Biomedical subjects

Qing-Xiang Guo

Publications and source records attributed to Qing-Xiang Guo.

At least 19 recordsLinked to original sources

PubMed2006

How to promote sluggish electrocyclization of 1,3,5-hexatrienes by captodative substitution.

Hexatriene electrocyclization, if not disfavored by its harsh reaction conditions, can be highly useful for the synthesis of complex organic molecules. Herein we developed a two-layer ONIOM method which could predict the activation free energy of hexatriene electrocyclization with an accuracy of about 1.0 kcal/mol. Using this carefully benchmarked method, we calculated the activation free energies for a variety of substituted hexatrienes. It was found that extraordinarily rapid electrocyclization could occur for certain patterns of captodative substituted hexatrienes, including 2-acceptor-3-donor hexatrienes, 2-acceptor-5-donor hexatrienes, and 3-acceptor-5-donor hexatrienes. The activation free energies for these systems could be up to 10 kcal/mol lower than that of the unsubstituted hexatriene, and therefore, their electrocyclization could proceed smoothly even at room temperature. The mechanism for the captodative effect on hexatriene electrocyclization could be understood by calculating the affinity between the donor and acceptor group in the reactant state and transition state of the reaction. If the affinity was stronger in the transition state, captodative substitution would produce an extra acceleration effect. It was shown that our theoretical results were in excellent agreement with the experimental data from the recent synthetic studies of hexatriene electrocyclizations. Thus, the theoretical tools developed in the present study could be used to predict not only how to accelerate the hexatriene electrocyclization via substituent manipulation but also under what conditions each particular electrocyclization could be accomplished in the real experiment.

Cyclization↗

PubMed2006

Significant effects of phosphorylation on relative stabilities of DNA and RNA sugar radicals: remarkably high susceptibility of h-2' abstraction in RNA.

The roles of nucleic acid radicals in DNA and RNA damage cannot be properly understood in the absence of knowledge of the C-H bond strengths depicting the energy cost to generate each of these radicals. However, previous theoretical studies on the relative energies of different nucleic acid radicals are not fully convincing mainly because of the use of oversimplified model compounds. In the present study we chose nucleoside 3',5'-bisphosphates as model compounds for DNA and RNA, in which the effects of both the nucleobase and phosphorylation were taken into consideration. Using the newly developed ONIOM-G3B3 methods, we calculated the gas-phase bond dissociation enthalpies and solution-phase bond dissociation free energies of all the carbohydrate C-H bonds in the model compounds. It was found that the monoanionic phosphate group (OPO3H-) was a better radical stabilization group than the OH group by 1.3 kcal/mol, whereas the neutral phosphate group (OPO3H2) was a significantly worse radical stabilization group than OH by 4.4 kcal/mol. Due to these reasons, the relative thermodynamic susceptibility of H-abstraction from deoxyribonucleotides and ribonucleotides varied considerably depending on the phosphorylation state and the charge carried by the phosphate groups. Strikingly, the bond dissociation free energy of C2'-H in ribonucleotides was dramatically lower than that of all the other C-H bonds by 5-6 kcal/mol regardless of the phosphorylation state and the charge carried by the phosphate group. This explained the previous experimental finding that radiation damage of RNA occurs mainly via H-abstraction at H-2'. A model study suggested that the strength of the hydrogen bonding interaction between the 2'-OH and 3-phosphate groups should dramatically increase from ribonucleoside 3',5'-bisphosphate to its C2' radical. The strengthened hydrogen bonding stabilized the C2' radical, rendering the C2'-H bond of RNA extraordinarily vulnerable to H-abstraction.

Carbohydrates↗

PubMed2006

N,N-dimethyl-beta-alanine as an inexpensive and efficient ligand for palladium-catalyzed Heck reaction.

N,N-Dimethyl-beta-alanine was found to be a more powerful phosphine-free ligand than the previously reported ligand, N,N-dimethylglycine, in the Pd-catalyzed Heck reaction for a variety of aryl bromides, aryl iodides, and activated aryl chlorides with a practical turnover number of 10(3). Both kinetic and theoretical studies suggested that N,N-dimethyl-beta-alanine led to faster oxidative addition of an aryl halide to Pd than N,N-dimethylglycine. [reaction: see text]

Catalysis↗

PubMed2006

Efficient photosensitized splitting of the thymine dimer/oxetane unit on its modifying beta-cyclodextrin by a binding electron donor.

Two modified beta-cyclodextrins (beta-CDs) with a thymine dimer and a thymine oxetane adduct respectively, TD-CD and Ox-CD, have been prepared, and utilized to bind an electron-rich chromophore, indole or N,N-dimethylaniline (DMA), to form a supramolecular complex. We have examined the photosensitized splitting of the dimer/oxetane unit in TD-CD/Ox-CD by indole or DMA via an electron-transfer pathway, and observed high splitting efficiencies of the dimer/oxetane unit. On the basis of measurements of fluorescence spectra and splitting quantum yields, it is suggested that the splitting reaction occurs in a supramolecular complex by an inclusion interaction between the modified beta-CDs and DMA or indole. The back electron transfer, which leads low splitting efficiencies for the covalently-linked chromophore-dimer/oxetane compounds, is suppressed in the non-covalently-bound complex, and the mechanism has been discussed.

Electrons↗

PubMed2006

Quantum-chemical predictions of redox potentials of organic anions in dimethyl sulfoxide and reevaluation of bond dissociation enthalpies measured by the electrochemical methods.

A first-principle theoretical protocol was developed that could predict the absolute pK(a) values of over 250 structurally unrelated compounds in DMSO with a precision of 1.4 pK(a) units. On this basis we developed the first theoretical protocol that could predict the standard redox potentials of over 250 structurally unrelated organic anions in DMSO with a precision of 0.11 V. Using the two new protocols we systematically reevaluated the bond dissociation enthalpies (BDEs) measured previously by the electrochemical methods. It was confirmed that for most compounds the empirical equation (BDE = 1.37 pK(HA) + 23.1E(o) + constant) was valid. The constant in this equation was determined to be 74.0 kcal/mol, compared to 73.3 kcal/mol previously reported. Nevertheless, for a few compounds the empirical equation could not be used because the solvation energy changed dramatically during the bond cleavage, which resulted from the extraordinary change of dipole moment during the reaction. In addition, we found 40 compounds (mostly oximes and amides) for which the experimental values were questionable by over 5 kcal/mol. Further analyses revealed that all these questionable BDEs could be explained by one of the three following reasons: (1) the experimental pK(a) value is questionable; (2) the experimental redox potential is questionable; (3) the solvent effect cannot be neglected. Thus, by developing practical theoretical methods and utilizing them to solve realistic problems, we hope to demonstrate that ab initio theoretical methods can now be developed to make not only reliable, but also useful, predictions for solution-phase organic chemistry.

Anions↗

PubMed2006

Zinc-mediated chain extension reaction of 1,3-diketones to 1,4-diketones and diastereoselective synthesis of trans-1,2-disubstituted cyclopropanols.

[reaction: see text] A variety of 1,3-diketones can be efficiently converted into the corresponding 1,4-diketones and trans-1,2-disubstituted cyclopropanols by using organozinc species in one-pot reactions. It was found that 2.3 equiv of CF3CO2ZnCH2I was effective to give the corresponding chain-extended products in 44-85% yields, while a mixture of organozinc species formed from 4.0 equiv of Et2Zn, 2.0 equiv of CF3CO2H, and 4.0 equiv of CH2I2 resulted in the formation of trans-1,2-disubstituted cyclopropanols with quite good yields and diastereoselectivity.

Journal Article↗

PubMed2006

Thermal conversion of rice husks and sawdust to liquid fuel.

The paper focuses on studying the conversion of rice husks and sawdust into liquid fuel. Rice husks, sawdust and their mixture are pyrolyzed at temperatures between 420 and 540 degrees C, and the main product of liquid fuel is obtained. The experimental result shows that the yield of liquid fuel depends on various factors such as feedstock and temperature. The maximum yields for rice husks, sawdust and their mixture are 56%, 61% and 60% at 465, 490 and 475 degrees C, respectively. Analyses with GC-MS and other apparatus show that the liquid fuel is a complicated compound with low caloric value and can be directly used as a fuel oil for combustion in a boiler or a furnace without any upgrading. Alternatively, the fuel can be refined to be used by vehicles.

Gas Chromatography-Mass Spectrometry↗

PubMed2005

Model studies of the (6-4) photoproduct photoreactivation: efficient photosensitized splitting of thymine oxetane units by covalently linked tryptophan in high polarity solvents.

Three covalently linked tryptophan-thymine oxetane compounds used as a model of the (6-4) photolyase-substrate complex have been prepared. Under 290 nm light, efficient splitting of the thymine oxetane with aromatic carbonyl compounds gives the thymine monomer and the corresponding carbonyl compounds by the covalently linked tryptophan via an intramolecular electron transfer, and exhibits a strong solvent dependence: the quantum yield (Phi) is ca. 0.1 in dioxane, and near 0.3 in water. Electron transfer from the excited tryptophan residue to the oxetane unit is the origin of fluorescence quenching of the tryptophan residue, and is more efficient in strong polar solvents. The splitting efficiency of the oxetane radical anion within the tryptophan.+-oxetane.- species is also solvent-dependent, ranging from ca. 0.2 in dioxane to near 0.35 in water. Thus, the back electron transfer reaction in the charge-separated species would be suppressed in water, but is still a main factor causing low splitting efficiencies in the tryptophan-oxetane systems. In contrast to the tryptophan-oxetane system, fast nonradiation processes are the main causes of low efficiency in the flavin-oxetane system. Hence, nonradiative processes of the excited FADH-, rather than electron transfer to oxetane, may be an important factor for the low repair efficiency of (6-4) photolyase.

Electrons↗

PubMed2005

Zinc-mediated ring-expansion and chain-extension reactions of beta-keto esters.

[Chemical reaction: see text] The reaction of cyclic beta-keto esters with CF3CO2ZnCH2I provided the corresponding ring-expanded products in moderate to good yields. Although alpha-substituted acyclic beta-keto esters reacted with much less efficient, chain-extension reaction of simple beta-keto esters also proceeded effectively to generate gamma-keto esters in high yields.

Esters↗

PubMed2005

Development of an ONIOM-G3B3 method to accurately predict C-H and N-H bond dissociation enthalpies of ribonucleosides and deoxyribonucleosides.

The roles of ribonucleoside and deoxyribonucleoside radicals in DNA and RNA damage cannot be properly understood in the absence of knowledge of the C-H and N-H bond dissociation enthalpies (BDEs) depicting the energy cost to generate each of these radicals. However, because the nucleoside radicals tend to be extremely short-lived and it is very difficult to separate and identify different nucleoside radicals, experimental BDEs for nucleosides have remained elusive. Herein, we developed an ONIOM-G3B3 method in order to reliably predict the BDEs of nucleosides and we carefully benchmarked this new method against over 60 experimental BDEs of diverse sizable molecules. It was found that the accuracy of the ONIOM-G3B3 method was about 1.4 kcal/mol for BDE calculations. Using the ONIOM-G3B3 method, a full scale of C-H and N-H BDEs were obtained for the first time for ribonucleosides and deoxyribonucleosides with an estimated error bar of +/-1.4 kcal/mol. Discussions were then made about the interesting connections between these BDE values and previously reported experimental observations concerning radical-mediated DNA and RNA lesions. The significance of the work is twofold: (i) Nucleosides represent one of the most important groups of compounds in science. A full scale of reliable bond dissociation enthalpies for nucleosides is of fundamental importance. (ii) This work demonstrates the feasibility to accurately predict the bond strength of various sizable molecules ranging from nanosize molecular devices to biologically significant compounds.

Carbon↗

PubMed2005

Quantum-chemical predictions of absolute standard redox potentials of diverse organic molecules and free radicals in acetonitrile.

A calibrated B3LYP/6-311++G(2df,2p)//B3LYP/6-31+G(d) method was found to be able to predict the gas-phase adiabatic ionization potentials of 160 structurally unrelated organic molecules with a precision of 0.14 eV. A PCM solvation model was benchmarked that could predict the pK(a)'s of 15 organic acids in acetonitrile with a precision of 1.0 pK(a) unit. Combining the above two methods, we developed a generally applicable protocol that could successfully predict the standard redox potentials of 270 structurally unrelated organic molecules in acetonitrile. The standard deviation of the predictions was 0.17 V. The study demonstrated that computational electrochemistry could become a powerful tool for the organic chemical community. It also confirmed that the continuum solvation theory could correctly predict the solvation energies of organic radicals. Finally, with the help of the newly developed protocol we were able to establish a scale of standard redox potentials for diverse types of organic free radicals for the first time. Knowledge about these redox potentials should be of great value for understanding the numerous electron-transfer reactions in organic and bioorganic chemistry.

Journal Article↗

PubMed2005

Substituent effects on the ring opening of 2-aziridinylmethyl radicals.

[reaction: see text] Substituent effects on the ring-opening reactions of 2-aziridinylmethyl radicals were studied systematically for the first time utilizing the ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p)) method. It was found that various substituents on the nitrogen atom had a relatively small effect on the ring opening of the 2-aziridinylmethyl radical. A pi-acceptor substituent at the C(1) position reduced the energy barrier for C-C cleavage dramatically, but it increased the energy barrier for C-N cleavage significantly at the same time. When the C(1) substituent is alkyl, the ring opening should always strongly favor the C-N cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is CHO (or CO-alkyl, CO-aryl, or CO-OR but not CO-NR(2)), the ring opening strongly favors the C-C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is aryl (or alkenyl or alkynyl), the ring opening should favor the C-C cleavage pathway if the N substituent is alkyl or COR. If both the C(1) substituent and the N substituent are aryl, the ring opening should proceed via both the C-C and C-N cleavage pathways. The solvent effect on the regioselectivity of the ring opening of the 2-aziridinylmethyl radicals was found to be very small. The substituent effects on C-C cleavage could be explained successfully by the spin-delocalization mechanism. For the substituent effects on C-N cleavage, an extraordinary through-bond pi-acceptor effect must be taken into account. Furthermore, studies on bicyclic 2-aziridinylmethyl radicals showed that the ring strain could also affect the regiochemistry of the ring-opening reactions.

Journal Article↗

PubMed2005

Origin of a large temperature dependence of regioselectivity observed for [2 + 2] photocycloaddition (Paternò-Büchi reaction) of 1,3-dimethylthymine with benzophenone and its derivatives: conformational property of the intermediary triplet 1,4-diradicals.

[reaction: see text] The [2 + 2] photochemical additions of 1,3-dimethylthymine (DMT) with benzophenone and its 4,4'-substituted derivatives (BPs), difluoro, di-tert-butyl, and dimethoxy benzophenones, have been investigated at a temperature range from -40 to 70 degrees C. The photochemical reactions, which are cycloaddition of the 5-6 double bond of DMT with the carbonyl group of BPs, the so-called the Paternò-Büchi (PB) reaction, reveal largely temperature-dependent regioselectivity. The chemical yields of one series of regioisomers, 2, decrease with the increase of the reaction temperature, but those of another regioisomer series, 3, increase, and thus the ratio of 2/3 is strongly dependent on the temperature (2/3 = ca. 70:30 to 30:70). The temperature dependence of the regioselectivity yields two linear functions in the corresponding Eyring diagrams. The Eyring plot with changed slopes is clearly indicative of the change for the selectivity-determining step in the PB reaction, in which the triplet 1,4-diradicals play a crucial role. Computational studies reveal the conformational equilibrium structures of the triplet 1,4-diradicals, energy barriers between the conformers, and the conjectural equilibrium constants from relative potential energies of the stable conformers. A proposed mechanism can reasonably explain the temperature-dependent regioselectivity and chemical yields of two regioisomers varying with the reaction temperature.

Journal Article↗

PubMed2005

Synthesis of alkyl and aryl C-pyranosides using organozinc reagents via a Ferrier-type rearrangement.

The reaction of 1,2-dihydropyranyl acetates with dimethylzinc, diethylzinc and diphenylzinc in the presence of CF3COOH gave the corresponding alky and aryl C-pyranosides via a Ferrier rearrangement in excellent yields. Use of the organozinc species, CF3CO2ZnPh, reacted with high stereoselectivity to give the phenyl C-glycosides. Arylzinc chlorides could also be successfully applied to this reaction in the presence of BF3.OEt2.

Alkanes↗

PubMed2004

Homolytic C-H and N-H bond dissociation energies of strained organic compounds.

High-level computations at G3, CBS-Q, and G3B3 levels were conducted, and good-quality C-H and N-H bond dissociation energies (BDEs) were obtained for a variety of saturated and unsaturated strained hydrocarbons and amines for the first time. From detailed NBO analyses, we found that the C-H BDEs of hydrocarbons are determined mainly by the hybridization of the parent compound, the hybridization of the radical, and the extent of spin delocalization of the radical. The ring strain has a significant effect on the C-H BDE because it forces the parent compound and radical to adopt certain undesirable hybridization. A structure-activity relationship equation (i.e., BDE (C-H) = 61.1-227.8 (p(parent)% - 0.75)(2) + 152.9 (p(radical)% - 1.00)(2) + 40.4 spin) was established, and it can predict the C-H BDEs of a variety of saturated and unsaturated strained hydrocarbons fairly well. For the C-H BDEs associated with the bridgehead carbons of the highly rigid strained compounds, we found that the strength of the C-H bond can also be predicted from the H-C-C bond angles of the bridgehead carbon. Finally, we found that N-H BDEs show less dependence on the ring strain than C-H BDEs.

Journal Article↗

PubMed2004

First-principle predictions of absolute pKa's of organic acids in dimethyl sulfoxide solution.

MP2/6-311++G(d,p) and B3LYP/6-311++G(2df,p) methods were found to be able to predict the gas-phase acidities of various organic acids with a precision of 2.2 and 2.3 kcal/mol. A PCM cluster-continuum solvation method was developed that could predict the solvation free energies of various neutral, cationic, and anionic organic species in DMSO with a precision of about 2.0 kcal/mol. Using these carefully tested methods, we successfully predicted the pKa's of 105 organic acids in DMSO with a precision of 1.7-1.8 pKa units. We also predicted the pKa's of a variety of organosilanes in DMSO for the first time using the newly developed methods. This study was one of the first that employed first-principle methods for calculating pKa's of unrelated compounds in organic solutions.

Journal Article↗

PubMed2003

Blue-shifted lithium bonds.

A number of lithium bonding systems (X-LiY) have been found in which the X-Li bond is shortened due to the lithium bond formation.

Journal Article↗

PubMed2003

The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase.

It has been reported that inhibition of fatty-acid synthase (FAS) is selectively cytotoxic to human cancer cells. Considerable interest has developed in identifying novel inhibitors of this enzyme complex. Our previous work showed that green tea (-)-epigallocatechin gallate can inhibit FAS in vitro. To elucidate the structure-activity relationship of the inhibitory effects of tea polyphenols, we investigated the inhibition kinetics of the major catechins and analogues. Ungallated catechins from green tea do not show obvious inhibition compared with gallated catechins. Another gallated catechin, (-)-epicatechin gallate, was also found as a potent inhibitor of FAS and its inhibition characteristics are similar to (-)-epigallocatechin gallate. Furthermore, the analogues of galloyl moiety without the catechin skeleton such as propyl gallate also showed obvious slow-binding inhibition, whereas the green tea ungallated catechin not. Atomic orbital energy analyses suggest that the positive charge is more distinctly distributed on the carbon atom of ester bond of galloyl moiety of gallate catechins, and that gallated forms are more susceptible for a nucleophilic attack than other catechins. Here we identify the galloyl moiety of green tea catechins as critical in the inactivation of the ketoacyl reductase activity of FAS for the first time.

Animals↗