1.
Jmol
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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 and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and 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 range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also 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, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
2.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
3.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
4.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
5.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in 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 modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a 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 generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally 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, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently 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, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
6.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
7.
Alpha hydroxy acid
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α-Hydroxy acids, or alpha hydroxy acids, are a class of chemical compounds that consist of a carboxylic acid substituted with a hydroxyl group on the adjacent carbon. They may be naturally occurring or synthetic. AHAs are well known for their use in the cosmetics industry and they are often found in products that aid in the reduction of wrinkles as well as to soften strong, defining lines and improve the overall look and feel of the skin. They are also used as chemical peels available in an office, beauty and health spas and home kits. Effective results through continuous treatment have resulted in AHAs being a successful & developmental method of curbing harsh ageing effects in the skin & cosmeceutical industry, understanding skin structure and cutaneous aging is helpful to a discussion of the topical action of AHAs. Human skin has two components, the avascular epidermis and the underlying vascular dermis. Cutaneous aging, while having epidermal concomitants, seems to involve primarily the dermis and is caused by intrinsic and extrinsic aging factors, AHAs are a group of organic carboxylic compounds. AHAs most commonly used in applications are typically derived from food products including glycolic acid, lactic acid, malic acid, citric acid. For any topical compound to be effective, including AHA, it must penetrate into the skin where it can act on living cells, bioavailability is an important factor in a compounds ability to penetrate the top layer of the skin. AHAs have an effect on keratinization, which is clinically detectable by the formation of a new stratum corneum. It appears that AHAs modulate this formation through diminished cellular cohesion between corneocytes at the lowest levels of the stratum corneum, AHAs with greater bioavailability appear to have deeper dermal effects. α-Hydroxy acids are useful building blocks in organic synthesis, for example, α-hydroxy acids are generally useful as precursors in the preparation aldehydes via oxidative cleavage. Compounds of this class are used on the industrial-scale and include glycolic acid, lactic acid, citric acid, in low concentrations, 5-10%, as is found in many over-the-counter products, glycolic acid reduces cell adhesion in the top layer of the skin. This action promotes exfoliation of the outermost layer of the accounting for smoother texture following regular use of topical glycolic acid. This relatively low concentration of GA lends itself to use as a monotherapy or a part of a broader skin care management for such conditions as acne, photo-damage. Care needs to be taken to avoid irritation as this may result in worsening of melasma or other pigmentary problems, newer formulations combine glycolic acid with an amino acid such as arginine and form a time-release system that reduces the risk of irritation without affecting glycolic acid efficacy. The use of an anti-irritant like allantoin is also helpful, because of its safety, glycolic acid at the concentrations below 10% can be used daily by most people except those with very sensitive skin. In higher concentrations, between 10 and 50%, its benefits are more pronounced but are limited to temporary skin smoothing without much long lasting results
8.
Glutaric acid
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Glutaric acid is the organic compound with the formula C3H62. Although the related linear dicarboxylic acids adipic and succinic acids are only to a few percent at room temperature. Glutaric acid is produced in the body during the metabolism of some amino acids, including lysine. Defects in this pathway can lead to a disorder called glutaric aciduria. Glutaric acid can be prepared by the ring-opening of butyrolactone with potassium cyanide to give the mixed potassium carboxylate-nitrile that is hydrolyzed to the diacid, alternatively hydrolysis, followed by oxidation of dihydropyran gives glutaric acid. It can also be prepared from reacting 1, 3-dibromopropane with sodium or potassium cyanide to obtain the dinitrile,1, 5-Pentanediol, a common plasticizer and precursor to polyesters is manufactured by hydrogenation of glutaric acid and its derivatives. Glutaric acid itself has used in the production of polymers such as polyester polyols. The odd number of atoms is useful in decreasing polymer elasticity. Uvitonic acid is obtained by the action of ammonia on pyrotartaric acid, glutaric acid may cause irritation to the skin and eyes. Acute hazards include the fact that this compound may be harmful by ingestion, inhalation or skin absorption, calculator, Water and solute activities in aqueous glutaric acid
9.
L2HGDH
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L-2-hydroxyglutarate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the L2HGDH gene, also known as C14orf160, on chromosome 14. This gene encodes L-2-hydroxyglutarate dehydrogenase, a flavin adenine dinucleotide -dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues, mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe mental retardation. L2HGDH codes for a protein that is 50 kDa in size, the L2HGDH protein contains a mitochondrial-targeting transit peptide and is localized to the mitochondrial inner membrane inside mitochondria inside the cell. The L2HGDH protein catalyzes the reaction, and requires flavin adenine dinucleotide as a co-factor. Mutations in the L2HGDH gene cause L-2-hydroxyglutaric aciduria, an autosomal recessive neurometabolic disorder. Individuals with L2HGDH mutations present toxic accumulation of high concentration of L-2-hydroxyglutaric acid in the plasma, at least 70 disease-causing variants in the L2HGDH gene have been discovered in patients. Patients with L-2-hydroxyglutaric aciduria are associated with moderate to severe mental retardation, psychomotor retardation, cerebellar ataxia, macrocephaly, kLK10 D2HGDH 2-hydroxyglutarate synthase 2-hydroxyglutarate dehydrogenase Hydroxyacid-oxoacid transhydrogenase
10.
Isocitrate dehydrogenase
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Isocitrate dehydrogenase and is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate and CO2. This is a process, which involves oxidation of isocitrate to oxalosuccinate, followed by the decarboxylation of the carboxyl group beta to the ketone. In humans, IDH exists in three isoforms, IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and they localize to the cytosol as well as the mitochondrion and peroxisome. All the known NADP-IDHs are homodimers, most isocitrate dehydrogenases are dimers, to be specific, homodimers. In comparing C. glutamicum and E. coli, monomer and dimer, respectively, however, C. glutamicum was recorded as having ten times as much activity than E. coli and seven times more affinitive/specific for NADP. C. glutamicum favored NADP+ over NAD+, in terms of stability with response to temperature, both enzymes had a similar Tm or melting temperature at about 55 °C to 60 °C. However, the monomer C. glutamicum showed a more consistent stability at higher temperatures, the dimer E. coli showed stability at a higher temperature than normal due to the interactions between the two monomeric subunits. The structure of Mycobacterium tuberculosis ICDH-1 bound with NADPH and Mn bound has been solved by X-ray crystallography and it is a homodimer in which each subunit has a Rossmann fold, and a common top domain of interlocking β sheets. Mtb ICDH-1 is most structurally similar to the R132H mutant human ICDH found in glioblastomas, similar to human R132H ICDH, Mtb ICDH-1 also catalyzes the formation of α-hydroxyglutarate. The reaction is stimulated by the mechanisms of substrate availability, product inhibition. Within the citric cycle, isocitrate, produced from the isomerization of citrate. Using the enzyme isocitrate dehydrogenase, isocitrate is held within its site by surrounding arginine, tyrosine, asparagine, serine, threonine. The first box shows the overall isocitrate dehydrogenase reaction, the reactants necessary for this enzyme mechanism to work are isocitrate, NAD+/NADP+, and Mn2+ or Mg2+. The products of the reaction are alpha-ketoglutarate, carbon dioxide, water molecules are used to help deprotonate the oxygens of isocitrate. The second box is Step 1, which is the oxidation of the alpha-C, oxidation is the first step that isocitrate goes through. The third box is Step 2, which is the decarboxylation of oxalosuccinate, in this step, the carboxyl group oxygen is deprotonated by a nearby Tyrosine amino acid and those electrons flow down to carbon 2. The lone pair on the alpha-C oxygen picks up a proton from a nearby Lysine amino acid, the fourth box is Step 3, which is the saturation of the alpha-beta unsaturated double bond between carbons 2 and 3
11.
Oncogene
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An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells will undergo a form of rapid cell death when critical functions are altered. Activated oncogenes can cause those cells designated for apoptosis to survive, most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer, many cancer drugs target the proteins encoded by oncogenes. The theory of oncogenes was foreshadowed by the German biologist Theodor Boveri in his 1914 book Zur Frage der Entstehung Maligner Tumoren, Gustav Fisher, Oncogenes that become amplified during tumour development. Later on the term oncogene was rediscovered in 1969 by National Cancer Institute scientists George Todaro, the first confirmed oncogene was discovered in 1970 and was termed src. Src was in fact first discovered as an oncogene in a chicken retrovirus, experiments performed by Dr. G. Steve Martin of the University of California, Berkeley demonstrated that the Src was indeed the oncogene of the virus. The first nucleotide sequence of v-src was sequenced in 1980 by A. P. Czernilofsky et al, for this discovery, proving Todaro and Heubners oncogene theory, Bishop and Varmus were awarded the Nobel Prize in Physiology or Medicine in 1989. The resultant protein encoded by an oncogene is termed oncoprotein, Oncogenes play an important role in the regulation or synthesis of proteins linked to tumorigenic cell growth. Some oncoproteins are accepted and used as tumor markers, a proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate growth and differentiation. Proto-oncogenes are often involved in transduction and execution of mitogenic signals. Upon acquiring an activating mutation, a proto-oncogene becomes a tumor-inducing agent, examples of proto-oncogenes include RAS, WNT, MYC, ERK, and TRK. The MYC gene is implicated in Burkitts Lymphoma, which starts when a chromosomal translocation moves an enhancer sequence within the vicinity of the MYC gene, the MYC gene codes for widely used transcription factors. When the enhancer sequence is placed, these transcription factors are produced at much higher rates. Bcr-Abl codes for a tyrosine kinase, which is constitutively active, the proto-oncogene can become an oncogene by a relatively small modification of its original function. This type of mutation in a stem cell in the bone marrow leads to adult leukemia Philadelphia Chromosome is an example of this type of translocation event
12.
PubMed Identifier
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
13.
Organic compound
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An organic compound is virtually any chemical compound that contains carbon, although a consensus definition remains elusive and likely arbitrary. Organic compounds are rare terrestrially, but of importance because all known life is based on organic compounds. The most basic petrochemicals are considered the building blocks of organic chemistry, for historical reasons discussed below, a few types of carbon-containing compounds, such as carbides, carbonates, simple oxides of carbon, and cyanides are considered inorganic. The distinction between organic and inorganic compounds, while useful in organizing the vast subject of chemistry. Organic chemistry is the science concerned with all aspects of organic compounds, Organic synthesis is the methodology of their preparation. The word organic is historical, dating to the 1st century, for many centuries, Western alchemists believed in vitalism. This is the theory that certain compounds could be synthesized only from their classical elements—earth, water, air, vitalism taught that these organic compounds were fundamentally different from the inorganic compounds that could be obtained from the elements by chemical manipulation. Vitalism survived for a while even after the rise of modern atomic theory and it first came under question in 1824, when Friedrich Wöhler synthesized oxalic acid, a compound known to occur only in living organisms, from cyanogen. A more decisive experiment was Wöhlers 1828 synthesis of urea from the inorganic salts potassium cyanate, urea had long been considered an organic compound, as it was known to occur only in the urine of living organisms. Wöhlers experiments were followed by others, in which increasingly complex organic substances were produced from inorganic ones without the involvement of any living organism. Even though vitalism has been discredited, scientific nomenclature retains the distinction between organic and inorganic compounds, still, even the broadest definition requires excluding alloys that contain carbon, including steel. The C-H definition excludes compounds that are considered organic, neither urea nor oxalic acid is organic by this definition, yet they were two key compounds in the vitalism debate. The IUPAC Blue Book on organic nomenclature specifically mentions urea and oxalic acid, other compounds lacking C-H bonds but traditionally considered organic include benzenehexol, mesoxalic acid, and carbon tetrachloride. Mellitic acid, which contains no C-H bonds, is considered an organic substance in Martian soil. The C-H bond-only rule also leads to somewhat arbitrary divisions in sets of carbon-fluorine compounds, for example, CF4 would be considered by this rule to be inorganic, whereas CF3H would be organic. Organic compounds may be classified in a variety of ways, one major distinction is between natural and synthetic compounds. Another distinction, based on the size of organic compounds, distinguishes between small molecules and polymers, natural compounds refer to those that are produced by plants or animals. Many of these are extracted from natural sources because they would be more expensive to produce artificially
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