Kinetics of Homogeneous Brønsted Acid Catalyzed Fructose Dehydration and 5‑Hydroxymethyl Furfural Rehydration: A Combined Experimental and Computational Study

We perform the first extensive experimental kinetic studies of fructose dehydration and 5-hydroxymethyl furfural (HMF) rehydration at low temperatures over a wide range of conditions (<i>T</i> ∼ 70–150 °C; pH values 0.7–1.6 and initial concentrations of fructose (5–20%w/v) and HMF (2.5–10%w/v)). Guided from insights from our first-principles calculations, we perform kinetic isotope effect (KIE) experiments of labeled fructose to validate the rate-limiting step. Subsequently, we develop the first skeleton model for fructose dehydration and HMF rehydration that integrates the fundamental kinetic experiments and accounts for the KIE, as well as the distribution of fructose tautomers, which changes significantly with temperature, and a direct path of fructose conversion to formic acid. It is shown that the skeleton mechanism of two steps consisting of fast protonation and dehydration followed by intramolecular hydride transfer as the rate-limiting step can capture the experimental kinetics and KIE experiments well. Fructose dehydration is found to result in stoichiometric excess of formic acid relative to levulinic acid, produced directly from fructose. All reactions are shown to be pseudo-first order in both catalyst and substrate. These insights are incorporated in a continuous flow reactor model; higher temperatures improve the optimum yield of HMF, while HMF selectivity at low conversions is less sensitive to temperature

Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth

The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB₂ receptor (CB₂R) as a new target and used a CB₂R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment. IR700DX-mbc94 was prepared by conjugating a photosensitizer, IR700DX, to mbc94, whose binding specificity to CB₂R has been previously demonstrated. We found that phototherapy treatment using IR700DX-mbc94 greatly inhibited the growth of CB₂R positive tumors but not CB₂R negative tumors. In addition, phototherapy treatment with nontargeted IR700DX did not show significant therapeutic effect. Similarly, treatment with IR700DX-mbc94 without light irradiation or light irradiation without the photosensitizer showed no tumor-inhibitory effect. Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB₂R appears to have great potential as a phototherapeutic target for cancer treatment