Hypnotic or soporific drugs known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to be used in the treatment of insomnia, or for surgical anesthesia. This group is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, the term hypnotic describes drugs whose main purpose is to initiate, sustain, or lengthen sleep; because these two functions overlap, because drugs in this class produce dose-dependent effects they are referred to collectively as sedative-hypnotic drugs. Hypnotic drugs are prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries. Many hypnotic drugs are habit-forming and, due to a large number of factors known to disturb the human sleep pattern, a physician may instead recommend changes in the environment before and during sleep, better sleep hygiene, the avoidance of caffeine or other stimulating substances, or behavioral interventions such as cognitive behavioral therapy for insomnia before prescribing medication for sleep.
When prescribed, hypnotic medication should be used for the shortest period of time necessary. Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines, while 10.8% are taking benzodiazepines, as of 2010. Early classes of drugs, such as barbiturates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or somnambulism. Elderly people are more sensitive to potential side effects of daytime fatigue and cognitive impairments, a meta-analysis found that the risks outweigh any marginal benefits of hypnotics in the elderly. A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs can have adverse effects, such as dependence and accidents, that optimal treatment uses the lowest effective dose for the shortest therapeutic time period, with gradual discontinuation in order to improve health without worsening of sleep.
Falling outside the above-mentioned categories, the neuro-hormone melatonin has a hypnotic function. Hypnotica was a class of somniferous drugs and substances tested in medicine of the 1890s and including: Urethan, Methylal, paraldehyde, Hypnon and Ohloralamid or Chloralimid. Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Treatment for insomnia in psychiatry dates back to 1869 when chloral hydrate was first used as a soporific. Barbiturates emerged as the first class of drugs that emerged in the early 1900s, after which chemical substitution allowed derivative compounds. Although the best drug family at the time they were dangerous in overdose and tended to cause physical and psychological dependence. During the 1970s, quinazolinones and benzodiazepines were introduced as safer alternatives to replace barbiturates. Benzodiazepines are not without their drawbacks. Questions have been raised as to. Nonbenzodiazepines are the most recent development.
Although it's clear that they are less toxic than their predecessors, comparative efficacy over benzodiazepines have not been established. Without longitudinal studies, it is hard to determine. Other sleep remedies that may be considered "sedative-hypnotics" exist. Examples of these include mirtazapine, clonidine and the over-the-counter sleep aid diphenhydramine. Off-label sleep remedies are useful when first-line treatment is unsuccessful or deemed unsafe. Barbiturates are drugs that act as central nervous system depressants, can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia, they are effective as anxiolytics and anticonvulsalgesic effects. They have dependence liability, both psychological. Barbiturates have now been replaced by benzodiazepines in routine medical practice – for example, in the treatment of anxiety and insomnia – because benzodiazepines are less dangerous in overdose. However, barbiturates are still used in general anesthesia, for epilepsy, assisted suicide.
Barbiturates are derivatives of barbituric acid. The principal mechanism of action of barbiturates is believed to be positive allosteric modulation of GABAA receptors. Examples include amobarbital, phenobarbital and sodium thiopental. Quinazolinones are a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core, their use has been proposed in the treatment of cancer. Examples of quinazolinones include cloroqualone, etaqualone, mebroqualone and methaqualone. Benzodiaz
In chemistry, an alcohol is any organic compound in which the hydroxyl functional group is bound to a carbon. The term alcohol referred to the primary alcohol ethanol, used as a drug and is the main alcohol present in alcoholic beverages. An important class of alcohols, of which methanol and ethanol are the simplest members, includes all compounds for which the general formula is CnH2n+1OH, it is these simple monoalcohols. The suffix -ol appears in the IUPAC chemical name of all substances where the hydroxyl group is the functional group with the highest priority; when a higher priority group is present in the compound, the prefix hydroxy- is used in its IUPAC name. The suffix -ol in non-IUPAC names typically indicates that the substance is an alcohol. However, many substances that contain hydroxyl functional groups have names which include neither the suffix -ol, nor the prefix hydroxy-. Alcohol distillation originated in India. During 2000 BCE, people of India used. Alcohol distillation was known to Islamic chemists as early as the eighth century.
The Arab chemist, al-Kindi, unambiguously described the distillation of wine in a treatise titled as "The Book of the chemistry of Perfume and Distillations". The Persian physician, alchemist and philosopher Rhazes is credited with the discovery of ethanol; the word "alcohol" is from a powder used as an eyeliner. Al- is the Arabic definite article, equivalent to the in English. Alcohol was used for the fine powder produced by the sublimation of the natural mineral stibnite to form antimony trisulfide Sb2S3, it was considered to be the essence or "spirit" of this mineral. It was used as an antiseptic and cosmetic; the meaning of alcohol was extended to distilled substances in general, narrowed to ethanol, when "spirits" was a synonym for hard liquor. Bartholomew Traheron, in his 1543 translation of John of Vigo, introduces the word as a term used by "barbarous" authors for "fine powder." Vigo wrote: "the barbarous auctours use alcohol, or alcofoll, for moost fine poudre."The 1657 Lexicon Chymicum, by William Johnson glosses the word as "antimonium sive stibium."
By extension, the word came to refer to any fluid obtained by distillation, including "alcohol of wine," the distilled essence of wine. Libavius in Alchymia refers to "vini alcohol vel vinum alcalisatum". Johnson glosses alcohol vini as "quando omnis superfluitas vini a vino separatur, ita ut accensum ardeat donec totum consumatur, nihilque fæcum aut phlegmatis in fundo remaneat." The word's meaning became restricted to "spirit of wine" in the 18th century and was extended to the class of substances so-called as "alcohols" in modern chemistry after 1850. The term ethanol was invented 1892, combining the word ethane with the "-ol" ending of "alcohol". IUPAC nomenclature is used in scientific publications and where precise identification of the substance is important in cases where the relative complexity of the molecule does not make such a systematic name unwieldy. In naming simple alcohols, the name of the alkane chain loses the terminal e and adds the suffix -ol, e.g. as in "ethanol" from the alkane chain name "ethane".
When necessary, the position of the hydroxyl group is indicated by a number between the alkane name and the -ol: propan-1-ol for CH3CH2CH2OH, propan-2-ol for CH3CHCH3. If a higher priority group is present the prefix hydroxy-is used, e.g. as in 1-hydroxy-2-propanone. In cases where the OH functional group is bonded to an sp2 carbon on an aromatic ring the molecule is known as a phenol, is named using the IUPAC rules for naming phenols. In other less formal contexts, an alcohol is called with the name of the corresponding alkyl group followed by the word "alcohol", e.g. methyl alcohol, ethyl alcohol. Propyl alcohol may be n-propyl alcohol or isopropyl alcohol, depending on whether the hydroxyl group is bonded to the end or middle carbon on the straight propane chain; as described under systematic naming, if another group on the molecule takes priority, the alcohol moiety is indicated using the "hydroxy-" prefix. Alcohols are classified into primary and tertiary, based upon the number of carbon atoms connected to the carbon atom that bears the hydroxyl functional group.
The primary alcohols have general formulas RCH2OH. The simplest primary alcohol is methanol, for which R=H, the next is ethanol, for which R=CH3, the methyl group. Secondary alcohols are those of the form RR'CHOH, the simplest of, 2-propanol. For the tertiary alcohols the general form is RR'R"COH; the simplest example is tert-butanol, for which each of R, R', R" is CH3. In these shorthands, R, R', R" represent substituents, alkyl or other attached organic groups. In archaic nomenclature, alcohols can be named as derivatives of methanol using "-carbinol" as the ending. For instance, 3COH can be named trimethylcarbinol. Alcohols have a long history of myriad uses. For simple mono-alcohols, the focus on this article, the following are most important industrial alcohols: methanol for the production of formaldehyde and as a fuel additive ethanol for alcoholic beverages, fuel additive, solvent 1-propanol, 1-butanol, isobutyl alcohol for use as a solvent a
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
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
The density, or more the volumetric mass density, of a substance is its mass per unit volume. The symbol most used for density is ρ, although the Latin letter D can be used. Mathematically, density is defined as mass divided by volume: ρ = m V where ρ is the density, m is the mass, V is the volume. In some cases, density is loosely defined as its weight per unit volume, although this is scientifically inaccurate – this quantity is more called specific weight. For a pure substance the density has the same numerical value as its mass concentration. Different materials have different densities, density may be relevant to buoyancy and packaging. Osmium and iridium are the densest known elements at standard conditions for temperature and pressure but certain chemical compounds may be denser. To simplify comparisons of density across different systems of units, it is sometimes replaced by the dimensionless quantity "relative density" or "specific gravity", i.e. the ratio of the density of the material to that of a standard material water.
Thus a relative density less than one means. The density of a material varies with pressure; this variation is small for solids and liquids but much greater for gases. Increasing the pressure on an object decreases the volume of the object and thus increases its density. Increasing the temperature of a substance decreases its density by increasing its volume. In most materials, heating the bottom of a fluid results in convection of the heat from the bottom to the top, due to the decrease in the density of the heated fluid; this causes it to rise relative to more dense unheated material. The reciprocal of the density of a substance is called its specific volume, a term sometimes used in thermodynamics. Density is an intensive property in that increasing the amount of a substance does not increase its density. In a well-known but apocryphal tale, Archimedes was given the task of determining whether King Hiero's goldsmith was embezzling gold during the manufacture of a golden wreath dedicated to the gods and replacing it with another, cheaper alloy.
Archimedes knew that the irregularly shaped wreath could be crushed into a cube whose volume could be calculated and compared with the mass. Baffled, Archimedes is said to have taken an immersion bath and observed from the rise of the water upon entering that he could calculate the volume of the gold wreath through the displacement of the water. Upon this discovery, he leapt from his bath and ran naked through the streets shouting, "Eureka! 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 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 many 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 cubic metre and the cgs unit of gram per cubic centimetre are the most used units for density. One g/cm3 is equal to one thousand kg/m3. One cubic centimetre is equal to one millilitre. In industry, other larger or smaller units of mass and or volume are more practical and US customary units may be used. See below for a list of some of the most common units of density. A number of techniques as well as standards exist for the measurement of density of materials; such techniques include the use of a hydrometer, Hydrostatic balance, immersed body method, air comparison pycnometer, oscillating densitometer, as well as pour and tap. However, each individual method or technique measures different types of density, therefore it is necessary to have an understanding of the type of density being measured as well as the type of material in question; the density at all points of a homogeneous object equals its total mass divided by its total volume. The mass is measured with a scale or balance.
To determine the density of a liquid or a gas, a hydrometer, a dasymeter or a Coriolis flow meter may be used, respectively. Hydrostatic weighing uses the displacement of water due to a submerged object to determine the density of the object. If the body is not homogeneous its density varies between different regions of the object. In that case the density around any given location is determined by calculating the density of a small volume around that location. In the limit of an infinitesimal volume the density of an inhomogeneous object at a point becomes: ρ = d m / d V, where d V is an elementary volume at position r; the mass of the body t
The melting point of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium; the melting point of a substance depends on pressure and is specified at a standard pressure such as 1 atmosphere or 100 kPa. When considered as the temperature of the reverse change from liquid to solid, it is referred to as the freezing point or crystallization point; because of the ability of some substances to supercool, the freezing point is not considered as a characteristic property of a substance. When the "characteristic freezing point" of a substance is determined, in fact the actual methodology is always "the principle of observing the disappearance rather than the formation of ice", that is, the melting point. For most substances and freezing points are 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. 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 not always the same as the melting point. In the absence of nucleators water can exist as a supercooled liquid down to −48.3 °C before freezing. The chemical element with the highest melting point is tungsten, at 3,414 °C; the often-cited carbon does not melt at ambient pressure but sublimes at about 3,726.85 °C. Tantalum hafnium carbide is a refractory compound with a high melting point of 4215 K. At the other end of the scale, helium does not freeze at all at normal pressure at temperatures arbitrarily close to absolute zero. 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 and a simple magnifier. The several grains of a solid are placed in a thin glass tube and immersed in the oil bath; the oil bath is heated and with the aid of the magnifier melting of the individual crystals at a certain temperature can be observed. In large/small devices, the sample is placed in a heating block, optical detection is automated; the measurement can be made continuously with an operating process. For instance, oil refineries measure the freeze point of diesel fuel online, meaning that the sample is taken from the process and measured automatically; this allows for more frequent measurements as the sample does not have to be manually collected and taken to a remote laboratory. For refractory materials the 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, 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; this extrapolation is accomplished by using Planck's law of radiation. The constants in this equation are not known with sufficient accuracy, causing errors in the extrapolation to become larger at higher temperatures. However, standard techniques have been developed to perform this extrapolation. Consider the case of using gold as the source. In this technique, the current through the filament of the pyrometer is adjusted until the light intensity of the filament matches that of a black-body at the melting point of gold.
This establishes the primary calibration temperature and can be expressed in terms of current through the pyrometer lamp. With the same current setting, the pyrometer is sighted on another black-body at a higher temperature. An absorbing medium of known transmission is inserted between this black-body; the temperature of the black-body is adjusted until a match exists between its intensity and that of the pyrometer filament. The true higher temperature of the black-body is determined from Planck's Law; the absorbing medium is removed and the current through the filament is adjusted to match the filament intensity to that of the black-body. This establishes a second calibration point for the pyrometer; this step is repeated to carry the calibration to hi
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In many preparations of delicate organic compounds, some specific parts of their molecules cannot survive the required reagents or chemical environments; these parts, or groups, must be protected. For example, lithium aluminium hydride is a reactive but useful reagent capable of reducing esters to alcohols, it will always react with carbonyl groups, this cannot be discouraged by any means. When a reduction of an ester is required in the presence of a carbonyl, the attack of the hydride on the carbonyl has to be prevented. For example, the carbonyl is converted into an acetal; the acetal is called a protecting group for the carbonyl. After the step involving the hydride is complete, the acetal is removed, giving back the original carbonyl; this step is called deprotection.
Protecting groups are more used in small-scale laboratory work and initial development than in industrial production processes because their use adds additional steps and material costs to the process. However, the availability of a cheap chiral building block can overcome these additional costs. Protection of alcohols: Acetyl -- Removed by base. Benzoyl – Removed by acid or base, more stable than Ac group. Benzyl – Removed by hydrogenolysis. Bn group is used in sugar and nucleoside chemistry. Β-Methoxyethoxymethyl ether – Removed by acid. Dimethoxytrityl, – Removed by weak acid. DMT group is used for protection of 5'-hydroxy group in nucleosides in oligonucleotide synthesis. Methoxymethyl ether – Removed by acid. Methoxytrityl – Removed by acid and hydrogenolysis. P-Methoxybenzyl ether – Removed by acid, hydrogenolysis, or oxidation. Methylthiomethyl ether – Removed by acid. Pivaloyl – Removed by acid, base or reductant agents, it is more stable than other acyl protecting groups. Tetrahydropyranyl – Removed by acid.
Tetrahydrofuran – Removed by acid. Trityl – Removed by acid and hydrogenolysis. Silyl ether – Removed by acid or fluoride ion.. TBDMS and TOM groups are used for protection of 2'-hydroxy function in nucleosides in oligonucleotide synthesis. Methyl ethers – Cleavage is by TMSI in dichloromethane or acetonitrile or chloroform. An alternative method to cleave methyl ethers is BBr3 in DCM Ethoxyethyl ethers – Cleavage more trivial than simple ethers e.g. 1N hydrochloric acid Protection of amines: Carbobenzyloxy group – Removed by hydrogenolysis p-Methoxybenzyl carbonyl group – Removed by hydrogenolysis, more labile than Cbz tert-Butyloxycarbonyl group – Removed by concentrated strong acid, or by heating to >80 °C. 9-Fluorenylmethyloxycarbonyl group – Removed by base, such as piperidine Acetyl group is common in oligonucleotide synthesis for protection of N4 in cytosine and N6 in adenine nucleic bases and is removed by treatment with a base, most with aqueous or gaseous ammonia or methylamine. Ac is too stable to be removed from aliphatic amides.
Benzoyl group is common in oligonucleotide synthesis for protection of N4 in cytosine and N6 in adenine nucleic bases and is removed by treatment with a base, most with aqueous or gaseous ammonia or methylamine. Bz is too stable to be removed from aliphatic amides. Benzyl group -- Removed by hydrogenolysis Carbamate group -- Removed by mild heating. P-Methoxybenzyl – Removed by hydrogenolysis, more labile than benzyl 3,4-Dimethoxybenzyl – Removed by hydrogenolysis, more labile than p-methoxybenzyl p-methoxyphenyl group – Removed by ammonium cerium nitrate Tosyl group – Removed by concentrated acid & strong reducing agents Troc group – Removed by Zn insertion in the presence of acetic acid Other Sulfonamides groups – Removed by samarium iodide, tributyltin hydride Protection of carbonyl groups: Acetals and Ketals – Removed by acid; the cleavage of acyclic acetals is easier than of cyclic acetals. Acylals – Removed by Lewis acids. Dithianes – Removed by metal salts or oxidizing agents. Protection of carboxylic acids: Methyl esters -- Removed by base.
Benzyl esters – Removed by hydrogenolysis. Tert-Butyl esters – Removed by acid and some reductants. Esters of 2,6-disubstituted phenols – Removed at room temperature by DBU-catalyzed methanolysis under high-pressure conditions. Silyl esters – Removed by acid and organometallic reagents. Orthoesters – Removed by mild aqueous acid to form ester, removed according to ester properties. Oxazoline – Removed by strong hot acid or alkali, but not e.g. LiAlH4, organolithium reagents or Grignard reagents 2-cyanoethyl – removed by mild base; the group is used in oligonucleotide synthesis. Methyl – removed by strong nucleophiles e.c. thiophenole/TEA. Propargyl alcohols in the Favorskii reactio