogenation process, XH2 release hydrides first, then the oxidation state XH+ release protons. However, in the case of YH2, YH2 release protons first, then YH- release hydrides. It is the differences on acidic properties of YH2 and XH2 that result in the behavioral and thermodynamic differences on YH2 and XH2 releasing two hydrogen ions (H--H+). The redox mechanisms and behaviors of Y, YH-, and YH2 as electron, hydrogen atom, hydride, and hydrogen molecule donors or acceptors in the chemical reaction are reasonably investigated and discussed in this paper using thermodynamics.

Thermodynamic Network Cards of Hantzsch Ester, Benzothiazoline, and Dihydrophenanthridine Releasing Two Hydrogen Atoms or Ions on 20 Elementary Steps.

In this work, thermodynamic driving forces on 20 possible elementary steps of Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydrophenanthridine (PDH2) releasing two hydrogen atoms or ions were measured or derived from the related thermodynamic data using Hess' law in acetonitrile. Furthermore, thermodynamic network cards of HEH2, BTH2, and PDH2 releasing two hydrogen atoms or ions on 20 elementary steps were first established. Based on the thermodynamic network cards, hydride-donating, hydrogen-atom-donating, and electron-donating abilities of XH2 and XH-, and two hydrogen-atom(ion)-donating abilities of XH2 are discussed in detail. Obviously, the thermodynamic network cards of HEH2, BTH2, and PDH2 not only offer rational data guidance for organic synthetic chemists to properly choose an appropriate reducer among the three reducing agents to hydrogenate various unsaturated compounds but also strongly promote elucidatation of the detailed hydrogenation mechanisms.

Prediction of Kinetic Isotope Effects for Various Hydride Transfer Reactions Using a New Kinetic Model.

In this work, kinetic isotope effect (KIEself) values of 68 hydride self-exchange reactions, XH(D) + X(+) → X(+) + XH(D), in acetonitrile at 298 K were determined using a new experimental method. KIE values of 4556 hydride cross transfer reactions, XH(D) + Y(+) → X(+) + YH(D), in acetonitrile were estimated from the 68 determined KIEself values of hydride self-exchange reactions using a new KIE relation formula derived from Zhu's kinetic equation and the reliability of the estimations was verified using different experimental methods. A new KIE kinetic model to explain and predict KIE values was developed according to Zhu's kinetic model using two different Morse free energy curves instead of one Morse free energy curve in the traditional KIE theories to describe the free energy changes of X-H bond and X-D bond dissociation in chemical reactions. The most significant contribution of this paper to KIE theory is to build a new KIE kinetic model, which can be used to not only uniformly explain the various (normal, enormous and inverse) KIE values but also safely prodict KIE values of various chemical reactions.

Elemental step thermodynamics of various analogues of indazolium alkaloids to obtaining hydride in acetonitrile.

A series of analogues of indazolium alkaloids were designed and synthesized. The thermodynamic driving forces of the 6 elemental steps for the analogues of indazolium alkaloids to obtain hydride in acetonitrile were determined using an isothermal titration calorimeter (ITC) and electrochemical methods, respectively. The effects of molecular structure and substituents on the thermodynamic driving forces of the 6 steps were examined. Meanwhile, the oxidation mechanism of NADH coenzyme by indazolium alkaloids was examined using the chemical mimic method. The result shows that the oxidation of NADH coenzyme by indazolium alkaloids in vivo takes place by one-step concerted hydride transfer mechanism.

Evaluation of the efficacy and safety of robot-assisted and video assisted thoracic surgery for early non-small cell lung cancer: A meta-analysis.

BACKGROUND: Radical resection of lung cancer and chemotherapy are the main methods for the treatment of early lung cancer, but surgical treatment is still the key and preferred method. OBJECTIVE: To evaluate the efficacy and safety of robotic-assisted thoracic surgery (RATS) and video assisted thoracic surgery (VATS) for non-small cell lung cancer (NSCLC). METHODS: The clinical cohort studies on the comparison of the effects of RATS and VATS in the treatment of NSCLC published in Web of Science, PubMed, The National Library of Medicine (NLM), China National Knowledge Infrastructure (CNKI) and Wanfang database from January 1, 2015 to December 31, 2022 were searched. Two researchers independently screened the literature, extracted the data, such as operation time, intraoperative conversion rate, intraoperative blood loss, number of lymph nodes dissected, and evaluated the quality of the included literature based on the Newcastle-Ottawa Scale (NOS). RevMan 5.3 software was used for Meat analysis. RESULTS: A total of 18 articles and 21,802 subjects were included. The results of the meta-analysis showed that the intraoperative blood loss of RATS was significantly less than that of VAS, and the difference was statistically significant [MD =-38.43 (95% CI: -57.71, -19.15, P< 0.001)]. Compared with VATS, the number of lymph nodes dissected in RATS was significantly higher [MD = 2.61 (95% CI: 0.47, 4.76, P= 0.02)]. The rate of conversion to thoracotomy in RATS was lower, and the difference was statistically significant [OR = 0.59 (95% CI: 0.50, 0.70, P< 0.001)]. There was no significant difference between RATS and VATS in operation time [MD =-9.34 (95% CI: -28.72, 10.04, P= 0.34)], postoperative thoracic drainage time [MD =-0.08 (95% CI: -0.42, 0.26, P= 0.64)], postoperative hospital stay [MD =-0.05 (95% CI: -0.19, 0.08, P= 0.42)], postoperative mortality [OR = 0.88 (95% CI: 0.56, 1.36, P= 0.56)] and postoperative complications [OR = 1.03 (95% CI: 0.93, 1.13, P= 0.57)]. CONCLUSION: Compared with VATS, the number of lymph nodes dissected in RATS was significantly more, and the removal of lesions and lymph nodes was more thorough and accurate. More flexible and precise operation avoids the injury of important blood vessels during operation, effectively reduces the amount of blood loss during operation, shortens the indwelling time of thoracic drainage tube, and is conducive to postoperative rehabilitation of patients.

Quantitative evaluation of H-donating abilities of C(sp3)-H bonds of nitrogen-containing heterocycles in hydrogen atom transfer reaction.

Nitrogen-containing heterocycles are an important class of antioxidants, and their reactivity and selectivity in hydrogen atom reactions have attracted significant interest from chemists. In this work, the kinetics of hydrogen atom transfer reactions from C(sp3)-H bonds of 28 nitrogen-containing heterocycles, oxygen-containing heterocycles, alicyclic amines and cycloalkanes, which were denoted as XH, to the CumO˙ radical, were investigated. The characteristic physical parameter of the substrate, i.e., the thermo-kinetic parameter ΔG≠o(XH), was determined using the kinetic equation [ΔG≠XH/Y = ΔG≠o(XH) + ΔG≠o(Y)] to quantitatively evaluate the H-donating ability of XH. The effects of the substrate structure, substituent attached to the nitrogen atom, and ring size on the H-donating ability were discussed carefully. By comparing the H-donating abilities of cycloalkanes, alicyclic amines and nitrogen/oxygen-containing heterocycles, the influence of the introduction of N, O, or carbonyl groups in the carbon ring on the H-donating ability of C(sp3)-H bond was determined. The electronic, steric and stereo-electronic effects of the groups were also discussed. Herein, we not only quantitatively determined the H-donating ability of the substrate, but also provided ideas for the synthesis of new antioxidants.

Quantitative evaluation of the actual hydrogen atom donating activities of O-H bonds in phenols: structure-activity relationship.

The H-donating activity of phenol and the H-abstraction activity of phenol radicals have been extensively studied. In this article, the second-order rate constants of 25 hydrogen atom transfer (HAT) reactions between phenols and PINO and DPPH radicals in acetonitrile at 298 K were studied. Thermo-kinetic parameters ΔG ≠o(XH) were obtained using a kinetic equation [ΔG ≠ XH/Y = ΔG ≠o(XH) + ΔG ≠o(Y)]. Bond dissociation free energies ΔG o(XH) were calculated by the iBonD HM method, whose details are available at https://pka.luoszgroup.com/bde_prediction. Intrinsic resistance energies ΔG ≠ XH/X and ΔG ≠o(X) were determined as ΔG ≠o(XH) and ΔG o(XH) were available. ΔG o(XH), ΔG ≠ XH/X, ΔG ≠o(XH) and ΔG ≠o(X) were used to assess the H-donating abilities of the studied phenols and the H-abstraction abilities of phenol radicals in thermodynamics, kinetics and actual HAT reactions. The effect of structures on these four parameters was discussed. The reliabilities of ΔG ≠o(XH) and ΔG ≠o(X) were examined. The difference between the method of determining ΔG ≠ XH/X mentioned in this study and the dynamic nuclear magnetic method mentioned in the literature was studied. Via this study, not only ΔG o(XH), ΔG ≠ XH/X, ΔG ≠o(XH) and ΔG ≠o(X) of phenols could be quantitatively evaluated, but also the structure-activity relationship of phenols is clearly demonstrated. Moreover, it lays the foundation for designing and synthesizing more antioxidants and radicals.

Thermodynamic Evaluations of Amines as Hydrides or Two Hydrogen Ions Reductants and Imines as Protons or Two Hydrogen Ions Acceptors, as Well as Their Application in Hydrogenation Reactions.

Since the hydrogenation of imines (X) and the dehydrogenation of amines (XH2) generally involve the two hydrogen ions (H- + H+) transfer, the thermodynamic abilities of various amines releasing hydrides or two hydrogen ions as well as various imines accepting protons or two hydrogen ions are important and characteristic physical parameters. In this work, the pKa values of 84 protonated imines (XH+) in acetonitrile were predicted. Combining Gibbs free energy changes of amines releasing hydrides in acetonitrile from our previous work with the pKa(XH+) values, the Gibbs free energy changes of amines releasing two hydrogen ions and imines accepting two hydrogen ions were derived using Hess's law by constructing thermochemical cycles, and the thermodynamic evaluations of amines as hydrides or two hydrogen ions reductants and imines as protons or two hydrogen ions acceptors are well compared and discussed. Eventually, the practical application of thermodynamic data for amines and imines on hydrogenation feasibility, mechanism, and possible elementary steps was shown and discussed in this paper from the point of thermodynamics.

Symmetry breaking and competition effect in phase transitions.

This study is started from a photon-magnon model with a competition effect of the level attraction and repulsion, its Hermiticity is mainly decided by a phase-dependent and asymmetric coupling factor, namelyφ = 0 for Hermitian andϕ=πfor non-Hermitian. Then an extensional study predicts the quantum critical behaviors using an Hermitian and even no-Hermitian photon-spins model with an additional second-order drive. The numerical results firstly indicate that this coupling phaseφcan function the protective effect on quantum phase transitions (QPTs), and the new tricritical points can not only be modulated by this nonlinear drive, but also be influenced by the dissipation and the collective decoherence. Secondly, this competition effect can also induce a reversal of the value of order parameters between the positive and negative. This study can also bring more important results of QPTs toward the issue of symmetry breaking and non-Hermiticity.

New Insights into the Actual H-Abstraction Activities of Important Oxygen and Nitrogen Free Radicals: Thermodynamics and Kinetics in Acetonitrile.

The H-abstraction activity of a free radical is a research hotspot and has been extensively studied. In this article, the second-order rate constants of 21 HAT reactions in acetonitrile at 298 K were chosen from several published literature. A kinetic study on the H-abstraction reaction from TEMPOH by a DPPH• radical was carried out. This reaction was researched as an insertion point. By combining this reaction with the 21 HAT reactions in this paper, the thermokinetic parameters of 28 free radicals X and their corresponding antioxidants XH were obtained by the cross-HAT reaction method. The scales of the H-abstraction activities of these 28 oxygen and nitrogen free radicals were determined by using the thermokinetic parameters ΔG ≠o(X). Applications of the thermokinetic parameter ΔG ≠o(X) in assessing the actual H-abstraction activity of a free radical quantitatively and selecting a suitable free radical in scientific research and chemical production were discussed. Predictions of the rate constants by using thermokinetic parameters of reactants were researched, and the reliabilities of the predicted activation free energies of XH/Y reactions were also examined.

Evaluation and comparison of antioxidant abilities of five bioactive molecules with C-H and O-H bonds in thermodynamics and kinetics.

In this work, the antioxidant abilities of NADH coenzyme analogue BNAH, F420 reduction prototype analogue F420H, vitamin C analogue iAscH-, caffeic acid, and (+)-catechin in acetonitrile in chemical reactions were studied and discussed. Three physical parameters of the antioxidant XH, homolytic bond dissociation free energy ΔG °(XH), self-exchange HAT reaction activation free energy ΔG ≠ XH/X, and thermo-kinetic parameter ΔG ≠°(XH), were used to evaluate the antioxidant ability of XH in thermodynamics, kinetics, and thermo-kinetics. By comparing ΔG °(XH), ΔG ≠ XH/X and ΔG ≠°(XH) of these five bioactive antioxidants to release hydrogen atoms, it is easy to find that iAscH- is the best hydrogen atom donor both thermodynamically and kinetically among these antioxidants. Caffeic acid is the worst hydrogen atom donor thermodynamically, and F420H is the worst hydrogen atom donor kinetically. In addition, the thermodynamic hydride donating abilities of BNAH, F420H, and iAscH- were also discussed, and the order of thermodynamic hydride donating abilities was BNAH > F420H > iAscH-. Four HAT reactions BNAH/DPPH˙, (+)-catechin/DPPH˙, F420H/DPPH˙, and caffeic acid/DPPH˙ in acetonitrile at 298 K were studied by the stopped-flow method. The actual order of H-donating abilities of these four antioxidants in the HAT reactions is consistent with the order predicted by thermo-kinetic parameters. It is feasible to predict accurately the antioxidant abilities of antioxidants using thermo-kinetic parameters.

Kinetic Studies of Hantzsch Ester and Dihydrogen Donors Releasing Two Hydrogen Atoms in Acetonitrile.

In this work, kinetic studies on HEH2, 2-benzylmalononitrile, 2-benzyl-1H-indene-1,3(2H)-dione, 5-benzyl-2,2-dimethyl-1,3-dioxane-4,6-dione, 5-benzyl-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, 2-(9H-fluoren-9-yl)malononitrile, ethyl 2-cyano-2-(9H-fluoren-9-yl)acetate, diethyl 2-(9H-fluoren-9-yl)malonate, and the derivatives (28 XH2) releasing two hydrogen atoms were carried out. The thermokinetic parameters ΔG ⧧° of 28 dihydrogen donors (XH2) and the corresponding hydrogen atom acceptors (XH•) in acetonitrile at 298 K were determined. The abilities of releasing two hydrogen atoms for these organic dihydrogen donors were researched using their thermokinetic parameters ΔG ⧧°(XH2), which can be used not only to compare the H-donating ability of different XH2 qualitatively and quantitatively but also to predict the rates of HAT reactions. Predictions of rate constants for 12 HAT reactions using thermokinetic parameters were determined, and the reliabilities of the predicted results were also examined.

Quantitative Estimation of the Hydrogen-Atom-Donating Ability of 4-Substituted Hantzsch Ester Radical Cations.

The purpose of this study is to investigate thermodynamic and kinetic properties on the hydrogen-atom-donating ability of 4-substituted Hantzsch ester radical cations (XRH•+), which are excellent NADH coenzyme models. Gibbs free energy changes and activation free energies of 17 XRH•+ releasing H• [denoted as ΔG HD o(XRH•+) and ΔG HD ≠(XRH•+)] were calculated using density functional theory (DFT) and compared with that of Hantzsch ester (HEH2) and NADH. ΔG HD o(XRH•+) range from 19.35 to 31.25 kcal/mol, significantly lower than that of common antioxidants (such as ascorbic acid, BHT, the NADH coenzyme, and so forth). ΔG HD ≠(XRH•+) range from 29.81 to 39.00 kcal/mol, indicating that XRH•+ spontaneously releasing H• are extremely slow unless catalysts or active intermediate radicals exist. According to the computed data, it can be inferred that the Gibbs free energies and activation free energies of the core 1,4-dihydropyridine radical cation structure (DPH•+) releasing H• [ΔG HD o(DPH•+) and ΔG HD ≠(DPH•+)] should be 19-32 kcal/mol and 29-39 kcal/mol in acetonitrile, respectively. The correlations between the thermodynamic driving force [ΔG HD o(XRH•+)] and the activation free energy [ΔG HD ≠(XRH•+)] are also explored. Gibbs free energy is the important and decisive parameter, and ΔG HD ≠(XRH•+) increases in company with the increase of ΔG HD o(XRH•+), but no simple linear correlations are found. Even though all XRH•+ are judged as excellent antioxidants from the thermodynamic view, the computed data indicate that whether XRH•+ is an excellent antioxidant in reaction is decided by the R substituents in 4-position. XRH•+ with nonaromatic substituents tend to release R• instead of H• to quench radicals. XRH•+ with aromatic substituents tend to release H• and be used as antioxidants, but not all aromatic substituted Hantzsch esters are excellent antioxidants.

Theoretical investigation on the nature of 4-substituted Hantzsch esters as alkylation agents.

Recently, a variety of 4-substituted Hantzsch esters (XRH) with different structures have been widely researched as alkylation reagents in chemical reactions, and the key step of the chemical process is the elementary step of XRH˙+ releasing R˙. The purpose of this work is to investigate the essential factors which determine whether or not an XRH is a great alkylation reagent using density functional theory (DFT). This study shows that the ability of an XRH acting as an alkylation reagent can be reasonably estimated by its ΔG ≠ RD(XRH˙+) value, which can be conveniently obtained through DFT computations. Moreover, the data also show that ΔG ≠ RD(XRH˙+) has no simple correlation with the structural features of XRH, including the electronegativity of the R substituent group and the magnitude of steric resistance; therefore, it is difficult to judge whether an XRH can provide R˙ solely by experience. Thus, these results are helpful for chemists to design 4-substituted Hantzsch esters (XRH) with novel structures and to guide the application of XRH as a free radical precursor in organic synthesis.