Electron microscope

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Electron_microscope

A modern transmission electron microscope (TITAN)

An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing it to produce magnified images or electron diffraction patterns. As the wavelength of an electron can be more than 100,000 times smaller than that of visible light, electron microscopes have a much higher resolution of about 0.1 nm, which compares to about 200 nm for light microscopes. Electron microscope may refer to:

• Transmission electron microscope (TEM) where swift electrons go through a thin sample
• Scanning transmission electron microscope (STEM) which is similar to TEM with a scanned electron probe
• Scanning electron microscope (SEM) which is similar to STEM, but with thick samples
• Electron microprobe similar to a SEM, but more for chemical analysis
• Low-energy electron microscope (LEEM), used to image surfaces
• Photoemission electron microscope (PEEM) which is similar to LEEM using electrons emitted from surfaces by photons

Additional details can be found in the above links. This article contains some general information mainly about transmission and scanning electron microscopes.

History

See also: Transmission electron microscopy § History

Many developments laid the groundwork of the electron optics used in microscopes. One significant step was the work of Hertz in 1883 who made a cathode-ray tube with electrostatic and magnetic deflection, demonstrating manipulation of the direction of an electron beam. Others were focusing of the electrons by an axial magnetic field by Emil Wiechert in 1899, improved oxide-coated cathodes which produced more electrons by Arthur Wehnelt in 1905 and the development of the electromagnetic lens in 1926 by Hans Busch. According to Dennis Gabor, the physicist Leó Szilárd tried in 1928 to convince him to build an electron microscope, for which Szilárd had filed a patent.

Reproduction of an early electron microscope constructed by Ernst Ruska in the 1930s

To this day the issue of who invented the transmission electron microscope is controversial. In 1928, at the Technische Hochschule in Charlottenburg (now Technische Universität Berlin), Adolf Matthias (Professor of High Voltage Technology and Electrical Installations) appointed Max Knoll to lead a team of researchers to advance research on electron beams and cathode-ray oscilloscopes. The team consisted of several PhD students including Ernst Ruska. In 1931, Max Knoll and Ernst Ruska successfully generated magnified images of mesh grids placed over an anode aperture. The device, a replicate of which is shown in the figure, used two magnetic lenses to achieve higher magnifications, the first electron microscope. (Max Knoll died in 1969, so did not receive a share of the 1986 Nobel prize for the invention of electron microscopes.)

Apparently independent of this effort was work at Siemens-Schuckert by Reinhold Rüdenberg. According to patent law (U.S. Patent No. 2058914 and 2070318, both filed in 1932), he is the inventor of the electron microscope, but it is not clear when he had a working instrument. He stated in a very brief article in 1932 that Siemens had been working on this for some years before the patents were filed in 1932, claiming that his effort was parallel to the university development. He died in 1961, so similar to Max Knoll, was not eligible for a share of the 1986 Nobel prize.

In the following year, 1933, Ruska and Knoll built the first electron microscope that exceeded the resolution of an optical (light) microscope. Four years later, in 1937, Siemens financed the work of Ernst Ruska and Bodo von Borries, and employed Helmut Ruska, Ernst's brother, to develop applications for the microscope, especially with biological specimens. Also in 1937, Manfred von Ardenne pioneered the scanning electron microscope. Siemens produced the first commercial electron microscope in 1938. The first North American electron microscopes were constructed in the 1930s, at the Washington State University by Anderson and Fitzsimmons  and at the University of Toronto by Eli Franklin Burton and students Cecil Hall, James Hillier, and Albert Prebus. Siemens produced a transmission electron microscope (TEM) in 1939. Although current transmission electron microscopes are capable of two million times magnification, as scientific instruments they remain similar but with improved optics.

In the 1940s, high-resolution electron microscopes were developed, enabling greater magnification and resolution. By 1965, Albert Crewe at the University of Chicago introduced the scanning transmission electron microscope using a field emission source, enabling scanning microscopes at high resolution. By the early 1980s improvements in mechanical stability as well as the use of higher accelerating voltages enabled imaging of materials at the atomic scale. In the 1980s, the field emission gun became common for electron microscopes, improving the image quality due to the additional coherence and lower chromatic aberrations. The 2000s were marked by advancements in aberration-corrected electron microscopy, allowing for significant improvements in resolution and clarity of images.

Types of electron microscopes

Transmission electron microscope (TEM)

Main article: Transmission electron microscope

Transmission Electron Microscope

The original form of the electron microscope, the transmission electron microscope (TEM), uses a high voltage electron beam to illuminate the specimen and create an image. An electron beam is produced by an electron gun, with the electrons typically having energies in the range 20 to 400 keV, focused by electromagnetic lenses, and transmitted through a thin specimen. When it emerges from the specimen, the electron beam carries information about the structure of the specimen that is then magnified by the lenses of the microscope. The spatial variation in this information (the "image") may be viewed by projecting the magnified electron image onto a detector. For example, the image may be viewed directly by an operator using a fluorescent viewing screen coated with a phosphor or scintillator material such as zinc sulfide. More commonly a high-resolution phosphor is coupled by means of a lens optical system or a fibre optic light-guide to the sensor of a digital camera. A different approach is to use a direct electron detector which has no scintillator, which addresses some of the limitations of scintillator-coupled cameras.

For many years the resolution of TEMs was limited by aberrations of the electron optics, primarily the spherical aberration. In most recent instruments hardware correctors can reduce spherical aberration and other aberrations, improving the resolution in high-resolution transmission electron microscopy (HRTEM) to below 0.5 angstrom (50 picometres), enabling magnifications of more than 50 million times. The ability of HRTEM to determine the positions of atoms within materials is useful for many areas of research and development.

Scanning electron microscope (SEM)

Main article: Scanning electron microscope

An SEM produces images by probing the specimen with a focused electron beam that is scanned across the specimen (raster scanning). When the electron beam interacts with the specimen, it loses energy and is scattered in different directions by a variety of mechanisms. These interactions lead to, among other events, emission of low-energy secondary electrons and high-energy backscattered electrons, light emission (cathodoluminescence) or X-ray emission. All of these signals carrying information about the specimen, such as the surface topography and composition. The image displayed when using an SEM shows the variation in the intensity of any of these signals as an image. In these each position in the image corresponding to a position of the beam on the specimen when the signal was generated.

TESCAN S8000X SEM

SEMs are different from TEMs in that they use electrons with much lower energy, generally below 20 keV, while TEMs generally use electrons with energies in the range of 80-300 keV. Thus, the electron sources and optics of the two microscopes have different designs, and they are normally separate instruments.

Scanning transmission electron microscope (STEM)

Main article: Scanning transmission electron microscopy

A STEM combines features of both a TEM and a SEM by rastering a focused incident probe across a specimen, but now mainly using the electrons which are transmitted through the sample. Many types of imaging are common to both TEM and STEM, but some such as annular dark-field imaging and other analytical techniques are much easier to perform with higher spatial resolutions in a STEM instrument. One drawback is that image data is acquired in serial rather than in parallel fashion.

Main operating modes

An image of an ant in an SEM

The most common methods of obtaining images in an electron microscope involve selecting different directions for the electrons that have been transmitted through a sample, and/or electrons of different energies. There are a very large number of methods of doing this, although not all are very common.

Secondary electrons

Electron–matter interaction volume and types of signal generated in a SEM

In a SEM the signals result from interactions of the electron beam with atoms within the sample. The most common mode is to use the secondary electrons (SE) to produce images. Secondary electrons have very low energies, on the order of 50 eV, which limits their mean free path in solid matter to a few nanometers below the sample surface. The electrons are detected by an Everhart–Thornley detector, which is a type of collector-scintillator-photomultiplier system. The signal from secondary electrons tends to be highly localized at the point of impact of the primary electron beam, making it possible to collect images of the sample surface with a resolution of better than 1 nm, and with specialized instruments at the atomic scale.

The brightness of the signal depends on the number of secondary electrons reaching the detector. If the beam enters the sample perpendicular to the surface, then the electrons come out symmetrically about the axis of the beam. As the angle of incidence increases, the interaction volume from which they cone increases and the "escape" distance from one side of the beam decreases, resulting in more secondary electrons being emitted from the sample. Thus steep surfaces and edges tend to be brighter than flat surfaces, which results in images with a well-defined, three-dimensional appearance that is similar to a reflected light image.

Backscattered electrons

Backscattered electrons (BSE) are those emitted back out from the specimen due to beam-specimen interactions where the electrons undergo elastic and inelastic scattering. They are conventionally defined as having energies from 50 eV up to the energy of the primary beam. Backscattered electrons can be used for both imaging and to form an electron backscatter diffraction (EBSD) image, the latter can be used to determine the crystallography of the specimen.

Electron backscatter diffraction pattern for (001) single crystal silicon crystals taken at 20kV using Oxford S2 detector

Heavy elements (high atomic number) backscatter electrons more strongly than light elements (low atomic number), and thus appear brighter in the image, BSE images can therefore be used to detect areas with different chemical compositions. To optimize the signal, dedicated backscattered electron detectors are positioned above the sample in a "doughnut" type arrangement, concentric with the electron beam, maximizing the solid angle of collection. BSE detectors are usually either scintillator or semiconductor types. When all parts of the detector are used to collect electrons symmetrically about the beam, atomic number contrast is produced. However, strong topographic contrast is produced by collecting back-scattered electrons from one side above the specimen using an asymmetrical, directional BSE detector; the resulting contrast appears as if there was illumination of the topography from that side. Semiconductor detectors can be made in radial segments that can be switched in or out to control the type of contrast produced and its directionality.

Diffraction contrast imaging

Diffraction contrast uses the variation in either or both the direction of diffracted electrons or their amplitude as a function of position as the contrast mechanism. It is one of the simplest ways to image in a transmission electron microscope, and widely used.

The idea is to use an objective aperture below the sample and select only one or a range of different diffracted directions, then use these to form an image. When the aperture includes the incident beam direction the images are called bright field, since in the absence of any sample the field of view would be uniformly bright. When the aperture excludes the incident beam the images are called dark field, since similarly without a sample the image would be uniformly dark. One variant of this is called weak-beam dark-field microscopy, and can be used to obtain high resolution images of defects such as dislocations.

High resolution imaging

Main articles: High-resolution transmission electron microscopy and Annular dark-field imaging

CuTe High resolution image

In high-resolution transmission electron microscopy (also sometimes called high-resolution electron microscopy) a number of different diffracted beams are allowed through the objective aperture. These interfere, leading to images which represent the atomic structure of the material. These can include the incident beam direction, or with scanning transmission electron microscopes they typically are for a range of diffracted beams excluding the incident beam. Depending upon how thick the samples are and the aberrations of the microscope, these images can either be directly interpreted in terms of the positions of columns of atoms, or require a more careful analysis using calculations of the multiple scattering of the electrons and the effect of the contrast transfer function of the microscope.

Main articles: Electron holography and 4D STEM

There are many other imaging variants that can also to lead to atomic level information. Electron holography uses the interference of electrons which have been through the sample and a reference beam. 4D STEM collects diffraction data at each point using a scanning instrument, then processes them to produce different types of images.

X-ray microanalysis

Main article: Energy-dispersive X-ray spectroscopy

EDS spectrum of the mineral crust of the vent shrimp Rimicaris exoculata Most of these peaks are K-alpha and K-beta lines. One peak is from the L shell of iron.

X-ray microanalysis is a method of obtaining local chemical information within electron microscopes of all types, although it is most commonly used in scanning instruments. When high energy electrons interact with atoms they can knock out electrons, particularly those in the inner shells and core electrons. These are then filled by valence electron, and the energy difference between the valence and core states can be converted into an x-ray which is detected by a spectrometer. The energies of these x-rays is somewhat specific to the atomic species, so local chemistry can be probed.

EELS

Main article: Electron energy loss spectroscopy

Experimental electron energy loss spectrum, showing the major features: zero-loss peak, plasmon peaks and core loss edge.

Similar to X-ray microanalysis, the energies of electrons which have transmitted through a sample can be analyzed and yield information ranging from details of the local electronic structure to chemical information.

Electron diffraction

Main article: Electron diffraction

Transmission electron microscopes can be used in electron diffraction mode where a map of the angles of the electrons leaving the sample is produced. The advantages of electron diffraction over X-ray crystallography are primarily in the size of the crystals. In X-ray crystallography, crystals are commonly visible by the naked eye and are generally in the hundreds of micrometers in length. In comparison, crystals for electron diffraction must be less than a few hundred nanometers in thickness, and have no lower boundary of size. Additionally, electron diffraction is done on a TEM, which can also be used to obtain other types of information, rather than requiring a separate instrument.

Variations in CBED with thickness for Si (001)

Main articles: Convergent beam electron diffraction and Precession electron diffraction

There are many variants on electron diffraction, depending upon exactly what type of illumination conditions are used. If a parallel beam is used with an aperture to limit the region exposed to the electrons then sharp diffraction features are normally observed, a technique called selected area electron diffraction. This is often the main technique used. Another common approach uses conical illumination and is called convergent beam electron diffraction (CBED). This is good for determining the symmetry of materials. A third is precession electron diffraction, where a parallel beam is spun around a large angle, producing a type of average diffraction pattern. These often have less multiple scattering.

Other electron microscope techniques

• Cathodoluminescence - analysing photons due to the electron beam
• Charge contrast imaging - using how charging varies with position to produce images
• CryoEM - using frozen samples, almost always biological samples
• EBSD - using the back-scattered electrons, typically in a SEM
  • TKD - using the Kikuchi lines in diffraction patterns
• ECCI - using contrast due to electron channelling
• EBIC - measuring the current produced as a function of the position of a small beam
• Electron tomography - methods to produce 3D information by combining images
• FEM - technique to interrogate nanocrystalline materials
• Immune electron microscopy - the use of electron microscopy in immunology
• Geometric phase analysis - a method to analyze high-resolution images
• Serial block-face scanning electron microscopy - a way to produce 3D information from many images
• WDXS - higher precision detection of x-rays to analyze local chemistry

Aberration corrected instruments

Scanning transmission electron microscope equipped with a 3rd-order spherical aberration corrector

Main article: Aberration-corrected transmission electron microscopy

Aberration-corrected transmission electron microscopy (AC-TEM) is the general term for electron microscopes where electro optical components are introduced to reduce the aberrations that would otherwise limit the resolution of the images. Historically electron microscopes had quite severe aberrations, and until about the start of the 21st century the resolution was limited, able to image the atomic structure of materials if the atoms were far enough apart. Around the turn of the century the electron optical components were coupled with computer control of the lenses and their alignment, enabling correction of aberrations. The first demonstration of aberration correction in TEM mode was by Harald Rose and Maximilian Haider in 1998 using a hexapole corrector, and in STEM mode by Ondrej Krivanek and Niklas Dellby in 1999 using a quadrupole/octupole corrector.

As of 2025 correction of geometric aberrations is standard in many commercial electron microscopes, and they are extensively used in many different areas of science. Similar correctors have also been used at much lower energies for LEEM instruments.

Sample preparation

An insect coated in gold for viewing with a scanning electron microscope (SEM)

Main articles: TEM Sample preparation, Ultramicrotomy, Staining, Cryofixation, Chemical milling, and Sputtering

Samples for electron microscopes mostly cannot be observed directly. The samples need to be prepared to stabilize the sample and enhance contrast. Preparation techniques differ vastly in respect to the sample and its specific qualities to be observed as well as the specific microscope used. Details can be found in the relevant main articles listed above.

Disadvantages

JEOL transmission and scanning electron microscope made in the mid-1970s

Electron microscopes are expensive to build and maintain. Microscopes designed to achieve high resolutions must be housed in stable buildings (sometimes underground) with special services such as magnetic field canceling systems and anti vibration mounts.

The samples largely have to be viewed in vacuum, as the molecules that make up air would scatter the electrons. An exception is liquid-phase electron microscopy using either a closed liquid cell or an environmental chamber, for example, in the environmental scanning electron microscope, which allows hydrated samples to be viewed in a low-pressure (up to 20 Torr or 2.7 kPa) wet environment. Various techniques for in situ electron microscopy of gaseous samples have also been developed.

Pleolipoviral virion (HRPV-6)

Samples of hydrated materials, including almost all biological specimens, have to be prepared in various ways to stabilize them, reduce their thickness (ultrathin sectioning) and increase their electron optical contrast (staining). These processes may result in artifacts, but these can usually be identified by comparing the results obtained by using radically different specimen preparation methods. Since the 1980s, analysis of cryofixed, vitrified specimens has also become increasingly used.

Many samples suffer from radiation damage which can change internal structures. This can be due to either or both radiolytic processes or ballistic, for instance with collision cascades. This can be a severe issue for biological samples.

Atomic electron transition

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Atomic_electron_transition 

An electron in a Bohr model atom, moving from quantum level n = 3 to n = 2 and releasing a photon. The energy of an electron is determined by its orbit around the atom, The n = 0 orbit, commonly referred to as the ground state, has the lowest energy of all states in the system.

In atomic physics and chemistry, an atomic electron transition (also called an atomic transition, quantum jump, or quantum leap) is an electron changing from one energy level to another within an atom or artificial atom. These energy levels are discrete, quantized, and obtain unique energy gaps specific to a given atom. Though not an exhaustive list, energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) are a few of the many characterization techniques that employ the "atomic fingerprint" phenomenon of atomic electron transitions obtained by the unique quantized energy levels to identify atomic presence and relative composition within samples.

Electrons can relax into states of lower energy by emitting electromagnetic radiation in the form of a photon. Electrons can also absorb passing photons, which excites the electron into a state of higher energy. The larger the energy separation between the electron's initial and final state, the shorter the photons' wavelength.

History

Danish physicist Niels Bohr first theorized that electrons can perform quantum jumps in 1913. Soon after, James Franck and Gustav Ludwig Hertz proved experimentally that atoms have quantized energy states.

The observability of quantum jumps was predicted by Hans Dehmelt in 1975, and they were first observed using trapped ions of barium at University of Hamburg and mercury at NIST in 1986.

Theory

An atom interacts with the oscillating electric field:

${\displaystyle E(t)=|{\mathbf{\text{E}}}_0|Re(e^{-i\omega t}{\widehat{\mathbf{\text{e}}}}_{\mathrm{r}\mathrm{a}\mathrm{d}})}$

1

with amplitude ${\displaystyle |{\mathbf{\text{E}}}_0|}$, angular frequency ${\displaystyle \omega }$, and polarization vector ${\displaystyle {\widehat{\mathbf{\text{e}}}}_{\mathrm{r}\mathrm{a}\mathrm{d}}}$. Note that the actual phase is ${\displaystyle (\omega t-\mathbf{\text{k}}\cdot \mathbf{\text{r}})}$. However, in many cases, the variation of ${\displaystyle \mathbf{\text{k}}\cdot \mathbf{\text{r}}}$ is small over the atom (or equivalently, the radiation wavelength is much greater than the size of an atom) and this term can be ignored. This is called the dipole approximation. The atom can also interact with the oscillating magnetic field produced by the radiation, although much more weakly.

The Hamiltonian for this interaction, analogous to the energy of a classical dipole in an electric field, is ${\displaystyle H_I=e\mathbf{\text{r}}\cdot \mathbf{\text{E}}(t)}$. The stimulated transition rate can be calculated using time-dependent perturbation theory; however, the result can be summarized using Fermi's golden rule: $${\displaystyle Rate\propto |e{E}_0{|}^2\times |⟨2|\mathbf{\text{r}}\cdot {\widehat{\mathbf{\text{e}}}}_{\mathrm{r}\mathrm{a}\mathrm{d}}|1⟩{|}^2}$$ The dipole matrix element can be decomposed into the product of the radial integral and the angular integral. The angular integral is zero unless the selection rules for the atomic transition are satisfied.

Electromagnetic radiation interactions

In order to excite an electron to a higher energy level, an incident photon or radiative force must come into and be absorbed by the atom and hit an electron with the exact energy necessary to complete a transition to a given higher energy level. The energy gaps between quantized energy levels of atoms are on the same scale as ultraviolet (UV) and X-ray radiation; therefore, it can be understood that the gaps between energy levels are on the order of hundreds of nanometers or smaller. The Franck-Condon principle states that, due to nuclear motion being much slower in comparison to electronic motion, the electronic transitions occur in a linear fashion and will only result in an excitation to an energy level if the incident radiation is equivalent in energy to the energy gap and if the probability of the initial and final wave functions overlap significantly. Lasers of UV and X-ray wavelengths can be used to probe such electronic excitations. The time scale of a quantum jump has not been measured experimentally. However, the Franck–Condon principle binds the upper limit of this parameter to the order of attoseconds.

Just as energy must go into and be absorbed by a system (atom) to excite an electron, either radiative or non-radiative emission occurs when an electron relaxes to a lower energy level. The subsequent radiative emission is also on the order of nanometers and can be detected in numerous ways.

Techniques employing electromagnetic radiation for electronic transitions

• UV-Vis Spectroscopy - Visible and/or ultraviolet light is shined on a sample to probe its contents. Either the intensity of light passed through (transmittance) or the lack of light transmitted (absorbance) is detected and plotted on a spectrum.
• Energy-dispersive X-ray Spectroscopy - A high-energy electron beam hits a sample and ejects electrons from the core electron shells of an atom. As electrons fall to lower energy levels to fill the vacancies, X-rays characteristic of the atom are the emitted. EDS is a common form of characterization used for elemental identification of a sample's composition.
• X-ray photoelectron spectroscopy - Incident X-rays are used to excite electrons on a sample surface. Electrons from the surface are then ejected with their respective energies and abundances being detected. Because different atoms have different binding energies, this type of characterization can also be used for determining elemental composition of synthesized materials.

Recent discoveries

In 2019, it was demonstrated in an experiment with a superconducting artificial atom consisting of two strongly-hybridized transmon qubits placed inside a readout resonator cavity at 15 mK, that the evolution of some jumps is continuous, coherent, deterministic, and reversible. On the other hand, other quantum jumps are inherently unpredictable.

Stereoisomerism

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Stereoisomerism 

Two kinds of stereoisomers

In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections or their order differs. By definition, molecules that are stereoisomers of each other represent the same structural isomer.

Enantiomers

Main articles: Chirality (chemistry) and Enantiomers

Enantiomers, also known as optical isomers, are two stereoisomers that are related to each other by a reflection: they are mirror images of each other that are non-superposable. Human hands are a macroscopic analog of this. Every stereogenic center in one has the opposite configuration in the other. Two compounds that are enantiomers of each other have the same physical properties, except for the direction in which they rotate polarized light and how they interact with different enantiomers of other compounds. As a result, different enantiomers of a compound may have substantially different biological effects. Pure enantiomers also exhibit the phenomenon of optical activity and can be separated only with the use of a chiral agent. In nature, only one enantiomer of most chiral biological compounds, such as amino acids (except glycine, which is achiral), is present. Enantiomers differ by the direction they rotate polarized light: the amount of a chiral compound's optical rotation in the (+) direction is equal to the amount of its enantiomer's rotation in the (–) direction.

Diastereomers

Main article: Diastereomer

Diastereomers are stereoisomers not related through a reflection operation. They are not mirror images of each other. These include meso compounds, cis–trans isomers, E–Z isomers, and non-enantiomeric optical isomers. Diastereomers seldom have the same physical properties. In the example shown below, the meso form of tartaric acid forms a diastereomeric pair with both levo- and dextro-tartaric acids, which form an enantiomeric pair.

(natural) tartaric acid L-tartaric acid L-(+)-tartaric acid levo-tartaric acid	D-tartaric acid D-(-)-tartaric acid dextro-tartaric acid	meso-tartaric acid
(1:1) DL-tartaric acid "racemic acid"

The D- and L- labeling of the isomers above is not the same as the d- and l- labeling more commonly seen, explaining why these may appear reversed to those familiar with only the latter naming convention.

A Fischer projection can be used to differentiate between L- and D-molecules (see Chirality (chemistry)). For instance, by definition, in a Fischer projection the penultimate carbon of D-sugars are depicted with hydrogen on the left and hydroxyl on the right. L-sugars will be shown with the hydrogen on the right and the hydroxyl on the left.

The other refers to optical rotation, when looking at the source of light, the rotation of the plane of polarization may be either to the right (dextrorotary — d-rotary, represented by (+), clockwise), or to the left (levorotary — l-rotary, represented by (−), counter-clockwise) depending on which stereoisomer is dominant. For instance, sucrose and camphor are d-rotary whereas cholesterol is l-rotary.

Cis–trans and E–Z isomerism

Main articles: Cis–trans isomerism and E–Z notation

Stereoisomerism about double bonds arises because rotation about the double bond is restricted, keeping the substituents fixed relative to each other. If the two substituents on at least one end of a double bond are the same, then there is no stereoisomer and the double bond is not a stereocenter, e.g. propene, CH₃CH=CH₂ where the two substituents at one end are both H.

Traditionally, double bond stereochemistry was described as either cis (Latin, on this side) or trans (Latin, across), in reference to the relative position of substituents on either side of a double bond. A simple example of cis–trans isomerism is the 1,2-disubstituted ethenes, like the dichloroethene (C₂H₂Cl₂) isomers shown below.

Molecule I is cis-1,2-dichloroethene and molecule II is trans-1,2-dichloroethene. Due to occasional ambiguity, IUPAC adopted a more rigorous system wherein the substituents at each end of the double bond are assigned priority based on their atomic number. If the high-priority substituents are on the same side of the bond, it is assigned Z (Ger. zusammen, together). If they are on opposite sides, it is E (Ger. entgegen, opposite). Since chlorine has a larger atomic number than hydrogen, it is the highest-priority group. Using this notation to name the above pictured molecules, molecule I is (Z)-1,2-dichloroethene and molecule II is (E)-1,2-dichloroethene. It is not the case that Z and cis, or E and trans, are always interchangeable. Consider the following fluoromethylpentene:

The proper name for this molecule is either trans-2-fluoro-3-methylpent-2-ene because the alkyl groups that form the backbone chain (i.e., methyl and ethyl) reside across the double bond from each other, or (Z)-2-fluoro-3-methylpent-2-ene because the highest-priority groups on each side of the double bond are on the same side of the double bond. Fluoro is the highest-priority group on the left side of the double bond, and ethyl is the highest-priority group on the right side of the molecule.

The terms cis and trans are also used to describe the relative position of two substituents on a ring; cis if on the same side, otherwise trans.

Conformers

Main article: Conformational isomerism

Conformational isomerism is a form of isomerism that describes the phenomenon of molecules with the same structural formula but with different shapes due to rotations about one or more bonds. Different conformations can have different energies, can usually interconvert, and are very rarely isolatable. For example, there exists a variety of Cyclohexane conformations (which cyclohexane is an essential intermediate for the synthesis of nylon–6,6) including a chair conformation where four of the carbon atoms form the "seat" of the chair, one carbon atom is the "back" of the chair, and one carbon atom is the "foot rest"; and a boat conformation, the boat conformation represents the energy maximum on a conformational itinerary between the two equivalent chair forms; however, it does not represent the transition state for this process, because there are lower-energy pathways. The conformational inversion of substituted cyclohexanes is a very rapid process at room temperature, with a half-life of 0.00001 seconds.

There are some molecules that can be isolated in several conformations, due to the large energy barriers between different conformations. 2,2',6,6'-Tetrasubstituted biphenyls can fit into this latter category.

Anomers

Anomerism is an identity for single bonded ring structures where "cis" or "Z" and "trans" or "E" (geometric isomerism) needs to name the substitutions on a carbon atom that also displays the identity of chirality; so anomers have carbon atoms that have geometric isomerism and optical isomerism (enantiomerism) on one or more of the carbons of the ring. Anomers are named "alpha" or "axial" and "beta" or "equatorial" when substituting a cyclic ring structure that has single bonds between the carbon atoms of the ring for example, a hydroxyl group, a methyl hydroxyl group, a methoxy group or another pyranose or furanose group which are typical single bond substitutions but not limited to these. Axial geometric isomerism will be perpendicular (90 degrees) to a reference plane and equatorial will be 120 degrees away from the axial bond or deviate 30 degrees from the reference plane.

Atropisomers

Main article: Atropisomer

Atropisomers are stereoisomers resulting from hindered rotation about single bonds where the steric strain barrier to rotation is high enough to allow for the isolation of the conformers.

More definitions

• A configurational stereoisomer is a stereoisomer of a reference molecule that has the opposite configuration at a stereocenter (e.g., R- vs S- or E- vs Z-). This means that configurational isomers can be interconverted only by breaking covalent bonds to the stereocenter, for example, by inverting the configurations of some or all of the stereocenters in a compound.
• An epimer is a diastereoisomer that has the opposite configuration at only one of the stereocenters.

Le Bel-van't Hoff rule

Le Bel-van't Hoff rule states that for a structure with n asymmetric carbon atoms, there is a maximum of 2ⁿ different stereoisomers possible. As an example, D-glucose is an aldohexose and has the formula C₆H₁₂O₆. Four of its six carbon atoms are stereogenic, which means D-glucose is one of 2⁴=16 possible stereoisomers.

Stereochemistry

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Stereochemistry 

The different types of isomers. Stereochemistry focuses on stereoisomers.

Stereochemistry, a subdiscipline of chemistry, studies the spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which are defined as having the same molecular formula and sequence of bonded atoms (constitution) but differing in the geometric positioning of the atoms in space. For this reason, it is also known as 3D chemistry—the prefix "stereo-" means "three-dimensionality" because many of the types of stereochemistry are based on 3D geometric relationships. Stereochemistry applies to all kinds of compounds and ions, organic and inorganic species alike. Stereochemistry affects biological, physical, and supramolecular chemistry.

Stereochemistry also studies the reactivity of the molecules in question (dynamic stereochemistry).

Cahn–Ingold–Prelog priority rules are part of a system for describing a molecule's stereochemistry. They rank the atoms around a stereochemical region of a molecule in a standard way, allowing unambiguous descriptions of their relative positions in the molecule.

Visual representations

Main article: Skeletal formula § stereochemistry

Rather than using a high-quality 3D rendering a molecule, there are several simplified standard ways of representing the 3D positioning of atoms around a stereocenter. One common convention uses a bond drawn as a solid wedge to indicate that a bond that is projecting towards the viewer, a dashed or hashed bond to indicate that a bond is receding away from the viewer, and plain lines to represent bonds that are in the plane of the molecule itself.

A Fischer projection represents the four directions around a tetrahedral atom by drawing the bonds horizontally or vertically, with vertical meaning the bond recedes away from the viewer and horizontal meaning the bond projects towards the viewer.

Thalidomide example

Enantiomers of thalidomide

Stereochemistry has important applications in the field of medicine, particularly pharmaceuticals. 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 serious genetic damage to early embryonic growth and development, leading to limb deformation in babies. Several proposed mechanisms of teratogenicity involve different biological functions for the (R)- and (S)-thalidomide enantiomers. In the human body, however, thalidomide undergoes racemization: even if only 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 that one stereoisomer is safe while the other is teratogenic. Thalidomide is currently used for the treatment of other diseases, notably cancer and leprosy. Strict regulations and controls have been implemented to avoid its use by pregnant women and prevent developmental deformities. This disaster was a driving force behind requiring strict testing of drugs before making them available to the public.

In yet another example, the drug ibuprofen can exist as (R)- and (S)-isomers. Only the (S)-ibuprofen is active in reducing inflammation and pain.

Diastereomers

For an Inorganic perspective on stereochemistry, see Coordination complex § Stereochemistry.

Isomers are of two types: diastereomers (also called diastereoisomers) and enantiomers. Enantiomers are non-superimposable mirror images. Diastereomers are all other types of isomers.

enantiomers of 2-butanol.

Epimers

Epimers are a subcategory of diastereomers that differ in absolute configuration configurations at only one corresponding stereocenter. They are commonly found in sugar chemistry, where two sugars can differ by the configuration of a single carbon atom. D-glucose and D-galactose are epimers, differing only at the C-4 position in their structure. (see sugar numbering)

This pair can also be classified as epimers.

Cis-Trans isomers

Cis-Trans isomers are often associated alkene double bonds.

cis-pent-2-ene		trans-pent-2-ene

The more general E/Z nomenclature refers to the concept of cis/trans isomerism, and is especially useful for more complex compounds.

(Z)-1-Bromo-1,2-dichloroethene		(E)-1-Bromo-1,2-dichloroethene

Atropisomers

Atropisomerism are another kind of diasteromer. They exist because of the inability to rotate about a bond, such as due to steric hindrance between functional groups on two sp²-hybridized carbon atoms. Usually atropisomers are chiral, and as such they are a form of axial chirality. Atropisomerism can be described as conformational isomerism

History

See also: Chemical crystallography before X-rays

In 1815, Jean-Baptiste Biot's observation of optical activity marked the beginning of organic stereochemistry history. He observed that organic molecules were able to rotate the plane of polarized light in a solution or in the gaseous phase. Despite Biot's discoveries, Louis Pasteur is commonly described as the first stereochemist, having observed in 1842 that salts of tartaric acid collected from wine production vessels could rotate the plane of polarized light, but that salts from other sources did not. This was the only physical property that differed between the two types of tartrate salts, which is due to optical isomerism. In 1874, Jacobus Henricus van 't Hoff and Joseph Le Bel explained optical activity in terms of the tetrahedral arrangement of the atoms bound to carbon. Kekulé explored tetrahedral models earlier, in 1862, but never published his work; Emanuele Paternò probably knew of these but was the first to draw and discuss three dimensional structures, such as of 1,2-dibromoethane in the Giornale di Scienze Naturali ed Economiche in 1869.^[9] The term "chiral" was introduced by Lord Kelvin in 1904. Arthur Robertson Cushny, a Scottish Pharmacologist, first provided a clear example in 1908 of a bioactivity difference between enantiomers of a chiral molecule viz. (−)-Adrenaline is two times more potent than the (±)- form as a vasoconstrictor and in 1926 laid the foundation for chiral pharmacology/stereo-pharmacology (biological relations of optically isomeric substances). Later in 1966, the Cahn–Ingold–Prelog nomenclature or Sequence rule was devised to assign absolute configuration to stereogenic/chiral center (R- and S- notation)  and extended to be applied across olefinic bonds (E- and Z- notation).