Dissecting Sperm Mitochondrial G-Quadruplex Structures Using a Fluorescent Probe Biomarker to Monitor and Regulate Fertilization Capability.

To monitor the levels of mitochondrial DNA G-quadruplexes (mtDNA G4s) in spermatozoa and to explore the possibility using mtDNA G4s as a reliable marker in patients with multiple clinical insemination failures, a novel chemical TPE-mTO probe engineered in our previous work was used on both samples from the mice sperm and from patients with fertilization failure. Expression of valosin-containing protein and the zona-free hamster egg assay were used to evaluate mitophagy and human sperm penetration. RNA-sequencing was used to explore expression changes of key genes affected by mtDNA G4s. Results showed that the probe can track mtDNA G4s in spermatozoa easily and quickly with fewer backgrounds. Significantly increased mtDNA G4s were also found in patients with fertilization failure, using the flow-cytometry-based TPE-mTO probe detection method. A sperm-hamster egg penetration experiment showed that abnormal fertilization caused by increased mtDNA G4s can be effectively restored by a mitophagy inducer. This study provides a novel method for monitoring etiological biomarkers in patients with clinical infertility and treatment for patients with abnormal fertilization caused by mtDNA G4 dysfunction.

A dual-site controlled pH probe revealing the pH of sperm cytoplasm and screening for healthy spermatozoa.

A dual-site controlled pH probe, which is composed of gold nanoparticles and modified with rhodamine and fluorescein derivatives, was applied to sensitively monitor intracellular pH changes in sperm. The pH probe revealed the intracellular pH of sperm under different conditions and demonstrated the lower pH in asthenozoospermia patients as compared to healthy individuals. Importantly, the pH probe can help screen for healthy sperm.

Novel coumarin-thiazolyl ester derivatives as potential DNA gyrase Inhibitors: Design, synthesis, and antibacterial activity.

The design and synthesis of novel coumarin-thiazolyl ester derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8p exhibited excellent antibacterial activity against four bacteria strains with MIC values of 0.05, 0.05, 8, and 0.05 µg/mL, respectively. In vitro drug-resistant bacterial inhibition experiments indicated that compound 8p exhibited the best bacteriostatic effect in the selected compounds and four positive control drugs with MIC values of 4 µg/mL. In vitro enzyme inhibitory assay showed that compound 8p exhibited potent inhibition against DNA gyrase with IC50 values of 0.13 µM. The molecular docking model indicated that compounds 8p can bind well to the DNA gyrase by interacting with amino acid residues. This study demonstrated that the compound 8p can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.

Discovery of novel multi-substituted benzo-indole pyrazole schiff base derivatives with antibacterial activity targeting DNA gyrase.

The design and synthesis of novel multi-substituted benzo-indole pyrazole Schiff base derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activities against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella. In addition, we selected 20 compounds for the in vitro antibacterial activities assay of 6 drug-resistant bacteria strains. The result revealed compound 8I-w exhibited excellent antibacterial activity against 4 drug-resistant E. coli bacteria strains with IC50 values of 7.0, 17.0, 13.5, and 1.0 µM, respectively. In vitro enzyme inhibitory assay showed that compound 8I-w displayed potent inhibition against DNA gyrase with IC50 values of 0.10 µM. The molecular docking model indicated that compounds 8I-w can bind well to the DNA gyrase by interacting with various amino acid residues. This study demonstrated that the compound 8I-w can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.

Total Synthesis of Bryostatin†8 Using an Organosilane-Based Strategy.

Convergent total synthesis of bryostatin 8 has been accomplished by an organosilane-based strategy. The C ring is constructed stereoselectively through a geminal bis(silane)-based [1,5]-Brook rearrangement, and the B ring through geminal bis(silane)-based Prins cyclization, thus efficiently joining the northern and southern parts of the molecule.

Chiral crotyl geminal bis(silane): a useful reagent for asymmetric Sakurai allylation by selective desilylation-enabled chirality transfer.

Enantioselective synthesis of SiMe3/SiPh2Me-substituted crotyl geminal bis(silane) has been developed. This compound is a useful reagent for Ph3C+B(C6F5)4--catalyzed asymmetric Sakurai allylation and one-pot Sakurai allylation/Prins cyclization processes. Chemoselective desilylation of SiPh2Me leads to efficient chirality transfer.

Tunable reactivity of geminal bis(silyl) enol derivatives leading to selective exo-IEDDA or Sakurai allylation with a ß,γ-unsaturated ketoester.

Two contrasting pathways in a SnCl4-catalyzed reaction of geminal bis(silyl) enol derivatives with ß,γ-unsaturated ketoesters have been achieved by tuning the R group in the enol moiety. While the electron-donating Bn-substituted enol ether undergoes an exo-selective inverse-electron-demand Diels-Alder (IEDDA) reaction to give dihydropyran, the electron-withdrawing Ac-substituted enol ester reacts as an allylsilane to provide a Sakurai-allylated product with predominant syn-selectivity.

Synthesis of functionalized γ-lactone via Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol ester with a tethered acetal.

An efficient synthesis of functionalized γ-lactones has been developed involving Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol esters with a tethered acetal. While the steric and electronic effects of geminal bis(silane) favor the desired Sakurai pathway, the methoxy species formed in the deprotection step also facilitates both cyclization and rearrangement. The synthetic value of this approach has been demonstrated by efficiently transforming the E-vinylsilane into enyne and the γ-lactone moiety into multisubstituted THF.