A cation-pi binding interaction with a tyrosine in the binding site of the GABAC receptor

GABA(C) (rho) receptors are members of the Cys-loop superfamily of neurotransmitter receptors, which includes nicotinic acetylcholine (nACh), 5-HT(3), and glycine receptors. As in other members of this family, the agonist binding site of GABA(C) receptors is rich in aromatic amino acids, but while other receptors bind agonist through a cation-pi interaction to a tryptophan, the GABA(C) binding site has tyrosine at the aligning positions. Incorporating a series of tyrosine derivatives at position 198 using unnatural amino acid mutagenesis reveals a clear correlation between the cation-pi binding ability of the side chain and EC(50) for receptor activation, thus demonstrating a cation-pi interaction between a tyrosine side chain and a neurotransmitter. Comparisons among four homologous receptors show variations in cation-pi binding energies that reflect the nature of the cationic center of the agonist.     

Application of ultra-performance liquid chromatography-tandem mass spectrometry for the determination of steroid oestrogens in wastewaters

An ultra-performance liquid chromatography method using a triple quadrupole mass spectrometer was developed and validated for the determination of steroid oestrogens in wastewater matrices. To date, analytical methods established in the literature for 17α-ethinylestradiol have been unable to achieve the proposed predicted no effect concentration of 0.1?ng?l^?1. The extensive sample pretreatment and analytical methodology proposed herein enable 17α-ethinylestradiol to be determined at very low background concentrations with a theoretical method detection limit of 0.06?ng?l^?1 which has been applied in real environmental matrices. During the validation process, a trickling filter wastewater treatment works was monitored to demonstrate the method's application. Oestrogen removal across the filters demonstrated good removals of natural free oestrogens (≥62.0%) with lower removals of the synthetic oestrogen 17α-ethinylestradiol (29.2%) from wastewaters at 10°C. The method's application illustrates its capability of detecting oestrogen concentrations in real wastewater samples comprising complex organics of comparatively high concentration. Furthermore, a complete process mass balance for 17α-ethinylestradiol is now attainable which has previously posed a challenge owing to the low environmental concentrations typically exhibited, but more significantly as a result of the lower sensitivity inherent in previously reported analytical methods.     

Matrix Infrared Spectroscopy and Quantum‐Chemical Calculations for the Coinage‐Metal Fluorides: Comparisons of Ar?AuF,Ne?AuF,and Molecules MF2 and MF3

The reactions of laser‐ablated Au, Ag, and Cu atoms with F₂ in excess argon and neon gave new absorptions in the M? F stretching region of their IR spectra, which were assigned to metal‐fluoride species. For gold, a Ng? AuF bond was identified in mixed neon/argon samples. However, this bonding was much weaker with AgF and CuF. Molecules MF₂ and MF₃ (M=Au, Ag, Cu) were identified from the isotopic distribution of the Cu and Ag atoms, comparison of the frequencies for three metal fluorides, and theoretical frequency calculations. The AuF₅ molecule was characterized by its strongest stretching mode and theoretical frequency calculations. Additional evidence was observed for the formation of the Au₂F₆ molecule.     

Are Words the Quanta of Human Language? Extending the Domain of Quantum Cognition

In previous research, we showed that ‘texts that tell a story’ exhibit a statistical structure that is not Maxwell–Boltzmann but Bose–Einstein. Our explanation is that this is due to the presence of ‘indistinguishability’ in human language as a result of the same words in different parts of the story being indistinguishable from one another, in much the same way that ’indistinguishability’ occurs in quantum mechanics, also there leading to the presence of Bose–Einstein rather than Maxwell–Boltzmann as a statistical structure. In the current article, we set out to provide an explanation for this Bose–Einstein statistics in human language. We show that it is the presence of ‘meaning’ in ‘texts that tell a story’ that gives rise to the lack of independence characteristic of Bose–Einstein, and provides conclusive evidence that ‘words can be considered the quanta of human language’, structurally similar to how ‘photons are the quanta of electromagnetic radiation’. Using several studies on entanglement from our Brussels research group, we also show, by introducing the von Neumann entropy for human language, that it is also the presence of ‘meaning’ in texts that makes the entropy of a total text smaller relative to the entropy of the words composing it. We explain how the new insights in this article fit in with the research domain called ‘quantum cognition’, where quantum probability models and quantum vector spaces are used in human cognition, and are also relevant to the use of quantum structures in information retrieval and natural language processing, and how they introduce ‘quantization’ and ‘Bose–Einstein statistics’ as relevant quantum effects there. Inspired by the conceptuality interpretation of quantum mechanics, and relying on the new insights, we put forward hypotheses about the nature of physical reality. In doing so, we note how this new type of decrease in entropy, and its explanation, may be important for the development of quantum thermodynamics. We likewise note how it can also give rise to an original explanatory picture of the nature of physical reality on the surface of planet Earth, in which human culture emerges as a reinforcing continuation of life.     

Open access atmospheric pressure chemical ionization Mass spectrometry for routine sample analysis

We report the introduction and use of an atmospheric pressure chemical ionization liquid chromatography-mass spectrometry instrument that has been designed specifically for use by the synthetic chemist on an open access, walk-in basis. This instrument has been configured with an easy-to-use sample log-in terminal that requires the user to provide only a sample identification number and a user name. Sample analysis takes approximately 4 min and provides the synthetic and medicinal chemist with rapid and reliable mass spectrometry analysis. Since installation of the system, it has analyzed an average of about 80 samples per day and has the capacity to run over 100 samples per day without the intervention of a specialist operator. This capability has eliminated the need for an operator to analyze routine samples and allows the mass spectroscopist more time to deal with problem solving.     

Infrared spectrum of the novel electron-deficient BH(4) radical in solid neon

Laser-ablated boron reacts with hydrogen on condensation in excess neon to give BH4 radical, BH4- anion, and B2H6 as the major products. Identifications are based on 10B and D substitution, DFT frequency calculations, and comparison to previous spectra. Infrared spectra of BH4 support the C2v structure deduced from previous ESR spectra and theoretical calculations with two normal B-H bonds and two long B-H bonds for this novel electron-deficient radical. NBO analysis suggests that the two long B-H bonds and the H- -H bond are one-electron bonds.     

A perturbed pK(a) at the binding site of the nicotinic acetylcholine receptor: implications for nicotine binding

A series of tethered quaternary ammonium derivatives of Tyr have been incorporated into the binding site of the nicotinic acetylcholine receptor (nAChR) using the in vivo nonsense suppression method, producing constitutively active (self-gating) receptors. We have incorporated primary, secondary, and tertiary amine tethered agonists to give receptors whose constitutive activity can be modulated by pH. Lowering the pH protonates the tethered amine, giving it a positive charge and allowing it to reversibly activate the receptor. Tertiary and secondary tethered amines, TyrO3T and TyrO3S, have been successfully incorporated at alpha149 in the nAChR. Constitutive currents at pH 5.5 are 6 times those at pH 9.0. The pKa of TyrO3T in the binding site appears to be 6 or lower, differing substantially from its pKa in solution ( approximately 9.3). This local pKa perturbation has substantial implications for pharmacological research on the nAChR: of the tertiary agonists considered, noracetylcholine experiences this pKa perturbation, while nicotine does not.