Electrochemical Behavior and Analytical Performance of an Iridium-Based Ultramicroelectrode Array (UMEA) Sensor

The electrochemical behavior of an iridium-based ultramicroelectrode array (UMEA) sensor was studied by cyclic voltammetry and chronoamperometry. At a ratio of interelectrode distance to electrode diameter of 14, the UMEA maintains the advantageous properties of individual microelectrodes. The analytical performance of the UMEA sensor was investigated using square wave anodic stripping voltammetry (SWASV). Analytical precision was found to be ±0.12µgL^–1 for Pb and ±0.14µgL^–1 for Cd (1s) based on 50 repetitive measurements of 1.00µgL^–1 Cd and Pb in a 0.02M acetate solution (pH = 4.5). Detection limits below ppb level were obtained for different heavy metals such as Cd, Pb, and Cu. Instrumental parameters were optimized and interferences were investigated. The UMEA sensor was applied to the analysis of heavy metals in river water, and the results were validated by high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS).     

The automorphism group of a coded system

We give a general construction of coded systems with an automorphism group isomorphic to where is any preassigned group which has a ``continuous block presentation' (the isomorphism will map the shift to . Several applications are given. In particular, we obtain automorphism groups of coded systems which are abelian, which are finitely generated and one which contains . We show that any group which occurs as a subgroup of the automorphism group of some subshift with periodic points dense already occurs for some synchronized system.

     

Modular PROTAC Design for the Degradation of Oncogenic BCR‐ABL

Proteolysis Targeting Chimera (PROTAC) technology is a rapidly emerging alternative therapeutic strategy with the potential to address many of the challenges currently faced in modern drug development programs. PROTAC technology employs small molecules that recruit target proteins for ubiquitination and removal by the proteasome. The synthesis of PROTAC compounds that mediate the degradation of c‐ABL and BCR‐ABL by recruiting either Cereblon or Von Hippel Lindau E3 ligases is reported. During the course of their development, we discovered that the capacity of a PROTAC to induce degradation involves more than just target binding: the identity of the inhibitor warhead and the recruited E3 ligase largely determine the degradation profiles of the compounds; thus, as a starting point for PROTAC development, both the target ligand and the recruited E3 ligase should be varied to rapidly generate a PROTAC with the desired degradation profile.     

CrAsH-quantum dot nanohybrids for smart targeting of proteins

Smart nanohybrids were prepared by conjugation of CrAsH to hydrosoluble and biocompatible quantum dots (QDs). The resulting probes were shown to bind efficiently and selectively to Cys-tagged proteins. The interaction with the protein was detected by an increase of the fluorescence emission of CrAsH. While the latter faded rapidly under continuous excitation, emission of the QD remained unaffected. The persistent fluorescence of the QD should thus allow extended monitoring of the target protein.     

Indenyl zirconium dinitrogen chemistry: N2 coordination to an isolated zirconium sandwich and synthesis of side-on, end-on dinitrogen compounds

Exposure of the isolable zirconocene sandwich compounds, (eta(5)-C5Me5)(eta(5)-C9H5-1-R(1)-3-R(2))Zr (R(1) = Me, (i)Pr, (t)Bu; R(2) = Me) to one atmosphere of dinitrogen resulted in N2 coordination. X-ray diffraction and NMR spectroscopy establish that the resulting dimeric dinitrogen compounds contain an unusual mu2,eta(2)-bridging indenyl ring and a weakly activated N2 ligand. N2 coordination from the isolable zirconium sandwich compounds is extremely sensitive to the number and size of the indenyl subsituents. Compounds bearing two [(i)Pr] or three methyl substituents are stable as eta(9) sandwich compounds for weeks under dinitrogen likely due to the inability to dimerize through a two-atom N2 bridge. Performing the reduction of (eta(5)-C5Me5)(eta(5)-C9H5-1-R(1)-3-R(2))ZrCl2 (R(1) = (i)Pr, (t)Bu; R(2) = Me; R(1) = R(2) = SiMe3) under an N2 atmosphere produced a different outcome; rare examples of side-on, end-on zirconium dinitrogen compounds were isolated and in one case, crystallographically characterized. Protonolysis studies with weak Br?nsted acids were used to evaluate the relative activation of the bridging dinitrogen ligands.     

Metabolism of a sulfur-containing heteroarotionoid antitumor agent, SHetA2, using liquid chromatography/tandem mass spectrometry

SHetA2 {[(4-nitrophenyl)amino][2,2,4,4-tetramethylthiochroman-6-yl)amino]methanethione], NSC 726189}, a sulfur-containing heteroarotinoid, selectively inhibits cancer cell growth and induces apoptosis without activation of nuclear retinoic acid receptors (RARs). The objective of this study was to investigate its in vitro metabolism in rat and human liver microsomes and in vivo metabolism in the mouse and rat using liquid chromatography-ultraviolet/multi-stage mass spectrometry (LC-UV/MS(n)) on an ion-trap mass spectrometer coupled with a photo-diode array (PDA) detector. In vitro, in the absence of glutathione (GSH), oxidation of the four aliphatic methyl groups of SHetA2 yielded one mono-, two di-, and one tri-hydroxylated SHetA2 metabolites, which were identified based on their UV and multi-stage mass spectra. In the presence of GSH, in addition to these primary oxidative metabolites, four GSH adducts of SHetA2 and a novel rare form thioether GSH adduct was detected and characterized. In vivo, the monohydroxylated SHetA2 metabolites were also detected in mouse and rat plasma and two GSH adducts were detected in rat liver following intravenous (i.v.) bolus administration of SHetA2 at 40 mg/kg.     

Lipase‐Catalyzed Ring‐Opening Polymerization of 3(S)‐sec‐Butylmorpholine‐2,5‐dione

Lipase‐catalyzed ring‐opening bulk polymerizations of 3(S)‐sec‐butylmorpholine‐2,5‐dione (BMD) were investigated. Selected commercial lipases were screened as catalysts for BMD polymerization at 110°C. Polymerizations catalyzed with 10 wt.‐% of lipase PPL and PC result in BMD conversions of about 70% and in molecular weights of the products ranging from 5 500 to 10 700. Lipases MJ, CR and ES showed lower catalytic activities for the polymerization of BMD. Poly(3‐sec‐butylmorpholine‐2,5‐dione) has a carboxylic acid group at one end and a hydroxy group at the other end. During the polymerization racemization of the isoleucine residue takes place. Lipase PPL was selected for a more detailed study. The apparent rate of polymerization increases with increasing PPL concentration when the polymerization temperature is 110°C. When the PPL concentration is 5 and 10 wt.‐% with respect to the monomer, a conversion of about 70% is reached after 5 d and 3 d, respectively, while for a PPL concentration of 1 wt.‐% the conversion is less than 7% even after 6  d. High concentrations of PPL (10 wt.‐%) result in high M_n values (< 4  d). The highest molecular weight poly(BMD), M_n = 19 900, resulted from a polymerization conducted at 120°C with 5 wt.‐% PPL for 6 d. The general trend observed by varying the polymerization temperature is as follows: (i) monomer conversion and M_n increase with increasing reaction temperature from 110 to 125°C, (ii) monomer conversion and M_n decrease with an increase in reaction temperature from 125 to 130°C. Water content was found to be an important factor that controls both the conversion and the molecular weight. With increasing water content, enhanced polymerization rates are achieved while the molecular weight of poly(BMD) decreases.