1.
Isomer
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An isomer is a molecule with the same molecular formula as another molecule, but with a different chemical structure. That is, isomers contain the number of atoms of each element. Isomers do not necessarily share similar properties, unless they also have the functional groups. There are two forms of isomerism, structural isomerism and stereoisomerism. In structural isomers, sometimes referred to as constitutional isomers, the atoms, Structural isomers have different IUPAC names and may or may not belong to the same functional group. For example, two position isomers would be 2-fluoropropane and 1-fluoropropane, illustrated on the side of the diagram above. In skeletal isomers the main chain is different between the two isomers. This type of isomerism is most identifiable in secondary and tertiary alcohol isomers, tautomers are structural isomers that spontaneously interconvert with each other, even when pure. They have different chemical properties and, as a consequence, distinct reactions characteristic to each form are observed, if the interconversion reaction is fast enough, tautomers cannot be isolated from each other. An example is when they differ by the position of a proton, such as in keto/enol tautomerism, there is, however, another isomer of C3H8O that has significantly different properties, methoxyethane. Unlike the isomers of propanol, methoxyethane has an oxygen connected to two carbons rather than to one carbon and one hydrogen. Methoxyethane is an ether, not an alcohol, because it lacks a hydroxyl group, propadiene and propyne are examples of isomers containing different bond types. Propadiene contains two double bonds, whereas propyne contains one triple bond, in stereoisomers the bond structure is the same, but the geometrical positioning of atoms and functional groups in space differs. This class includes enantiomers which are non-superposable mirror-images of each other, and diastereomers, enantiomers always contain chiral centers and diastereomers often do, but there are some diastereomers that neither are chiral nor contain chiral centers. Another type of isomer, conformational isomers, may be rotamers, diastereomers, for example, ortho- position-locked biphenyl systems have enantiomers. E/Z isomers, which have restricted rotation at a bond, are configurational isomers. They are classified as diastereomers, whether or not they contain any chiral centers, e/Z notation depicts absolute stereochemistry, which is an unambiguous descriptor based on CIP priorities. Cis–trans isomers are used to describe any molecules with restricted rotation in the molecule, for molecules with C=C double bonds, these descriptors describe relative stereochemistry only based on group bulkiness or principal carbon chain, and so can be ambiguous
2.
Stereochemistry
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Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. An important branch of stereochemistry is the study of chiral molecules, stereochemistry is also known as 3D chemistry because the prefix stereo- means three-dimensionality. The study of stereochemistry focuses on stereoisomers and spans the spectrum of organic, inorganic, biological, physical. This property, the physical property in which the two types of tartrate salts differed, is due to optical isomerism. In 1874, Jacobus Henricus van t Hoff and Joseph Le Bel explained optical activity in terms of the arrangement of the atoms bound to carbon. Cahn–Ingold–Prelog priority rules are part of a system for describing a molecules stereochemistry and they rank the atoms around a stereocenter in a standard way, allowing the relative position of these atoms in the molecule to be described unambiguously. A Fischer projection is a way to depict the stereochemistry around a stereocenter. An often cited example of the importance of stereochemistry relates to the thalidomide disaster, thalidomide is a pharmaceutical drug, first prepared in 1957 in Germany, prescribed for treating morning sickness in pregnant women. The drug was discovered to be teratogenic, causing genetic damage to early embryonic growth and development. Some of the proposed mechanisms of teratogenecity involve a different biological function for the -. In the human body however, thalidomide undergoes racemization, even if one of the two enantiomers is administered as a drug, the other enantiomer is produced as a result of metabolism. Accordingly, it is incorrect to state one of the stereoisomer is safe while the other is teratogenic. Thalidomide is currently used for the treatment of diseases, notably cancer. Strict regulations and controls have been enabled to avoid its use by pregnant women and this disaster was a driving force behind requiring strict testing of drugs before making them available to the public. Torsional strain results from resistance to twisting about a bond
3.
Structural isomer
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Structural isomerism, or constitutional isomerism, is a form of isomerism in which molecules with the same molecular formula have bonded together in different orders, as opposed to stereoisomerism. There are multiple synonyms for constitutional isomers, three categories of constitutional isomers are skeletal, positional, and functional isomers. Positional isomers are also called regioisomers, in chain isomerism, or skeletal isomerism, components of the skeleton are distinctly re-ordered to create different structures. Pentane exists as three isomers, n-pentane, isopentane and neopentane, in position isomerism a functional group or other substituent changes position on a parent structure. In the table below, the group can occupy three different positions on an n-pentane chain forming three different compounds. Many aromatic isomers exist because substituents can be positioned on different parts of the benzene ring, only one isomer of phenol or hydroxybenzene exists but cresol or methylphenol has three isomers where the additional methyl group can be placed on three different positions on the ring. Xylenol has one group and two methyl groups and a total of 6 isomers exist. Functional isomers are structural isomers that have the molecular formula. These groups of atoms are called groups, functionalities. Another way to say this is that two compounds with the molecular formula, but different functional groups, are functional isomers. For example, cyclohexane and 1-hexene both have the formula C6H12 and these two are considered functional group isomers because cyclohexane is a cycloalkane and hex-1-ene is an alkene. For two molecules to be functional isomers, they must contain key groups of atoms arranged in particular ways, some of the best examples come from organic chemistry. Depending on how the atoms are arranged, it can represent two different compounds dimethyl ether CH3-O-CH3 or ethanol CH3CH2-O-H, dimethyl ether and ethanol are functional isomers. The carbon chain-oxygen-carbon chain functionality is called an ether, the carbon chain-oxygen-hydrogen functionality is called an alcohol. If the functionalities stay the same, but their locations change, 1-Propanol and 2-propanol are structural isomers, but they are not functional isomers. The functional group is present in both of these compounds, but they are not the same, while some chemists use the terms structural isomer and functional isomer interchangeably, not all structural isomers are functional isomers. Functional isomers are most often identified in chemistry using infrared spectroscopy, infrared radiation corresponds to the energies associated primarily with molecular vibration. The alcohol functionality has a very distinct vibration called OH-stretch that is due to hydrogen bonding, all alcohols in liquid and solid form absorb infrared radiation at certain wavelengths
4.
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
5.
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
6.
Enantiomer
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A single chiral atom or similar structural feature in a compound causes that compound to have two possible structures which are non-superposable, each a mirror image of the other. Each member of the pair is termed an enantiomorph, the property is termed enantiomerism. The presence of multiple features in a given compound increases the number of geometric forms possible. Enantiopure compounds refer to samples having, within the limits of detection and they are sometimes called optical isomers for this reason. Enantiomer members often have different chemical reactions with other enantiomer substances, since many biological molecules are enantiomers, there is sometimes a marked difference in the effects of two enantiomers on biological organisms. Owing to this discovery, drugs composed of one enantiomer can be developed to enhance the pharmacological efficacy. An example is eszopiclone, which is enantiopure and therefore administered in doses that are exactly 1/2 of the older, in the case of eszopiclone, the S enantiomer is responsible for all the desired effects, while the other enantiomer seems to be inactive. A dose of 2 mg of zopiclone must be administered to produce the therapeutic effect as 1 mg of eszopiclone. In chemical synthesis of enantiomeric substances, non-enantiomeric precursors inevitably produce racemic mixtures, in the absence of an effective enantiomeric environment, separation of a racemic mixture into its enantiomeric components is impossible. The R/S system is an important nomenclature system for denoting distinct enantiomers, another system is based on prefix notation for optical activity, - and - or d- and l-. The Latin for left and right is laevus and dexter, respectively, left and right have always had moral connotations, and the Latin words for these are sinister and rectus. The English word right is a cognate of rectus and this is the origin of the D, L and S, R notations, and the employment of prefixes levo- and dextro- in common names. Most compounds that one or more asymmetric carbon atoms show enantiomerism. There are a few compounds that do have asymmetric carbon atoms. An example of such an enantiomer is the sedative thalidomide, which was sold in a number of countries across the world from 1957 until 1961 and it was withdrawn from the market when it was found to cause of birth defects. One enantiomer caused the desirable effects, while the other, unavoidably present in equal quantities. The herbicide mecoprop is a mixture, with the --enantiomer possessing the herbicidal activity. Another example is the antidepressant drugs escitalopram and citalopram, citalopram is a racemate, escitalopram is a pure enantiomer
7.
Mirror image
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A mirror image is a reflected duplication of an object that appears almost identical, but is reversed in the direction perpendicular to the mirror surface. As an optical effect it results from reflection off of such as a mirror or water. It is also a concept in geometry and can be used as a process for 3-D structures. Two-dimensional mirror images can be seen in the reflections of mirrors or other reflecting surfaces, or on a printed surface seen inside out. If we look at an object that is effectively two-dimensional and then turn it towards a mirror, in this example, it is the change in orientation rather than the mirror itself that causes the observed reversal. Another example is when we stand with our backs to the mirror, then we compare the object with its reflection by turning ourselves 180 degrees, towards the mirror. Again we perceive a left-right reversal due to a change in orientation, so, in these examples the mirror does not actually cause the observed reversals. The concept of reflection can be extended to three-dimensional objects, including the inside parts, the term then relates to structural as well as visual aspects. A three-dimensional object is reversed in the perpendicular to the mirror surface. In physics, mirror images are investigated in the subject called geometrical optics, in chemistry, two versions of a molecule, one a mirror image of the other, are called enantiomers if they are not superposable on each other. That is an example of chirality, in general, an object and its mirror image are called enantiomorphs. If a point of an object has coordinates then the image of this point has coordinates, thus reflection is a reversal of the coordinate axis perpendicular to the mirrors surface. In everyday use, a mirror does not reverse right and left, however, there is often a perception of left-right reversal, probably because the left and right of an object are defined by its top and front. Reflection in a mirror does result in a change in chirality, as a consequence, if one looks in a mirror and lets two axes coincide with those in the mirror, then this gives a reversal of the third axis. Similarly, if you stand side-on to a mirror your left and its important to realise there are only two enantiomorphs, the object and its image. So, no matter how the object is oriented towards the mirror, all the images are fundamentally identical. In the photograph of the urn and mirror, the urn is fairly symmetrical front-back, so, its not surprising that no obvious reversal of the urn can be seen in the mirror image. A mirror image appears more obviously three-dimensional if the observer moves and this is because the relative position of objects changes as the observers perspective changes, or is different viewed with each eye
8.
Polarization (waves)
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Polarization is a parameter applying to transverse waves that specifies the geometrical orientation of the oscillations. In a transverse wave the direction of the oscillation is transverse to the direction of motion of the wave, a simple example of a polarized transverse wave is vibrations traveling along a taut string for example in a musical instrument like a guitar string. Depending on how the string is plucked, the vibrations can be in a direction, horizontal direction. Transverse waves that exhibit polarization include electromagnetic waves such as light and radio waves, gravitational waves, in some types of transverse waves the wave displacement is limited to a single direction, so these also dont exhibit polarization. For example, in waves in liquids the wave displacement of the particles is always in a vertical plane. In linear polarization the fields oscillate in a single direction, in circular or elliptical polarization the fields rotate at a constant rate in a plane as the wave travels. Polarized light can be produced by passing unpolarized light through a polarizing filter, some of these are used to make polarizing filters. Light is also partially polarized when it reflects from a surface, according to quantum mechanics, electromagnetic waves consist of particles called photons. When viewed in this way, the polarization of a wave is determined by a quantum mechanical property of photons called their spin. A photon has one of two spins, it can either spin in a right hand sense or a left hand sense about its direction of travel. Circularly polarized electromagnetic waves are composed of photons with one type of spin. Linearly polarized waves consist of numbers of right and left hand spinning photons. Polarization is an important parameter in areas of science dealing with transverse waves, such as optics, seismology, radio, especially impacted are technologies such as lasers, wireless and optical fiber telecommunications, and radar. And incoherent states can be modeled stochastically as a combination of such uncorrelated waves with some distribution of frequencies, phases. Considering a monochromatic wave of optical frequency f, let us take the direction of propagation as the z axis. Being a transverse wave the E and H fields must then contain components only in the x and y directions whereas Ez=Hz=0. Using complex notation, we understand the instantaneous electric and magnetic fields to be given by the real parts of the complex quantities occurring in the following equations. Here ex, ey, hx, and hy are complex numbers, in the second more compact form, as these equations are customarily expressed, these factors are described using the wavenumber k =2 π n / λ and angular frequency ω =2 π f
9.
Optical rotation
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Optical rotation or optical activity is the rotation of the plane of polarization of linearly polarized light as it travels through certain materials. Optical activity occurs only in chiral materials, those lacking microscopic mirror symmetry, unlike other sources of birefringence which alter a beams state of polarization, optical activity can be observed in fluids. This can include gases or solutions of chiral molecules such as sugars, molecules with helical secondary structure such as some proteins and it can also be observed in chiral solids such as certain crystals with a rotation between adjacent crystal planes or metamaterials. The rotation of the plane of polarization may be either clockwise, to the right, for instance, sucrose and camphor are d-rotary whereas cholesterol is l-rotary. For a given substance, the angle by which the polarization of light of a wavelength is rotated is proportional to the path length through the material and proportional to its concentration. The rotation is not dependent on the direction of propagation, unlike the Faraday effect where the rotation is dependent on the direction of the applied magnetic field. Optical activity is measured using a source and polarimeter. Modulation of a liquid crystals optical activity, viewed between two polarizers, is the principle of operation of liquid-crystal displays. The rotation of the orientation of polarized light was first observed in 1811 in quartz by French physicist François Jean Dominique Arago. Jean Baptiste Biot also observed the rotation of the axis of polarization in certain liquids, simple polarimeters have been used since this time to measure the concentrations of simple sugars, such as glucose, in solution. In fact one name for D-glucose, is dextrose, referring to the fact that it causes linearly polarized light to rotate to the right or dexter side. In a similar manner, levulose, more known as fructose. Fructose is even more strongly levorotatory than glucose is dextrorotatory, in 1849, Louis Pasteur resolved a problem concerning the nature of tartaric acid. Pasteur noticed that the crystals come in two forms that are mirror images of one another. Sorting the crystals by hand gave two forms of the compound, Solutions of one form rotate polarized light clockwise, while the other form rotate light counterclockwise, an equal mix of the two has no polarizing effect on light. If the 4 neighbors are all different, then there are two possible orderings of the neighbors around the tetrahedron, which will be mirror images of each other and this led to a better understanding of the three-dimensional nature of molecules. Optical activity occurs due to molecules dissolved in a fluid or due to the fluid itself only if the molecules are one of two stereoisomers, this is known as an enantiomer, the structure of such a molecule is such that it is not identical to its mirror image. In mathematics, this property is known as chirality
10.
Amino acid
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Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an acid are carbon, hydrogen, oxygen. About 500 amino acids are known and can be classified in many ways, in the form of proteins, amino acids comprise the second-largest component of human muscles, cells and other tissues. Outside proteins, amino acids perform critical roles in such as neurotransmitter transport. In biochemistry, amino acids having both the amine and the acid groups attached to the first carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids and they include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins. These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as standard amino acids. The other two are selenocysteine, and pyrrolysine, pyrrolysine and selenocysteine are encoded via variant codons, for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine is generally considered as a form of methionine rather than as a separate proteinogenic amino acid, codon–tRNA combinations not found in nature can also be used to expand the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids also play critical roles within the body. Nine proteinogenic amino acids are called essential for humans because they cannot be created from other compounds by the human body, others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species, because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production of drugs, biodegradable plastics, the first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. Glycine and leucine were discovered in 1820, usage of the term amino acid in the English language is from 1898. Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis, in the structure shown at the top of the page, R represents a side chain specific to each amino acid. The carbon atom next to the group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as amino acids
11.
Glycine
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Glycine is the amino acid that has a single hydrogen atom as its side chain. It is the simplest possible amino acid, the chemical formula of glycine is NH2‐CH2‐COOH. Glycine is one of the amino acids. Its codons are GGU, GGC, GGA, GGG of the genetic code, Glycine is a colorless, sweet-tasting crystalline solid. It is unique among the amino acids in that it is achiral. It can fit into hydrophilic or hydrophobic environments since it exists as zwitterion at natural pH, Glycine was first isolated from gelatin in 1820. The name comes from the ancient Greek word γλυκύς sweet tasting, Glycine was discovered in 1820, by Henri Braconnot who boiled a gelatinous object with sulfuric acid. Glycine is manufactured industrially by treating chloroacetic acid with ammonia, ClCH2COOH +2 NH3 → H2NCH2COOH + NH4Cl About 15 million kg are produced annually in this way, in the USA and in Japan, glycine is produced via the Strecker amino acid synthesis. Glycine is also cogenerated as an impurity in the synthesis of EDTA, arising from reactions of the ammonia coproduct. In aqueous solution, glycine itself is amphoteric, at low pH the molecule can be protonated with a pKa of about 2.4, the nature of glycine in aqueous solution has been investigated by theoretical methods. In solution the ratio of concentrations of the two isomers is independent of both the concentration and of pH. This ratio is simply the equilibrium constant for isomerization, K = / Both isomers of glycine have been observed by microwave spectroscopy in the gas phase. The solid-state structure has been analyzed in detail and this conversion is readily reversible, CO2 + NH+4 + N5, N10-Methylene tetrahydrofolate + NADH + H+ → Glycine + tetrahydrofolate + NAD+ Glycine is coded by codons GGU, GGC, GGA and GGG. Most proteins incorporate only small quantities of glycine, a notable exception is collagen, which contains about 35% glycine. Glycine is degraded via three pathways, the first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to pyruvate by serine dehydratase, in the third pathway of glycine degradation, glycine is converted to glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by lactate dehydrogenase to oxalate in an NAD+-dependent reaction. The half-life of glycine and its elimination from the body varies significantly based on dose, in one study, the half-life was between 0.5 and 4.0 hours
12.
Diastereomer
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Diastereomers are a type of a stereoisomer. Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more of the equivalent stereocenters and are not mirror images of each other, when two diastereoisomers differ from each other at only one stereocenter they are epimers. Each stereocenter gives rise to two different configurations and thus increases the number of stereoisomers by a factor of two, diastereomers differ from enantiomers in that the latter are pairs of stereoisomers that differ in all stereocenters and are therefore mirror images of one another. Enantiomers of a compound more than one stereocenter are also diastereomers of the other stereoisomers of that compound that are not their mirror image. Diastereomers have different physical properties and different chemical reactivity, diastereoselectivity is the preference for the formation of one or more than one diastereomer over the other in an organic reaction. When the single bond between the two centres is free to rotate, cis/trans descriptors are invalid, two widely accepted prefixes used to distinguish diastereomers on sp³-hybridised bonds in an open-chain molecule are syn and anti. Masamune proposed the descriptors which work even if the groups are not on adjacent carbons and it also works regardless of CIP priorities. Syn describes groups on the face while anti describes groups on opposite faces. The concept applies only to the Zigzag projection, the descriptors only describe relative stereochemistry rather than absolute stereochemistry. Two older prefixes still commonly used to distinguish diastereomers are threo, in the case of carbohydrates, when drawn in the Fischer projection the erythro isomer has two identical substituents on the same side and the threo isomer has them on opposite sides. When drawn as a chain, the erythro isomer has two identical substituents on different sides of the plane. The names are derived from the diastereomeric aldoses erythrose and threose and these prefixes are not recommended for use outside of the realm of carbohydrates because their definitions can lead to conflicting interpretations. Another threo compound is threonine, one of the amino acids. The erythro diastereomer is called allo-threonine, if a molecule contains two asymmetric carbons, there are up to 4 possible configurations, and they cannot all be non-superimposable mirror images of each other. The possibilities continue to multiply as there are more asymmetric centers in a molecule, in general, the number of configurational isomers of a molecule can be determined by calculating 2n, where n = the number of chiral centers in the molecule. This holds true except in cases where the molecule has meso forms, for n =3, there are eight stereoisomers. There are four pairs of enantiomers, R, R, R and S, S, S, R, R, S and S, S, R, R, S, S and S, R, R, and R, S, R and S, R, S. There are four diastereomers, because each of the pairs of enantiomers is a diastereomer with respect to the other three, for n =4, there are sixteen stereoisomers, or eight pairs of enantiomers
13.
Meso compound
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A meso compound or meso isomer is a non-optically active member of a set of stereoisomers, at least two of which are optically active. This means that despite containing two or more centers, the molecule is not chiral. A meso compound is superposable on its image and it does not produce a or reading when analyzed with a polarimeter. For example, tartaric acid can exist as any of three stereoisomers depicted below in a Fischer projection, of the four colored pictures at the top of the diagram, the first two represent the meso compound, followed by the optically active pair of dextrotartaric acid and levotartaric acid. The meso compound is bisected by a plane of symmetry that is not present for the non-meso isomers. The meso compound must not be confused with a 50,50 racemic mixture of the two compounds, although neither will rotate light in a polarimeter. It is a requirement for two of the stereocenters in a compound to have at least two substituents in common. For example, in 2, 4-pentanediol, both the second and fourth carbon atoms, which are stereocenters, have all four substituents in common. Since a meso isomer has a mirror image, a compound with a total of n chiral centers cannot attain the theoretical maximum of 2n stereoisomers if one of the stereoisomers is meso. 1, 2-substituted cyclopropane has a meso cis-isomer and two trans-enantiomers, The two cis stereoisomers of 1, 2-substituted cyclohexanes behave like meso compounds at room temperature in most cases. At room temperature, most 1, 2-disubstituted cyclohexanes undergo rapid ring flipping, and as a result, at low temperatures, however, this is not the case, as the activation energy for the ring-flip cannot be overcome, and they therefore behave like enantiomers. Also noteworthy is the fact that when a cyclohexane undergoes a ring flip, the absolute configurations of the sterocenters do not change
14.
E-Z notation
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E-Z configuration, or the E-Z convention, is the IUPAC preferred method of describing the absolute stereochemistry of double bonds in organic chemistry. It is an extension of cis/trans notation that can be used to double bonds having two, three or four substituents. Following the Cahn–Ingold–Prelog priority rules, each substituent on a bond is assigned a priority. If the two groups of higher priority are on sides of the double bond, the bond is assigned the configuration E. If the two groups of higher priority are on the side of the double bond, the bond is assigned the configuration Z. The letters E and Z are conventionally printed in italic type, within parentheses and they are always printed as full capitals, but do not constitute the first letter of the name for English capitalization rules. For organic molecules with multiple alkenes, it is necessary to indicate the alkene location for each E or Z symbol. Molecular geometry Geometric isomerism Panico R, Powell WH, Richer JC, a Guide to IUPAC Nomenclature of Organic Compounds
15.
Atomic number
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The atomic number or proton number of a chemical element is the number of protons found in the nucleus of an atom of that element. It is identical to the number of the nucleus. The atomic number identifies a chemical element. In an uncharged atom, the number is also equal to the number of electrons. The atomic number Z, should not be confused with the mass number A and this number of neutrons, N, completes the weight, A = Z + N. Atoms with the atomic number Z but different neutron numbers N. Historically, it was these atomic weights of elements that were the quantities measurable by chemists in the 19th century. Only after 1915, with the suggestion and evidence that this Z number was also the nuclear charge, loosely speaking, the existence or construction of a periodic table of elements creates an ordering of the elements, and so they can be numbered in order. Dmitri Mendeleev claimed that he arranged his first periodic tables in order of atomic weight, however, in consideration of the elements observed chemical properties, he changed the order slightly and placed tellurium ahead of iodine. This placement is consistent with the practice of ordering the elements by proton number, Z. A simple numbering based on periodic table position was never entirely satisfactory and this central charge would thus be approximately half the atomic weight. This proved eventually to be the case, the experimental position improved dramatically after research by Henry Moseley in 1913. To do this, Moseley measured the wavelengths of the innermost photon transitions produced by the elements from aluminum to gold used as a series of movable anodic targets inside an x-ray tube. The square root of the frequency of these photons increased from one target to the next in an arithmetic progression and this led to the conclusion that the atomic number does closely correspond to the calculated electric charge of the nucleus, i. e. the element number Z. Among other things, Moseley demonstrated that the series must have 15 members—no fewer. After Moseleys death in 1915, the numbers of all known elements from hydrogen to uranium were examined by his method. There were seven elements which were not found and therefore identified as still undiscovered, from 1918 to 1947, all seven of these missing elements were discovered. By this time the first four transuranium elements had also been discovered, in 1915 the reason for nuclear charge being quantized in units of Z, which were now recognized to be the same as the element number, was not understood
16.
Conformational isomerism
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In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted exclusively by rotations about formally single bonds. Such isomers are generally referred to as conformational isomers or conformers and, specifically, rotations about single bonds are restricted by a rotational energy barrier which must be overcome to interconvert one conformer to another. Conformational isomerism arises when the rotation about a bond is relatively unhindered. That is, the barrier must be small enough for the interconversion to occur. Conformational isomers are thus distinct from the classes of stereoisomers where interconversion necessarily involves breaking and reforming of chemical bonds. The study of the energetics between different rotamers is referred to as conformational analysis and it is useful for understanding the stability of different isomers, for example, by taking into account the spatial orientation and through-space interactions of substituents. In addition, conformational analysis can be used to predict and explain product selectivity, mechanisms, the types of conformational isomers are related to the spatial orientations of the substituents between two vicinal atoms. The staggered conformation includes the gauche and anti conformations, depending on the orientations of the two substituents. The energy difference between gauche and anti is 0.9 kcal/mol associated with the energy of the gauche conformer. The anti conformer is, therefore, the most stable, the three eclipsed conformations with dihedral angles of 0°, 120°, and 240° are not considered to be rotamers, but are instead transition states of higher energy. While simple molecules can be described by these types of conformations, more specific examples of conformational isomerism are detailed elsewhere, Ring conformation Cyclohexane conformations with chair and boat conformers. Allylic strain – energetics related to rotation about the bond between sp2 and sp3 carbons. Atropisomerism – due to restricted rotation about a bond, a molecule can become chiral, folding of molecules, where some shapes are stable and functional, but others are not. Three isotherms are given in the depicting the equilibrium distribution of two conformers at different temperatures. At a free energy difference of 0 kcal/mol, this gives a constant of 1. The two have equal energy, neither is more stable, so neither predominates compared to the other. A negative difference in free energy means that a conformer interconverts to a more stable conformation. For example, the ΔG of butane from gauche to anti is −0.9 kcal/mol, therefore the equilibrium constant is 4.5, conversely, a positive difference in free energy means the conformer already is the more stable one, so the interconversion is an unfavorable equilibrium
17.
Cyclohexane conformation
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A cyclohexane conformation is any of several three-dimensional shapes that a cyclohexane molecule can assume while maintaining the integrity of its chemical bonds. The internal angles of a regular hexagon are 120°, while the preferred angle between successive bonds in a carbon chain is about 109. 5°, the tetrahedral angle. Therefore, the ring tends to assume certain non-planar conformations. The most important shapes are called chair, half-chair, boat, the molecule can easily switch between these conformations, and only two of them — chair and twist-boat — can be isolated in pure form. In 1890, Hermann Sachse, a 28-year-old assistant in Berlin and he clearly understood that these forms had two positions for the hydrogen atoms, that two chairs would probably interconvert, and even how certain substituents might favor one of the chair forms. Because he expressed all this in language, few chemists of the time understood his arguments. He had several attempts at publishing these ideas, but none succeeded in capturing the imagination of chemists and his death in 1893 at the age of 31 meant his ideas sank into obscurity. Derek Barton and Odd Hassel shared the 1969 Nobel Prize for work on the conformations of cyclohexane, the carbon-carbon bonds along the cyclohexane ring are sp³ hybrid orbitals, which have tetrahedral symmetry. Therefore, the angles between bonds of a tetravalent carbon atom have a preferred value θ ≈109. 5°, the bonds also have a fairly fixed bond length λ. On the other hand, adjacent carbon atoms are free to rotate about the axis of the bond, there are exactly eight warped polygons with six distinguished corners that have all internal angles equal to θ and all sides equal to λ. In theory, a molecule with any of those ring conformations would be free of angle strain, however, due to interactions between the hydrogen atoms, the angles and bond lengths of the actual chair forms are slightly different from the nominal values. For the same reasons, the boat forms have slightly higher energy than the chair forms. Indeed, the forms are unstable, and deform spontaneously to twist-boat conformations that are local minima of the total energy. Each of the stable ring conformations can be transformed into any other without breaking the ring, however, such transformations must go through other states with stressed rings. In particular, they must go through unstable states where four successive carbon atoms lie on the same plane and these shapes are called half-chair conformations. The two chair conformations have the lowest total energy, and are therefore the most stable, and have D3d symmetry. In the basic chair conformation, the carbons C1 through C6 alternate between two planes, one with C1, C3 and C5, the other with C2, C4. The molecule has an axis perpendicular to these two planes, and is congruent to itself after a rotation of 120° about that axis
18.
Transition state
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The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the corresponding to the highest potential energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules always go on to form products and it is often marked with the double dagger ‡ symbol. The concept of a state has been important in many theories of the rates at which chemical reactions occur. This started with the state theory, which was first developed around 1935 by Eyring, Evans and Polanyi. A collision between reactant molecules may or may not result in a successful reaction, the outcome depends on factors such as the relative kinetic energy, relative orientation and internal energy of the molecules. Even if the partners form an activated complex they are not bound to go on and form products. Because of the rules of quantum mechanics, the state cannot be captured or directly observed. This is sometimes expressed by stating that the state has a fleeting existence. However, cleverly manipulated spectroscopic techniques can get us as close as the timescale of the technique allows, femtochemical IR spectroscopy was developed for precisely that reason, and it is possible to probe molecular structure extremely close to the transition point. Often along the reaction coordinate reactive intermediates are present not much lower in energy from a transition state making it difficult to distinguish between the two, Transition state structures can be determined by searching for first-order saddle points on the potential energy surface of the chemical species of interest. A first-order saddle point is a point of index one, that is. This is further described in the geometry optimization. The Hammond–Leffler Postulate states that the structure of the state more closely resembles either the products or the starting material. A transition state resembles the reactants more than the products is said to be early. Thus, the Hammond–Leffler Postulate predicts a transition state for an endothermic reaction. A dimensionless reaction coordinate that quantifies the lateness of a state can be used to test the validity of the Hammond–Leffler Postulate for a particular reaction. One demonstration of principle is found in the two bicyclic compounds depicted below
19.
Anomer
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An anomer is a type of stereoisomer and epimer found in carbohydrate chemistry. The anomeric carbon is the derived from the carbonyl carbon of the open-chain form of the carbohydrate molecule. Anomerization is the process of conversion of one anomer to the other, two anomers are designated alpha or beta, according to the configurational relationship between the anomeric centre and the anomeric reference atom, hence they are relative stereodescriptors. The anomeric centre in hemiacetals is the anomeric carbon C-1, in hemiketals it is the carbon derived from the carbonyl of the ketone. In aldohexoses the anomeric reference atom is the stereocenter that is farthest from anomeric carbon in the ring, in α-D-glucopyranose the reference atom is C-5. If in the cyclic Fischer projection the exocyclic oxygen atom at the centre is cis to the exocyclic oxygen attached to the anomeric reference atom the anomer is α. If the two oxygens are trans the anomer is β, anomerization is the process of conversion of one anomer to the other. For reducing sugars, anomerization is referred to as mutarotation and occurs readily in solution and is catalyzed by acid and this reversible process typically leads to an anomeric mixture in which eventually an equilibrium is reached between the two single anomers. The ratio of the two anomers is specific for the regarding sugar, for example, regardless of the configuration of the starting D-glucose, a solution will gradually move towards being a mixture of approximately 64% β-D-glucopyranoside and 36% of α-D-glucopyranose. As the ratio changes, the rotation of the mixture changes. Though the cyclic forms of sugars are usually heavily favoured, hemiacetals in aqueous solution are in equilibrium with their open-chain forms, in aldohexoses this equilibrium is established as the hemiacetal bond between C-1 and C-5 oxygen is cleaved and reformed. When the hemiacetal group is reformed, the OH group on C-5 may attack either of the two distinct sides of the aldehyde group on C-1. Which side it attacks on determines whether the α or β anomer is formed, anomerization of glycosides typically occurs under acidic conditions. Anomers are different in structure, and thus have different stabilizing and destabilizing effects from each other, the major contributors to the stability of a certain anomer are, The anomeric effect, which stabilizes the anomer that has an electron withdrawing group in axial orientation on the ring. This effect is abolished in polar solvents such as water,1, 3-diaxial interactions, which usually destabilize the anomer that has the anomeric group in an axial orientation on the ring. This effect is noticeable in pyranoses and other six-membered ring compounds. This is a factor in water. Hydrogen bonds between the group and other groups on the ring, leading to stabilization of the anomer
20.
Atropisomer
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The word atropisomer was coined in application to a theoretical concept by German biochemist Richard Kuhn for Karl Freudenbergs seminal Stereochemie volume in 1933. Atropisomerism was first experimentally detected in a tetra substituted biphenyl, a diacid, by George Christie, the importance of atropisomers arises to significant degree because with sufficient stability of a conformer, they can display axial chirality. Atropisomers that display axial chirality often have substituents ortho to the joining the aryl rings. The degree of hindrance correlates with the van der Waals radii of the particular substituents, determining the axial stereochemistry of biaryl atropisomers can be accomplished through the use of a Newman projection along the axis of hindered rotation. The ortho, and in some cases meta substituents are first assigned priority based on Cahn–Ingold–Prelog priority rules, in the example shown, A has priority over B. One way to synthesize these axially chiral biaryl compounds is through a direct atroposelective coupling e. g. Ullmann coupling, Suzuki-Miyaura reaction, or palladium-catalyzed arylation of arenes. Enantioselective coupling can be achieved through the use of a leaving group on one of the biaryls or under oxidative conditions that utilize chiral amines to set the axial configuration. Another method of synthesizing atropisomers is through the use of aromatic amides, by utilizing the planar rigid amide bond as seen in amino acids, and adding larger groups to the ortho position, chemists have been able to synthesize single atropisomers. The atropisomer is an iodoaryl compound synthesised starting from -valine and exists as the isomer, the interconversion barrier between the two is 24.3 kcal/mol. The isomer can be obtained exclusively from this mixture by recrystallisation from hexanes, the iodine group is homolytically removed to form an aryl radical by a tributyltin hydride/triethylboron/oxygen mixture as in the Barton-McCombie reaction. In this way the isomer yields the dihydroindolone, the most important class of atropisomers are biaryls such as diphenic acid, which is a derivative of biphenyl with a complete set of ortho substituents. Heteroaromatic analogues of the biphenyl compounds also exist, where hindered rotation occurs about a carbon-nitrogen or a nitrogen-nitrogen bond, others are dimers of naphthalene derivatives such as 1, 1-bi-2-naphthol. In a similar way, aliphatic ring systems like cyclohexanes linked through a bond may display atropisomerism provided that bulky substituents are present. The use of chiral biaryl compounds such as BINAP, QUINAP. Their ability to provide stereoinduction has led to use in metal catalyzed hydrogenation, epoxidation, addition, other reactions that can be catalyzed by the use of chiral biaryl compounds are the Grignard reaction, Ullmann reaction, and the Suzuki reaction. A recent example in the area of chiral biaryl asymmetric catalysis employs a five-membered imidazole as part of the atropisomer scaffold and this specific phosphorus, nitrogen-ligand has been shown to perform enantioselective A3-coupling. Some natural products can be used as drugs and an example of this is mastigophorene A. Mastigophorene A has been found to aid in nerve growth. Other examples of naturally occurring atropisomers include vancomycin isolated from an Actinobacterium, and knipholone, knipholone, with its axial chirality, occurs in nature and has been shown to offer good antimalarial and antitumor activities particularly in the M form
21.
Covalent bond
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A covalent bond, also called a molecular bond, is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs, for many molecules, the sharing of electrons allows each atom to attain the equivalent of a full outer shell, corresponding to a stable electronic configuration. Covalent bonding includes many kinds of interactions, including σ-bonding, π-bonding, metal-to-metal bonding, agostic interactions, bent bonds, the term covalent bond dates from 1939. In the molecule H2, the atoms share the two electrons via covalent bonding. Covalency is greatest between atoms of similar electronegativities, thus, covalent bonding does not necessarily require that the two atoms be of the same elements, only that they be of comparable electronegativity. Covalent bonding that entails sharing of electrons more than two atoms is said to be delocalized. The term covalence in regard to bonding was first used in 1919 by Irving Langmuir in a Journal of the American Chemical Society article entitled The Arrangement of Electrons in Atoms and Molecules. Langmuir wrote that we shall denote by the term covalence the number of pairs of electrons that an atom shares with its neighbors. The idea of covalent bonding can be traced several years before 1919 to Gilbert N. Lewis and he introduced the Lewis notation or electron dot notation or Lewis dot structure, in which valence electrons are represented as dots around the atomic symbols. Pairs of electrons located between atoms represent covalent bonds, multiple pairs represent multiple bonds, such as double bonds and triple bonds. An alternative form of representation, not shown here, has bond-forming electron pairs represented as solid lines, Lewis proposed that an atom forms enough covalent bonds to form a full outer electron shell. In the diagram of methane shown here, the atom has a valence of four and is, therefore, surrounded by eight electrons, four from the carbon itself. Each hydrogen has a valence of one and is surrounded by two electrons – its own one electron plus one from the carbon, walter Heitler and Fritz London are credited with the first successful quantum mechanical explanation of a chemical bond in 1927. Their work was based on the valence bond model, which assumes that a bond is formed when there is good overlap between the atomic orbitals of participating atoms. Atomic orbitals have specific directional properties leading to different types of covalent bonds, sigma bonds are the strongest covalent bonds and are due to head-on overlapping of orbitals on two different atoms. A single bond is usually a σ bond, pi bonds are weaker and are due to lateral overlap between p orbitals. A double bond between two given atoms consists of one σ and one π bond, and a bond is one σ. Covalent bonds are also affected by the electronegativity of the atoms which determines the chemical polarity of the bond
22.
Absolute configuration
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Absolute configurations for a chiral molecule are most often obtained by X-ray crystallography. All enantiomerically pure chiral molecules crystallise in one of the 65 Sohncke groups, alternative techniques are Optical rotatory dispersion, vibrational circular dichroism and the use of chiral shift reagents in proton NMR and Coulomb Explosion Imaging. When the absolute configuration is obtained the assignment of R or S is based on the Cahn–Ingold–Prelog priority rules, absolute configurations are also relevant to characterization of crystals. Until 1951 it was not possible to obtain the absolute configuration of chiral compounds and it was at some time decided that -glyceraldehyde was the -enantiomer. The configuration of chiral compounds was then related to that of -glyceraldehyde by sequences of chemical reactions. For example, oxidation of -glyceraldehyde with mercury oxide gives -glyceric acid, thus the absolute configuration of -glyceric acid must be the same as that of -glyceraldehyde. Nitric acid oxidation of -isoserine gives -glyceric acid, establishing that -isoserine also has the absolute configuration. -Isoserine can be converted by a process of bromination and zinc reduction to give -lactic acid. If a reaction gave the enantiomer of a configuration, as indicated by the opposite sign of optical rotation. The compound investigated was -sodium rubidium tartrate and from its configuration it was deduced that the original guess for -glyceraldehyde was correct, the R / S system is an important nomenclature system for denoting enantiomers. is written in italics and parentheses. If there are multiple chiral carbons, e. g. a number specifies the location of the carbon preceding each configuration, the R / S system also has no fixed relation to the D/L system. For example, the one of serine contains a hydroxyl group. If a thiol group, -SH, were swapped in for it, but this substitution would invert the molecules R / S labeling, because the CIP priority of CH2OH is lower than that for CO2H but the CIP priority of CH2SH is higher than that for CO2H. In the D/L system, they are nearly all consistent—naturally occurring amino acids are all L, in the R / S system, they are mostly S, but there are some common exceptions. An enantiomer can be named by the direction in which it rotates the plane of polarized light, if it rotates the light clockwise, that enantiomer is labeled. The and isomers have also been termed d- and l-, respectively, naming with d- and l- is easy to confuse with D- and L- labeling and is therefore discouraged by IUPAC. An optical isomer can be named by the configuration of its atoms. The D/L system, not to be confused with the d- and l-system, see above, glyceraldehyde is chiral itself, and its two isomers are labeled D and L
23.
International Union of Pure and Applied Chemistry
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The International Union of Pure and Applied Chemistry /ˈaɪjuːpæk/ or /ˈjuːpæk/ is an international federation of National Adhering Organizations that represents chemists in individual countries. It is a member of the International Council for Science, IUPAC is registered in Zürich, Switzerland, and the administrative office, known as the IUPAC Secretariat, is in Research Triangle Park, North Carolina, United States. This administrative office is headed by IUPACs executive director, currently Lynn Soby, IUPAC was established in 1919 as the successor of the International Congress of Applied Chemistry for the advancement of chemistry. Its members, the National Adhering Organizations, can be national chemistry societies, national academies of sciences, there are fifty-four National Adhering Organizations and three Associate National Adhering Organizations. IUPACs Inter-divisional Committee on Nomenclature and Symbols is the world authority in developing standards for the naming of the chemical elements. Since its creation, IUPAC has been run by different committees with different responsibilities. These committees run different projects which include standardizing nomenclature, finding ways to bring chemistry to the world, IUPAC is best known for its works standardizing nomenclature in chemistry and other fields of science, but IUPAC has publications in many fields including chemistry, biology and physics. IUPAC is also known for standardizing the atomic weights of the elements through one of its oldest standing committees, the need for an international standard for chemistry was first addressed in 1860 by a committee headed by German scientist Friedrich August Kekulé von Stradonitz. This committee was the first international conference to create an international naming system for organic compounds, the ideas that were formulated in that conference evolved into the official IUPAC nomenclature of organic chemistry. IUPAC stands as a legacy of this meeting, making it one of the most important historical international collaborations of chemistry societies, since this time, IUPAC has been the official organization held with the responsibility of updating and maintaining official organic nomenclature. IUPAC as such was established in 1919, one notable country excluded from this early IUPAC is Germany. Germanys exclusion was a result of prejudice towards Germans by the Allied powers after World War I, Germany was finally admitted into IUPAC during 1929. However, Nazi Germany was removed from IUPAC during World War II, during World War II, IUPAC was affiliated with the Allied powers, but had little involvement during the war effort itself. After the war, East and West Germany were eventually readmitted to IUPAC, since World War II, IUPAC has been focused on standardizing nomenclature and methods in science without interruption. In 2016, IUPAC denounced the use of chlorine as a chemical weapon, the letter stated, Our organizations deplore the use of chlorine in this manner. According to the CWC, the use, stockpiling, distribution, IUPAC is governed by several committees that all have different responsibilities. Each committee is made up of members of different National Adhering Organizations from different countries, the steering committee hierarchy for IUPAC is as follows, All committees have an allotted budget to which they must adhere. Any committee may start a project, if a projects spending becomes too much for a committee to continue funding, it must take the issue to the Project Committee
24.
IUPAC books
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The Compendium of Chemical Terminology is a book published by the International Union of Pure and Applied Chemistry containing internationally accepted definitions for terms in chemistry. Work on the first edition was initiated by Victor Gold, hence its informal name, the first edition was published in 1987 and the second edition, edited by A. D. McNaught and A. Wilkinson, was published in 1997. A slightly expanded version of the Gold Book is also freely searchable online, translations have also been published in French, Spanish and Polish
25.
International Standard Book Number
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The International Standard Book Number is a unique numeric commercial book identifier. An ISBN is assigned to each edition and variation of a book, for example, an e-book, a paperback and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, the method of assigning an ISBN is nation-based and varies from country to country, often depending on how large the publishing industry is within a country. The initial ISBN configuration of recognition was generated in 1967 based upon the 9-digit Standard Book Numbering created in 1966, the 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108. Occasionally, a book may appear without a printed ISBN if it is printed privately or the author does not follow the usual ISBN procedure, however, this can be rectified later. Another identifier, the International Standard Serial Number, identifies periodical publications such as magazines, the ISBN configuration of recognition was generated in 1967 in the United Kingdom by David Whitaker and in 1968 in the US by Emery Koltay. The 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108, the United Kingdom continued to use the 9-digit SBN code until 1974. The ISO on-line facility only refers back to 1978, an SBN may be converted to an ISBN by prefixing the digit 0. For example, the edition of Mr. J. G. Reeder Returns, published by Hodder in 1965, has SBN340013818 -340 indicating the publisher,01381 their serial number. This can be converted to ISBN 0-340-01381-8, the check digit does not need to be re-calculated, since 1 January 2007, ISBNs have contained 13 digits, a format that is compatible with Bookland European Article Number EAN-13s. An ISBN is assigned to each edition and variation of a book, for example, an ebook, a paperback, and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, a 13-digit ISBN can be separated into its parts, and when this is done it is customary to separate the parts with hyphens or spaces. Separating the parts of a 10-digit ISBN is also done with either hyphens or spaces, figuring out how to correctly separate a given ISBN number is complicated, because most of the parts do not use a fixed number of digits. ISBN issuance is country-specific, in that ISBNs are issued by the ISBN registration agency that is responsible for country or territory regardless of the publication language. Some ISBN registration agencies are based in national libraries or within ministries of culture, in other cases, the ISBN registration service is provided by organisations such as bibliographic data providers that are not government funded. In Canada, ISBNs are issued at no cost with the purpose of encouraging Canadian culture. In the United Kingdom, United States, and some countries, where the service is provided by non-government-funded organisations. Australia, ISBNs are issued by the library services agency Thorpe-Bowker
26.
Enantioselective synthesis
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Enantioselective synthesis, also called chiral synthesis or asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as, a reaction in which one or more new elements of chirality are formed in a substrate molecule. Put more simply, it is the synthesis of a compound by a method that favors the formation of a specific enantiomer or diastereomer, many of the building blocks of biological systems, such as sugars and amino acids, are produced exclusively as one enantiomer. As a result, living systems possess a degree of chemical chirality. Examples of this selectivity include, Flavour, the sweetener aspartame has two enantiomers. L-aspartame tastes sweet, yet D-aspartame is tasteless Odor, R--carvone smells like spearmint yet S--carvone, drug effectiveness, the antidepressant drug Citalopram is sold as a racemic mixture. However, studies have shown only the - enantiomer is responsible for the drugs beneficial effects. Drug safety, D‑penicillamine is used in therapy and for the treatment of rheumatoid arthritis. However L‑penicillamine is toxic as it inhibits the action of pyridoxine, as such, enantioselective synthesis is of great importance, but it can also be difficult to achieve. Asymmetric induction can occur intramolecularly when given a starting material. This behaviour can be exploited, especially when the goal is to make several consecutive chiral centres to give a specific enantiomer of a specific diastereomer. An aldol reaction, for example, is inherently diastereoselective, if the aldehyde is enantiopure, enantioselective catalysis is a widely practiced method for generating chiral compounds. Enantiomers possess identical enthalpies and entropies and hence should be produced in equal amounts by an undirected process – leading to a racemic mixture, the nonselectivity can be biased using a chiral feature that favors the formation of one enantiomer over another via interactions at the transition state. Enantioselectivity is usually determined by the rates, k1/k2, of an enantiodifferentiating step. The differing barrier heights, ΔΔG*, for these divergent steps determines the rates, k1/k2 = 10^ k1/k2 is also sensitive to temperature. In general, enantioselective catalysis are chiral coordination complexes, catalysis is effective for a broader range of transformations than any other method of enantioselective synthesis. The catalysts are almost invariably rendered chiral by using chiral ligands, most enantioselective catalysts are effective at low substrate/catalyst ratios. Given their high efficiencies, they are suitable for industrial scale synthesis
27.
Planar chirality
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Planar chirality is the special case of chirality for two dimensions. Most fundamentally, planar chirality is a term, finding use in chemistry, physics and related physical sciences, for example, in astronomy, optics. Recent occurrences in latter two fields are dominated by microwave applications and micro- and nanostructured planar interfaces for visible and infrared light. This term is used in contexts, e. g. Planar chirality is also exhibited by molecules like -cyclooctene, some di- or poly-substituted metallocenes. Nature rarely provides planar chiral molecules, cavicularin being an exception, when viewed from the side of the pilot atom, if the three atoms form a clockwise direction when followed in order of priority, the molecule is assigned as R, otherwise it is assigned as S. The study of chiral metamaterials has revealed that planar chirality is associated with an optical effect. Planar chiral metamaterials, which are also anisotropic and lossy exhibit different total transmission levels for the same circularly polarized wave incident on their front, in particular left-handed and right-handed circularly polarized waves experience opposite directional transmission asymmetries
28.
Chiral ligand
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In chemistry a chiral ligand is a specially adapted ligand used for asymmetric synthesis. This ligand is an organic compound that combines with a metal center by chelation to form an asymmetric catalyst. This catalyst engages in a reaction and transfers its chirality to the reaction product which as a result also becomes chiral. Many thousands of chiral ligands have been prepared and tested since then and these ligands are therefore called privileged ligands. Important members depicted below are BINOL, BINAP, TADDOL, DIOP, BOX and DuPhos, other members are Salen, cinchona alkaloids and phosphoramidites. Many of these ligands possess C2 symmetry which limits the number of possible reaction pathways, chiral ligands work asymmetric induction somewhere along the reaction coordinate. The image depicted on the right gives an idea how a chiral ligand may induce an enantioselective reaction. The ligand has C2 symmetry with its nitrogen, oxygen or phosphorus atoms hugging a central metal atom, in this particular ligand the right side is sticking out and its left side points away. The substrate in this reduction is acetophenone and the reagent a hydride ion, in absence of the metal and the ligand the re face approach of the hydride ion gives the -enantiomer and the si face approach the -enantiomer in equal amounts. The ligand/metal presence changes all that, the re face will simply hit the chiral fence. Note that when the ligand is replaced by its image the other enantiomer will form. Also note that if the bulk of both carbonyl substituents is very similar the strategy will fail
29.
Axial chirality
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Certain allene compounds and spirans also display axial chirality. The enantiomers of chiral compounds are usually given the stereochemical labels Ra. The designations are based on the same Cahn-Ingold-Prelog priority rules used for tetrahedral stereocenters and this property can also be called helicity, since the axis of the structure has a helical, propeller, or screw-shaped geometry. P or Δ is a helix, where M or Λ is a left-handed helix. The P/M or Δ/Λ terminology is used particularly for molecules that resemble a helix. It can also be applied to other structures having axial chirality by considering the helical orientation of the front vs back Cahn–Ingold–Prelog rankings, axial Chirality in 6, 6-Dinitrobiphenyl-2, 2-dicarboxylic acid 3D representation
30.
Enantiomeric excess
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Enantiomeric excess is a measurement of purity used for chiral substances. It reflects the degree to which a sample contains one enantiomer in greater amounts than the other, a racemic mixture has an ee of 0%, while a single completely pure enantiomer has an ee of 100%. A sample with 70% of one enantiomer and 30% of the other has an ee of 40%, E e = ×100 The enantiomeric excess can be determined in another way if we know the amount of each enantiomer produced. For mixtures of diastereomers, there are analogous definitions and uses for diastereomeric excess, as an example, a sample with 70% of R isomer and 30% of S will have an enantiomeric excess of 40%. This can also be thought of as a mixture of 40% pure R with 60% of a racemic mixture, a non-racemic mixture of two enantiomers will have a net optical rotation. It is possible to determine the rotation of the mixture and, with knowledge of the specific rotation of the pure enantiomer. This has led to use the two terms as interchangeable, especially because optical purity was the traditional way of measuring enantiomeric excess. However, other such as chiral column chromatography and NMR spectroscopy can now be used for measuring the amount of each enantiomer individually. The ideal equivalence between enantiomeric excess and optical purity does not always hold. d. in the succinic acid example the optical activity at 50% ee is lower than expected, the specific rotation of enantiopure 1-phenylethanol can be enhanced by the addition of achiral acetophenone as an impurity. The term enantiomeric excess was introduced in 1971 by Morrison and Mosher in their publication Asymmetric Organic Reactions, the use of enantiomeric excess has established itself because of its historic ties with optical rotation. The same arguments are valid for changing diastereomeric excess to diastereomeric ratio
31.
Diastereomeric excess
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Enantiomeric excess is a measurement of purity used for chiral substances. It reflects the degree to which a sample contains one enantiomer in greater amounts than the other, a racemic mixture has an ee of 0%, while a single completely pure enantiomer has an ee of 100%. A sample with 70% of one enantiomer and 30% of the other has an ee of 40%, E e = ×100 The enantiomeric excess can be determined in another way if we know the amount of each enantiomer produced. For mixtures of diastereomers, there are analogous definitions and uses for diastereomeric excess, as an example, a sample with 70% of R isomer and 30% of S will have an enantiomeric excess of 40%. This can also be thought of as a mixture of 40% pure R with 60% of a racemic mixture, a non-racemic mixture of two enantiomers will have a net optical rotation. It is possible to determine the rotation of the mixture and, with knowledge of the specific rotation of the pure enantiomer. This has led to use the two terms as interchangeable, especially because optical purity was the traditional way of measuring enantiomeric excess. However, other such as chiral column chromatography and NMR spectroscopy can now be used for measuring the amount of each enantiomer individually. The ideal equivalence between enantiomeric excess and optical purity does not always hold. d. in the succinic acid example the optical activity at 50% ee is lower than expected, the specific rotation of enantiopure 1-phenylethanol can be enhanced by the addition of achiral acetophenone as an impurity. The term enantiomeric excess was introduced in 1971 by Morrison and Mosher in their publication Asymmetric Organic Reactions, the use of enantiomeric excess has established itself because of its historic ties with optical rotation. The same arguments are valid for changing diastereomeric excess to diastereomeric ratio
32.
Chiral derivatizing agent
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Analysis can be conducted by spectroscopy or by chromatography. The use of chiral derivatizing agents has declined with the popularization of chiral HPLC, besides analysis, chiral derivatization is also used for chiral resolution, the actual physical separation of the enantiomers. Since NMR spectroscopy has been available to chemists, there have been studies on the applications of this technique. One of these noted the difference in the shift of two diastereomers. Conversely, two compounds that are enantiomers have the same NMR spectral properties, the first popular example of this technique was published in 1969 by Harry S. Mosher. The chiral agent used was a single enantiomer of MTPA, also known as Moshers acid, the corresponding acid chloride is also known as Moshers acid chloride, and the resultant diastereomeric esters are known as Moshers esters. Another system is Pirkles Alcohol developed in 1977, the reaction of the CDA with both enantiomers should go to completion under reaction conditions. This acts to avoid enrichment or depletion of one enantiomer of the analyte by kinetic resolution, CDA must not racemize under derivatization or analysis conditions. Its attachment should be enough so that the substrate does not racemize either. If analysis is completed by HPLC, the CDA must contain a chromophore to enhance detectability, if analysis is completed by NMR, the CDA should have a functional group that gives a singlet in the resultant NMR spectrum, where the singlet must be remote from other peaks. Moshers acid, via its acid derivative, reacts readily with alcohols and amines to give esters and amides. The lack of an alpha-proton on the acid prevents loss of stereochemical fidelity under the reaction conditions, thus, using an enantiomerically pure Moshers acid allows for determination of the configuration of simple chiral amines and alcohols. For example, the - and -enantiomers of 1-phenylethanol react with acid chloride to yield - and -diastereomers, respectively. A newer chiral derivatizing agent, α-cyano-α-fluoro -acetic acid was prepared in optically pure form by the chiral HPLC separation of a racemic 2-CFNA methyl ester and this ester was obtained by fluorination of methyl α-cyano acetate with FClO3. 2-CFNA has been shown to be a superior CDA than Mosher’s agent to determine the enantiomeric excess of a primary alcohol, upon reaction of a CDA with the target analyte, chromatography can be used to separate the resulting products. In general, chromatography can be used to separate chiral compounds to bypass difficult crystallizations and/or to collect all diastereomer pairs in solution, chromatography also has many variations with a wide array of applicability to diverse categories of molecules. Although Helmchen’s postulates are specific for amides on silica gel using liquid chromatography, Helmchen’s Postulates are, Conformations are the same is a in solution and when adsorbed. Diastereomers bind to surfaces mainly with hydrogen bonding, significant resolution of diastereomers is only expected when molecules can adsorb to silica through two contact points
33.
Chiral resolution
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Chiral resolution in stereochemistry is a process for the separation of racemic compounds into their enantiomers. It is an important tool in the production of optically active drugs, other terms with the same meaning are optical resolution and mechanical resolution. One disadvantage of chiral resolution of racemates compared to direct asymmetric synthesis of one of the enantiomers is that only 50% of a desired enantiomer is obtained, 5-10% of all racemates are known to crystallize as mixtures of enantiopure crystals, so-called conglomerates. Louis Pasteur was the first to conduct chiral resolution when he discovered the concept of activity by the manual separation of left-handed and right-handed tartaric acid crystals in 1849. This type of resolution, called spontaneous resolution, has also demonstrated with racemic methadone. In a typical setup 50 grams dl-methadone is dissolved in petroleum ether, two millimeter-sized d- and l-crystals are added and after stirring for 125 hours at 40 °C two large d- and l-crystals are recovered in 50% yield. Another form of direct crystallization is preferential crystallization also called resolution by entrainment of one of the enantiomers, for example, an added seed of -hydrobenzoin to an ethanol solution of -hydrobenzoin will have the -enantiomer crystallizing out and after 15 cycles 97% optical purity can be obtained. Derivatization of racemic compounds is possible with optically pure reagents forming pairs of diastereomers which can be separated by conventional techniques in physical chemistry, derivatization is possible by salt formation between an amine and a carboxylic acid. Simple deprotonation affords the pure enantiomer, examples of chiral derivatizing agents are tartaric acid and brucine. The method was introduced by Louis Pasteur in 1853 by resolving racemic tartaric acid with optically active -cinchotoxine, the alcohol -enantiomer forms an insoluble diastereomeric salt with the mandelic acid and can be filtered from the solution. Simple deprotonation with sodium hydroxide liberates free -alcohol, in the meanwhile the -alcohol remains in solution unaffected and is recycled back to the racemic mixture by epimerization with hydrochloric acid in toluene. This process is known as RRR synthesis in which the Rs stand for Resolution-Racemization-Recycle, in chiral column chromatography the stationary phase is made chiral with similar resolving agents as described above
34.
Recrystallization (chemistry)
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In chemistry, recrystallization is a technique used to purify chemicals. By dissolving both impurities and a compound in a solvent, either the desired compound or impurities can be removed from the solution. It is named for the crystals often formed when the compound precipitates out, alternatively, recrystallization can refer to the natural growth of larger ice crystals at the expense of smaller ones. In chemistry, recrystallization is a procedure for purifying compounds, the most typical situation is that a desired compound A is contaminated by a small amount of impurity B. There are various methods of purification that may be attempted, recrystallization being one of them, the solution is then allowed to cool. As the solution cools the solubility of compounds in solution drops and this results in the desired compound dropping from solution. The slower the rate of cooling, the bigger the crystals form, in an ideal situation the solubility product of the impurity, B, is not exceeded at any temperature. In that case the solid crystals will consist of pure A, the solid crystals are collected by filtration and the filtrate is discarded. If the solubility product of the impurity is exceeded, some of the impurity will co-precipitate, however, because of the relatively low concentration of the impurity, its concentration in the precipitated crystals will be less than its concentration in the original solid. Repeated recrystallization will result in an even purer crystalline precipitate, the purity is checked after each recrystallization by measuring the melting point, since impurities lower the melting point. NMR spectroscopy can also be used to check the level of impurity, repeated recrystallization results in some loss of material because of the non-zero solubility of compound A. The crystallization process requires a step, such as the addition of a seed crystal. In the laboratory a minuscule fragment of glass, produced by scratching the side of the glass recrystallization vessel, successful recrystallization depends on finding the right solvent. This is usually a combination of prediction/experience and trial/error, the compounds must be more soluble at the higher temperature than at the lower temperatures. Any insoluble impurity is removed by the technique of hot filtration and this method is the same as the above but where two solvents are used. This relies on both compound A and impurity B being soluble in a first solvent, a second solvent is slowly added. Either compound A or impurity B will be insoluble in this solvent and precipitate, thus the proportion of first and second solvents is critical. Typically the second solvent is added slowly until one of the compounds begins to crystallize from solution, heating is not required for this technique but can be used
35.
Kinetic resolution
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In organic chemistry, kinetic resolution is a means of differentiating two enantiomers in a racemic mixture. This enantiomeric excess of the starting material continually rises as more product is formed. Kinetic resolution relies upon differences in reactivity between enantiomers or enantiomeric complexes, Kinetic resolution is a concept in organic chemistry and can be used for the preparation of chiral molecules in organic synthesis. The first reported kinetic resolution was achieved by Louis Pasteur, after reacting aqueous racemic ammonium tartrate with a mold from Penicillium glaucum, he reisolated the remaining tartrate and found it was levorotatory. The chiral microorganisms present in the mold catalyzed the metabolization of -tartrate selectively, Kinetic resolution by synthetic means was first reported by Marckwald and McKenzie in 1899 in the esterification of racemic mandelic acid with optically active -menthol. With an excess of the racemic acid present, they observed the formation of the derived from -mandelic acid to be quicker than the formation of the ester from -mandelic acid. The unreacted acid was observed to have an excess of -mandelic acid. The importance of observation was that, in theory, if a half equivalent of -menthol had been used. This observation led to the kinetic resolution of other chiral acids. Kinetic resolution is a method for irreversibly differentiating a pair of enantiomers due to different activation energies. In the image below, the R enantiomer has a lower Δ G ‡, the ideal kinetic resolution is that in which only one enantiomer reacts, i. e. kR>>kS. The selectivity of a resolution is related to the rate constants of the reaction of the R and S enantiomers, kR and kS respectively, by s=kR/kS. This selectivity can also be referred to as the rates of reaction. This can be written in terms of the energy difference between the high- and low-energy transitions states, Δ Δ G ‡. S = k R k S = e Δ Δ G ‡ / R T The selectivity can also be expressed in terms of ee of the starting material and conversion. Note that for c=0, which signifies the beginning of the reaction, S0 = R0 =12, C can be generated with t as the parameter and different values of s generating different curves, as shown below. As can be seen, high enantiomeric excesses are much more attainable for the unreacted starting material. There is however a tradeoff between ee and conversion, with higher ee obtained at higher conversion, and therefore lower isolated yield, for example, with a selectivity factor of just 10, 99% ee is possible with approximately 70% conversion, resulting in a yield of about 30%
36.
Asymmetric induction
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Asymmetric induction is a key element in asymmetric synthesis. Asymmetric induction was introduced by Hermann Emil Fischer based on his work on carbohydrates, internal asymmetric induction makes use of a chiral center bound to the reactive center through a covalent bond and remains so during the reaction. The starting material is derived from chiral pool synthesis. In relayed asymmetric induction the chiral information is introduced in a separate step, special synthons are called chiral auxiliaries. In external asymmetric induction chiral information is introduced in the state through a catalyst of chiral ligand. This method of synthesis is economically most desirable. Several models exist to describe chiral induction at carbonyl carbons during nucleophilic additions and these models are based on a combination of steric and electronic considerations and are often in conflict with each other. Models have been devised by Cram, Cornforth, Felkin and others, the Crams rule of asymmetric induction developed by Donald J. Cram in 1952 is an early concept relating to the prediction of stereochemistry in certain acyclic systems. The rule indicates that the presence of a center in a molecule induces the formation of an asymmetric center adjacent to it based on steric hindrance. In experiment one 2-phenylpropionaldehyde was reacted with the Grignard reagent of bromobenzene to 1, 2-diphenyl-1-propanol as a mixture of diastereomers, now a hydride anion is the nucleophile attacking from the least hindered side. The Felkin model named after Hugh Felkin also predicts the stereochemistry of nucleophilic addition reactions to carbonyl groups, Felkin argued that the Cram model suffered a major drawback, an eclipsed conformation in the transition state between the carbonyl substituent and the largest α-carbonyl substituent. Torsional strain involving partial bonds represents a fraction of the strain between fully formed bonds, even when the degree of bonding is quite low. The conformation in the TS is staggered and not eclipsed with the substituent R skew with respect to two adjacent groups one of them the smallest in TS A, for comparison TS B is the Cram transition state. The main steric interactions involve those around R and the nucleophile, a polar effect or electronic effect stabilizes a transition state with maximum separation between the nucleophile and an electron-withdrawing group. For instance haloketones do not obey Crams rule, and, in the example above, the Felkin-Anh model is an extension of the Felkin model that incorporates improvements suggested by Nguyễn Trọng Anh and Odile Eisenstein to correct for two key weaknesses in Felkins model. Anhs solution was to offer the antiperiplanar effect as a consequence of asymmetric induction being controlled by both substituent and orbital effects. In this effect, the best nucleophile acceptor σ* orbital is aligned parallel to both the π and π* orbitals of the carbonyl, which provide stabilization of the incoming anion. The second weakness in the Felkin Model was the assumption of substituent minimization around the carbonyl R, however, many examples exist of reactions that display stereoselectivity opposite of what is predicted by the basic tenets of the Cram and Felkin–Anh models
37.
Chiral pool synthesis
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Chiral pool synthesis is a strategy that aims to improve the efficiency of chiral synthesis. It starts the organic synthesis of a complex enantiopure chemical compound from a stock of readily available enantiopure substances, common chiral starting materials include monosaccharides and amino acids. The built-in chirality is preserved in the remainder of the reaction sequence. This strategy is especially helpful if the desired molecule bears a resemblance to cheap enantiopure natural products. Otherwise, a long, tortuous synthesis involving many steps with attendant losses in yield may be required, at times, it may be difficult to find a suitable enantiopure starting material, other techniques may prove more fruitful. General methods used in chiral pool synthesis are the use of protecting groups, chiral pool synthesis is used to build a part of the epothilone molecule, from readily available enantiopure -pantolactone
