DFT Studies of the Selective C–O Hydrogenolysis and Ring-Opening of Biomass-Derived Tetrahydrofurfuryl Alcohol over Rh(111) surfaces

Tetrahydrofurfuryl alcohol (THFA) has been identified as a platform chemical of interest because of its production from biomass. It can be converted into valuable alcohols and ethers by selective hydrogenation/hydrogenolysis reaction over Rh-based metal catalysts. To better understand the chemistry of THFA, the reaction energies and the corresponding energy barriers of selective C–O bond hydrogenolysis and ring-opening of THFA on Rh(111) for the formation of 2-methyltetrahydrofuran (2-MeTHF), 1,5-pentanediol (1,5-PeD), and 1,2-pentanediol (1,2-PeD) were studied using density functional theory (DFT) calculations. The results indicate that starting from THFA to produce 2-MeTHF, the direct C–O bond cleavage of the CH₂OH group is not favored. Alternatively and more preferentially, the reaction occurs through the initial activation of C–H bond on the side chain, followed by dehydroxylation and hydrogenation. On the other hand, in the metal catalyzed ring-opening process of THFA to 1,5-PeD and 1,2-PeD, the first dehydrogenation of secondary CH–O or primary CH₂–O moiety in the ring decreases the barriers of the subsequent C–O bond dissociation. Moreover, the energy span theory shows that the ring-opening at the sterically less-hindered primary C–O bond exhibits a lower effective barrier than that for ring-opening at the more sterically hindered secondary C–O bond, as well as hydrogenolysis at the side CH₂OH chain, suggesting that the formation of 1,2-PeD is much kinetically favored than the formation of 1,5-PeD and 2-MeTHF. Our theoretical results give a good explanation for the experimental fact that 1,2-PeD was the dominant product observed on unprompted Rh/SiO₂

Role of MoO₃ on a Rhodium Catalyst in the Selective Hydrogenolysis of Biomass-Derived Tetrahydrofurfuryl Alcohol into 1,5-Pentanediol

Selective hydrogenolysis of biomass-derived tetrahydrofurfuryl alcohol (THFA) to produce 1,5-pentanediol (1,5-PeD) is accomplished by a binary catalyst consisting of MoO₃ and supported Rh nanoparticles; a 1,5-PeD selectivity up to 80% is achieved in the present work. Moreover, a very interesting phase-transfer behavior for MoO₃ during the reaction is observed with the assistance of different characterization techniques. In this process, MoO₃ dissolves partially in the liquid phase under the reaction conditions and is transformed into the soluble hydrogen molybdenum oxide bronzes (H_<i>x</i>MoO₃) in the presence of H₂, which are recognized as the genuinely active sites for the C–O bond breaking of THFA. Density functional theory (DFT) calculations were then carried out to simulate the plausible mechanisms and highlight the role of Mo in the ring-opening process of THFA in more detail. We propose that the formation of 1,5-PeD takes place in a two consecutive reactions. THFA first undergoes acid-catalyzed ring-opening process to form the key intermediate 5-hydroxypentanal with the homogeneous catalysis of dissolved H_<i>x</i>MoO₃. The intermediate is then quickly hydrogenated into 1,5-PeD under the heterogeneous catalysis of Rh. The concerted “hydrogen-transfer–ring-opening” mechanism plausibly explains the high reaction selectivity toward 1,5-PeD in the hydrogenolysis of THFA and is verified by the reactivity trends of related substrates

Selection of sAPRIL-BP.

<p>(A) The binding affinity of phage clones No.1–20 for sAPRIL were determined by ELISA. Clone 21 was used as a positive control. The fold change of the optical density was normalized to the positive control. Clones that had at least a 6-fold greater affinity than the positive control were considered ‘positive’ for sAPRIL binding. (B) Three binding peptides were synthesized and their binding affinity with sAPRIL (black bars) was determined and compared with the negative control (NC) using ELISA. Cross-reactivity was assessed by measuring the binding affinity to BAFF (grey bars). (C) Clone BP1 (sAPRIL-BP) was mixed with sAPRIL at different doses to compete for binding with fixed LOVO cells.</p

Effect of sAPRIL-BP on the proliferation of LOVO and SW620 cells.

<p>(A) APRIL^high LOVO and HCT116 cells and (B) APRIL^low SW620 and HT-29 cells were treated with the indicated doses of sAPRIL binding peptides for 24, 48, and 72 h, and proliferation was determined using the CCK-8 kit. The rate of proliferation inhibition was calculated as: (%) = [(mean of OD_control—mean of OD_experimental) / mean of OD_control]×100%.</p

<i>In vivo</i> effect of sAPRIL-BP on liver metastasis.

<p>LOVO cells were injected into the spleens of nude mice to observe experimental liver metastasis. Three weeks after injection, the mice were divided into 3 groups (N = 5) and treated with PBS (control), low (20 mg/kg), or high (40 mg/kg) doses of sAPRIL-BP every other day. Mice were sacrificed after two weeks of treatment with sAPRIL-BP. (A) Representative pictures of the metastatic liver tumors from each group are shown. (B) Numbers of metastatic nodules per mouse were recorded. *<i>P</i> <0.05 compared to control. #<i>P</i> <0.05 compared to the low dose group. (C) Numbers of metastatic nodules with the indicated size were recorded. Total numbers of metastatic nodules: n = 197 (Con), n = 130 (20 mg/kg), and n = 84 (40 mg/kg).</p

Effect of sAPRIL-BP on the expression of cell cycle-related proteins.

<p>LOVO cells were treated with the indicated doses of sAPRIL-BP for 48 h. (A) The expression levels of the indicated cell cycle proteins were assessed by Western Blotting analysis. GAPDH was used as the internal control. The protein size of Cyclin D1 is 34 kDa, Cyclin A 49 kDa, Cyclin E 50 kDa, Cyclin B1 55 kDa, CDK4 34 kDa, CDK6 37 kDa, p53 53 kDa, p27 27 kDa, p16 40 kDa, and GAPDH 36 kDa. The optical densities of the cyclin D1 (B) and CDK4 (C) protein bands were analyzed and normalized to the internal control as fold change. *<i>P</i><0.05 compared to Vehicle group; #<i>P</i><0.05 compared to 10 μM group, †<i>P</i><0.05 compared to 20 μM group.</p

<i>In vivo</i> effect of sAPRIL-BP on proliferation and apoptosis in xenograft tumors.

<p>Paraffin embedded tumor tissues were used for morphological analysis with H&E staining (A), proliferation analysis with Ki67 staining (B), and apoptosis analysis with cleaved caspase-3 (cle-casp-3) staining (C). Representative pictures of the tumors from each group are shown (magnification 200×). The proliferation index (D) and apoptosis index (E) were calculated and normalized to the control (Con) group. *<i>p</i> <0.05 compared to control. #<i>p</i> <0.05 compared to 20 mg/kg group.</p

APRIL mRNA and protein expression in human colorectal cell lines.

<p>APRIL expression was assessed in five human colorectal cell lines (indicated) using RT-PCR (A) and Western Blotting (C). Representative gel images are shown. GAPDH was used as the internal control. The optical densities of the APRIL mRNA (B) and protein (D) bands were analyzed and normalized to the internal control. *<i>P</i><0.05 compared to SW620, HT-29, or SW480.</p

<i>In vivo</i> effects of sAPRIL-BP on tumor development.

<p>LOVO cells were injected subcutaneously into nude mice and allowed to grow for 3 weeks. Once the tumor was establishes, the mice were divided into 3 groups (N = 5) and treated with PBS (control), low (20 mg/kg), or high (40 mg/kg) dose of sAPRIL-BP every other day. (A) Representative examples of the tumors from each group are shown. Top panel: Scale bar, 8 mm. Bottom panel: Scale bar, 7 mm. (B) Mice were sacrificed after two weeks of treatment with sAPRIL-BP and the tumor weights were recorded. *<i>p</i> <0.05 compared to control. #<i>p</i> <0.05 compared to the low dose group. (C) The tumor volume was recorded every two days during treatment. *<i>p</i> <0.05 compared to control.</p

Characteristics of included studies.

<p>CTP, CT perfusion; HE, hematoma expansion; NA, not available; PCCT, post-contrast CT; SS, spot sign.</p><p>*Multicenter included Canada, Spain, Germany, Poland, India, and USA.</p><p>Characteristics of included studies.</p