1.
Drug nomenclature
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Drug nomenclature is the systematic naming of drugs, especially pharmaceutical drugs. Generic names for drugs are nowadays constructed out of affixes and stems that classify the drugs into different categories, a marketed drug might also have a company code or compound code. The chemical names are the names, based on the molecular structure of the drug. There are various systems of nomenclature and thus various chemical names for any one substance. The most important is the IUPAC name, chemical names are typically very long and too complex to be commonly used in referring to a drug. Sometimes, a company that is developing a drug might give the drug a company code, for example, CDP870 is UCB’s company code for Cimzia. Many of these codes, although not all, have prefixes that correspond to the company name, during development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, and it will apply for a generic name for that country. It will also apply for an International Nonproprietary Name through the World Health Organization, nowadays the national nonproprietary names are usually the same as the INN. The generic names usually indicate via their stems what drug class the drug belongs to, for example, one can tell that aciclovir is an antiviral drug because its name ends in the -vir suffix. Otherwise the 2 names are both given, joined by hyphens or slashes. For example, suspensions combining trimethoprim and sulfamethoxazole are called either trimethoprim/sulfamethoxazole or co-trimoxazole, similarly, co-codamol is codeine-acetaminophen, and co-triamterzide is triamterene-hydrochlorothiazide. The USP ceased maintaining PENs, but the similar co-prefixed BANs are still current, for drugs that make it all the way through development, testing, and regulatory acceptance, the pharmaceutical company then gives the drug a trade name. The term trade name is a term in the pharmaceutical industry for a brand name or trademark name. For example, Lipitor is Pfizers trade name for atorvastatin, a cholesterol-lowering medication, Drug names are often subject to legal regulation, including approval for new drugs and on packaging to establish clear rules about adulterants and fraudulent or misleading labelling. A national formulary is often designated to define drug names for regulatory purposes, unbiased mentions of a drug place the nonproprietary name first and follow it with the trade name in parentheses, if relevant. This pattern is important for the literature, where conflict of interest is disclosed or avoided. The authors reporting on a study are not endorsing any particular brand of drug and they will often state which brand was used, for methodologic validity, but they do so in a way that makes clear the absence of endorsement. For example, the 2015 American Society of Hematology publication policies say, Non-proprietary names should be used and he first letter of the name of a proprietary drug should be capitalized
2.
Drugs.com
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Drugs. com is an online pharmaceutical encyclopedia which provides drug information for consumers and healthcare professionals primarily in the USA. The domain Drugs. com was registered by Bonnie Neubeck in 1994. In 1999 at the height of the boom, Eric MacIver purchased an option to buy the domain from Neubeck. com. Venture Frogs sold the drugs. com domain name to an investor in June 2001. The Drugs. com website is owned and operated by the Drugsite Trust, the Drugsite Trust is a privately held Trust administered by two New Zealand pharmacists, Karen Ann and Phillip James Thornton The Drugs. com website was officially launched in September 2001. Stedmans, AHFS, Harvard Health Publications, Mayoclinic, North American Compendiums, in March 2008, Drugs. com announced the release of Mednotes —an online personal medication record application which connected to Google Health. In May 2010, U. S. FDA announced a collaboration with Drugs. com to distribute consumer health updates on the Drugs. com website, Drugs. com is certified by the TRUSTe online privacy certification program and the HONcode Health on the Net Foundation
3.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc
4.
European Medicines Agency
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The European Medicines Agency is a European Union agency for the evaluation of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products, roughly parallel to the drug part of the U. S. The EU is currently the source of about one-third of the new drugs brought onto the market each year. After the United Kingdom withdrawal from the European Union referendum the agency is preparing to relocate, more specifically, it coordinates the evaluation and monitoring of centrally authorised products and national referrals, developing technical guidance and providing scientific advice to sponsors. Its scope of operations is medicinal products for human and veterinary use including biologics and advanced therapies, the agency is composed of the Secretariat, a management board, seven scientific committees and a number of scientific working parties. The Management Board provides administrative oversight to the Agency, including approval of budgets and plans, the Agency decentralises its scientific assessment of medicines by working through a network of about 4500 experts throughout the EU. The EMA draws on resources of over 40 National Competent Authorities of EU Member states, the centralised procedure is also open to products that bring a significant therapeutic, scientific or technical innovation, or is in any other respect in the interest of patient or animal health. As a result, the majority of genuinely novel medicines are authorised through the EMA, for products eligible for or requiring centralised approval, a company submits an application for a marketing authorisation to the EMA. A single evaluation is carried out through the Committee for Medicinal Products for Human Use, if the Committee concludes that the quality, safety and efficacy of the medicinal product is sufficiently proven, it adopts a positive opinion. This is sent to the European Commission to be transformed into a marketing authorisation valid for the whole of the EU, a special type of approval is the paediatric-use marketing authorisation, which can be granted for medical products intended exclusively for paediatric use. The CHMP is obliged by the regulation to reach decisions within 210 days and this compares well with the average of 500 days taken by the U. S. Food and Drug Administration. The Committee for Medicinal Products for Veterinary Use operates in analogy to the CHMP as described above, the Committee on Orphan Medicinal Products administers the granting of orphan drug status since 2000. The COMP evaluates the application and makes a recommendation for the designation which is granted by the European Commission. The Paediatric Committee deals with the implementation of the legislation in Europe Regulation No 1901/2006 since 2007. It assesses the quality, safety and efficacy of ATMPs, a seventh committee, the Pharmacovigilance Risk Assessment Committee has come into function in 2012 with the implementation of the new EU pharmacovigilance legislation. Referrals The Agency coordinates arbitration procedures relating to medicinal products that are approved or under consideration by Member States in non-centralized authorisation procedures, telematics projects The Agency is responsible for implementing a central set of pan-European systems and databases such as EudraVigilance, EudraCT and EudraPharm. Following the decision of the United Kingdom to vote to leave the European Union, according to EU Law the European Commission will need to decide the criteria surrounding the fate of the EMAs location. The heads of state will then meet to vote on their preferred successor, the EUs Health Commissioner Vytenis Andriukaitis has said in the past that the preferred choice would be a location where an easy set up and guarantee of smooth operations would be available
5.
Food and Drug Administration
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The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. As of 2017, 3/4th of the FDA budget is funded by the pharmaceutical companies due to the Prescription drug user fee act and these include regulating lasers, cellular phones, condoms and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice, the Commissioner reports to the Secretary of Health and Human Services. Dr. Robert M. Califf, MD is the current commissioner, who took over in February 2016 for Dr. Stephen Ostroff, the FDA has its headquarters in unincorporated White Oak, Maryland. The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, in 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. The site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak, the first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the facility was kept. All other buildings are new construction, the project is slated to be completed by 2017, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. The Office of Regulatory Affairs is considered the eyes and ears of the agency, the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based roughly on the divisions of the federal court system. Each district comprises a main office and a number of Resident Posts. ORA also includes the Agencys network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and dont focus on aspects of the regulated industries. In many cases, OCI pursues cases involving Title 18 violations, OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI receives cases from a variety of sources—including ORA, local agencies, OCI is a smaller branch, comprising about 200 agents nationwide. The FDA frequently works with federal agencies, including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection. Often local and state government agencies also work with the FDA to provide regulatory inspections, the FDA regulates more than US$1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States
6.
Intravenous therapy
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Intravenous therapy is the infusion of liquid substances directly into a vein. Intravenous infusions are commonly referred to as drips, the intravenous route is the fastest way to deliver fluids and medications throughout the body. Intravenous therapy may be used for administration, to correct electrolyte imbalances, to deliver medications. IVs can be categorized by type of vein the tube inserted, called the catheter. A peripheral IV is used on peripheral veins and this is the most common type of IV therapy used. Central IV lines have their catheters that are advanced through a vein and empty into a central vein, usually the superior vena cava. Other advantages are that because it empties near the heart, medications can also be distributed to the rest of the body. As there is room for multiple parallel compartments within the catheter, caregivers can also measure central venous pressure and other physiological variables through the line. They are also longer, which as reflected in Poiseuilles law, requires higher pressure to achieve the same flow, central IV lines carry risks of bleeding, infection, gangrene, thromboembolism and gas embolism. Surrounding structures such as the pleura and carotid artery are also at risk of damage with the potential for pneumothorax or even cannulation of the artery. There are several types of central IVs, depending on the route that the catheter takes from the outside of the body to the vein, typical uses for a PICC include, long chemotherapy regimens, extended antibiotic therapy, or total parenteral nutrition. This is usually done by measuring the distance to a landmark, such as the suprasternal notch. An X-ray must be used to verify that the tip is in the place when fluoroscopy was not used during the insertion. A PICC may have a tube and connector, two or three compartments, each with its own external connector. Power-injectable PICCs are now available as well, from the outside, a single-lumen PICC resembles a peripheral IV, except that the tubing is slightly wider. The insertion site requires better protection than that of a peripheral IV, however, a PICC poses less of a systemic infection risk than other central IVs, because the insertion site is usually cooler and dryer than the sites typically used for other central lines. This helps to slow the growth of bacteria which could reach the bloodstream by traveling under the skin along the outside of the catheter, although special training is required, a PICC does not require the skill level of a physician or surgeon. It is also externally unobtrusive, and with proper hygiene and care can be left in place for months to years if needed for patients who require extended treatment, also, as a PICC travels through the axilla, it can become kinked, causing poor function
7.
Over-the-counter drug
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In many countries, OTC drugs are selected by a regulatory agency to ensure that they are ingredients that are safe and effective when used without a physicians care. OTC drugs are regulated by active pharmaceutical ingredients, not final products. By regulating APIs instead of specific drug formulations, governments allow manufacturers freedom to formulate ingredients, or combinations of ingredients, into proprietary mixtures. The term over-the-counter may be somewhat counterintuitive, since, in many countries, in contrast, prescription drugs are almost always passed over a counter from the pharmacist to the customer. Some drugs may be classified as over-the-counter, but may only be dispensed by a pharmacist after an assessment of the patients needs or the provision of patient education. In many countries, a number of OTC drugs are available in establishments without a pharmacy, such as stores, supermarkets. Regulations detailing the establishments where drugs may be sold, who is authorized to dispense them, as of 2011, around a third of older adults in the U. S. reportedly use OTC drugs. In Canada, there are four drug schedules, Schedule 1, Schedule 2, Do not require a prescription, but require an assessment by a pharmacist prior to sale. These drugs are kept in an area of the pharmacy where there is no public access, Schedule 3, Do not require a prescription, but must be kept in an area under the supervision of a pharmacist. These drugs are kept in an area of the outlet where self-selection is possible. Unscheduled, Do not require a prescription and may be sold in any retail outlet, all medications outside of Schedule 1 may be considered an OTC drug, as they do not require prescriptions for sale. While the National Association of Pharmacy Regulatory Authorities provides recommendations on the scheduling of drugs for sale in Canada, due to this, the exact drugs found in each schedule may vary from province to province. The drug can be on the shelves like any other product, examples are domperidone,400 mg ibuprofen up to 50 tablets and dextromethorphan. The drugs are usually on the shelves and the store sells items like toys, gadgets, perfumes. The drugs in this category have limited risk and addiction potential, examples are naproxen and diclofenac in small amounts, cinnarizine,400 mg ibuprofen up to 20 tablets and also 500 mg paracetamol up to 50 tablets. In the United States, the manufacture and sale of OTC substances is regulated by the Food, the FDA requires that all new drugs obtain a New Drug Application before entering interstate commerce, but the act exempts any drugs generally recognized as safe and effective from this requirement. Thus, in the United States an OTC drug product is allowed to be marketed either pursuant to an FDA monograph, the Federal Trade Commission regulates advertising of OTC products. This is in contrast to prescription drug advertising, which is regulated by the FDA, the FDA requires that OTC products are labeled with an approved Drug Facts label to educate consumers about their medications
8.
Prescription drug
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A prescription drug is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription, the reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient education. Different jurisdictions have different definitions of what constitutes a prescription drug, rx is often used as a short form for prescription drug in North America- a contraction of the Latin word recipe meaning take. Prescription drugs are often dispensed together with a monograph that gives detailed information about the drug, the use of prescription drugs has been increasing since the 1960s. In the U. S. 88% of older adults use at least 1 prescription drug, who is able to prescribe the drug. When purchasing a drug under the PBS the maximum price a consumer pays is the patient co-payment contribution and those covered by government entitlements and those covered under the Repatriation Pharmaceutical Benefits Scheme have a reduced co-payment, which is $6.00 in 2014. The table below indicates the changes in co-payments over the years and these co-payments are compulsory and cannot be discounted by pharmacies under any circumstances. Private prescriptions are issued for medicines not covered on the PBS, or being used off-label, the patient pays the pharmacy for medicines privately prescribed. In the United Kingdom the Medicines Act 1968 and Prescription Only Medicines Order 1997 contain regulations that cover the supply of sale, use, prescribing is also covered by this legislation. A patient visits a medical practitioner or dentist authorised to prescribe drugs and certain other medical items, also, suitably qualified and experienced nurses and pharmacists may be independent prescribers. Both can prescribe all POMs but pharmacists are not allowed to prescribe schedule 1 controlled drugs, once issued, a prescription is taken by the patient to a pharmacy, which dispenses the medicine. Most prescriptions in the UK are NHS prescriptions, subject to a standard charge unrelated to what is dispensed, the NHS prescription fee was increased to £8. The pharmacy charges the NHS the actual cost of the medicine, a patient can consolidate prescription charges using a prescription payment certificate, effectively capping costs at £29.10 per quarter or £104.00 per year. Outside the NHS, private prescriptions are issued by private medical practitioners, NHS supply beyond three months worth is not covered, and must be purchased privately. A patient pays the pharmacy the normal price for medicine prescribed outside the NHS, in the United States, the Federal Food, Drug, and Cosmetic Act defines what substances require a prescription in order to be dispensed by a pharmacy. The Controlled Substances Act was enacted into law by the Congress of the United States in 1970, the CSA is the federal U. S. drug law under which the manufacture, importation, possession, use and distribution of certain substances is regulated. The legislation created five schedules with varying qualifications for a substance to be included in each, the safety and effectiveness of prescription drugs in the US is regulated by the federal Prescription Drug Marketing Act of 1987. The Food and Drug Administration is charged with implementing this law, misuse or abuse of prescription drugs can lead to adverse drug events, including those due to dangerous drug interactions
9.
Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism
10.
Bioavailability
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By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient, Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration. Bioavailability is defined differently for drugs as opposed to dietary supplements primarily due to the method of administration and Food. Bioaccessibility is a related to bioavailability in the context of biodegradation. A molecule is said to be bioaccessible when is available to cross a cellular membrane from the environment. In pharmacology, bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action and it is denoted by the letter f. Therefore, bioavailability for dietary supplements can be defined as the proportion of the administered substance capable of being absorbed, in both pharmacology and nutrition sciences, bioavailability is measured by calculating the area under curve of the drug concentration time profile. Bioavailability is commonly a factor in the production of crops. Toxic materials in soil, such as lead from paint may be rendered unavailable to animals ingesting contaminated soil by supplying phosphorus fertilizers in excess and it is the fraction of the drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug. The comparison must be normalized, consequently, the amount absorbed is corrected by dividing the corresponding dose administered. The absolute bioavailability is the area under curve non-intravenous divided by AUC intravenous. For example, the formula for calculating F for a drug administered by the route is given below. If we compare the two different dosage forms having same active ingredients and compare the two drug bioavailability is called comparative bioavailability, although knowing the true extent of systemic absorption is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is that its assessment requires a reference, that is. These limitations may be overcome, however, by administering a low dose of an isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be administered with a minimum of toxicology, the technique was first applied using stable-isotopes such as 13C and mass-spectrometry to distinguish the isotopes by mass difference. More recently, 14C labelled drugs are administered intravenously and accelerator mass spectrometry used to measure the isotopically labelled drug along with mass spectrometry for the unlabelled drug, in all such cases, to conduct an absolute bioavailability study requires that the drug be given intravenously. Intravenous administration of a drug can provide valuable information on the fundamental pharmacokinetic parameters of volume of distribution
11.
Drug metabolism
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Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. These pathways are a form of biotransformation present in all groups of organisms. These reactions often act to detoxify poisonous compounds, the study of drug metabolism is called pharmacokinetics. The metabolism of drugs is an important aspect of pharmacology. For example, the rate of metabolism determines the duration and intensity of a drugs pharmacologic action, the enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also 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 enzymes such as glutathione S-transferases. Finally, in phase III, the conjugated xenobiotics may be processed, before being recognised by efflux transporters. Drug metabolism often converts lipophilic compounds into hydrophilic products that are readily excreted. The exact compounds an organism is exposed to will be unpredictable, and may differ widely over time. The solution that has evolved to address this problem is an elegant combination of physical barriers, all organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. This selective uptake means that most hydrophilic molecules cannot enter cells, in contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, 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 and these systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general one or more charged groups. However, since these compounds are few in number, specific enzymes can recognize, the metabolism of xenobiotics is often divided into three phases, - modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells, in phase I, a variety of enzymes act to introduce reactive and polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system and 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
12.
CYP2C9
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Cytochrome P450 2C9 is an enzyme that in humans is encoded by the CYP2C9 gene. CYP2C9 is an important cytochrome P450 enzyme with a role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes and it likewise metablizes docosahexaenoic acid to epoxydocosapentaenoic acids and eicosapentaenoic acid to epoxyeicosatetraenoic acids. 20-Hydroxyeicosatetraenoic acid, principally in the areas of blood pressure regulation, blood vessel thrombosis, genetic polymorphism exists for CYP2C9 expression because the CYP2C9 gene is highly polymorphic. Multiple in vivo studies show that several mutant CYP2C9 genotypes are associated with significant reduction of in metabolism. In fact, adverse drug reactions often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms, allele frequencies of CYP2C9 polymorphism Most inhibitors of CYP2C9 are competitive inhibitors. Noncompetitive inhibitors of CYP2C9 include nifedipine, phenethyl isothiocyanate, medroxyprogesterone acetate and it was indicated that the noncompetitive binding site of 6-hydroxyflavone is the reported allosteric binding site of the CYP2C9 enzyme. Following is a table of selected substrates, inducers and inhibitors of CYP2C9, where classes of agents are listed, there may be exceptions within the class. Inhibitors of CYP2C9 can be classified by their potency, such as, Strong being one that causes at least a 5-fold increase in the plasma AUC values, moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance. Weak being one that causes at least a 1. 25-fold but less than 2-fold increase in the plasma AUC values, CYP2C9 attacks various long-chain polyunsaturated fatty acids at their double bonds to form epoxide products that act as signaling molecules
13.
Excretion
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Excretion is the process by which metabolic wastes and other non-useful materials are eliminated from an organism. In vertebrates this is carried out by the lungs, kidneys. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell, excretion is an essential process in all forms of life. For example, in urine is expelled through the urethra. In unicellular organisms, waste products are discharged directly through the surface of the cell, green plants produce carbon dioxide and water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis, oxygen is a by product generated during photosynthesis, and exits through stomata, root cell walls, and other routes. Plants can get rid of water by transpiration and guttation. These latter processes do not need added energy, they act passively, however, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants also excrete some waste substances into the soil around them, in animals, the main excretory products are carbon dioxide, ammonia, urea, uric acid, guanine and creatine. The liver and kidneys clear many substances from the blood, aquatic animals usually excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution. In terrestrial animals ammonia-like compounds are converted into other materials as there is less water in the environment. Birds excrete their nitrogenous wastes as uric acid in the form of a paste and this is metabolically more expensive, but allows more efficient water retention and it can be stored more easily in the egg. Many avian species, especially seabirds, can also excrete salt via specialized nasal salt glands, in insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is actively transported into the tubule, which transports the wastes to the intestines, the metabolic waste is then released from the body along with fecal matter. The excreted material may be called dejecta or ejecta, in pathology the word ejecta is more commonly used. UAlberta. ca, Animation of excretion Brian J Ford on leaf fall in Nature
14.
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
15.
Guide to Pharmacology
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The IUPHAR/BPS Guide to PHARMACOLOGY is an open-access website, acting as a portal to information on the biological targets of licensed drugs and other small molecules. The Guide to PHARMACOLOGY is developed as a joint venture between the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society and this replaces and expands upon the original 2009 IUPHAR Database. The information featured includes pharmacological data, target and gene nomenclature, overviews and commentaries on each target family are included, with links to key references. The Guide to PHARMACOLOGY was initially made available online in December 2011 with additional material released in July 2012 and its network of over 700 specialist advisors contribute expertise and data. The current PI and Grant holder of the GtoPdb project is Prof. Jamie A. Davies, the development and release of the first version of the GtoPdb in 2012 was described in an editorial published in the British Journal of Pharmacology entitled Guide to Pharmacology. org- an update. The IUPHAR-DB is no longer being developed and all the contained within this site is now available through the Guide to PHARMACOLOGY. A complete list of all the approved drugs included on the website is available via the ligand list. The Guide to PHARMACOLOGY is being expanded to include information on targets and ligands. Search features on the website include quick and advanced search options, other features include Hot topic news items and a recent receptor-ligand pairing list. A hard copy summary of the database is published as The Concise Guide to Pharmacology 2015/2016 as a series of papers as a bi-annual supplement to the British Journal of Pharmacology. The Guide to PHARMACOLOGY includes links to other relevant resources via target, many of these resources maintain reciprocal links with the relevant Guide to PHARMACOLOGY pages. As of November 2015 the Wellcome Trust is supporting a new project to develop the Guide to Immumopharmacology, the latter continues to be supported by the British Pharmacological Society
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DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result, links to DrugBank are maintained for nearly all drugs listed in Wikipedia, DrugBank is widely used by the drug industry, medicinal chemists, pharmacists, physicians, students and the general public. Its extensive drug and drug-target data has enabled the discovery and repurposing of a number of existing drugs to treat rare, the latest release of the database contains 8227 drug entries including 2003 FDA-approved small molecule drugs,221 FDA-approved biotech drugs,93 nutraceuticals and over 6000 experimental drugs. Additionally,4270 non-redundant protein sequences are linked to these drug entries, each DrugCard entry contains more than 200 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Four additional databases, HMDB, T3DB, SMPDB and FooDB are also part of a suite of metabolomic/cheminformatic databases. The first version of DrugBank was released in 2006 and this early release contained relatively modest information about 841 FDA-approved small molecule drugs and 113 biotech drugs. It also included information on 2133 drug targets, the second version of DrugBank was released in 2009. This greatly expanded and improved version of the database included 1344 approved small molecule drugs and 123 biotech drugs as well as 3037 unique drug targets. Version 2.0 also included, for the first time, withdrawn drugs and illicit drugs, version 3.0 was released in 2011. This version contained 1424 approved small molecule drugs and 132 biotech drugs as well as >4000 unique drug targets, version 3.0 also included drug transporter data, drug pathway data, drug pricing, patent and manufacturing data as well as data on >5000 experimental drugs. Version 4.0 was released in 2014 and this version included 1558 FDA-approved small molecule drugs,155 biotech drugs and 4200 unique drug targets. Version 4.0 also incorporated information on drug metabolites, drug taxonomy, drug spectra, drug binding constants. Table 1 provides a complete statistical summary of the history of DrugBank’s development. All data in DrugBank is non-proprietary or is derived from a non-proprietary source and it is freely accessible and available to anyone. In addition, nearly every item is fully traceable and explicitly referenced to the original source. DrugBank data is available through a web interface and downloads
17.
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
18.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
19.
Protein Data Bank
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The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
20.
Ligand (biochemistry)
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In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein, the binding typically results in a change of conformation of the target protein. In DNA-ligand binding studies, the ligand can be a molecule, ion. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure, the instance of binding occurs over an infinitesimal range of time and space, so the rate constant is usually a very small number. Binding occurs by intermolecular forces, such as bonds, hydrogen bonds. The association of docking is actually reversible through dissociation, measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of ligand in metalorganic and inorganic chemistry, in biochemistry it is whether the ligand generally binds at a metal site. In general, the interpretation of ligand is contextual with regards to what sort of binding has been observed, the etymology stems from ligare, which means to bind. Ligand binding to a receptor protein alters the chemical conformation by affecting the shape orientation. The conformation of a receptor protein composes the functional state, ligands include substrates, inhibitors, activators, and neurotransmitters. The rate of binding is called affinity, and this measurement typifies a tendency or strength of the effect, binding affinity is actualized not only by host-guest interactions, but also by solvent effects that can play a dominant, steric role which drives non-covalent binding in solution. The solvent provides an environment for the ligand and receptor to adapt. Radioligands are radioisotope labeled compounds are used in vivo as tracers in PET studies, the interaction of most ligands with their binding sites can be characterized in terms of a binding affinity. In general, high-affinity binding results in a degree of occupancy for the ligand at its receptor binding site than is the case for low-affinity binding. A ligand that can bind to a receptor, alter the function of the receptor, high-affinity ligand binding implies that a relatively low concentration of a ligand is adequate to maximally occupy a ligand-binding site and trigger a physiological response. The lower the Ki concentration is, the more likely there will be a reaction between the pending ion and the receptive antigen. In the example shown to the right, two different ligands bind to the receptor binding site. Only one of the agonists shown can maximally stimulate the receptor and, thus, an agonist that can only partially activate the physiological response is called a partial agonist
21.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks 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 commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling 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, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is 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 export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and 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 officially identified in the EU as being of very 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 then move to another list
22.
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
23.
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
24.
Chirality (chemistry)
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Chirality /kaɪˈrælɪti/ is a geometric property of some molecules and ions. A chiral molecule/ion is non-superposable on its mirror image, the presence of an asymmetric carbon center is one of several structural features that induce chirality in organic and inorganic molecules. The term chirality is derived from the Greek word for hand, the mirror images of a chiral molecule/ion are called enantiomers or optical isomers. Individual enantiomers are often designated as either right- or left-handed, Chirality is an essential consideration when discussing the stereochemistry in organic and inorganic chemistry. The concept is of practical importance because most biomolecules and pharmaceuticals are chiral. Chirality is based on molecular symmetry elements, specifically, a chiral compound can contain no improper axis of rotation, which includes planes of symmetry and inversion center. Chiral molecules are always dissymmetric but not always asymmetric, in general, chiral molecules have point chirality at a single stereogenic atom, which has four different substituents. The two enantiomers of such compounds are said to have different absolute configurations at this center, the stereogenic atom is usually carbon, as in many biological molecules. However chirality can exist in any atom, including metals, phosphorus, Chiral nitrogen is equally possible, although the effects of nitrogen inversion can make many of these compounds impossible to isolate. While the presence of a stereogenic atom describes the great majority of cases, for instance it is not necessary for the chiral substance to have a stereogenic atom. Examples include 1-bromo-1-chloro-1-fluoroadamantane, methylethylphenyltetrahedrane, certain calixarenes and fullerenes, which have inherent chirality, the C2-symmetric species 1, 1-bi-2-naphthol,1, 3-dichloro-allene have axial chirality. -cyclooctene and many ferrocenes have planar chirality, when the optical rotation for an enantiomer is too low for practical measurement, the species is said to exhibit cryptochirality. Even isotopic differences must be considered when examining chirality, illustrative is the derivative of benzyl alcohol PhCHDOH is chiral. The S enantiomer has D = +0. 715°, many biologically active molecules are chiral, including the naturally occurring amino acids and sugars. In biological systems, most of these compounds are of the chirality, most amino acids are levorotatory. Typical naturally occurring proteins, made of L amino acids, are known as left-handed proteins, d-amino acids are very rare in nature and have only been found in small peptides attached to bacteria cell walls. The origin of this homochirality in biology is the subject of much debate, however, there is some suggestion that early amino acids could have formed in comet dust. Enzymes, which are chiral, often distinguish between the two enantiomers of a chiral substrate, one could imagine an enzyme as having a glove-like cavity that binds a substrate
25.
Density
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The density, or more precisely, the volumetric mass density, of a substance is its mass per unit volume. The symbol most often used for density is ρ, although the Latin letter D can also be used. Mathematically, density is defined as mass divided by volume, ρ = m V, where ρ is the density, m is the mass, and V is the volume. In some cases, density is defined as its weight per unit volume. For a pure substance the density has the numerical value as its mass concentration. Different materials usually have different densities, and density may be relevant to buoyancy, purity, osmium and iridium are the densest known elements at standard conditions for temperature and pressure but certain chemical compounds may be denser. Thus a relative density less than one means that the floats in water. The density of a material varies with temperature and pressure and this variation is typically small for solids and liquids but much greater for gases. Increasing the pressure on an object decreases the volume of the object, increasing the temperature of a substance decreases its density by increasing its volume. In most materials, heating the bottom of a results in convection of the heat from the bottom to the top. This causes it to rise relative to more dense unheated material, the reciprocal of the density of a substance is occasionally called its specific volume, a term sometimes used in thermodynamics. Density is a property in that increasing the amount of a substance does not increase its density. Archimedes knew that the irregularly shaped wreath could be crushed into a cube whose volume could be calculated easily and compared with the mass, upon this discovery, he leapt from his bath and ran naked through the streets shouting, Eureka. As a result, the term eureka entered common parlance and is used today to indicate a moment of enlightenment, the story first appeared in written form in Vitruvius books of architecture, two centuries after it supposedly took place. Some scholars have doubted the accuracy of this tale, saying among other things that the method would have required precise measurements that would have been difficult to make at the time, from the equation for density, mass density has units of mass divided by volume. As there are units of mass and volume covering many different magnitudes there are a large number of units for mass density in use. The SI unit of kilogram per metre and the cgs unit of gram per cubic centimetre are probably the most commonly used units for density.1,000 kg/m3 equals 1 g/cm3. In industry, other larger or smaller units of mass and or volume are often more practical, see below for a list of some of the most common units of density
26.
Melting point
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The melting point of a solid is the temperature at which it changes state from solid to liquid at atmospheric pressure. At the melting point the solid and liquid phase exist in equilibrium, the melting point of a substance depends on pressure and is usually specified at standard pressure. When considered as the temperature of the change from liquid to solid. Because of the ability of some substances to supercool, the point is not considered as a characteristic property of a substance. For most substances, melting and freezing points are approximately equal, for example, the melting point and freezing point of mercury is 234.32 kelvins. However, certain substances possess differing solid-liquid transition temperatures, for example, agar melts at 85 °C and solidifies from 31 °C to 40 °C, such direction dependence is known as hysteresis. The melting point of ice at 1 atmosphere of pressure is close to 0 °C. In the presence of nucleating substances the freezing point of water is the same as the melting point, the chemical element with the highest melting point is tungsten, at 3687 K, this property makes tungsten excellent for use as filaments in light bulbs. Many laboratory techniques exist for the determination of melting points, a Kofler bench is a metal strip with a temperature gradient. Any substance can be placed on a section of the strip revealing its thermal behaviour at the temperature at that point, differential scanning calorimetry gives information on melting point together with its enthalpy of fusion. A basic melting point apparatus for the analysis of crystalline solids consists of an oil bath with a transparent window, the several grains of a solid are placed in a thin glass tube and partially immersed in the oil bath. The oil bath is heated and with the aid of the melting of the individual crystals at a certain temperature can be observed. In large/small devices, the sample is placed in a heating block, the measurement can also be made continuously with an operating process. For instance, oil refineries measure the point of diesel fuel online, meaning that the sample is taken from the process. This allows for more frequent measurements as the sample does not have to be manually collected, for refractory materials the extremely high melting point may be determined by heating the material in a black body furnace and measuring the black-body temperature with an optical pyrometer. For the highest melting materials, this may require extrapolation by several hundred degrees, the spectral radiance from an incandescent body is known to be a function of its temperature. An optical pyrometer matches the radiance of a body under study to the radiance of a source that has been previously calibrated as a function of temperature, in this way, the measurement of the absolute magnitude of the intensity of radiation is unnecessary. However, known temperatures must be used to determine the calibration of the pyrometer, for temperatures above the calibration range of the source, an extrapolation technique must be employed
27.
Boiling point
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The boiling point of a substance is the temperature at which the vapor pressure of the liquid equals the pressure surrounding the liquid and the liquid changes into a vapor. The boiling point of a liquid varies depending upon the environmental pressure. A liquid in a vacuum has a lower boiling point than when that liquid is at atmospheric pressure. A liquid at high pressure has a boiling point than when that liquid is at atmospheric pressure. For a given pressure, different liquids boil at different temperatures, for example, water boils at 100 °C at sea level, but at 93.4 °C at 2,000 metres altitude. The normal boiling point of a liquid is the case in which the vapor pressure of the liquid equals the defined atmospheric pressure at sea level,1 atmosphere. At that temperature, the pressure of the liquid becomes sufficient to overcome atmospheric pressure. The standard boiling point has been defined by IUPAC since 1982 as the temperature at which boiling occurs under a pressure of 1 bar, the heat of vaporization is the energy required to transform a given quantity of a substance from a liquid into a gas at a given pressure. Liquids may change to a vapor at temperatures below their boiling points through the process of evaporation, evaporation is a surface phenomenon in which molecules located near the liquids edge, not contained by enough liquid pressure on that side, escape into the surroundings as vapor. On the other hand, boiling is a process in which molecules anywhere in the liquid escape, a saturated liquid contains as much thermal energy as it can without boiling. The saturation temperature is the temperature for a corresponding saturation pressure at which a liquid boils into its vapor phase, the liquid can be said to be saturated with thermal energy. Any addition of energy results in a phase transition. If the pressure in a system remains constant, a vapor at saturation temperature will begin to condense into its liquid phase as thermal energy is removed, similarly, a liquid at saturation temperature and pressure will boil into its vapor phase as additional thermal energy is applied. The boiling point corresponds to the temperature at which the pressure of the liquid equals the surrounding environmental pressure. Thus, the point is dependent on the pressure. Boiling points may be published with respect to the NIST, USA standard pressure of 101.325 kPa, at higher elevations, where the atmospheric pressure is much lower, the boiling point is also lower. The boiling point increases with increased pressure up to the critical point, the boiling point cannot be increased beyond the critical point. Likewise, the point decreases with decreasing pressure until the triple point is reached
28.
Aqueous solution
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An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending to the relevant chemical formula, for example, a solution of table salt, or sodium chloride, in water would be represented as Na+ + Cl−. The word aqueous means pertaining to, related to, similar to, as water is an excellent solvent and is also naturally abundant, it is a ubiquitous solvent in chemistry. Substances that are hydrophobic often do not dissolve well in water, an example of a hydrophilic substance is sodium chloride. Acids and bases are aqueous solutions, as part of their Arrhenius definitions, the ability of a substance to dissolve in water is determined by whether the substance can match or exceed the strong attractive forces that water molecules generate between themselves. If the substance lacks the ability to dissolve in water the molecules form a precipitate, reactions in aqueous solutions are usually metathesis reactions. Metathesis reactions are another term for double-displacement, that is, when a cation displaces to form a bond with the other anion. The cation bonded with the latter anion will dissociate and bond with the other anion, aqueous solutions that conduct electric current efficiently contain strong electrolytes, while ones that conduct poorly are considered to have weak electrolytes. Those strong electrolytes are substances that are ionized in water. Nonelectrolytes are substances that dissolve in water yet maintain their molecular integrity, examples include sugar, urea, glycerol, and methylsulfonylmethane. When writing the equations of reactions, it is essential to determine the precipitate. To determine the precipitate, one must consult a chart of solubility, soluble compounds are aqueous, while insoluble compounds are the precipitate. Remember that there may not always be a precipitate, when performing calculations regarding the reacting of one or more aqueous solutions, in general one must know the concentration, or molarity, of the aqueous solutions. Solution concentration is given in terms of the form of the prior to it dissolving. Metal ions in aqueous solution Solubility Dissociation Acid-base reaction theories Properties of water Zumdahl S.1997, 4th ed. Boston, Houghton Mifflin Company
29.
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
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