Dual hepatocyte-targeting fluorescent probe with high sensitivity to tumorous pH: Precise detection of hepatocellular carcinoma cells

A new dual hepatocyte-targeting fluorescent probe HPL-1, which can precisely distinguish tumorous pH from physiological pH, was developed. The OFF-ON switch of HPL-1 can be triggered via pH-induced structural change of the lactam group of the rhodamine moiety from closed-ring to open-ring. Our results showed that the phosphate group of HPL-1 is beneficial to its accumulation in liver cells, and combination of the phosphate and galactose units could synergistically increase the hepatocyte-targeting capacity. HPL-1 could selectively distinguish hepatoma cells from other tissue cells, and precisely distinguish cancerous liver cells from normal liver cells. Compared with other reported probes, HPL-1 not only enable a simple and convenient detection method, but also has good hepatocyte-targeting capacity and precise recognition capacity of tumors under weak acid micro-environment, which opens new avenues for precise diagnosis and treatment of hepatocellular carcinoma

Copper-catalyzed diastereoselective aerobic intramolecular dehydrogenative coupling of hydrazones via sp3 C–H functionalization

Transition metal-catalyzed cross dehydrogenative coupling is an important tool for functionalization of the α Csp3–H bond of amines. Among this reaction category, copper-catalyzed selective C–C bond formation under atmospheric O2 is of considerable research interest and significant progress has been achieved in recent years. In comparison, development of the intramolecular version of this transformation is still in its infancy. Furthermore, diastereoselective cyclization with this transformation has not been achieved. Here, we describe the highly diastereoselective intramolecular dehydrogenative cyclization of N,N-disubstituted hydrazones by a copper-catalyzed sp3 C–H bond functionalization process. The reaction protocol utilizes O2 as the oxidant and shows great functional group compatibility. Computational studies suggest that a 5-center/6-electron disrotatory cyclization mechanism is probably involved in the process for controlling the diastereoselectivity. This work represents the first example of a copper-catalyzed, direct intramolecular diastereoselective coupling reaction via an iminium ion intermediate. Additionally, it provides an environmentally friendly and atom efficient approach to access substituted pyrazolines, an important structural unit in many biologically active compounds

Regulatory mechanisms of leaf color change in Acer pictum subsp. mono

Acer pictum subsp. mono is a colored leaf tree with vital ornamental and economic value. However, insufficient color change and early leaf fall in cities restrict its ornamental value. In this research, green and red leaves from wild A. p. subsp. mono were collected to study the regulatory mechanisms of leaf color change. Through the determination of plant physiological indexes, we found that the photosynthetic pigment content in red leaves decreased significantly compared with green leaves, while the anthocyanin content and antioxidant activity increased significantly compared with green leaves during the leaf color change process. Using transcriptome sequencing, we found more than 5500 differentially expressed genes, most of which were up-regulated. Many of the differentially expressed genes are involved in the anthocyanin metabolic pathway. The expression patterns of 15 key genes were investigated by quantitative real-time polymerase chain reaction. Among these genes, AmDFR and PAL1 are significant genes involved in the anthocyanin metabolic pathway, and CIPKs2, CIPKs6, CMLs1, CMLs38, AmGST1, AmGST2, GPX3, CBF, AmAPX, AmSOD, POD5, AmGR, and PSBY might be stress response genes that indirectly regulated the anthocyanin accumulation. The results showed that these genes play vital roles in the leaf color change of A. p. subsp. mono. This research will be helpful in further study of the molecular regulatory mechanisms of leaf color change and for the improvement of colored leaf plants.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp3 carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp3)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp3)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br /

Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp³ carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp³)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp³)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br