The spin-crossover (SCO) phenomenon is an active area of research. This paper describes the synthesis of an Fe-Ag Hofmann-type complex, Fe(4-methylpyrimidine)2[Ag(CN)2]2, which demonstrates a one-step SCO and single-layer Hofmann-type structure with Ag-N interactions and no Ag-Ag interactions, which is strikingly different from the previously synthesized complex Fe(4-methylpyrimidine)2[Au(CN)2]2 that contains Au-Au interactions and no Au-N interactions. This difference can be explained in terms of the lack of relativistic effect in the Ag atoms and the different cooperative effects caused by their different structures. A scan-rate-dependent hysteresis is observed using magnetic measurement whereas not using 57Fe Mössbauer spectroscopy, suggesting that the spin transition is relatively slow.Humans are constantly exposed to antimicrobial triclocarban (TCC) via direct skin contact with personal care and consumer products, but the safety of long-term dermal exposure to TCC remains largely unknown. Herein, we used a mouse model to evaluate the potential health risks from the continuous dermal application of TCC at human-relevant concentrations. After percutaneous absorption, TCC circulated in the bloodstream and largely entered the liver-gut axis for metabolic disposition. Nontargeted metabolomics approach revealed that TCC exposure perturbed mouse liver homeostasis, as evidenced by the increased oxidative stress and impaired methylation capacity, leading to oxidative damage and enhancement of upstream glycolysis and folate-dependent one-carbon metabolism. Meanwhile, TCC was transformed in the liver through hydroxylation, dechlorination, methylation, glucuronidation, sulfation, and glutathione conjugation. TCC-derived xenobiotics were subsequently excreted into the gut, and glucuronide and sulfate metabolites could be further deconjugated by the gut microbiota into their active free forms. In addition, microbial community analysis showed that the composition of gut microbiome was altered in response to TCC exposure, indicating the perturbation of gut homeostasis. Together, through tracking the xenobiotic-biological interactions in vivo, this study provides novel insights into the underlying impacts of dermally absorbed TCC on the liver and gut microenvironments.Nematode chitinases play crucial roles in various processes of the nematode lifecycle, including hatching, molting, and reproduction. Small-molecule inhibitors of nematode chitinases have shown promise for controlling nematode pests. However, the lack of structural information makes it a challenge to develop nematicides targeting nematode chitinases. Here, we report the first crystal structure of a representative nematode chitinase, that of CeCht1 from the model nematode Caenorhabditis elegans, to a 1.7 Å resolution. CeCht1 is a highly conserved chitinase among nematodes, and structural comparison with other chitinases revealed that CeCht1 has a classical TIM-barrel fold with some subtle structural differences in the substrate-binding cleft. Benefiting from the obtained crystal structure, we identified a series of novel inhibitors by hierarchical virtual screening. Analysis of the structure-activity relationships of these compounds provided insight into their interactions with the enzyme active site, which may inform future work in improving the potencies of their inhibitory activities. This work gives an insight into the structural features of nematode chitinases and provides a solid basis for the development of inhibitors.Herein, we describe the design, synthesis, and biological evaluation of novel betulin and N-acetyl-d-galactosamine (GalNAc) glycoconjugates and suggest them as targeted agents against hepatocellular carcinoma. We prepared six conjugates derived via the C-3 and C-28 positions of betulin with one or two saccharide ligands. These molecules demonstrate high affinity to the asialoglycoprotein receptor (ASGPR) of hepatocytes assessed by in silico modeling and surface plasmon resonance tests. Cytotoxicity studies in vitro revealed a bivalent conjugate with moderate activity, selectivity of action, and cytostatic properties against hepatocellular carcinoma cells HepG2. An additional investigation confirmed the specific engagement with HepG2 cells by the enhanced generation of reactive oxygen species. Stability tests demonstrated its lability to acidic media and to intracellular enzymes. Therefore, the selected bivalent conjugate represents a new potential agent targeted against hepatocellular carcinoma. Further extensive studies of the cellular uptake in vitro and the real-time microdistribution in the murine liver in vivo for fluorescent dye-labeled analogue showed its selective internalization into hepatocytes due to the presence of GalNAc ligand in comparison with reference compounds. The betulin and GalNAc glycoconjugates can therefore be considered as a new strategy for developing therapeutic agents based on natural triterpenoids.Herein, we investigated the molecular dynamics as well as intramolecular interactions in two primary monohydroxy alcohols (MA), 2-ethyl-1-hexanol (2EHOH) and n-butanol (nBOH), by means of broad-band dielectric (BDS) and Fourier transform infrared (FTIR) spectroscopy. The modeling data obtained from dielectric studies within the Rubinstein approach [ Macromolecules 2013, 46, 7525-7541] originally developed to describe the dynamical properties of self-assembling macromolecules allowed us to calculate the energy barrier (Ea) of dissociation from the temperature dependences of relaxation times of Debye and structural processes. We found Ea ∼ 19.4 ± 0.8 and 5.3 ± 0.4 kJ/mol for the former and latter systems, respectively. On the other hand, FTIR data analyzed within the van’t Hoff relationship yielded the energy barriers for dissociation Ea ∼ 20.3 ± 2.1 and 12.4 ± 1.6 kJ/mol for 2EHOH and nBOH, respectively. Hence, there was almost a perfect agreement between the values of Ea estimated from dielectric and FTIR studies for the 2EHOH, while some notable discrepancy was noted for the second alcohol. A quite significant difference in the activation barrier of dissociation indicates that there are probably supramolecular clusters of varying geometry or a ring-chain-like equilibrium is strongly affected in both alcohols. check details Nevertheless, our analysis showed that the association/dissociation processes undergoing within nanoassociates are one of the main factors underlying the molecular origin of the Debye process, supporting the transient chain model.