The Un(f)told Story of General Anesthesia

Abstract

Inhalational anesthetics are routinely employed in clinical practice to accomplish general anesthesia. Concerns have recently emerged regarding the deleterious impact of these volatile agents on cognitive performance, immune functions, and tumor recurrence and metastasis. These agents have been shown to modify the gene-expression pattern as well as cell signaling in tumor cells, but the underlying molecular mechanisms remain a matter of conjecture. Regulatory/signaling proteins either of cytosolic or membrane origin abundantly contain intrinsically disordered sequences, the conformational pliability of which is pivotal in their biological functions. It is well known that chloroform (an anesthetic itself), trifluoroethanol, hexafluoroisopropanol, and related haloalcohols markedly affect the structure of disordered proteins and protein regions by inducing folding, misfolding, or even aggregation. Taking into consideration the physicochemical similarities and protein interaction modes of these volatile solvents and inhaled anesthetics, it is postulated that administration of these drugs can also modify the secondary structure of disordered protein segments. Accordingly, pharmacological effects of anesthetics may, at least in part, be mediated by conformational perturbations of intrinsic disorder-based regulatory protein networks of cells.

Resonance Raman optical activity of zeaxanthin aggregates

“…The bisignate ECD bands at 515, 479 and 419 nm do not coincide with the maxima of the vibrational components in the absorption spectrum. The ECD bands of J aggregate are a result of the chiral exciton coupling, which is greatly different from that observed in H aggregate and come from the vibrionic components, which split individually . On the other hand, the sequence of ECD bands suggests the direction of packing arrangements for each type of aggregate .…”

“…Thus, the typical spectral changes that have been observed result from the arrangement of monomers into the aggregate structure, as well as from weak and reversible interactions like hydrogen bonds, van der Waals forces, π–π stacking and hydrophobic effects. Prior studies have highlighted the hydrogen bonding as a valid factor in the formation of carotenoid's H aggregate, especially in the case of ZXT and LUT . The hypothesis is affirmed by the fact that the formation of ZXT aggregates can be monitored by changing pH.…”

“…An increase of pH causes deprotonation of the terminal hydroxyl groups, so ZXT molecules are not able to create hydrogen bonds, which in turn favours aggregation of the J self‐assemblies . Moreover, the importance of the hydrogen bonding also confirms the fact that esterification of xanthophylls leads to the formation of the J aggregate rather than the blue‐shifted H aggregate like in the case of the LUT derivatives packing arrangements . Besides, the π,π stacking of polyene chains is strongly involved in the structure of H formation .…”

“…Unlike the monomer, the ECD spectrum of H arrangement occurs within the absorption band and passes through zero near the UV–Vis maximum. The narrow, blue‐shifted Cotton couplets at 395 and 377 nm may be explained from the exciton interaction between the closely packed carotenoid molecules . Upon aggregation, the excited‐state levels of monomers split in two as a result of the two possible orientations of the electronic transition moments of the polyene chains: in phase (allowed) and out of phase (forbidden).…”

Study and Modeling of Extraction Properties of Fluoroorganic Solvents in Regard to Low-Polar Biologically Active Substances From Plant Raw Materials

“…The analysis of the literature revealed that at the moment, fluoroorganic solvents of a new generation have appeared on an industrial scale in Russia; they have the advantages in a number of parameters in comparison to liquefied gases and supercritical fluids. Some fundamental parameters of fluoroorganic solvents and liquefied gases (from the technological point view) are presented in Table I [8][9][10][11][12][13]. As can be seen from the data in Table I, fluoroorganic solvents in many physical, chemical, environmental, and toxicological parameters do not differ very much from freons, but are inferior to carbon dioxide.…”