The selective binding of six (S)-quinuclidine-triazoles and their (R)-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes α3β4 and α7, respectively, were analyzed by in silico docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary β4-subunit of the α3β4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the α3β4 selectivity of the quinuclidine-triazole chemotype, explaining the 47–327-fold affinity of the (S)-enantiomers as compared to their (R)-enantiomer counterparts. Regarding the α7 nAChR subtype, the amino acids promoting a however significantly lower preference for the (R)-enantiomers were the conserved TyrA93, TrpA149 and TrpB55 residues. The non-conserved amino acid residue in the complementary subunit of nAChR subtypes appeared to play a significant role for the nAChR subtype-selective binding, particularly at the heteropentameric subtype, whereas the conserved amino acid residues in both principal and complementary subunits are essential for ligand potency and efficacy.
α3β4 Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α3β4 nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, (S)-QND8 and (S)-T2, for the development of an α3β4 nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a p-hydroxyl motif for ligand-receptor binding affinity. Four (R)- and (S)-quinuclidine-triazole (AK1-AK4) were synthesized and the binding affinity, together with selectivity to α3β4 nAChR subtype, were determined by competitive radioligand binding assay using [3H]epibatidine as a radioligand. Among all modified compounds, AK3 showed the highest binding affinity and selectivity to α3β4 nAChR with a Ki value of 3.18 nM, comparable to (S)-QND8 and (S)-T2 and 3069-fold higher affinity to α3β4 nAChR in comparison to α7 nAChR. The α3β4 nAChR selectivity of AK3 was considerably higher than those of (S)-QND8 (11.8-fold) and (S)-T2 (294-fold). AK3 was shown to be a promising α3β4 nAChR tracer for further development as a radiotracer for drug addiction.
20 July 2021 in Environment and Natural Resources Journal
Recently, levels of air pollution caused by exhaust gases from infectious waste combustion have been rising at a startling rate. Pollutant gases such as carbon monoxide (CO) and nitrogen dioxide (NO2) have numerous health implications when unsafe amounts are released into the atmosphere. Thus, Pollution Control Systems (PCS) and Gas Cleaner Systems (GCS) play an important role in industries and the monitoring of incinerators. This research evaluated the GCS of rotary kilns in medical facilities located in the Northeast of Thailand. Data was collected from various sites, analyzed, and examined. Furthermore, Ozone (O3) technology was applied to the rotary kiln allowing for the collection of new information on the pollution treatment systems. O3 technology was installed along with the Wet Scrubber System (WSS) catalyzing the oxidation of O3 and pollutant gases. In addition, a chiller was added to control and stabilize the temperature of the water. After the water temperature was controlled, the concentration of O3 increased resulting in an efficient pollution treatment system. Levels of pollutant gas emission were found to be beneath control standards of both Thailand and those of the U.S. EPA. TSP content was reduced significantly from 22.0 mg/m³ to 3.4 mg/m³ (97%), CO content from 13.6 mg/m³ to 1.7 mg/m³ (96%), and NO₂ content fell from 16.3 (mg/m³) to 2.0 mg/m³ (99%). It is clear that the rotary kiln and Ozone technology should be used together in order to create a new and far more effective method of pollution treatment in small and mid-sized cities of Thailand.
An ever-increasing demand for electrical power and soaring levels of energy consumption around the world have led to an energy crisis. Thus, this paper aims to review the conventional technologies against those of newer developments in electrical power generation such as using nitrogen generators. The nitrogen generator method is most appealing as it is a seemingly free energy already existing in nature. A nitrogen generator with a 5000 (Nm3/h) capacity has the potential to be used to analyze gas composition and the results are compared with the gas composition of a conventional steam turbine, which is used to pressurize 6000 (kWh) injection steam turbines. The magnetic bearing must be installed in both systems to modify all centrifuged systems which reduces all energy consumption in all systems by more than 50%. Artificial intelligence is used with the machine to analyze and control nitrogen gas flow to provide a more precise evaluation resulting in a more efficient technology. It should further be noted that the nitrogen turbine is superior to the steam turbine because it does not require the burning of fossil fuel to generate power. Hence, it is crucial to modify conventional technologies to improve energy sustainability and begin the long task of tackling environmental issues.