To facilitate the data interpretation, positive and negative polarity ToF-SIMS image data were transformed into a single hyperspectral data set and analyzed using principal component analysis. The combination of a novel protocol and the use of multivariate data analysis allowed us to discover new marker ions that are attributable to leucodopachrome, a metabolite specific to the biosynthesis of eumelanin. The described methodology may be adapted for the investigation of other classes of molecules in frozen tissues from zebrafish and other organisms.A growing number of copper(II) complexes have been identified as suitable candidates for biomedical applications. Here, we show that the biocompatibility and stability of copper(II) complexes can be tuned by directed ligand design and complex geometry. We demonstrate that azamacrocycle-based chelators that envelope copper(II) in a five-coordinate, distorted trigonal-bipyramidal structure are more chemically inert to redox-mediated structural changes than their six-coordinate, Jahn-Teller-distorted counterparts, as evidenced by electrochemical, crystallographic, electron paramagnetic resonance, and density functional theory studies. We further validated our hypothesis of enhanced inertness in vitro and in vivo by employing Cu-64 radiolabeling of bifunctional analogues appended to a prostate-specific membrane antigen targeting dipeptide. The corresponding Cu-64 complexes were tested for stability in vitro and in vivo, with the five-coordinate system demonstrating the greatest metabolic stability among the studied picolinate complex series.Research on heterogeneous single-atom catalysts (SACs) has become an emerging frontier in catalysis science because of their advantages in high utilization of noble metals, precisely identified active sites, high selectivity, and tunable activity. Graphene, as a one-atom-thick two-dimensional carbon material with unique structural and electronic properties, has been reported to be a superb support for SACs. Herein, we provide an overview of recent progress in investigations of graphene-based SACs. Among the large number of publications, we will selectively focus on the stability of metal single-atoms (SAs) anchored on different sites of graphene support and the catalytic performances of graphene-based SACs for different chemical reactions, including thermocatalysis and electrocatalysis. We will summarize the fundamental understandings on the electronic structures and their intrinsic connection with catalytic properties of graphene-based SACs, and also provide a brief perspective on the future design of efficient SACs with graphene and graphene-like materials.Temephos is an organophosphorothioate (OPT) larvicide used for controlling vectors of diseases such as dengue, chikungunya, and Zika. OPTs require a metabolic activation mediated by cytochrome P540 (CYP) to cause toxic effects, such as acetylcholinesterase (AChE) activity inhibition. There is no information about temephos biotransformation in humans, and it is considered to have low toxicity in mammals. Recent studies have reported that temephos-oxidized derivatives cause AChE inhibition. The aim of this study was to propose the human biotransformation pathway of temephos using in silico tools. The metabolic pathway was proposed using the MetaUltra program of MultiCase software as well as the Way2Drug and Xenosite web servers. The results show the following three essential reactions of phase I metabolism (1) S-oxidation, (2) oxidative desulfurization, and (3) dephosphorylation, as well as the formation of 19 possible intermediary metabolites. Temephos dephosphorylation is the most likely reaction, and it enables phase II metabolism for glucuronidation to be excreted. However, the CYP-dependent metabolism showed that temephos oxon can be formed, which could lead to toxic effects in mammals. CYP2B6, 2C9, and 2C19 are the main isoforms involved in temephos metabolism, and CYP3A4 and 2D6 have minor contributions. According to computational predictions, the highest probability of temephos metabolism is dephosphorylation and phase II reactions that do not produce cholinergic toxic effects; nonetheless, the participation of CYPs is highly possible if the primary reaction is depleted.Introducing trifluoromethyl groups is a common strategy to improve the properties of biologically active compounds. However, N-trifluoromethyl moieties on amines and azoles are very rarely used. To evaluate their suitability in drug design, we synthesized a series of N-trifluoromethyl amines and azoles, determined their stability in aqueous media, and investigated their properties.  https://www.selleckchem.com/products/ver155008.html  We show that N-trifluoromethyl amines are prone to hydrolysis, whereas N-trifluoromethyl azoles have excellent aqueous stability. Compared to their N-methyl analogues, N-trifluoromethyl azoles have a higher lipophilicity and can show increased metabolic stability and Caco-2 permeability. Furthermore, N-trifluoromethyl azoles can serve as bioisosteres of N-iso-propyl and N-tert-butyl azoles. Consequently, we suggest that N-trifluoromethyl azoles are valuable substructures to be considered in medicinal chemistry.An approach to access functionalized 3,4-dihydro-1,3-oxazin-2-ones has been developed by reacting semicyclic N,O-acetals 5 and 6 with ynamides 7 or terminal alkynes 8 in a one-pot fashion. The reaction went through a formal [4 + 2] cycloaddition process to generate a number of functionalized 3,4-dihydro-1,3-oxazin-2-ones 9a-9ak and 10a-10bc in yields of 34-97%. In addition, the utility of this transformation was demonstrated by the synthesis of (±)-sedamine 13.Surimi gel is a commonly found gelled product in Japan. Disintegration of the surimi gel is mainly caused by proteolytic degradation of the myosin heavy chain (MHC) under an inappropriate heating process. Many studies have reported the decrease in MHC in the disintegrated surimi gel but the mechanistic details of this degradation remain unclear. This study employed peptidomic analysis of disintegrated surimi gels from deep-sea bonefish Pterothrissus gissu to reveal the MHC cleavage causing gel disintegration. More peptides derived from an MHC rod were found in the disintegrated P. gissu surimi gels than in the integrated gel. Most MHC peptides were derived from the Src homology 3 domain or near the skip residues. The results of the terminome analysis suggest that the catalytic type of the proteases is responsible for light meromyosin cleavage activated at ∼35 °C. These results showed the temperature-dependent cleavage of the MHC rod, causing disintegration of the P. gissu surimi gel.