A novel carbon-11 radiolabelling methodology for the synthesis of the dialkylcarbonate functional group has been developed. The method uses cyclotron-produced short-lived [C]CO (half-life 20.4 min) directly from the cyclotron target in a one-pot synthesis. Alcohol in the presence of base trapped [C]CO efficiently forming an [C]alkylcarbonate intermediate that subsequently reacted with an alkylchloride producing the di-substituted [C]carbonate (34% radiochemical yield, determined by radio-HPLC) in 5 minutes from the end of [C]CO cyclotron delivery.

Pyrroloquinone ring systems are important structural units present in many biologically active molecules including a number of marine alkaloids. For example, they are found in a series of marine metabolites, such as tsitsikammamines, zyzzyanones, wakayin, and terreusinone. Several of these alkaloids have exhibited antimicrobial, antimalarial, antifungal, antitumor, and photoprotecting activities. Synthesis of pyrroloquinone unit is the key step in the synthesis of many of these important organic molecules. Here, we present a ceric (IV) ammonium nitrate (CAN) mediated oxidative free radical cyclization reaction of 1,3-dicarbonyl compounds with aminoquinones as a facile methodology for making various substituted pyrroloquinones. 1,3-dicarbonyl compounds used in this study are ethyl acetoacetate, acetylacetone, benzoyl acetone, and -dimethyl acetoacetamide. The aminoquinones used in this study are 2-(benzylamino)naphthalene-1,4-dione and 6-(benzylamino)-1-tosyl-1-indole-4,7-dione. The yields of the synthesized pyrroloquinones ranged from 23-91%.

The solvolyses of -tolyl chlorothionoformate and -chlorophenyl chlorothionoformate are studied in a variety of organic mixtures of widely varying nucleophilicity and ionizing power values. This solvolytic data is accumulated at 25.0 °C using the titration method. An analysis of the rate data using the extended (two-term) Grunwald-Winstein equation, and the concept of similarity of substrates based on their ratios, shows the occurrence of simultaneous side-by-side addition-elimination and unimolecular S1 mechanisms.

Diisopropylfluorophosphate (DFP) is a potent acetylcholinesterase inhibitor commonly used in toxicological studies as an organophosphorus nerve agent surrogate. However, LD values for DFP in the same species can differ widely even within the same laboratory, possibly due to the use of degraded DFP. The objectives here were to identify an efficient synthesis route for high purity DFP and assess the storage stability of both the in-house synthesized and commercial source of DFP at the manufacturer-recommended storage temperature of 4°C, as well as -10°C and -80°C. After 393 days, the commercial DFP stored at 4°C experienced significant degradation, while only minor degradation was observed at -10°C and none was observed at -80°C. DFP prepared using the newly identified synthesis route was significantly more stable, exhibiting only minor degradation at 4°C and none at -10°C or -80°C. The major degradation product was the monoacid derivative diisopropylphosphate, formed via hydrolysis of DFP. It was also found that storing DFP in glass containers may accelerate the degradation process by generating water as hydrolytically generated hydrofluoric acid attacks the silica in the glass. Based on the results here, it is recommended that DFP be stored at or below -10°C, preferably in air-tight, nonglass containers.

Protein degradation is a fundamental feature of cellular life, and malfunction of this process is implicated in human disease. Ubiquitin tagging is the best characterized mechanism of targeting a protein for degradation; however, there are a growing number of distinct mechanisms which have also been identified that carry out this essential function. For example, covalent tagging of proteins with sequestosome-1 targets them for selective autophagy. Degradation signals are not exclusively polypeptides such as ubiquitin, NEDD8, and sequestosome-1. Phosphorylation, acetylation, and methylation are small covalent additions that can also direct protein degradation. The diversity of substrate sequences and overlap with other pleotrophic functions for these smaller signaling moieties has made their characterization more challenging. However, these small signals might be responsible for orchestrating a large portion of the protein degradation activity in the cell. As such, there has been increasing interest in lysine methylation and associated lysine methyltransferases (KMTs), beyond canonical histone protein modification, in mediating protein degradation in a variety of contexts. This review focuses on the current evidence for lysine methylation as a protein degradation signal with a detailed discussion of the class of enzymes responsible for this phenomenon.