A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough and sometimes rigid, it provides the cell with both structural support and protection, acts as a filtering mechanism. Cell walls are present in most prokaryotes, in algae and fungi but in other eukaryotes including animals. A major function is to act as pressure vessels, preventing over-expansion of the cell when water enters; the composition of cell walls varies between species and may depend on cell type and developmental stage. The primary cell wall of land plants is composed of the polysaccharides cellulose and pectin. Other polymers such as lignin, suberin or cutin are anchored to or embedded in plant cell walls. Algae possess cell walls made of glycoproteins and polysaccharides such as carrageenan and agar that are absent from land plants. In bacteria, the cell wall is composed of peptidoglycan; the cell walls of archaea have various compositions, may be formed of glycoprotein S-layers, pseudopeptidoglycan, or polysaccharides.
Fungi possess cell walls made of the N-acetylglucosamine polymer chitin. Unusually, diatoms have a cell wall composed of biogenic silica. A plant cell wall was first observed and named by Robert Hooke in 1665. However, "the dead excrusion product of the living protoplast" was forgotten, for three centuries, being the subject of scientific interest as a resource for industrial processing or in relation to animal or human health. In 1804, Karl Rudolphi and J. H. F. Link proved. Before, it had been thought that fluid passed between them this way; the mode of formation of the cell wall was controversial in the 19th century. Hugo von Mohl advocated the idea. Carl Nägeli believed that the growth of the wall in thickness and in area was due to a process termed intussusception; each theory was improved in the following decades: the apposition theory by Eduard Strasburger, the intussusception theory by Julius Wiesner. In 1930, Ernst Münch coined the term apoplast in order to separate the "living" symplast from the "dead" plant region, the latter of which included the cell wall.
By the 1980s, some authors suggested replacing the term "cell wall" as it was used for plants, with the more precise term "extracellular matrix", as used for animal cells, but others preferred the older term. Cell walls serve similar purposes in those organisms, they may give cells offering protection against mechanical stress. In multicellular organisms, they permit the organism to hold a definite shape. Cell walls limit the entry of large molecules that may be toxic to the cell, they further permit the creation of stable osmotic environments by preventing osmotic lysis and helping to retain water. Their composition and form may change during the cell cycle and depend on growth conditions. In most cells, the cell wall is flexible, meaning that it will bend rather than holding a fixed shape, but has considerable tensile strength; the apparent rigidity of primary plant tissues is enabled by cell walls, but is not due to the walls' stiffness. Hydraulic turgor pressure creates this rigidity, along with the wall structure.
The flexibility of the cell walls is seen when plants wilt, so that the stems and leaves begin to droop, or in seaweeds that bend in water currents. As John Howland explains Think of the cell wall as a wicker basket in which a balloon has been inflated so that it exerts pressure from the inside; such a basket is rigid and resistant to mechanical damage. Thus does the prokaryote cell gain strength from a flexible plasma membrane pressing against a rigid cell wall; the apparent rigidity of the cell wall thus results from inflation of the cell contained within. This inflation is a result of the passive uptake of water. In plants, a secondary cell wall is a thicker additional layer of cellulose which increases wall rigidity. Additional layers may be formed by suberin in cork cell walls; these compounds are rigid and waterproof. Both wood and bark cells of trees have secondary walls. Other parts of plants such as the leaf stalk may acquire similar reinforcement to resist the strain of physical forces.
The primary cell wall of most plant cells is permeable to small molecules including small proteins, with size exclusion estimated to be 30-60 kDa. The pH is an important factor governing the transport of molecules through cell walls. Cell walls evolved independently including within the photosynthetic eukaryotes. In these lineages, the cell wall is related to the evolution of multicellularity, terrestrialization and vascularization; the walls of plant cells must have sufficient tensile strength to withstand internal osmotic pressures of several times atmospheric pressure that result from the difference in solute concentration between the cell interior and external solutions. Plant cell walls vary from 0.1 to several µm in thickness. Up to three strata or layers may be found in plant cell walls: The primary cell wall a thin and extensible layer formed while the cell is growing; the secondary cell wall, a thick layer formed inside the primary cell wall after the cell is grown. It is not found in all cell types.
Some cells, such as the conducting cells in xylem, possess a secondary wall containing lignin, which strengthens and waterproofs the wall. The middle lamella, a layer rich in pectins; this outermost layer
Pseudomonas aeruginosa is a common encapsulated, Gram-negative, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. The organism is considered opportunistic insofar as serious infection occurs during existing diseases or conditions – most notably cystic fibrosis and traumatic burns, it affects the immunocompromised but can infect the immunocompetent as in hot tub folliculitis. Treatment of P. aeruginosa infections can be difficult due to its natural resistance to antibiotics. When more advanced antibiotic drug regimens are needed adverse effects may result, it is citrate and oxidase positive. It is found in soil, skin flora, most man-made environments throughout the world.
It thrives not only in normal atmospheres, but in low-oxygen atmospheres, thus has colonized many natural and artificial environments. It uses a wide range of organic material for food; the symptoms of such infections are generalized sepsis. If such colonizations occur in critical body organs, such as the lungs, the urinary tract, kidneys, the results can be fatal; because it thrives on moist surfaces, this bacterium is found on and in medical equipment, including catheters, causing cross-infections in hospitals and clinics. It is able to decompose hydrocarbons and has been used to break down tarballs and oil from oil spills. P. aeruginosa is not virulent in comparison with other major pathogenic bacterial species – for example Staphylococcus aureus and Streptococcus pyogenes – though P. aeruginosa is capable of extensive colonization, can aggregate into enduring biofilms. The word Pseudomonas means "false unit", from the Greek pseudēs and; the stem word mon was used early in the history of microbiology to refer to germs, e.g. kingdom Monera.
The species name aeruginosa is a Latin word meaning verdigris, referring to the blue-green color of laboratory cultures of the species. This blue-green pigment is a combination of two metabolites of P. aeruginosa and pyoverdine, which impart the blue-green characteristic color of cultures. Another assertion is that the word may be derived from the Greek prefix ae- meaning "old or aged", the suffix ruginosa means wrinkled or bumpy; the names pyocyanin and pyoverdine are from the Greek, with pyo-, meaning "pus", meaning "blue", verdine, meaning "green". Pyoverdine in the absence of pyocyanin is a fluorescent-yellow color; the genome of P. aeruginosa consists of a large circular chromosome that carries between 5,500 and 6,000 open reading frames, sometimes plasmids of various sizes depending on the strain. This part of the genome is the P. aeruginosa core genome. P. aeruginosa is a facultative anaerobe, as it is well adapted to proliferate in conditions of partial or total oxygen depletion. This organism can achieve anaerobic growth with nitrite as a terminal electron acceptor.
When oxygen and nitrite are absent, it is able to ferment arginine and pyruvate by substrate-level phosphorylation. Adaptation to microaerobic or anaerobic environments is essential for certain lifestyles of P. aeruginosa, for example, during lung infection in cystic fibrosis and primary ciliary dyskinesia, where thick layers of lung mucus and bacterially-produced alginate surrounding mucoid bacterial cells can limit the diffusion of oxygen. P. aeruginosa growth within the human body can be asymptomatic until the bacteria form a biofilm, which overwhelms the immune system. These biofilms are found in the lungs of people with cystic fibrosis and primary ciliary dyskinesia, can prove fatal. P. aeruginosa relies on iron as a nutrient source to grow. However, iron is not accessible because it is not found in the environment. Iron is found in a insoluble ferric form. Furthermore, excessively high levels of iron can be toxic to P. aeruginosa. To overcome this and regulate proper intake of iron, P. aeruginosa uses siderophores, which are secreted molecules that bind and transport iron.
These iron-siderophore complexes, are not specific. The bacterium that produced the siderophores does not receive the direct benefit of iron intake. Rather, all members of the cellular population are likely to access the iron-siderophore complexes. Members of the cellular population that can efficiently produce these siderophores are referred to as cooperators. Research has shown when cooperators and cheaters are grown together, cooperators have a decrease in fitness, while cheaters have an increase in fitness; the magnitude of change in fitness increases with increasing iron limitation. With an increase in fitness, the cheaters can outcompete the cooperators; these observations suggest that having a mix of cooperators and cheaters can reduce the virulent nature of P. aeruginosa. An opportunistic, nosocomial pathogen of immunocompromised individuals, P. aeruginosa infects the airway, urinary tract and wounds, causes other
Gram-positive bacteria are bacteria that give a positive result in the Gram stain test, traditionally used to classify bacteria into two broad categories according to their cell wall. Gram-positive bacteria take up the crystal violet stain used in the test, appear to be purple-coloured when seen through a microscope; this is because the thick peptidoglycan layer in the bacterial cell wall retains the stain after it is washed away from the rest of the sample, in the decolorization stage of the test. Gram-negative bacteria cannot retain the violet stain after the decolorization step, their peptidoglycan layer is much thinner and sandwiched between an inner cell membrane and a bacterial outer membrane, causing them to take up the counterstain and appear red or pink. Despite their thicker peptidoglycan layer, gram-positive bacteria are more receptive to certain cell wall targeting antibiotics than gram-negative bacteria, due to the absence of the outer membrane. In general, the following characteristics are present in gram-positive bacteria: Cytoplasmic lipid membrane Thick peptidoglycan layer Teichoic acids and lipoids are present, forming lipoteichoic acids, which serve as chelating agents, for certain types of adherence.
Peptidoglycan chains are cross-linked to form rigid cell walls by a bacterial enzyme DD-transpeptidase. A much smaller volume of periplasm than that in gram-negative bacteria. Only some species have a capsule consisting of polysaccharides. Only some species are flagellates, when they do have flagella, have only two basal body rings to support them, whereas gram-negative have four. Both gram-positive and gram-negative bacteria have a surface layer called an S-layer. In gram-positive bacteria, the S-layer is attached to the peptidoglycan layer. Gram-negative bacteria's S-layer is attached directly to the outer membrane. Specific to gram-positive bacteria is the presence of teichoic acids in the cell wall; some of these are lipoteichoic acids, which have a lipid component in the cell membrane that can assist in anchoring the peptidoglycan. Along with cell shape, Gram staining is a rapid method used to differentiate bacterial species; such staining, together with growth requirement and antibiotic susceptibility testing, other macroscopic and physiologic tests, forms the full basis for classification and subdivision of the bacteria.
The kingdom Monera was divided into four divisions based on Gram staining: Firmicutes, Gracilicutes and Mendocutes. Based on 16S ribosomal RNA phylogenetic studies of the late microbiologist Carl Woese and collaborators and colleagues at the University of Illinois, the monophyly of the gram-positive bacteria was challenged, with major implications for the therapeutic and general study of these organisms. Based on molecular studies of the 16S sequences, Woese recognised twelve bacterial phyla. Two of these were both gram-positive and were divided on the proportion of the guanine and cytosine content in their DNA; the high G + C phylum was made up of the Actinobacteria and the low G + C phylum contained the Firmicutes. The Actinobacteria include the Corynebacterium, Mycobacterium and Streptomyces genera; the Firmicutes, have a 45 -- 60 % GC content. Although bacteria are traditionally divided into two main groups, gram-positive and gram-negative, based on their Gram stain retention property, this classification system is ambiguous as it refers to three distinct aspects, which do not coalesce for some bacterial species.
The gram-positive and gram-negative staining response is not a reliable characteristic as these two kinds of bacteria do not form phylogenetic coherent groups. However, although Gram staining response is an empirical criterion, its basis lies in the marked differences in the ultrastructure and chemical composition of the bacterial cell wall, marked by the absence or presence of an outer lipid membrane. All gram-positive bacteria are bounded by a single-unit lipid membrane, and, in general, they contain a thick layer of peptidoglycan responsible for retaining the Gram stain. A number of other bacteria—that are bounded by a single membrane, but stain gram-negative due to either lack of the peptidoglycan layer, as in the Mycoplasmas, or their inability to retain the Gram stain because of their cell wall composition—also show close relationship to the Gram-positive bacteria. For the bacterial cells bounded by a single cell membrane, the term "monoderm bacteria" or "monoderm prokaryotes" has been proposed.
In contrast to gram-positive bacteria, all archetypical gram-negative bacteria are bounded by a cytoplasmic membrane and an outer cell membrane. The presence of inner and outer cell membranes defines a new compartment in these cells: the periplasmic space or the periplasmic compartment; these bacteria have been designated as "diderm bacteria." The distinction between the monoderm and diderm bacteria is supported by conserved signature indels in a number of important proteins. Of these two structurally distinct groups of bacteria, monoderms are indicated to be ancestral. Based upon a number of observations including that the gram-positive bacteria are the major producers of antibiotics and that, in general, gram-negative bacteria are resistant to them, it h
Drug metabolism is the metabolic breakdown of drugs by living organisms through specialized enzymatic systems. More xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison; these pathways are a form of biotransformation present in all major groups of organisms, are considered to be of ancient origin. These reactions act to detoxify poisonous compounds; the study of drug metabolism is called pharmacokinetics. The metabolism of pharmaceutical drugs is an important aspect of medicine. For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Drug metabolism affects multidrug resistance in infectious diseases and in chemotherapy for cancer, the actions of some drugs as substrates or inhibitors of enzymes involved in xenobiotic metabolism are a common reason for hazardous drug interactions; these pathways are important in environmental science, with the xenobiotic metabolism of microorganisms determining whether a pollutant will be broken down during bioremediation, or persist in the environment.
The enzymes of xenobiotic metabolism the glutathione S-transferases are important in agriculture, since they may produce resistance to pesticides and herbicides. Drug metabolism is divided into three phases. In phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics; these modified compounds are conjugated to polar compounds in phase II reactions. These reactions are catalysed by transferase enzymes such as glutathione S-transferases. In phase III, the conjugated xenobiotics may be further processed, before being recognised by efflux transporters and pumped out of cells. Drug metabolism converts lipophilic compounds into hydrophilic products that are more excreted; the exact compounds an organism is exposed to will be unpredictable, may differ over time. The major challenge faced by xenobiotic detoxification systems is that they must be able to remove the almost-limitless number of xenobiotic compounds from the complex mixture of chemicals involved in normal metabolism.
The solution that has evolved to address this problem is an elegant combination of physical barriers and low-specificity enzymatic systems. All organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. Polar compounds cannot diffuse across these cell membranes, the uptake of useful molecules is mediated through transport proteins that select substrates from the extracellular mixture; this selective uptake means that most hydrophilic molecules cannot enter cells, since they are not recognised by any specific transporters. In contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, organisms, cannot exclude lipid-soluble xenobiotics using membrane barriers. However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics; these systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise any non-polar compound.
Useful metabolites are excluded since they are polar, in general contain one or more charged groups. The detoxification of the reactive by-products of normal metabolism cannot be achieved by the systems outlined above, because these species are derived from normal cellular constituents and share their polar characteristics. However, since these compounds are few in number, specific enzymes can remove them. Examples of these specific detoxification systems are the glyoxalase system, which removes the reactive aldehyde methylglyoxal, the various antioxidant systems that eliminate reactive oxygen species; the metabolism of xenobiotics is divided into three phases:- modification and excretion. These reactions act in concert to remove them from cells. In phase I, a variety of enzymes act to introduce polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system; these enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates.
The reaction mechanism of the P-450 oxidases proceeds through the reduction of cytochrome-bound oxygen and the generation of a highly-reactive oxyferryl species, according to the following scheme: O2 + NADPH + H+ + RH → NADP+ + H2O + ROHPhase I reactions may occur by oxidation, hydrolysis, cyclization and addition of oxygen or removal of hydrogen, carried out by mixed function oxidases in the liver. These oxidative reactions involve a cytochrome P450 monooxygenase, NADPH and oxygen; the classes of pharmaceutical drugs that utilize this method for their metabolism include phenothiazines and steroids. If the metabolites of phase I reactions are sufficiently polar, they may be excreted at this point. However, many phase I products are not eliminated and undergo a subsequent reaction in which an endogenous substrate combines with the newly incorporated functional group to
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
Zoetis Inc. is the world's largest producer of medicine and vaccinations for pets and livestock. The company was a subsidiary of Pfizer, the world's largest drug maker, but with Pfizer's spinoff of its 83% interest in the firm it is now a independent company; the company directly markets the products in 45 countries, sells the products in more than 100 countries. Operations outside the United States accounted for 50% of the total revenue. Contemporaneous with the spinoff in June 2013 S&P Dow Jones Indices announced that Zoetis would replace First Horizon National Corporation in the S&P 500 stock market index. In the 1950s, Pfizer began research on several drugs including Oxytetracycline. John McKeen, a chemical engineer with Pfizer products, discovered its effective use in livestock. In 1952, the Pfizer Agriculture Division opened a 732-acre research and development facility in Terre Haute, Indiana called Vigo. By 1988 the division was renamed Pfizer Animal Health; the acquisition of GlaxoSmithKline’s Norden Laboratories in 1995 boosted Pfizer's animal health division into small animal care including domestic pets.
Secondary research and development centres were opened in Kalamazoo, Michigan in 2003. In the same year, Pfizer acquired Pharmacia Corporation for US$60 billion in stock options. Between 2007 and 2011 the company acquired Embrex Inc, Catapult Genetics, Wyeth, Fort Dodge Animal Health, Vetnex Animal Health Ltd, Synbiotics Corporation, King Pharmaceuticals, Alpharma; these acquisitions increased Pfizer's market, range of products, countries it operated in, resources. Plans to break away Pfizer Animal Health into a separate company were announced in 2012; the name chosen, Zoetis translates from the derived Latin zoological word zoetic, meaning'pertaining to life'. Zoetis Inc.'s revenues exceeded $4.2 billion in 2011 and $4.34 billion in 2012. The animal health industry worldwide is an estimated US$22 billion dollar industry. On 22 May 2013, The Wall Street Journal reported that Pfizer plans to sell its majority stake in the company. According to the report, shareholders will have the option to swap their Pfizer shares for Zoetis shares.
The sell-off of Zoetis is consistent with Pfizer's recent decision to shed other non-pharmaceuticals subsidiaries in an effort to save costs, raise capital, pay off debt. The company has announced that JPMorgan Chase, Bank of America Merrill Lynch, Goldman Sachs & Co. and Morgan Stanley will be the lead underwriters. In November 2014, activist investor Bill Ackman disclosed that Pershing Square Capital Management had taken an 8.5% stake in the company, amassing 41.8 million shares, causing the share price to hit its highest price since the IPO. On 17 November, the company announced it would acquire a portfolio of pet drugs from Abbott Laboratories for $255 million. Records show that Pfizer filed for registration of a Class A stock with the U. S. Securities and Exchange Commission on 10 August 2012. Zoetis' IPO on 1 February 2013 sold 86.1 million shares for US$2.2 billion. Shares rose 19% by the end of the trading day to $35.01 a share, up from $26. At the time, it was the largest IPO from a U.
S. company since Facebook's $16 billion IPO on 18 May 2012. Pfizer retained 414 million Class B shares giving it an 83% controlling stake in the firm. Stock investors were attracted to the steep profit margin in proportion to revenue and consumer confidence in potential future growth of the subsidiary; the offering's lead underwriters were JPMorgan Chase, Bank of America Merrill Lynch and Morgan Stanley. Most of the money raised through the IPO was used to pay off existing Pfizer debt. In November 2015, the company announced it would acquire developer of aquaculture treatments and diseases, for $765 million. In 2017, Zoetis acquired Ireland-based Nexvet, a company with a biologics focused technology and product candidate pipeline. In May 2018, the company announced its intention to acquire Abaxis for $1.9 billion in cash. Twenty-eight sites in 11 countries make up Zoetis manufacturing network, each facility designed to meet chemical and infectious agent safety regulatory requirements. Many R&D operations are co-located with manufacturing sites, a collaboration that allows bringing new products to market faster.
Zoetis builds on six-decade Pfizer history and aims for high tech innovative manufacturing technologies. Zoetis products include: Zoetis.com
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.