Computational Studies on Pd-Catalyzed Functionalization of Csp(2)-H Bonds Using a 1,2,3-Triazole Directing Group: Cyclization versus Substitution.

The Pd-catalyzed functionalization of Csp(2)-H bonds using a 1,2,3-triazole directing group has been investigated by density functional theory calculations at the B3LYP level. The results of these calculations showed that the substitution pathway was kinetically favored over the cyclization pathway for the N2-pyridine-1,2,3-triazole-4-carboxylic acid (TAPy)-directed functionalization of Csp(2)-H bonds, while the cyclization pathway was kinetically favored over the substitution pathway for the N1-aryl-1,2,3-triazole-4-carboxylic acid (TAA)-directed Csp(2)-H functionalization. The kinetic preference of the TAPy directing group for the substitution reaction can be attributed the reduced level of bond cleavage in the transition structure of the substitution step because the pyridine moiety of the TAPy directing group can act as a ligand for the Pd center.

A mechanistic study of Pd(OAc)2-catalyzed intramolecular C-H functionalization reaction involving CO/isonitrile insertion.

The mechanism of the Pd(OAc)2-catalyzed intramolecular C-H functionalization reaction involving CO/isonitrile insertion was investigated with the aid of density functional theory calculations at the B3LYP level. The similarity between the CO and isonitrile systems includes the following: (1) the anagostic bonding mechanism rather than the concerted metallation-deprotonation (CMD) mechanism is operative for the C-H cleavage step, (2) the CO/isonitrile insertion step is rate-determining, and (3) the C-H activation and CO/isonitrile insertion steps are accomplished with Pd(II) and Pd(III), respectively. For the reaction including isonitrile insertion, the arene C-H activation step occurs after deprotonation of the imino group. However, for reaction including CO insertion, the arene C-H activation step is the first step of the reaction mechanism. The difference between CO and isonitrile systems in the reaction mechanism can be attributed to the difference in the oxidants used. In the reaction including isonitrile insertion, the high endergonicity of the oxidation step suppresses prior C-H activation and favors prior deprotonation of the imino group. In the reactions including CO insertion, the low endergonicity of the oxidation step allows prior C-H activation to occur.

The mechanism of transition-metal (Cu or Pd)-catalyzed synthesis of benzimidazoles from amidines: theoretical investigation.

In this study, the Cu(OAc)2- and [PdCl2(PhCN)2]-catalyzed syntheses of benzimidazoles from amidines were theoretically investigated using density functional theory calculations. For the Cu-catalyzed system, our calculations supported a four-step-pathway involving C-H activation of an arene with Cu(II) via concerted metalation-deprotonation (CMD), followed by oxidation of the Cu(II) intermediate and deprotonation of the imino group by Cu(III), and finally reductive elimination from Cu(III). In our calculations, the barriers for the CMD step and the oxidation step are the same. The results are different from the ones reported by Fu et al. in which the whole reaction mechanism includes three steps and the CMD step is rate determining. On the basis of the calculation results for the [PdCl2(PhCN)2]-catalyzed system, C-H bond breaking by CMD occurs first, followed by the rate-determining C-N bond formation and N-H deprotonation. Pd(III) species is not involved in the [PdCl2(PhCN)2]-catalyzed syntheses of benzimidazoles from amidines.

A DFT study of the mechanism of copper-catalyzed synthesis of 2H-indazoles from aryl azide.

DFT calculations have been performed to study the reaction mechanism of N-N bond formation from aryl azide catalyzed by the copper(I) iodide complex. We studied various activation modes for the azide group, and found that the azide group is activated by the Cu(µ-I)2Cu(TMEDA) dimer coordinating to the N-atom of phenyl imine and the internal N-atom of azide.

[Effects of immature dendritic cells to express CCR7 on graft-versus-host disease in allogeneic bone marrow transplant mouse model].

OBJECTIVE: To investigate the effects of immature dendritic cells (imDC) expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD) in allogeneic bone marrow transposed (allo-BMT) mouse model. METHODS: We constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC effectively in vitro. GVHD model was established with C57BL/6(H-2b) donor mice and BALB/c (H-2d) recipient mice. After irradiation, recipients were injected with donor bone marrow and spleen cells along with CCR7-modified dendritic cells. Mice were randomized into irradiation, transplant control, pXZ9-imDC (empty vector control) and CCR7-imDC groups. Survival, GVHD score, histopathological analysis and plasma levels of inflammatory cytokines were observed. RESULTS: The mean survival in irradiation, transplantation, pXZ9-imDC and CCR7-imDC groups were (8.20±1.48)d, (12.20±2.78)d, (20.70±6.01)d and (27.5±7.55)d respectively. The survival in CCR7- imDC group was significantly improved compared with other groups (P<0.05). GVHD scores in transplantation, pXZ9-imDC and CCR7-imDC groups were (6.90±1.66), (5.60±0.97) and (4.10±1.79) respectively. CCR7-imDC group had significantly lower GVHD score and minor tissue damages shown by histopathological analysis than the other groups. Plasma IFN-γ level increased and reached the peak at +10 day in transplant group, while it gradually decreased in pXZ9-imDC and CCR7-imDC groups, and then reached the nadir at +20 day post-allo-BMT, with the lowest level in CCR7-imDC group (P<0.01). Plasma IL-4 decreased in transplant group, while it gradually increased in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in CCR7- imDC group (P<0.01). The 95%-100% of H-2b positive cells in recipient mice on + 30 day post-allo-BMT demonstrated the complete donor- type implantation. CONCLUSION: Genetically modified immature DC by CCR7 gene could alleviate damages by GVHD and prolong survival of recipient mice after allo-BMT.