A designer drug is a structural or functional analog of a controlled substance, designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances as well as analogs of performance-enhancing drugs such as designer steroids; some of these were synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects and were co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories; because the efficacy and safety of these substances have not been evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects. The development of designer drugs may be considered a subfield of drug design; the exploration of modifications to known active drugs—such as their structural analogues and derivatives—yields drugs that may differ in effects from their "parent" drug.
In some instances, designer drugs have similar effects to other known drugs, but have dissimilar chemical structures. Despite being a broad term, applicable to every synthetic drug, it is used to connote synthetic recreational drugs, sometimes those which have not been designed at all. In some jurisdictions, drugs that are similar in structure to a prohibited drug are illegal to trade regardless of that drug's legal status. In other jurisdictions, their trade is a legal grey area; some jurisdictions may have analogue laws which ban drugs similar in chemical structure to other prohibited drugs, while some designer drugs may be prohibited irrespective of the legal status of structurally similar drugs. Following the passage of the second International Opium Convention in 1925, which banned morphine, the diacetyl ester of morphine, a number of alternative esters of morphine started to be manufactured and sold; the most notable of these were dibenzoylmorphine and acetylpropionylmorphine, which have identical effects to heroin but were not covered by the Opium Convention.
This led the Health Committee of the League of Nations to pass several resolutions attempting to bring these new drugs under control leading in 1930 to the first broad analogues provisions extending legal control to all esters of morphine and hydromorphone. Another early example of what could loosely be termed designer drug use, was during the Prohibition era in the 1930s, when diethyl ether was sold and used as an alternative to illegal alcoholic beverages in a number of countries. During the 1960s and 1970s, a number of new synthetic hallucinogens were introduced, with a notable example being the sale of potent tablets of DOM in San Francisco in 1967. There was little scope to prosecute people over drug analogues at this time, with new compounds instead being added to the controlled drug schedules one by one as they became a problem, but one significant court case from this period was in 1973, when Tim Scully and Nicholas Sand were prosecuted for making the acetyl amide of LSD, known as ALD-52.
At this time ALD-52 was not a controlled drug, but they were convicted on the grounds that in order to make ALD-52, they would have had to be in possession of LSD, illegal. The late 1970s saw the introduction of various analogues of phencyclidine to the illicit market; the modern use of the term designer drug was coined in the 1980s to refer to various synthetic opioid drugs, based on the fentanyl molecule. The term gained widespread popularity; when the term was coined in the 1980s, a wide range of narcotics were being sold as heroin on the black market. Many were based on meperidine. One, MPPP, was found in some cases to contain an impurity called MPTP, which caused brain damage that could result in a syndrome identical to full-blown Parkinson's disease, from only a single dose. Other problems were potent fentanyl analogues, which were sold as China White, that caused many accidental overdoses; because the government was powerless to prosecute people for these drugs until after they had been marketed laws were passed to give the DEA power to emergency schedule chemicals for a year, with an optional 6-month extension, while gathering evidence to justify permanent scheduling, as well as the analogue laws mentioned previously.
Emergency-scheduling power was used for the first time for MDMA. In this case, the DEA scheduled MDMA as a Schedule I drug and retained this classification after review though their own judge ruled that MDMA should be classified Schedule III on the basis of its demonstrated uses in medicine; the emergency scheduling power has subsequently been used for a variety of other drugs including 2C-B, AMT, BZP. In 2004, a piperazine drug, TFMPP, became the first drug, emergency-scheduled to be denied permanent scheduling and revert to legal status; the late 1980s and early 1990s saw the re-emergence of methamphetamine in the United States as a widespread public health issue, leading to increasing controls on precursor chemicals in an attempt to cut down on domestic manufacture of the drug. This led to several alternative stimulant drugs emerging, the most notable ones being methcathinone and 4-m
Transition state analog
Transition state analogs, are chemical compounds with a chemical structure that resembles the transition state of a substrate molecule in an enzyme-catalyzed chemical reaction. Enzymes interact with a substrate by means of strain or distortions, moving the substrate towards the transition state. Transition state analogs can be used as inhibitors in enzyme-catalyzed reactions by blocking the active site of the enzyme. Theory suggests that enzyme inhibitors which resembled the transition state structure would bind more to the enzyme than the actual substrate. Examples of drugs that are transition state analog inhibitors include flu medications such as the neuraminidase inhibitor oseltamivir and the HIV protease inhibitors saquinavir in the treatment of AIDS; the transition state of a structure can best be described in regards to statistical mechanics where the energies of bonds breaking and forming have an equal probability of moving from the transition state backwards to the reactants or forward to the products.
In enzyme-catalyzed reactions, the overall activation energy of the reaction is lowered when an enzyme stabilizes a high energy transition state intermediate. Transition state analogs mimic this high energy intermediate but do not undergo a catalyzed chemical reaction and can therefore bind much stronger to an enzyme than simple substrate or product analogs. To design a transition state analogue, the pivotal step is the determination of transition state structure of substrate on the specific enzyme of interest with experimental method, for example, kinetic isotope effect. In addition, the transition state structure can be predicted with computational approaches as a complementary to KIE. We will explain these two methods in brief. Kinetic isotope effect is a measurement of the reaction rate of isotope-labeled reactants against the more common natural substrate. Kinetic isotope effect values are a ratio of the turnover number and include all steps of the reaction. Intrinsic kinetic isotope values stem from the difference in the bond vibrational environment of an atom in the reactants at ground state to the environment of the atom's transition state.
Through the kinetic isotope effect much insight can be gained as to what the transition state looks like of an enzyme-catalyzed reaction and guide the development of transition state analogs. Computational approaches have been regarded as a useful tool to elucidate the mechanism of action of enzymes. Molecular mechanics itself can not predict the electron transfer, the fundamental of organic reaction but the molecular dynamics simulation provide sufficient information considering the flexibility of protein during catalytic reaction; the complementary method would be combined molecular mechanics/ quantum mechanics simulation methods. With this approach, only the atoms responsible for enzymatic reaction in the catalytic region will be reared with quantum mechanics and the rest of the atoms were treated with molecular mechanics. After determining the transition state structures using either KIE or computation simulations, the inhibitor can be designed according to the determined transition state structures or intermediates.
The following three examples illustrate how the inhibitors mimic the transition state structure by changing functional groups correspond to the geometry and electrostatic distribution of the transition state structures. Methylthioadenosine nucleosidase are enzymes that catalyse the hydrolytic deadenylation reaction of 5'-methylthioadenosine and S-adenosylhomocysteine, it is regarded as an important target for antibacterial drug discovery because it is important in the metabolic system of bacteria and only produced by bacteria. Given the different distance between nitrogen atom of adenine and the ribose anomeric carbon, the transition state structure can be defined by early or late dissociation stage. Based on the finding of different transition state structures and coworkers designed two transition state analogues mimicking the early and late dissociative transition state; the early and late transition state analogue shown binding affinity of 140 pM, respectively. Thermolysin is an enzyme produced by Bacillus thermoproteolyticus that catalyses the hydrolysis of peptides containing hydrophobic amino acids.
Therefore, it is a target for antibacterial agents. The enzymatic reaction mechanism starts form the small peptide molecule and replaces the zinc binding water molecule towards Glu143 of thermolysin; the water molecule is activated by both the zinc ion and the Glu143 residue and attacks the carbonyl carbon to form a tetrahedral transition state. Holden and coworkers mimicked that tetrahedral transition state to design a series of phosphonamidate peptide analogues. Among the synthesized analogues, R = L-Leu possesses the most potent inhibitory activity. Arginase is a binuclear manganese metallopritein that catalyse the hydrolysis of L-arginine to L-ornithine and urea, it is regarded as a drug target for the treatment of asthma. The mechanism of hydrolysis of L-arginine was carryout by nucleophilic attack of water molecule forming a tetrahedral intermediate. Studies shown that boronic acid serve as an inhibitor. In addition, the sulfonamide functional group can mimic that transition state structure.
The evidence of boronic acid mimic as transitions state analogue inhibitor was elucidated by x-ray crystal structure complex with human arginase I. Enzyme Structural analog, compounds with similar chemical structure Enzyme inhibitor Substrate analog Suicide inhibitor Substrate
Phenethylamine is an organic compound, natural monoamine alkaloid, trace amine, which acts as a central nervous system stimulant in humans. Phenethylamine functions as a monoaminergic neuromodulator, to a lesser extent, a neurotransmitter in the human central nervous system, it is biosynthesized from the amino acid L-phenylalanine by enzymatic decarboxylation via the enzyme aromatic L-amino acid decarboxylase. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate after microbial fermentation, it is sold as a dietary supplement for purported weight loss-related therapeutic benefits. This means that for significant concentrations to reach the brain, the dosage must be higher than for other methods of administration. Phenethylamines, or more properly, substituted phenethylamines, are the group of phenethylamine derivatives that contain phenethylamine as a "backbone"; the class of substituted phenethylamines includes all substituted amphetamines, substituted methylenedioxyphenethylamines, contains many drugs which act as empathogens, psychedelics, bronchodilators, and/or antidepressants, among others.
Phenethylamine is produced by a wide range of species throughout the plant and animal kingdoms, including humans. Phenethylamine is a primary amine, the amino-group being attached to a benzene ring through a two-carbon, or ethyl group, it is a colourless liquid at room temperature that has a fishy odor, is soluble in water and ether. Its density is 0.964 g/ml and its boiling point is 195 °C. Upon exposure to air, it combines with carbon dioxide to form a solid carbonate salt. Phenethylamine is basic, pKb = 4.17, as measured using the HCl salt, forms a stable crystalline hydrochloride salt with a melting point of 217 °C. Substituted phenethylamines are a chemical class of organic compounds based upon the phenethylamine structure. Many substituted phenethylamines are psychoactive drugs, which belong to a variety of different drug classes, including central nervous system stimulants, entactogens, appetite suppressants, nasal decongestants and bronchodilators, antiparkinson agents, vasopressors, among others.
Many of these psychoactive compounds exert their pharmacological effects by modulating monoamine neurotransmitter systems. Numerous endogenous compounds – including hormones, monoamine neurotransmitters, many trace amines – are substituted phenethylamines. Several notable recreational drugs, such as MDMA, cathinones, are members of the class. All of the substituted amphetamines are phenethylamines, as well. Pharmaceutical drugs that are substituted phenethylamines include phenelzine and fanetizole, among many others. One method for preparing β-phenethylamine, set forth in J. C. Robinson and H. R. Snyder's Organic Syntheses, involves the reduction of benzyl cyanide with hydrogen in liquid ammonia, in the presence of a Raney-Nickel catalyst, at a temperature of 130 °C and a pressure of 13.8 MPa. Alternative syntheses are outlined in the footnotes to this preparation. A much more convenient method for the synthesis of β-phenethylamine is the reduction of ω-nitrostyrene by lithium aluminum hydride in ether, whose successful execution was first reported by R. F. Nystrom and W. G. Brown in 1948.
Phenethylamine can be produced via the cathodic reduction of benzyl cyanide in a divided cell. Assembling phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines and dopamine by adding the beta-aminoethyl side chain to the phenyl ring is possible; this can be done via Friedel-Crafts acylation with N-protected acyl chlorides when the arene is activated, or by Heck reaction of the phenyl with N-vinyloxazolone, followed by hydrogenation, or by cross-coupling with beta-amino organozinc reagents, or reacting a brominated arene with beta-aminoethyl organolithium reagents, or by Suzuki cross-coupling. Reviews that cover attention deficit hyperactivity disorder and phenethylamine indicate that several studies have found abnormally low urinary phenethylamine concentrations in ADHD individuals when compared with controls. In treatment-responsive individuals and methylphenidate increase urinary phenethylamine concentration. An ADHD biomarker review indicated that urinary phenethylamine levels could be a diagnostic biomarker for ADHD.
Skydiving induces a marked increase in urinary phenethylamine concentrations. Thi
Illegal drug trade
The illegal drug trade or drug trafficking is a global black market dedicated to the cultivation, manufacture and sale of drugs that are subject to drug prohibition laws. Most jurisdictions prohibit trade, except under license, of many types of drugs through the use of drug prohibition laws; the United Nations Office on Drugs and Crime's World Drug Report 2005 estimates the size of the global illicit drug market at US$321.6 billion in 2003 alone. With a world GDP of US$36 trillion in the same year, the illegal drug trade may be estimated as nearly 1% of total global trade. Consumption of illegal drugs is widespread globally and remains difficult for local authorities to thwart its popularity. Chinese authorities issued edicts against opium smoking in 1729, 1796 and 1800; the West prohibited addictive drugs throughout the late early 20th centuries. In the early 19th century, an illegal drug trade in China emerged; as a result, by 1838 the number of Chinese opium-addicts had grown to between four and twelve million.
The Chinese government responded by enforcing a ban on the import of opium. The United Kingdom forced China to allow British merchants to sell Indian-grown opium. Trading in opium was lucrative, smoking opium had become common in the 19th century, so British merchants increased trade with the Chinese; the Second Opium War broke out in 1856. After the two Opium Wars, the British Crown, via the treaties of Nanking, Tianjin, obligated the Chinese government to pay large sums of money for opium they had seized and destroyed, which were referred to as "reparations". In 1868, as a result of the increased use of opium, the UK restricted the sale of opium in Britain by implementing the 1868 Pharmacy Act. In the United States, control of opium remained under the control of individual US states until the introduction of the Harrison Act in 1914, after 12 international powers signed the International Opium Convention in 1912. Between 1920 and 1933 the Eighteenth Amendment to the United States Constitution banned alcohol in the United States.
Prohibition proved impossible to enforce and resulted in the rise of organized crime, including the modern American Mafia, which identified enormous business opportunities in the manufacturing and sale of illicit liquor. The beginning of the 21st century saw drug use increase in North America and Europe, with a increased demand for marijuana and cocaine; as a result, international organized crime syndicates such as the Sinaloa Cartel and'Ndrangheta have increased cooperation among each other in order to facilitate trans-Atlantic drug-trafficking. Use of another illicit drug, has increased in Europe. Drug trafficking is regarded by lawmakers as a serious offense around the world. Penalties depend on the type of drug, the quantity trafficked, where the drugs are sold and how they are distributed. If the drugs are sold to underage people the penalties for trafficking may be harsher than in other circumstances. Drug smuggling carries severe penalties in many countries. Sentencing may include lengthy periods of incarceration and the death penalty.
In December 2005, Van Tuong Nguyen, a 25-year-old Australian drug smuggler, was hanged in Singapore after being convicted in March 2004. In 2010, two people were sentenced to death in Malaysia for trafficking 1 kilogram of cannabis into the country. Execution is used as a deterrent, many have called upon much more effective measures to be taken by countries to tackle drug trafficking; the countries of drug production and transit are some of the most affected by the drug trade, though countries receiving the illegally imported substances are adversely affected. For example, Ecuador has absorbed up to 300,000 refugees from Colombia who are running from guerrillas and drug lords. While some applied for asylum, others are still illegal immigrants; the drugs that pass from Colombia through Ecuador to other parts of South America create economic and social problems. Honduras, through which an estimated 79% of cocaine passes on its way to the United States, has the highest murder rate in the world. According to the International Crisis Group, the most violent regions in Central America along the Guatemala–Honduras border, are correlated with an abundance of drug trafficking activity.
In many countries worldwide, the illegal drug trade is thought to be directly linked to violent crimes such as murder. This is true in all developing countries, such as Honduras, but is an issue for many developed countries worldwide. In the late 1990s in the United States the Federal Bureau of Investigation estimated that 5% of murders were drug-related. In Colombia, Drug violence can be caused by factors such as, the economy, poor governments, no authority within the law enforcement. After a crackdown by US and Mexican authorities in the first decade of the 21st century as part of tightened border security in the wake of the September 11 attacks, border violence inside Mexico surged; the Mexican government estimates. A report by the UK government's Drug Strategy Unit, leaked to the press, stated that due to the expensive price of addictive drugs heroin and coc
Methamphetamine is a potent central nervous system stimulant, used as a recreational drug and less as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine. Methamphetamine properly refers to a specific chemical, the racemic free base, an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms, it is prescribed over concerns involving human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy. Dextromethamphetamine is a much stronger CNS stimulant than levomethamphetamine. Both methamphetamine and dextromethamphetamine are illicitly trafficked and sold owing to their potential for recreational use; the highest prevalence of illegal methamphetamine use occurs in parts of Asia, in the United States, where racemic methamphetamine, levomethamphetamine, dextromethamphetamine are classified as schedule II controlled substances.
Levomethamphetamine is available as an over-the-counter drug for use as an inhaled nasal decongestant in the United States. Internationally, the production, distribution and possession of methamphetamine is restricted or banned in many countries, due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. While dextromethamphetamine is a more potent drug, racemic methamphetamine is sometimes illicitly produced due to the relative ease of synthesis and limited availability of chemical precursors. In low to moderate doses, methamphetamine can elevate mood, increase alertness and energy in fatigued individuals, reduce appetite, promote weight loss. At high doses, it can induce psychosis, breakdown of skeletal muscle and bleeding in the brain. Chronic high-dose use can precipitate unpredictable and rapid mood swings, stimulant psychosis and violent behavior. Recreationally, methamphetamine's ability to increase energy has been reported to lift mood and increase sexual desire to such an extent that users are able to engage in sexual activity continuously for several days.
Methamphetamine is known to possess a high addiction liability and high dependence liability. Heavy recreational use of methamphetamine may lead to a post-acute-withdrawal syndrome, which can persist for months beyond the typical withdrawal period. Unlike amphetamine, methamphetamine is neurotoxic to human midbrain dopaminergic neurons, it has been shown to damage serotonin neurons in the CNS. This damage includes adverse changes in brain structure and function, such as reductions in grey matter volume in several brain regions and adverse changes in markers of metabolic integrity. Methamphetamine belongs to the substituted phenethylamine and substituted amphetamine chemical classes, it is related to the other dimethylphenethylamines as a positional isomer of these compounds, which share the common chemical formula: C10H15N1. In the United States, dextromethamphetamine hydrochloride, under the trade name Desoxyn, has been approved by the FDA for treating ADHD and obesity in both adults and children.
Methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia. In the United States, methamphetamine's levorotary form is available in some over-the-counter nasal decongestant products; as methamphetamine is associated with a high potential for misuse, the drug is regulated under the Controlled Substances Act and is listed under Schedule II in the United States. Methamphetamine hydrochloride dispensed in the United States is required to include a boxed warning regarding its potential for recreational misuse and addiction liability. Methamphetamine is used recreationally for its effects as a potent euphoriant and stimulant as well as aphrodisiac qualities. According to a National Geographic TV documentary on methamphetamine, an entire subculture known as party and play is based around sexual activity and methamphetamine use. Participants in this subculture, which consists entirely of homosexual male methamphetamine users, will meet up through internet dating sites and have sex.
Due to its strong stimulant and aphrodisiac effects and inhibitory effect on ejaculation, with repeated use, these sexual encounters will sometimes occur continuously for several days on end. The crash following the use of methamphetamine in this manner is often severe, with marked hypersomnia; the party and play subculture is prevalent in major US cities such as San Francisco and New York City. Methamphetamine is contraindicated in individuals with a history of substance use disorder, heart disease, or severe agitation or anxiety, or in individuals experiencing arteriosclerosis, hyperthyroidism, or severe hypertension; the FDA states that individuals who have experienced hypersensitivity reactions to other stimulants in the past or are taking monoamine oxidase inhibitors should not take methamphetamine. The FDA advises individuals with bipolar disorder, elevated blood pressure, liver or kidney problems, psychosis, Raynaud's phenomenon, thyroid problems, tics, or Tourette s
A chemical compound is a chemical substance composed of many identical molecules composed of atoms from more than one element held together by chemical bonds. A chemical element bonded to an identical chemical element is not a chemical compound since only one element, not two different elements, is involved. There are four types of compounds, depending on how the constituent atoms are held together: molecules held together by covalent bonds ionic compounds held together by ionic bonds intermetallic compounds held together by metallic bonds certain complexes held together by coordinate covalent bonds. A chemical formula is a way of expressing information about the proportions of atoms that constitute a particular chemical compound, using the standard abbreviations for the chemical elements, subscripts to indicate the number of atoms involved. For example, water is composed of two hydrogen atoms bonded to one oxygen atom: the chemical formula is H2O. Many chemical compounds have a unique numerical identifier assigned by the Chemical Abstracts Service: its CAS number.
A compound can be converted to a different chemical composition by interaction with a second chemical compound via a chemical reaction. In this process, bonds between atoms are broken in both of the interacting compounds, bonds are reformed so that new associations are made between atoms. Any substance consisting of two or more different types of atoms in a fixed stoichiometric proportion can be termed a chemical compound, it follows from their being composed of fixed proportions of two or more types of atoms that chemical compounds can be converted, via chemical reaction, into compounds or substances each having fewer atoms. The ratio of each element in the compound is expressed in a ratio in its chemical formula. A chemical formula is a way of expressing information about the proportions of atoms that constitute a particular chemical compound, using the standard abbreviations for the chemical elements, subscripts to indicate the number of atoms involved. For example, water is composed of two hydrogen atoms bonded to one oxygen atom: the chemical formula is H2O.
In the case of non-stoichiometric compounds, the proportions may be reproducible with regard to their preparation, give fixed proportions of their component elements, but proportions that are not integral. Chemical compounds have a unique and defined chemical structure held together in a defined spatial arrangement by chemical bonds. Chemical compounds can be molecular compounds held together by covalent bonds, salts held together by ionic bonds, intermetallic compounds held together by metallic bonds, or the subset of chemical complexes that are held together by coordinate covalent bonds. Pure chemical elements are not considered chemical compounds, failing the two or more atom requirement, though they consist of molecules composed of multiple atoms. Many chemical compounds have a unique numerical identifier assigned by the Chemical Abstracts Service: its CAS number. There is varying and sometimes inconsistent nomenclature differentiating substances, which include non-stoichiometric examples, from chemical compounds, which require the fixed ratios.
Many solid chemical substances—for example many silicate minerals—are chemical substances, but do not have simple formulae reflecting chemically bonding of elements to one another in fixed ratios. It may be argued that they are related to, rather than being chemical compounds, insofar as the variability in their compositions is due to either the presence of foreign elements trapped within the crystal structure of an otherwise known true chemical compound, or due to perturbations in structure relative to the known compound that arise because of an excess of deficit of the constituent elements at places in its structure. Other compounds regarded as chemically identical may have varying amounts of heavy or light isotopes of the constituent elements, which changes the ratio of elements by mass slightly. Compounds are held together through a variety of different types of bonding and forces; the differences in the types of bonds in compounds differ based on the types of elements present in the compound.
London dispersion forces are the weakest force of all intermolecular forces. They are temporary attractive forces that form when the electrons in two adjacent atoms are positioned so that they create a temporary dipole. Additionally, London dispersion forces are responsible for condensing non polar substances to liquids, to further freeze to a solid state dependent on how low the temperature of the environment is. A covalent bond known as a molecular bond, involves the sharing of electrons between two atoms; this type of bond occurs between elements that fall close to each other on the periodic table of elements, yet it is observed between some metals and nonmetals. This is due to the mechanism of this type of bond. Elements that fall close to each other on the periodic table tend to have similar electronegativities, which means they have a similar affinity for electrons. Since neither element has a stronger affinity to donate or gain electrons, it causes the elements to share electrons so both elements have a more stable octet.
Ionic bonding occurs when valence electrons are transferred between elements. Opposite to covalent bonding, this chemical bond creates two oppositely charged ions; the metals in ionic bonding
A silanol is a functional group in silicon chemistry with the connectivity Si–O–H. It is related to the hydroxy functional group found in all alcohols. Silanols are invoked as intermediates in organosilicon chemistry and silicate mineralogy. If a silanol contains one or more organic residue, it is an organosilanol; the first isolated example of a silanol was Et3SiOH, reported in 1871 by Albert Ladenburg. He prepared the “silicol” by hydrolysis of Et3SiOEt. Silanols are synthesized by hydrolysis of halosilanes, alkoxysilanes, or aminosilanes. Chlorosilanes are the most common reactants: R3Si–Cl + H2O → R3Si–OH + HClThe hydrolysis of fluorosilanes requires more forcing reagents, i.e. alkali. The alkoxysilanes of the type R3Si are slow to hydrolyze. Compared to the silyl ethers, silyl acetates are faster to hydrolyze, with the advantage that the released acetic acid is less aggressive. For this reason silyl acetates are sometimes recommended for applications. An alternative route involves oxidation of hydrosilanes.
A wide range of oxidants have been employed including air, peracids and potassium permanganate. In the presence of metal catalysts, silanes undergo hydrolysis: R3Si–H + H2O → R3Si–OH + H2 The Si–O bond distance is about 1.65 Å. In the solid state, silanols engage in hydrogen-bonding. Most silanols have only one OH group, e.g. trimethylsilanol. Known are some silanediols, e.g. diphenylsilanediol. For sterically bulky substituents silanetriols have been prepared. Silanols are more acidic than the corresponding alcohols; this trend contrasts with the fact. For Et3SiOH, the pKa is estimated at 13.6 vs. 19 for tert-butyl alcohol. The pKa of Si2OH is 11; because of their greater acidity, silanols can be deprotonated in aqueous solution the arylsilanols. The conjugate base is called a silanolate. Despite the disparity in acidity, the basicities of the two series are similar. Silanols condense to give disiloxanes: 2 R3SiOH → R3Si-O-SiR3 + H2OThe conversions of silyl halides and ethers to siloxanes proceed via silanols.
The sol-gel process, which entails the conversion of, for example, Si4 into hydrated SiO2, proceeds via silanol intermediates. Silanols exist not only as chemical compounds, but are pervasive on the surface of silica and related silicates, their presence is responsible for the absorption properties of silica gel. In chromatography, derivitization of accessible silanol groups in a bonded stationary phase with trimethylsilyl groups is referred to as endcapping. Organosilanols occur as intermediates in industrial processes such as the manufacturing of silicones. Moreover, organosilanols occur as metabolites in the biodegration of small ring silicones in mammals; some silanediols and silanetriols inhibit hydrolytic enzymes such as thermolysin, acetycholinesterase. Silanol refers to a single compound with the formula H3SiOH; the family SiH4−nn are unstable and are of interest to theoretical chemists. The perhydroxylated silanol, sometimes called orthosilicic acid, is discussed in vague terms, but has not been well characterized