O-Acetylserine sulfhydrylase (isoform A, OASS-A) is a pyridoxal-5 0 -phosphate-dependent enzyme responsible for cysteine biosynthesis in many pathological microorganisms. It is proposed that inhibition of OASS-A could represent a novel strategy to overcome bacterial resistance to antibiotics. A class of 2-substituted-cyclopropane-1-carboxylic acids was synthesized, based on structural determinants grasped by analyzing a group of synthetic pentapeptides known to efficiently bind OASS-A from Haemophilus influenzae (HiOASS-A). The cyclopropane derivatives were submitted to a binding affinity assay with HiOASS-A and three of them, with K diss in the low micromolar range, showed higher affinity than the most active synthetic pentapeptide. Thus, in this communication we report the first example of potent non-natural small molecule inhibitors of HiOASS-A. In addition, a molecular modelling study suggested a possible inhibition mechanism, through which the new cyclopropane ligands block HiOASS-A. Noteworthily, the novel, small-sized, non-peptidic inhibitors retain the structural motifs of the bulky peptides, which are relevant for the enzyme inhibition.
Abstract. The chemical composition of ambient organic aerosols was analyzed using complementary mass spectrometric techniques during a field study in central Europe in July 2014 (Fichtelgebirge – Biogenic Emission and Aerosol Chemistry, F-BEACh 2014). Among several common biogenic secondary organic aerosol (BSOA) marker compounds, 93 acidic oxygenated hydrocarbons were detected with elevated abundances and were thus attributed to be characteristic for the organic aerosol mass at the site. Monoterpene measurements exhibited median mixing ratios of 1.6 and 0.8 ppbV for in and above canopy levels respectively. Nonetheless, concentrations for early-generation oxidation products were rather low, e.g., pinic acid (c = 4.7 (±2.5) ng m−3). In contrast, high concentrations were found for later-generation photooxidation products such as 3-methyl-1,2,3-butanetricarboxylic acid (MBTCA, c = 13.8 (±9.0) ng m−3) and 3-carboxyheptanedioic acid (c = 10.2 (±6.6) ng m−3), suggesting that aged aerosol masses were present during the campaign period. In agreement, HYSPLIT trajectory calculations indicate that most of the arriving air masses traveled long distances (> 1500 km) over land with high solar radiation. In addition, around 47 % of the detected compounds from filter sample analysis contained sulfur, confirming a rather high anthropogenic impact on biogenic emissions and their oxidation processes. Among the sulfur-containing compounds, several organosulfates, nitrooxy organosulfates, and highly oxidized organosulfates (HOOS) were tentatively identified by high-resolution mass spectrometry. Correlations among HOOS, sulfate, and highly oxidized multifunctional organic compounds (HOMs) support the hypothesis of previous studies that HOOS are formed by reactions of gas-phase HOMs with particulate sulfate. Moreover, periods with high relative humidity indicate that aqueous-phase chemistry might play a major role in HOOS production. However, for dryer periods, coinciding signals for HOOS and gas-phase peroxyradicals (RO2•) were observed, suggesting RO2• to be involved in HOOS formation.
The Fries, Beckmann, and Claisen rearrangements have been investigated in ionic liquid media. The effect of the structural elements of the latter on the direction of these rearrangements and the product yields has been studied.Imidazolium and pyridinium salts are currently the most widely studied and used ionic liquids (IL) in organic synthesis and they are often simultaneously used as solvent and catalyst in very varied reactions [1][2][3][4][5][6][7]. With careful choice of substituents in the heterocyclic cations and the type of anions in the IL it is possible to change the rate, direction, and even mechanism of many organic reactions. The effect of heterocyclic salt IL on molecular rearrangements is rarely represented in the chemical literature and that has prompted us to a systematic investigation in this direction. N N Me R R N R X + + X 1a-j 2a-d 1 2 --1ae R 1 = H, R 2 = Bu [bmim]; a X = Br, b X = Cl, c X = I, d X = BF 4 , e X = PF 6 ; fh R 1 = H, X = Br, f R 2 = Et [emim], g R 2 = C 6 H 13 [hmim], h R 2 = C 8 H 15 [omim]; i R 1 = Me, R 2 = Bu, X = Br [bmmim]; j R 1 = H, R 2 = Et, X = OMs; 2ac R = C 7 H 15 [C 7 Py]; a X = Br, b X = BF 4 , c X = PF 6 , d R = Me [mPy], X = OTs
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