Infrared photodissociation spectroscopy of mass-selected [TaO3(CO2)n]+ (n = 2-5) complexes in the gas phase.

We report a joint experimental and theoretical study on the structures of gas-phase [TaO3(CO2)n]+ (n = 2-5) ion-molecule complexes. Infrared photodissociation spectra of mass-selected [TaO3(CO2)n]+ complexes were recorded in the frequency region from 2200 to 2450 cm-1 and assigned through comparing with the simulated infrared spectra of energetically low-lying structures derived from quantum chemical calculations. With the increasing number of attached CO2 molecules, the larger clusters show significantly enhanced fragmentation efficiency and a strong band appears at around 2350 cm-1 near the free CO2 antisymmetric stretching vibration band, indicating only a small perturbation of CO2 molecules on the secondary solvation sphere while higher frequency bands corresponding to the core structure remain largely unaffected. A core structure [TaO3(CO2)3]+ is identified to which subsequent CO2 ligands are weakly attached and the most favorable cluster growth path is verified to proceed on the triplet potential energy surface higher in energy than that of ground states. Theoretical exploration reveals a two-state reactivity (TSR) scenario in which the energetically favored triplet transition state crosses over the singlet ground state to form a TaO3+ core ion, providing new information on the cluster formation correlated with the reactivity of tantalum metal oxides towards CO2.

Observation of inserted oxocarbonyl species in the tantalum cation-mediated activation of carbon dioxide dictated by two-state reactivity.

Reductive activation of carbon dioxide (CO2) has drawn increasing attention as an effective and convenient method to unlock this stable molecule, especially via transition metal-catalyzed reactions. Taking the [TaC4O8]+ ion-molecule complex formed in the laser ablation source as a representative, the reactivity of the tantalum metal cation towards CO2 molecules is explored using infrared photodissociation spectroscopy combined with quantum chemical calculations. The strong absorption in the carbonyl stretching region provides solid evidence for the insertion reactions into CO bonds by the tantalum cation. Two inserted oxocarbonyl products are identified based on the great agreement between the experimental results and simulated infrared spectra of energetically low-lying structures in the singlet and triplet states. The pivotal role of two-state reactivity in driving CO2 activation among three different spin states is rationalized by potential energy surface analysis. Our conclusion provides valuable insight into the intrinsic mechanisms of CO2 activation by the tantalum metal cation, highlighting the affinity of tantalum for CO bond insertion in addition to typical "end-on" binding configurations.

Inhibition of 32Dp210 cells harboring T315I mutation by a novel derivative of emodin correlates with down-regulation of BCR-ABL and its downstream signaling pathways.

PURPOSE: The clinical outcome of chronic myeloid leukemia (CML) patients has been changed dramatically due to the development of imatinib (IM). However, the emergence of IM resistance, commonly associated with point mutations within the BCR-ABL kinase domain, remains a major clinical problem. Here, we investigated the effects of E35, a novel derivative of emodin, on the IM-resistant 32Dp210-T315I cells. METHODS: Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide and colony formation assay. Induction of apoptosis was confirmed by DNA fragmentation assay and annexin V/PI staining assay. Real-time quantitative PCR was used to access the BCR-ABL gene expression. Changes of related signaling molecules were detected through Western blot. RESULTS: E35 was found to potently inhibit proliferation of 32Dp210-T315I cells with an average IC50 of 2.4 µM at 48 h. Colony formation was almost fully suppressed in 1.0 µM E35 group. DNA fragmentation and annexin V/PI staining assay exhibited the typical DNA fragmentation and the increased proportion of early apoptotic cells, respectively. The induction of apoptosis was associated with increase of Bax to Bcl-2 expression ratio and activation of caspase cascades involving decrease of pro-caspase 9 and pro-caspase 3 and increase of PARP cleavage. The protein expression of P210(BCR-ABL) and p-P210(BCR-ABL) was down-regulated in the presence of E35, although the mRNA levels remained almost unchanged. Moreover, the activation of the P210(BCR-ABL) downstream signaling pathways including CrkL, Akt/mTOR and MEK/ERK was fully suppressed by E35. CONCLUSION: Our study indicated that E35 might be a potential antileukemia agent against IM resistance in CML.