Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Jmol
Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool, or for research e.g. in chemistry and biochemistry. It is written in the programming language Java, so it can run on the operating systems Windows, macOS, Unix, if Java is installed, it is free and open-source software released under a GNU Lesser General Public License version 2.0. A standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways. For example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a wide range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile, Chemical Markup Language. There is a JavaScript-only version, JSmol, that can be used on computers with no Java.
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
5-HT3 receptor
The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels and therefore differs structurally and functionally from all other 5-HT receptors receptors which are G protein-coupled receptors. This ion channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems; as with other ligand gated ion channels, the 5-HT3 receptor consists of five subunits arranged around a central ion conducting pore, permeable to sodium and calcium ions. Binding of the neurotransmitter 5-hydroxytryptamine to the 5-HT3 receptor opens the channel, which, in turn, leads to an excitatory response in neurons; the activating, inward current is predominantly carried by sodium and potassium ions. 5-HT3 receptors have a negligible permeability to anions. They are most related by homology to the nicotinic acetylcholine receptor; the 5-HT3 receptor differs markedly in structure and mechanism from the other 5-HT receptor subtypes, which are all G-protein-coupled.
A functional channel may be composed of five identical 5-HT3A subunits or a mixture of 5-HT3A and one of the other four 5-HT3B, 5-HT3C, 5-HT3D, or 5-HT3E subunits. It appears. All other subunit subtypes must heteropentamerize with 5-HT3A subunits to form functional channels. Additionally, there has not been any pharmacological difference found between the heteromeric 5-HT3AC, 5-HT3AD, 5-HT3AE, the homomeric 5-HT3A receptor. N-terminal glycosylation of receptor subunits is critical for subunit assembly and plasma membrane trafficking; the subunits surround a central ion channel in a pseudo-symmetric manner. Each subunit comprises an extracellular N-terminal domain which comprises the orthosteric ligand-binding site. Whereas extracellular domain is the site of action of agonists and competitive antagonists, the transmembrane domain contains the central ion pore, receptor gate, principle selectivity filter that allows ions to cross the cell membrane; the 5-HT3 receptor gene is located on human chromosomal region 11q23.1-q23.2.
It is similar in structure to the mouse gene, spread over ~ 13 kb. Four of its introns are in the same position as the introns in the homologous α7-acetylcholine receptor gene proving their evolutionary relationship. Additional genes that code for the subunits of the 5-HT3 receptor have been identified. HTR3A and HTR3B for the 5-HT3A and 5-HT3B subunits and in addition HTR3C, HTR3D and HTR3E genes encoding 5-HT3C, 5-HT3D and 5-HT3E subunits. HTR3C and HTR3E do not seem to form functional homomeric channels, but when co-expressed with HTR3A they form heteromeric complex with decreased or increased 5-HT efficacies; the pathophysiological role for these additional subunits has yet to be identified. Expression; the 5-HT3C, 5-HT3D and 5-HT3E genes tend to show peripherally restricted pattern of expression, with high levels in the gut. In human duodenum and stomach, for example, 5-HT3C and 5-HT3E mRNA might be greater than for 5-HT3A and 5-HT3B. Polymorphism. In patients treated with chemotherapeutic drugs, certain polymorphism of the HTR3B gene could predict successful antiemetic treatment.
This could indicate that the 5-HTR3B receptor subunit could be used as biomarker of antiemetic drug efficacy. The 5-HT3 receptor is expressed throughout the central and peripheral nervous systems and mediates a variety of physiological functions. On a cellular level, it has been shown that postsynaptic 5-HT3 receptors mediate fast excitatory synaptic transmission in rat neocortical interneurons and hippocampus, in ferret visual cortex. 5-HT3 receptors are present on presynaptic nerve terminals. There is some evidence for a role in modulation of neurotransmitter release, but evidence is inconclusive; when the receptor is activated to open the ion channel by agonists, the following effects are observed: CNS: nausea and vomiting center in brain stem, seizure propensity, pro-nociception PNS: neuronal excitation, emesis Agonists for the receptor include: Cereulide 2-methyl-5-HT Alpha-Methyltryptamine Bufotenin Chlorophenylbiguanide Ethanol Ibogaine Phenylbiguanide Quipazine RS-56812: Potent and selective 5-HT3 partial agonist, 1000x selectivity over other serotonin receptors SR-57227 Varenicline YM-31636 Antagonists for the receptor include: Antiemetics AS-8112 Granisetron Ondansetron Tropisetron Gastroprokinetics Alosetron Batanopride Metoclopramide Renzapride Zacopride M1, the major active metabolite of mosapride Antidepressants Mianserin Mirtazapine Vortioxetine Antipsychotics Clozapine Olanzapine Quetiapine Antimalarials Quinine Chloroquine Mefloquine Others 3-Tropanyl indole-3-carboxylate Lamotrigine Memantine Menthol Thujone These agents are not agonists at the receptor, but increase the affinity or efficacy of the receptors for an agonist: Indole Derivatives 5-chloroindole Small Organic Anaesthetics Ethanol Chloroform Halothane Isoflurane Identification of the 5-HT3 receptor did not take place until 1986 because of a lack of selective pharmacological tool.
However, with the discovery that the 5-HT3 receptor plays a prominent role in chemotherapy- and radiotherapy-induced vomiting, the conc
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
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