Narrow Results

The notable three oxygen stacking that occurs upon binding of ribonucleoside substrate and phosphate nucleophile by human purine nucleoside phosphorylase (hPNP) enables the coupling of protein dynamic modes to compress this stack, squeezing the ribosyl O4' between ribosyl O5' and the nuclophilic O_P. Created primarily by the motion of active site residue H257, this compression dynamically lowers the barrier height for N9–C1' ribosidic bond cleavage by as much as 20%. As such, this compression constitutes a protein promoting vibration (PPV) (S. Nuñez et al.). Presently, we demonstrate charge fluctuations in the ribose and purine components of the ribonucleoside substrate, as well as specifically across the N9–C1' ribosidic bond, that are correlated with the PPV and can explain the decrease in reaction barrier height due to their facilitating cleavage of the ribosidic bond. hPNP apparently employs protein dynamics to push electrons, a finding that suggests that this coupling may be found more generally in enzymes that catalyze substitution and elimination reactions.

The complex singlet and triplet potential energy surfaces (PESs) of the [C₂N₂O₂] system are performed at the B3LYP and Gaussian-3//B3LYP levels in order to investigate the possibility of the carbyne radical CCN in removal of nitrogen dioxide. Thirty minimum isomers and 36 transition states are located. Starting from the very energy-rich reactant RCCN + NO₂, the terminal C-attack adduct NCCN(O)O (singlet at -48.6 and triplet at -48.1 kcal/mol) is first formed on both singlet and triplet PESs. Subsequently, the singlet NCCN(O)O takes an O-transfer to form the intermediate singlet cis-NCC(O)NO (-120.1), which can lead to the fragments NCCO + NO (-94.4) without barrier. The simpler evolution of the triplet NCCN(O)O is the direct N–O rupture to form the final fragmentation NCCNO + ³O (-31.0). However, the lower lying products ³NCNO + CO (-103.3) and NCNCO + ³O (-86.5) are kinetically much less competitive. All the involved transition states for the generation of NCCO + NO and NCCNO + ³O lie much lower than the reactants, and it indicates that this reaction can proceed effectively even at low temperatures. We expect that the reaction CCN + NO₂ can play a role in both combustion and interstellar processes. Comparison is made between the CCN + NO₂ and CH + NO₂ reaction mechanisms.

The formation mechanisms of pentafulvenone and azafulvenone were extensively investigated at the B3LYP/6-311++G** level and the potential energy surfaces were drawn out. Ketene pentafulvenone (A) and 3-carbonyl-3H-pyrrole (C) can be formed by eliminating N₂ from the diazo ketone via α elimination reaction and ketene 2-carbonyl-2H-pyrrole (B), 4-carbonyl-4H-imidazole (D), and 2-carbonyl-2H-imidazole (E) were formed by the elimination of water or methanol from pyrrole-2-carboxylic acid (rB) and carboxylate (rD and rE) via β elimination reaction. The structures of these monomers were compared and showed some information about the bond changed characters. The structure investigation indicated that the C=C bond is activated when the nitrogen atom locates in the ortho position of the C=C=O part, and therefore ortho-monomers are more facile to react. The difference of the amount and stability of the corresponding dimers are caused by differing the position and number of nitrogen atom and the variety of the ortho-dimer is complicated. In addition, the infrared spectra of the title species were also analyzed including the vibrational frequencies, IR relative intensities, and vibrational mode assignment.

Kinetics and mechanism of the reaction between cyclohexyl isocyanide and 1,1,1,5,5,5-hexafluropentane-2,4-dione has been investigated by utilizing transition state theory and using B3LYP/6-31G* method. Based on previous experimental studies, two paths namely direct attack and conjugate addition have been proposed. Energy changes vs intrinsic reaction coordinate (IRC) along these paths have been studied both in the gas phase and considering nonspecific solvent effect under Onsager's model while all intermediate and possible transition states' geometries obtained and optimized. Small differences have been observed between gas phase and solution phase results. Taking advantage of the thermodynamic and kinetic calculated parameters, observed reaction rate constants and activation energies have been acquired. Computational results suggest that the conjugate addition path is totally unacceptable, while a new path has been proposed, which is both energetically and kinetically preferred to direct attack path. This new path undergoes the Michael addition along with a Cope–Claisen-type rearrangement. In this path, a new intermediate has been encountered for the first time, which contains a five-membered ring of four carbon atoms and one oxygen atom. NBO analysis has revealed that in such intermediate, oxygen lone pair has resonance with C–C π bond inside and C–N π bond outside of the ring leading to this species special stability. Molecular orbital calculations satisfy NBO findings.

Theoretical insight into the mechanism of C8 adducts formation in a series of complicated carcinogenic reactions has been provided in a previous work. However, two important issues involved in this mechanism still need to be elucidated in detail. Hence, in this paper, we first present a new theoretical model to study the direct formation mechanism of C8 adduct. It is found that this model can well reflect the actual interactions in the real carcinogenic reactions. Thus, a better theoretical model to simulate other properties of these complicated reactions is found using ab initio and density functional theory (DFT) methods. Second, we simulate the formation process of C8 adduct in this new theoretical model using ABEEM/MM-MD method. According to the MD study, we approve that the higher aqueous-phase activation energy for transition state in this kind of reaction contributes to weaker interactions between central sites of reaction and water compared with those for reactants. This study once more supports the mechanism of formation of C8 adducts in the actual carcinogenic reactions where arylnitrenium ions directly attack at C8 positions of nucleoside bases in DNA.

The trimethylamine-catalyzed Baylis–Hillman reaction of formaldehyde and vinylaldehyde has been studied with the density functional theory (DFT) method of B3LYP/6-31+G(d,p). In the gas phase, the reaction involves an amine–formaldehyde–vinylaldehyde trimolecular addition transition structure followed by rate-determining intramolecular 1,3-hydrogen shift. When a bulk solvent effect of water was considered with conductor-like polarizable continuum model (CPCM), the reaction was found to follow the sequence of Michael-addition of amine to vinylaldehyde (step 1), addition of formaldehyde (step 2), and 1,3-hydrogen shift (step 3), with the 1,3-hydrogen shift as rate-determining. The overall reaction barrier is significantly reduced. When a molecule of water is involved in the reaction, the 1,3-hydrogen shift is significantly promoted so that the rate-determining step becomes the C–C bond formation. The calculated overall reaction barrier is in agreement with experimental observations.

We present an ab initio investigation on the chiral discrimination of 2-methylol oxirane (M-olOx)· · · ethanol (EtOH) complexes, for the sake of comparison with previous report on propylene oxide (PO)· · · EtOH complexes. Second-order Møller–Plesset perturbation theory (MP2) with the 6-311++G(d,p) basis set was used to elucidate the diastereomeric interactions between ethanol (EtOH), a transient chiral alcohol, and the chiral molecule 2-methylol oxirane (R). Six complexes of M-olOx· · · EtOH have been identified and their structures as well as their calculated stability ordering have been determined. The six complexes were defined in a similar way as for PO· · · EtOH. The primary O–H· · · O hydrogen bonds are predicted to be important contributions to chiral discrimination in M-olOx· · · EtOH. The three syn structures, with ethanol and the methylol group on the same side of the oxirane ring, are energetically favored over the three anti structures. The larger chirodiastaltic energy between synG- and synG+ is 0.52 kJ mol^-1. The largest diastereofacial energy between synG- and antiG- is 13.90 kJ mol^-1. The obtained results are compared with previously reported results on the PO· · · EtOH complexes and the mechanisms of chiral discrimination in PO· · · EtOH and M-olOx· · · EtOH are discussed. The harmonic frequencies, IR intensities, rotational constants, and dipole moments for the M-olOx· · · EtOH complexes are also presented. Such a theoretical study should be valuable to further spectroscopic investigations on M-olOx· · · EtOH complexes.

A theoretical survey on the potential energy surface for the CH (X²Π) + CH₂CO reaction has been carried out. The geometries and energies of all stationary points involved in the reaction are calculated at the UB3LYP/6-311+G(d, p) level. And the more accurate energy information is provided by single point calculations at the UCCSD(T)/6-311++G(2d, 2p) level. Relationships of the reactants, transition states, intermediates, and products are confirmed by the intrinsic reaction coordinate (IRC) calculations. Our calculations demonstrate that this reaction is most likely initiated by carbon-to-olefinic carbon attack manners. The results suggest that P1 (C₂H₃ + CO) is the most important product through two competitive channels R → IM1 → TS1/P1 → P1(C₂H₃ + CO) and R → IM1 → TS1/6 → IM6 → TS6/P1 → P1(C₂H₃ + CO). This study presents highlights of the mechanism of the title reaction, which is in good agreement with experimental results.

The CH₃OH with NH(³Σ^-) and NH₂(²B₁) reactions are key processes in methanol combustion. Optimized geometries and frequencies have been computed at UMP2 and UB3lYP levels. Energy values are improved using UQCISD(T), G3MP2, and BMC-CCSD methods using UMP2/6-311+G(d,p) optimized structures. For the two reactions, hydrogen abstraction and S_N2 substitution mechanisms have been investigated. Due to high barriers, the S_N2 substitution pathways play negligible roles. Methyl hydrogen abstraction channels are preferred to that of hydroxyl hydrogen, and the final products of NH₃ with CH₂OH are major.

Quantum chemistry calculations together with modeling of ligand–water exchange reactions are used to investigate, for the first time, the interaction mechanisms between emodin of anthraquinones and the catalytic zinc ion in matrix metalloproteinases (MMPs), and the coordinating mode between them is determined. The calculations indicate that the electron transfer from the emodin molecule to the catalytic zinc ion in MMPs occurs when the catalytic zinc ion coordinates with the O atoms of substituent groups at various positions of emodin molecule, and the more the number of the electron transfer from the coordinating O atom of substituent group of emodin molecule to the catalytic zinc ion, the stronger the coordinating ability between them. It is found that comparing with the O atoms of hydroxy groups at 1-position, 8-position and 3-position and the O atom of carbonyl group at 9-position of emodin molecule, the coordinating ability for the O atom of carbonyl group at 10-position of emodin molecule with the catalytic zinc ion in MMPs is the strongest. Therefore, when emodin inhibits MMPs activity, the catalytic zinc ion in MMPs should coordinate with the carbonyl group at 10-position of emodin molecule, rather than the hydroxy groups and carbonyl group at its other positions. Our calculated results are in agreement with previous relevant experimental results. This paper may be helpful for designing the new MMPs inhibitors having higher biological activities by carrying out the structural modifications of emodin molecule.

The first dehydration of protonated glycerol taking place at its secondary site was investigated by density functional calculations by considering different conformations of glycerol. Five parallel reaction pathways via different conformers of protonated glycerol were found. One of these pathways leads to a direct formation of protonated 3-hydroxylpropanal (HPA), another one of these pathways produces protonated glycidol, and the other three produce protonated 3-hydroxy-1,1-propanediol (HPD). One of these pathways producing protonated HPD was found to have obviously larger relative reaction rate than other pathways. The dehydration of protonated HPD to afford protonate HPA requires a rather low reaction barrier (12 kcal/mol). These results show that the production of HPA via a stepwise process with protonated HPD as a key intermediate, is energetically favorable than via a one-step concerted process producing HPA.

A MP2/6-31++G(d,p)//B3LYP/6-31++G(d,p) method was used to investigate the mechanisms of α-H and proton transfers of glycine induced by Mg²⁺. Eight complexes were obtained, six of which were neutral and the other two were zwitterionic. Among them, the zwitterion with a binding energy of 159.4 kcal/mol was the most stable structure. Conformation transformations of the complexes caused by the rotation of single bond and the transfers of α-H and proton were completed via seven transition states. The inductive effect of Mg²⁺ made the electron cloud of glycine deviate to Mg²⁺, which activated the covalent bond involving the transferred proton. The neutral complex can be turned into the zwitterionic one by the transfers of both carboxyl hydrogen and α-H, and the energy barrier of each reaction was less than 9.2 kcal/mol. After the transfer of α-H, a delocalized π bond was formed in glycine skeleton and the α-C atom took 0.19 positive charges. So the chemical activity of the glycine enhanced, and glycine was readily available for addition and nucleophilic substitution reactions. The path from the most stable glycine conformer G1 to the zwitterionic conformation I is G1 → G1–G3 → G3 → G3–G4 → G4 → G2–G4 → G2 → VI → I–VI → I, and the highest energy barrier of this path is 9.2 kcal/mol.

Ketenes are excellent precursors for catalytic asymmetric reactions, creating chiral centers mainly through addition across their C=C bonds. Density functional theory (DFT) calculations at the MO6/LACVP* and B3LYP/LACVP* levels of theory were employed in a systematic investigation of the peri-, chemo- and regio-selectivity of the addition of transition metal oxo complexes of the type ReO₃L(L=Cl^-, O^-, OCH₃, CH₃) to substituted ketenes O=C=C(CH₃)(X) [X=CH₃, H, CN, Ph] with the aim of elucidating the effects of substituents on the mechanism of the reactions. The [2 + 2] addition pathway across the C=C or C=O (depending on the ligand) is the most preferred in the reactions of dimethyl ketene with all the metal complexes studied. The [2 + 2] pathway is also the most preferred in the reactions of ReO₃Cl with all the substituted ketenes studied except when X=Cl. Thus of all the reactions studied, it is only the reaction of ReO₃Cl with O=C=C(CH₃)(Cl) that prefers the [3 + 2] addition pathway. Reactions of dimethyl ketene with ReO₃L favors addition across C=O bonds of the ketene when L=O^- and CH₃ but favors addition across C=C bonds when L=OCH₃ and Cl. In the reactions of ReO₃Cl with substituted ketenes, addition across C=O bonds is favored only when X=H while addition across C=C bonds is favored when X=CH₃, Cl, Ph, CN. The reactions of dimethyl ketene with ReO₃L will most likely lead to the formation of an ester precursor in each case. A zwitterionic intermediate is formed in the reactions except in the reactions of . The order in the activation energies of the reactions of dimethyl ketenes with the metal complexes ReO₃L with respect to changing ligand L is O^- < CH₃O^- < Cl^- < CH₃ while the order in reaction energies is CH₃ < CH₃O^- < O^- < Cl^-. For the reactions of substituted ketenes with ReO₃Cl, the order in activation barriers is CH₃ < Ph < CN < Cl < H while the reaction energies follow the order Cl < CH₃ < H < Ph < CN. In the reactions of dimethyl ketenes with ReO₃L, the trend in the selectivity of the reactions with respect to ligand L is Cl^- < CH₃O^- < CH₃ < O^- while the trend in selectivity is CH₃ < CN < Cl < Ph in the reactions of ReO₃Cl with substituted ketenes. It is seen that reactions involving a change in oxidation state of metal from the reactant to product have high activation barriers while reactions that do not involve a change in oxidation state have low activation barriers. For both [3 + 2] and [2 + 2] additions, low activation barriers are obtained when the substituent on the ketene is electron-donating while high activation barriers are obtained when the substituent is electron-withdrawing.

The deamination reaction of 8-oxoguanine (8-oxoG) catalyzed by 8-oxoguanine deaminase (8-oxoGD) plays a critically important role in the DNA repair activity for oxidative damage. In order to elucidate the complete enzymatic catalysis mechanism at the stages of 8-oxoguanine binding, departure of 2-hydroxy-1H-purine-6,8(7H,9H)-dione from the active site, and formation of 8-oxoxanthine, extensive combined QM(PM3)/MM molecular dynamics simulations have been performed. Computations show that the rate-limiting step corresponds to the nucleophilic attack from zinc-coordinate hydroxide group to free 8-oxoguanine. Through conformational analyses, we demonstrate that Trp115, Trp123 and Leu119 connect to O₈@8-oxoguanine with hydrogen bonds, and we suggest that mutations of tryptophan (115 and 123) to histidine or phenylalanine and mutation of leucine (119) to alanine could potentially lead to a mutant with enhanced activity. On this ground, a proton transfer mechanism for the formation of 8-oxoxanthine was further discussed. Both Glu218 and water molecule could be used as proton shuttles, and water molecule plays a major role in proton transfer in substrate. On the other hand, comparative simulations on the deamination of guanine and isocytosine reveal that, for the helping of hydrogen bonds between O₈@8-oxoguanine and enzyme, O₈@8-oxoguanine is the fastest to be deaminated among the three substrates which are also supported by the experimental kinetic constants.

In this work, the reaction mechanisms for the selective catalytic reduction (SCR) of nitrogen oxides (NO_x) with NH₃ on a (MnO)${}^{2+}$/ZSM-5 catalyst were investigated based on the density functional theory (DFT) method. Our calculations showed that the NH₃ could strongly adsorb on the (MnO)${}^{2+}$/ZSM-5 catalyst as compared to NO. The proposed reaction pathway, NH₃(ads)$\to$NH${}_2+$H$\to$NH₂(ads) $+$ NO(ads)$\to$ NH₂NO$\to$NHNO $+$ H$\to$N${}_2+$H₂O, was more favorable with smaller activation barrier (1.40eV) of the rate-determining step. The compared reaction process that the adsorbed NH₃ reacted directly with adsorbed NO was difficult to happen for the higher activation barrier. Meanwhile, the framework oxygen participated in the oxidation process from ammonia to NH₂, thereby increasing its availability for the reaction. In addition, the regeneration process of active site in the presence of NH₃ and NO₂ was explored, and the rate-limiting step possessed an activation barrier of 1.46eV. The NH₂NO species was formed as the crucial intermediate and subsequently decomposed into the N₂ and H₂O.

This study employed first principles calculations to investigate Fe-doped Bi₄O₅Br₂ as a potential photocatalyst with high efficiency. Based on formation energy calculation, the Fe atoms prefer to replace the Bi atoms with coordination bond of 3, and the optimal concentration for Fe-doping is 6.06wt.%. From surface energy calculations, the $(10\bar{1})$ surface has the lowest surface energy, and therefore the easiest cleavage facet is $\{10\bar{1}\}$. The key factors for the improvement of photocatalytic efficiency after Fe-doped Bi₄O₅Br₂ are estimated as follows. First, the band gap decreases from 2.63eV in pristine case to 2.40eV in 4 Fe-doped Bi₄O₅Br₂ case, resulting in the photon absorption edge shift to lower energy range and the absorption coefficient increase. Secondly, the work functions decrease from 5.66 eV (pristine) to 4.92eV (4 Fe-doped Bi₄O₅Br₂), which facilitate the electrons escaping from the surface. Thirdly, the relative mass ratio of photo-induced electrons and holes increases with Fe concentration. Because the Fe 3$d$ impurity states in the forbidden band gap become wider, the relative ratio increased after Fe-doped Bi₄O₅Br₂. Finally, the Fe doping process introduces more active sites on the surface, which can effectively improve the capacity of target molecules adsorption. Therefore, it is reasonable to believe that Fe-doped Bi₄O₅Br₂ can effectively improve the photocatalytic efficiency because the abovementioned key factors have tremendously improved. Our work provides a reasonable reason for choosing Fe as a dopant, which can help our experimental work and provide explanation for photocatalytic efficiency improvement.

Structure and energies of capsaicin and its probable transients formed in oxidation processes (single electron transfer and hydrogen atom transfer) have been investigated using theoretical calculations. Molecular geometries and energies of truncated and complete capsaicin structures have been optimized using density functional theory (DFT) with Becke three-parameter Lee-Yang-Parr (B3LYP) functional and 6–31$++$G(d) basis set. The stable geometries have been confirmed by vibrational analysis. The calculations suggest that single-electron transfer takes place at phenolic O-atom in the first step followed by delocalization of positive charge over the whole molecule. Further, the first step of hydrogen atom abstraction should take place at phenolic group due to lowest dissociation energy but post-optimization bond dissociation energy is least for benzylic group in the side chain as compared to other transients. Effect of water as a solvent on the energies has also been studied using self-consistent reaction field calculation. Similar results are obtained for truncated and complete capsaicin structures. The present study also includes Mulliken spin, charge, vibrational frequencies and assignments of frequencies of the transients. The present study provides explanation for the observation of phenoxyl radical in fast kinetic studies using pulse radiolysis study and, formation of breakdown and dimeric products in other studies.

Although the conversion of furfural to formic acid oxidized by H₂O₂ in formic acid is very high, the molecular mechanism remains unknown. This work describes the entire reaction process of the condensation reaction based on the density functional theory (DFT). It is found that H acts as a shuttle throughout most of the basic reaction steps during this transformation. Besides, Baeyer–Villiger oxidation and Baeyer–Villiger rearrangement are also discovered during this process with the opening of furan ring following afterward. The reactants, products and intermediates in the reaction process are optimized; all possible reaction paths are considered as well as the energy barriers to be overcome at each step. Thermochemical data concerned with the conversion of furfural to maleic acid showed that the maximum energy barrier at 378.15K was 39.83kcal/mol. The results of this study do not only correspond with the existing conclusions about the reaction in question from previous research but also supplement to the study of the pathways and mechanisms of the reaction, which can provide reference and guidance for further research, both experimentally and theoretically.

The knowledge base in the field of vaccination research and development has greatly improved. In the present era, utilizing a novel vaccine design and optimization strategy improves the vaccination efficiency and activity. In this regard, a novel drug delivery system produces nanosized, vaccine-loaded carrier molecules, which is called Nanovaccine. The advancement in nanovaccine and improved technology comes under preclinical and clinical trials, whereas different routes of administration strategy are applied against infectious diseases. The nanovaccine has high efficiency and immunogenicity compared to the traditional vaccine. Its long-lasting effect reduces the booster dose as well. One of the factors like routes of administration affects the efficiency of nanovaccine. The parenteral and mucosal vaccination is a traditional administration approach. In order to increase the safety and effectiveness of vaccines, innovative administration methods such as needless injection and polymeric formulations are now being developed. The presented paper shows a mechanism involved in nanovaccine delivery, and a method of administration via a different route, to learn more about their possible effects on immunogenicity, effectiveness, safety, sustained release and dose frequency reduction. The various advanced vaccine delivery methods, with special emphasis on its industrial and regulatory requirements for the higher production of nanovaccine, are also discussed.