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Trimeric Scaffold Ligand-Gated Ion Channels
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Xiao-Na Yang, Si-Yu Wang, Jin Wang, Ye Yu
Enriching many acidic residues in the extracellular domain produces many protonation/deprotonation sites. Previous studies have figured out that four interaction pairs of residues participate in protonation through carboxyl-carboxyl interaction: D238-D350, E239-D346, and E220-D408 (cASIC1 numbering) that are located in the acidic pocket, as well as the E80-E417 pair in the lower palm domain (42,55). The acidic pocket is formed by residues from the thumb, finger, and β-ball, including several negative-charged amino acid side chains (42) (Figure 3.4A,B). As revealed by the desensitized ASIC crystal structures, these four pairs of amino acids are protonated under acidic conditions (55,56). Mutations carried out in these regions could significantly shift the curve of the pH-dependent response of ASIC (42,57,58). However, recent researches have shown that despite mutating residues of the acidic pocket being capable of altering pH dependence, ASIC still could be activated and desensitized regardless of studies from biochemical or computational approaches, suggesting that instead of an acidic pocket dispensable for acid activation, there are other protonation/deprotonation sites existing in the ASIC channels (59).
Application of Bioresponsive Polymers in Drug Delivery
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Manisha Lalan, Deepti Jani, Pratiksha Trivedi, Deepa H. Patel
A pH-responsive micelle was designed for oral application using poly(ethylene glycol)-b-poly(alkyl acrylate-co-methacrylic acid) (PEG-b-P(AlA-co-MAA)). The micelle core which was hydrophobic becomes hydrophilic on deprotonation. The deprotonation also destabilizes the assembly [37].
Glutathione, Cysteine, and the Neuromelanin Pathway : Potential Roles in the Pathogenesis of Parkinson’s Disease—a New Hypothesis
Published in Christopher A. Shaw, Glutathione in the Nervous System, 2018
Glutathione (GSH) also diverts and, at sufficiently high concentrations, blocks the oxidation of DA to insoluble indolic melanin polymer by initially scavenging DA-o-quinone to give 5-S-Glu-DA (Fig. 5) (Zhang and Dryhurst 1995a). The latter conjugate is more easily oxidized than DA to give o-quinone 14, which reacts with free GSH to give 2,5-bis-S-Glu-DA, an even more easily oxidized compound. The resulting o-quinone 15 can then react by several pathways. Nucleophilic addition of GSH gives 2,5,6-tri-S-Glu-DA. Deprotonation gives 16, which cyclizes to 2,5-bis-S-glutathionyl-5,6-dihydroxyindoline (17), which is very easily oxidized to p-quinone imine 18. Rearrangement (aromatization) of 18 then gives 4,7-bis-S-glutathionyl-5,6-dihydroxyindole (19). Ortho-quinone 15 also tautomerizes to p-quinone methide 20, which serves as the precursor of glutathionyl conjugates 21 and 23 containing glutathionyl residues substituted at the β-position of the ethylamino side chain of DA.
Synthesis and in vivo evaluation of three fluid spray dried hybrid ciprofloxacin microparticles in Sprague Dawley rats
Published in Pharmaceutical Development and Technology, 2023
Dina Dashty Mudher, Heshu Sulaiman Rahman, Sadat Abdulla Aziz, Amanpreet Kaur, Tareq Zeyad Bahjat, Hisham Al-Obaidi
To confirm the above findings, the samples were further analysed to assess molecular interactions and surface morphology. As can be seen in Figure 3, the results showed broadening in carbonyl group stretching of CFX at 1612 cm−1. The ionised COO- can be seen as symmetric and asymmetric vibrations at 1585 and 1375 cm−1 respectively (Mohammed et al. 2020). Among assigned peaks, it is clear that there is a significant shift in peaks positions 1612, 1585, 1540, 1499, 1282 cm−1. CFX is known to exhibit a zwitterion behavior due to electronic cloud movement promoting ionization (Mohammed et al. 2020). This pattern, however, is altered when hydrogen bonds are formed minimising deprotonation. This suggests molecular interactions with the chitosan chain, which is rich with hydrogen bond donor groups.
Anastrozole and related glucuronic acid conjugate are electrophilic species
Published in Xenobiotica, 2022
Siyu Ding, Siyu Liu, Yaxuan Chen, Ying Peng, Jiang Zheng
Surprisingly, the ANA-derived GSH conjugate was also detected in the incubation mixture containing ANA, GSH and a buffer system. The observed spontaneous GSH conjugation suggests that ANA itself is an electrophilic species. Additionally, proton concentration (pH) was found to dramatically alter the rate of the reaction. Specifically, the efficiency of the spontaneous conjugation increased with the increase of pH value of the incubation system. The deprotonation (pH 10) of the sulfhydryl group facilitated the conjugation reaction, while the protonation (pH 4) proceeded in the opposite way. It may explain that the deprotonation by alkaline resulted in the development of sulfhydryl anion which is much more nucleophilic than free thiol group. The elevation of nucleophilicity accelerated the substitution reaction.
Feasible and eco-friendly removal of hexavalent chromium toxicant from aqueous solutions using chemically modified sugarcane bagasse cellulose
Published in Toxin Reviews, 2021
Ahmed Eleryan, Ahmed El Nemr, Abubakr M. Idris, Majed M. Alghamdi, Adel A. El-Zahhar, Tarek O. Said, Taher Sahlabji
The effect of pH on the removal efficiency of Cr(VI) by CST was studied in the range of 1.0–10.3. The results are shown in Figure 3(A). The highest removal percentage was recorded at pH 1.0, while the lowest removal percentage was recorded at pH 8.2. The effect of pH could be attributed to both Cr(VI) species and CST active sites. Low pH was found to significantly control the presence of negatively charged Cr(VI) species, namely CrO4−, Cr2O72−, Cr4O132−, and C3O102− (Demiral et al. 2008). On the other hand, the solution pH also affects the protonation and deprotonation of the CST active groups, which control the adsorption equilibrium and the reaction kinetics (Gurgel and Gil 2009a). The amino groups of TETA in CST have values of pKa1, pKa2, pKa3, and pKa4 of 0.32, 6.67, 9.20, and 9.92, respectively. Therefore, the amine groups in CST are protonated (associated to H3O+) and are positively charged at low pH. Therefore, the adsorption of Cr(VI) was increased at low pH by electrostatic interaction between adsorbent groups and Cr(VI) negative species (Gurgel and Gil 2009a). From another side, the ion-pair donation of the amino ligands is favorable at low pH, which also enhances the complexation of Cr(VI) with CST at low pH.