Solvent effects play a critical role in ionic chemical reactions and have been a research topic for a long time. The solvent molecules in the first solvation shell of the solute are the most important Show more
Solvent effects play a critical role in ionic chemical reactions and have been a research topic for a long time. The solvent molecules in the first solvation shell of the solute are the most important solvating species. Consequently, manipulation of the structure of this shell can be used to control the reactivity and selectivity of ionic reactions. In this work, we report extensive experimental and insightful computational studies of the effects of adding diverse fluorinated bulky alcohols with different solvation abilities to the fluorination reaction of alkyl bromides with potassium fluoride promoted by 18-crown-6. We found that adding a stoichiometric amount of these alcohols to the acetonitrile solution has an important effect on the kinetics and selectivity. The most effective alcohol was 2-trifluoromethyl-2-propanol (TBOH-F3), and the use of 3 equiv of this alcohol to fluorinate a primary alkyl bromide led to a 78% fluorination yield in just 6 h of reaction time at a mild temperature of 82 °C, with 8% of E2 yield. The more challenging secondary alkyl bromide substrate obtained 44% fluorination yield and 56% E2 yield at 18 h of reaction time. More fluorinated alcohols with six or more fluorine atoms have resulted in relatively acidic alcohols, leading to large amounts of the corresponding ethers of these alcohols as side products. The widely used hexafluoroisopropanol (HFIP) was the least effective one for monofluorination, indicating that both acidity and bulkiness are important features of the alcohols for promoting fluorination using KF salt. Nevertheless, the ether of HFIP can be easily formed with the substrate, generating a highly fluorinated ether product. Theoretical calculations predict ΔG‡ in close agreement with the experiments and explain the higher selectivity induced by the fluorinated bulky alcohols in relation to the use of crown ether alone. Show less
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000 Show more
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC. Show less
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology Show more
Abstract Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δ p or its potential component, Δ Ψ , which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1–5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δ p dissipation decreases superoxide formation dependent on Δ p . UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells. Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg 2+ , or increased pyruvate accumulation may initiate UCP-mediated redox signaling. Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667–714. Show less