Accurate Estimation of the One-Electron Reduction Potentials of Various Substituted Quinones in DMSO and CH₃CN

The one-electron reduction potentials of 116 important p- and o-quinones in DMSO and CH3CN were predicted for the first time by using the B3LYP/DZP++ method and the PCM cluster continuum model. The calculated gas-phase electron affinities and one-electron reduction potentials agree well with the available experimental observations, respectively. The study showed the one-electron reduction potentials of the 116 quinones range from −0.949 to 1.128 V in DMSO and from −0.904 to 0.971 V in CH3CN. The one-electron reduction potentials of p-quinones are generally smaller than those of the o-quinones by about 0.132 V. For quinones with aromatic properties, 2-substituted-1,4-naphthquinones have the largest one-electron reduction potentials, followed by substituted-1,4-anthraquinones and then by substituted-9,10-anthraquinones. The study also showed that the one-electron reduction potentials of quinones in DMSO are linearly dependent on the sum of the Hammett substituent parameters σp: ENHE(p-Q/p-Q• −) = 0.45Σσp − 0.194 (V) and ENHE(o-Q/o-Q• −) = 0.45Σσp − 0.059 (V). Combined with the hydride affinities of quinones in the former paper [ΔGH-A(p-Q) = −16.0Σσp − 70.5 (kcal/mol) and ΔGH-A(o-Q) = −16.2Σσp − 81.5 (kcal/mol)] and the one-electron reduction potentials of quinones estimated in this work, we obtained the homolytic bond dissociation energies of the hydroquinone anions (QH−) and found that these thermodynamic parameters also have linear correlations against the sum of the Hammett substituent parameters σp if only the substituents have no larger electrostatic inductive force and no large steric hindrance: BDE(p-QH−) = 5.05Σσp + 63.18 (kcal/mol) and BDE(o-QH−) = 5.33Σσp + 71.30 (kcal/mol). Knowledge about the redox potentials of the quinones should be of great value for the understanding of the nature of chemical reactions of quinones, the designing of new electronic materials of quinones, and the examining of biological activities of quinones

Hydride Affinity Scale of Various Substituted Arylcarbeniums in Acetonitrile

Combined with the integral equation formalism polarized continuum model (IEFPCM), the hydride affinities of 96 various acylcarbenium ions in the gas phase and CH3CN were estimated by using the B3LYP/6-31+G(d)//B3LYP/6-31+G(d), B3LYP/6-311++G(2df,2p)//B3LYP/6-31+G(d), and BLYP/6-311++G(2df,2p)//B3LYP/6-31+G(d) methods for the first time. The results show that the combination of the BLYP/6-311++G(2df,2p)//B3LYP/6-31+G(d) method and IEFPCM could successfully predict the hydride affinities of arylcarbeniums in MeCN with a precision of about 3 kcal/mol. On the basis of the calculated results from the BLYP method, it can be found that the hydride affinity scale of the 96 arylcarbeniums in MeCN ranges from −130.76 kcal/mol for NO2−PhCH+−CN to −63.02 kcal/mol for p-(Me)2N−PhCH+−N(Me)2, suggesting most of the arylcarbeniums are good hydride acceptors. Examination of the effect of the number of phenyl rings attached to the carbeniums on the hydride affinities shows that the increase of the hydride affinities takes place linearly with increasing number of benzene rings in the arylcarbeniums. Analyzing the effect of the substituents on the hydride affinities of arylcarbeniums indicates that electron-donating groups decrease the hydride affinities and electron-withdrawing groups show the opposite effect. The hydride affinities of arylcarbeniums are linearly dependent on the sum of the Hammett substituent parameters σp+. Inspection of the correlation of the solution-phase hydride affinities with gas-phase hydride affinities and aqueous-phase pKR+ values reveals a remarkably good correspondence of ΔGH−A(R+) with both the gas-phase relative hydride affinities only if the α substituents X have no large electron-donating or -withdrawing properties and the pKR+ values even though the media are dramatically different. The solution-phase hydride affinities also have a linear relationship with the electrophilicity parameter E, and this dependence can certainly serve as one of the most effective ways to estimate the new E values from ΔGH−A(R+) or vice versa. Combining the hydride affinities and the reduction potentials of the arylcarbeniums, we obtained the bond homolytic dissociation Gibbs free energy changes of the C−H bonds in the corresponding hydride adducts in acetonitrile, ΔGHD(RH), and found that the effects of the substituent on ΔGHD(RH) are very small. Simple thermodynamic analytic platforms for the three C−H cleavage modes were constructed. It is evident that the present work would be helpful in understanding the nature of the stabilities of the carbeniums and mechanisms of the hydride transfers between carbeniums and other hydride donors

Scales of Oxidation Potentials, p<i>K</i>_a, and BDE of Various Hydroquinones and Catechols in DMSO

The one-electron oxidation potentials [EoxNHE(H2Q)], pKa (pKa1 and pKa2) values, and bond dissociation energies (BDE1 and BDE2) of 118 important p- and o-dihydroquinones in DMSO were systematically predicted for the first time by using DFT method and the PCM cluster continuum model. The calculated results agree well with the available experimental determinations. The study shows that all the five thermodynamic parameters correlate well with the Hammett substituent parameters σp (for p-H2Q, EoxNHE(H2Q·+/H2Q) = 1.66Σσp + 0.54, pKa1 = −5.69Σσp + 16.54, pKa2 = −5.19Σσp + 23.91, BDE1 = 3.43Σσp + 82.29, BDE2 = 4.64Σσp + 67.70 and for o-H2Q, EoxNHE(H2Q·+/H2Q) = 1.85Σσp + 0.46, pKa1 = −5.53Σσp + 13.28, pKa2 = −5.24Σσp + 26.70, BDE1 = 3.54Σσp + 82.08, BDE2 = 3.82Σσp + 75.93), which hints that we can get these thermodynamic parameters as long as the structure of the hydroquinones were known. The comparisons of the calculated five thermodynamic parameters between p-hydroquinones and o-hydroquinones and the number of the phenyl ring effects on these thermodynamic parameters were also studied. At last, intramolecular hydrogen bond energies in hydroquinones at neutral, radical cation, radical, anion different state were systematically calculated and analyzed. Combined with the papers published in our group before, we will have a systematic thermodynamic picture of the transfer details between different kinds of quinones and corresponding hydroquinones, which strongly promote the fast development of the understanding and applications of quinones

Theoretical Prediction of the Hydride Affinities of Various <i>p</i>- and <i>o</i>-Quinones in DMSO

The hydride affinities of 80 various p- and o-quinones in DMSO solution were predicted by using B3LYP/6-311++G (2df,p)//B3LYP/6-31+G* and MP2/6-311++G**//B3LYP/6-31+G* methods, combined with the PCM cluster continuum model for the first time. The results show that the hydride affinity scale of the 80 quinones in DMSO ranges from −47.4 kcal/mol for 9,10-anthraquinone to −124.5 kcal/mol for 3,4,5,6-tetracyano-1,2-quinone. Such a long scale of the hydride affinities (−47.4 to −124.5 kcal/mol) indicates that the 80 quinones can form a large and useful library of organic oxidants, which can provide various organic hydride acceptors that the hydride affinities are known for chemists to choose in organic syntheses. By examining the effect of substituent on the hydride affinities of quinones, it is found that the hydride affinities of quinones in DMSO are linearly dependent on the sum of the Hammett substituent parameters σ:  ΔGH-(Q) ≈ −16.0Σσi − 70.5 (kcal/mol) for p-quinones and ΔGH-(Q) ≈ −16.2Σσi − 81.5 (kcal/mol) for o-quinones only if the substituents have no large electrostatic inductive effect and large ortho-effect. Study of the effect of the aromatic properties of quinone on the hydride affinities showed that the larger the aromatic system of quinone is, the smaller the hydride affinity of the quinone is, and the decrease of the hydride affinities is linearly to take place with the increase of the number of benzene rings in the molecule of quinones, from which the hydride affinities of aromatic quinones with multiple benzene rings can be predicted. By comparing the hydride affinities of p-quinones and the corresponding o-quinones, it is found that the hydride affinities of o-quinones are generally larger than those of the corresponding p-quinones by ca. 11 kcal/mol. Analyzing the effect of solvent on the hydride affinities of quinones showed that the effects of solvent (DMSO) on the hydride affinities of quinones are mainly dependent on the electrostatic interaction of the charged hydroquinone anions (QH-) with solvent (DMSO). All the information disclosed in this work should provide some valuable clues to chemists to choose suitable quinones or hydroquinones as efficient hydride acceptors or donors in organic syntheses and to predict the thermodynamics of hydride exchange between quinones and hydroquinones in DMSO solution

Actual Structure, Thermodynamic Driving Force, and Mechanism of Benzofuranone-Typical Compounds as Antioxidants in Solution

5,7-Ditert-butyl-3-(3,4-dimethylphenyl)benzofuran-2(3H)-one (HP-136) (1H) and its 30 analogues (2H−5H) as benzofuranone-typical antioxidants were synthesized. The structures of the benzofuranones in solid and solution were examined by using experimental and theoretical methods. The results show that the dominant structure is the lactone form rather than the enol form both in solid and solution. The thermodynamic driving forces of the 31 benzofuranone-typical compounds to release protons [ΔGPD(XH)], hydrogen atoms [ΔGHD(XH)], and electrons [Eox(XH)] and the thermodynamic driving forces of the anions (X−) of the benzofuranones to release electrons [Eox(X−)] were determined for the first time in DMSO. The ΔGHD(XH) scale of these compounds in DMSO ranges from 65.2 to 74.1 (kcal/mol) for 1H−4H and from 73.8 to 75.0 (kcal/mol) for 5H, respectively, which are all smaller than that of the most widely used commercial antioxidant BHT (2,6-ditert-butyl-4-methylphenol, 81.6 kcal/mol), suggesting that the 31 XH could be used as good hydrogen-atom-donating antioxidants. The ΔGPD(XH) were observed to range from 11.5 to 16.0 (kcal/mol) for 1H−4H and from 18.6 to 22.4 (kcal/mol) for 5H, indicating that benzofuranones (1H−4H) are good proton donors, and their analogues (5H) should belong to middle-strong proton donors. Eox(XH) of the 31 XH to release an electron vary from 1.346 to 1.962 (V versus Fc+/0), implying that the 31 XH are weak electron donors, whereas the quite negative Eox(X−) show that X− are good electron donors. The Gibbs free-energy changes of the radical cations (XH+•) to release protons [ΔGPD(XH+•)] were evaluated according to the corresponding thermodynamic cycle, and the results reveal that XH+• are good proton donors. Further inspection of our experimental results showed the ΔGHD(XH), ΔGPD(XH), ΔGPD(XH+•), Eox(XH), and Eox(X−) of the five chemical and electrochemical processes are all linearly dependent on the sum of Hammett substituent parameters σ with very good correlation coefficients, indicating that for any one- or multisubstituted species at the para- and/or meta-position of benzofuranones and their various reaction intermediates, the five thermodynamic driving force parameters all can be easily and safely estimated from the corresponding Hammett substituent parameters. The rates of hydrogen atom transfer from XH to DPPH• were determined by using the UV−vis absorption spectroscopy technique. Combining these important thermodynamic parameters and dynamic determination results, the mechanism of hydrogen transfer from HP-136 and its analogues to DPPH• was studied. The results suggest that the hydrogen transfer from HP-136 and its analogues 2H to DPPH• actually includes two steps, proton transfer and the following electron transfer, but the proton transfer is rate-determined

Hydride, Hydrogen Atom, Proton, and Electron Transfer Driving Forces of Various Five-Membered Heterocyclic Organic Hydrides and Their Reaction Intermediates in Acetonitrile

The enthalpy changes of 47 five-membered heterocyclic compounds (ZH) [33 substituted 2,3-dihydro-2-phenylbenzo[d]imidazoles (1H-5H), 9 substituted 2,3-dihydro-2-phenylbenzo[d]thiazoles (6H), and 5 substituted 2,3-dihydro-2-phenylbenzo[d]oxazoles (7H)] as a class of very important organic hydride donors to release hydride anion were determined by using titration calorimetry. The result shows that the enthalpy change scale of the 47 ZH in acetonitrile ranges from 49.0 to 93.4 kcal/mol. Such a long energy scale evidently shows that the 47 ZH can construct a large and useful library of organic hydride donors, which can provide various organic hydride donors that the hydride-releasing enthalpies are known. The enthalpy changes of the 47 ZH to release hydrogen atom and the 47 ZH+• to release proton and hydrogen atom were also evaluated by using relative thermodynamic cycles according to Hess' law. The results show:  (1) the enthalpy change scale of the 47 ZH to release hydrogen atom covers a range from 71.8 to 91.4 kcal/mol, indicating that the 47 ZH all should be weak hydrogen atom donors. (2) The enthalpy change scales of the 47 ZH+• to release proton and to release hydrogen atom range from 17.5 to 25.7 and from 27.2 to 52.4 kcal/mol, respectively, implying that the proton-donating abilities of ZH+• are generally quite larger than the corresponding hydrogen atom-donating abilities. The standard redox potentials of the 47 ZH and the 47 corresponding salts (Z+) were measured by using cyclic voltammetry (CV) and Osteryoung square wave voltammetry (OSWV), the results display that the standard oxidation potential scale of ZH ranges from −0.254 to −0.002 V for 1H−5H and from 0.310 to 0.638 V for 6H−7H, implying that 1H−5H should be strong one-electron reducing agents and 6H−7H should be weak one-electron reducing agents; the standard reduction potential scale of Z+ ranges from −1.832 to −2.200 V for 1+−5+ and from −1.052 to −1.483V for 6+−7+, meaning that 1+−5+ belong to very weak one-electron oxidation agents. The energies of the intramolecular hydrogen bond in 3H, 3H+•, and 3• with a hydroxyl group at ortho-position on the 2-phenyl ring were estimated by using experimental method, the results disclose that the hydrogen bond energy is 3.2, 2.8−3.0, and 3.9−4.0 kcal/mol for 3H, 3H+•, and 3• in acetonitrile, respectively, which is favorable for hydrogen atom transfer but unfavorable for hydride transfer from 3H. The relative effective charges on the active center in ZH, ZH+•, Z•, and Z+, which is an efficient measurement of electrophilicity or nucleophilicity as well as dimerizing ability of a chemical species, were estimated by using experimental method; the results indicate that 1•−5• belong to electron-sufficient carbon-radicals, 6•−7• belong to electron-deficient carbon radicals, they are all difficult to dimerize, and that 1+−5+ belong to weak electrophilic agents, 6+−7+ belong to strong electrophilic agents. All these information disclosed in this work could not only supply a gap of the chemical thermodynamics of the five-membered heterocyclic compounds as organic hydride donors, but also strongly promote the fast development of the chemistry and applications of the five-membered heterocyclic organic hydrides

Additional file 1: of Cisplatin resistant lung cancer cells promoted M2 polarization of tumor-associated macrophages via the Src/CD155/MIF functional pathway

Table S1. CDDP sensitivity assay of tissue samples from lung cancer patients (please refer to Additional file 2: Table S2 for patients’ characteristics). (DOCX 17 kb

Additional file 3: of Cisplatin resistant lung cancer cells promoted M2 polarization of tumor-associated macrophages via the Src/CD155/MIF functional pathway

Figure S1. Prolonged, escalating CDDP treatment enriched CDDP-resistant H460R and A549R NSCLC cells. MTT assay demonstrated that H460R and A549R cells with a significantly higher IC50 values against CDDP treatment. (DOCX 19 kb

Additional file 2: of Cisplatin resistant lung cancer cells promoted M2 polarization of tumor-associated macrophages via the Src/CD155/MIF functional pathway

Table S2. Pathological characteristics of patients. (DOCX 14 kb

Actual Structure, Thermodynamic Driving Force, and Mechanism of Benzofuranone-Typical Compounds as Antioxidants in Solution

5,7-Ditert-butyl-3-(3,4-dimethylphenyl)benzofuran-2(3H)-one (HP-136) (1H) and its 30 analogues (2H−5H) as benzofuranone-typical antioxidants were synthesized. The structures of the benzofuranones in solid and solution were examined by using experimental and theoretical methods. The results show that the dominant structure is the lactone form rather than the enol form both in solid and solution. The thermodynamic driving forces of the 31 benzofuranone-typical compounds to release protons [ΔGPD(XH)], hydrogen atoms [ΔGHD(XH)], and electrons [Eox(XH)] and the thermodynamic driving forces of the anions (X−) of the benzofuranones to release electrons [Eox(X−)] were determined for the first time in DMSO. The ΔGHD(XH) scale of these compounds in DMSO ranges from 65.2 to 74.1 (kcal/mol) for 1H−4H and from 73.8 to 75.0 (kcal/mol) for 5H, respectively, which are all smaller than that of the most widely used commercial antioxidant BHT (2,6-ditert-butyl-4-methylphenol, 81.6 kcal/mol), suggesting that the 31 XH could be used as good hydrogen-atom-donating antioxidants. The ΔGPD(XH) were observed to range from 11.5 to 16.0 (kcal/mol) for 1H−4H and from 18.6 to 22.4 (kcal/mol) for 5H, indicating that benzofuranones (1H−4H) are good proton donors, and their analogues (5H) should belong to middle-strong proton donors. Eox(XH) of the 31 XH to release an electron vary from 1.346 to 1.962 (V versus Fc+/0), implying that the 31 XH are weak electron donors, whereas the quite negative Eox(X−) show that X− are good electron donors. The Gibbs free-energy changes of the radical cations (XH+•) to release protons [ΔGPD(XH+•)] were evaluated according to the corresponding thermodynamic cycle, and the results reveal that XH+• are good proton donors. Further inspection of our experimental results showed the ΔGHD(XH), ΔGPD(XH), ΔGPD(XH+•), Eox(XH), and Eox(X−) of the five chemical and electrochemical processes are all linearly dependent on the sum of Hammett substituent parameters σ with very good correlation coefficients, indicating that for any one- or multisubstituted species at the para- and/or meta-position of benzofuranones and their various reaction intermediates, the five thermodynamic driving force parameters all can be easily and safely estimated from the corresponding Hammett substituent parameters. The rates of hydrogen atom transfer from XH to DPPH• were determined by using the UV−vis absorption spectroscopy technique. Combining these important thermodynamic parameters and dynamic determination results, the mechanism of hydrogen transfer from HP-136 and its analogues to DPPH• was studied. The results suggest that the hydrogen transfer from HP-136 and its analogues 2H to DPPH• actually includes two steps, proton transfer and the following electron transfer, but the proton transfer is rate-determined