Ionic liquids (ILs) are considered in the majority of cases green solvents, due to their virtually null vapor pressure and to the easiness in recycling them. In particular, imidazolium ILs are widely used in many fields of Chemistry, as solvents or precursors of N-heterocyclic carbenes (NHCs). The latter are easily obtained by deprotonation of the C2-H, usually using strong bases or cathodic reduction. Nevertheless, it is known that weaker bases (e.g., triethylamine) are able to promote C2-H/D exchange. From this perspective, the possibility of deprotonating C2-H group of an imidazolium cation by means of a basic counter-ion was seriously considered and led to the synthesis of imidazolium ILs spontaneously containing NHCs. The most famous of this class of ILs are N,N'-disubstituted imidazolium acetates. Due to the particular reactivity of this kind of ILs, they were appointed as “organocatalytic ionic liquids” or “proto-carbenes.” Many papers report the use of these imidazolium acetates in organocatalytic reactions (i. e., catalyzed by NHC) or in stoichiometric NHC reactions (e.g., with elemental sulfur to yield the corresponding imidazole-2-thiones). Nevertheless, the actual presence of NHC in N,N'-disubstituted imidazolium acetate is still controversial. Moreover, theoretical studies seem to rule out the presence of NHC in such a polar environment as an IL. Aim of this Mini Review is to give the reader an up-to-date overview on the actual or potential presence of NHC in such an “organocatalytic ionic liquid,” both from the experimental and theoretical point of view, without the intent to be exhaustive on N,N'-disubstituted imidazolium acetate applications.
The electrochemical oxidation of theophylline was investigated by controlled potential electrolysis in two different organic solvents and in water for comparison. The anodic oxidation was monitored by cyclic voltammetry in situ and UV‐Vis spectrophotometry ex situ and the final electrolyzed solutions were analyzed by tandem mass spectrometry after chromatographic separation with an HPLC‐PDA‐ESI‐MS/MS system. The main oxidation products evidenced as the main diode array chromatographic peaks were tentatively assigned to dimeric forms of theophylline, two of which have never been reported before, on the base of retention time, UV‐Vis spectrum, m/z ratio in both positive and negative ESI modes and fragmentation pattern. Two chemical paths following the primary mono‐electronic anodic oxidation of theophylline to the final evidenced oxidation products have been proposed.
The cathodic reduction of dicationic imidazolium bromides, whose spacer is either an aliphatic chain or a xylyl group, leads to the formation of the corresponding N‐heterocyclic carbenes (NHCs), which were isolated as the corresponding thiones, after reaction with elemental sulfur. The behaviour of the dications was compared with the corresponding monocations. The behaviour of dicarbenes depends on the nature of the spacer. This study evidenced that dicarbenes deriving from xylyl dications are less stable than the corresponding aliphatic ones (giving lower yields in thiones), due to a debenzylation reaction. On the other hand, the yields in thiones starting from aliphatic dications are higher than the corresponding monocations, suggesting a cooperative reduction at the electrode of the two imidazolium moieties. The cathodic process was confirmed using the co‐electrogenerated hydrogen to reduce 2,2,2‐trifluoroacetophenone to the corresponding alcohol.
Persistent HIV infection requires lifelong treatment and among the 2.1 million new HIV infections that occur every year there is an increased rate of transmitted drug-resistant mutations. This fact requires a constant and timely effort in order to identify and develop new HIV inhibitors with innovative mechanisms. The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only viral encoded enzyme that still lacks an efficient inhibitor despite the fact that it is a well-validated target whose functional abrogation compromises viral infectivity. Identification of new drugs is a long and expensive process that can be speeded up by methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15 inhibited the RNase H function below 100 μM with three hits exhibiting IC values <10 μM. The most active compound, , inhibits HIV-1 RNase H with an IC of 5.1 μM and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly identified compounds; for instance, compound involves extensive interactions with a lipophilic pocket formed by Ala502, Lys503, and Trp (406, 426 and 535) and polar interactions with Arg557 and the highly conserved RNase H primer-grip residue Asn474. The structural insights obtained from this work provide the bases for further lead optimization.
We discovered novel and selective sulfonamides/amides acting as inhibitors of the a-carbonic anhydrase\ud
(CA, EC 188.8.131.52) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is\ud
the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present\ud
at a high concentration. The secondary sulfonamides and amides investigated here were potent, low\ud
nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in\ud
the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with\ud
a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment
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