X-ray optics

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/X-ray_optics 

X-ray optics is the branch of optics that manipulates X-rays instead of visible light. It deals with focusing and other ways of manipulating the X-ray beams for research techniques such as X-ray crystallography, X-ray fluorescence, small-angle X-ray scattering, X-ray microscopy, X-ray phase-contrast imaging, and X-ray astronomy.

Since X-rays and visible light are both electromagnetic waves they propagate in space in the same way, but because of the much higher frequency and photon energy of X-rays they interact with matter very differently. Visible light is easily redirected using lenses and mirrors, but because the real part of the complex refractive index of all materials is very close to 1 for X-rays, they instead tend to initially penetrate and eventually get absorbed in most materials without changing direction much.

X-ray techniques

There are many different techniques used to redirect X-rays, most of them changing the directions by only minute angles. The most common principle used is reflection at grazing incidence angles, either using total external reflection at very small angles or multilayer coatings. Other principles used include diffraction and interference in the form of zone plates, refraction in compound refractive lenses that use many small X-ray lenses in series to compensate by their number for the minute index of refraction, Bragg reflection from a crystal plane in flat or bent crystals.

X-ray beams are often collimated or reduced in size using pinholes or movable slits typically made of tungsten or some other high-Z material. Narrow parts of an X-ray spectrum can be selected with monochromators based on one or multiple Bragg reflections by crystals. X-ray spectra can also be manipulated by having the X-rays pass through a filter (optics). This will typically reduce the low-energy part of the spectrum, and possibly parts above absorption edges of the elements used for the filter.

Focusing optics

Analytical X-ray techniques such as X-ray crystallography, small-angle X-ray scattering, wide-angle X-ray scattering, X-ray fluorescence, X-ray spectroscopy and X-ray photoelectron spectroscopy all benefit from high X-ray flux densities on the samples being investigated. This is achieved by focusing the divergent beam from the X-ray source onto the sample using one out of a range of focusing optical components. This is also useful for scanning probe techniques such as scanning transmission X-ray microscopy and scanning X-ray fluorescence imaging.

Polycapillary optics

A polycapillary lens for focusing X-rays

Polycapillary lenses are arrays of small hollow glass tubes that guide the X-rays with many total external reflections on the inside of the tubes. The array is tapered so that one end of the capillaries points at the X-ray source and the other at the sample. Polycapillary optics are achromatic and thus suitable for scanning fluorescence imaging and other applications where a broad X-ray spectrum is useful. They collect X-rays efficiently for photon energies of 0.1 to 30 keV and can achieve gains of 100 to 10000 in flux over using a pinhole at 100 mm from the X-ray source. Since only X-rays entering the capillaries within a very narrow angle will be totally internally reflected, only X-rays coming from a small spot will be transmitted through the optic. Polycapillary optics cannot image more than one point to another, so they are used for illumination and collection of X-rays.

Zone plates

Main article: Zone plate

Zone plates consist of a substrate with concentric zones of a phase-shifting or absorbing material with zones getting narrower the larger their radius. The zone widths are designed so that a transmitted wave gets constructive interference in a single point giving a focus. Zone plates can be used as condensers to collect light, but also for direct full-field imaging in e.g. an X-ray microscope. Zone plates are highly chromatic and usually designed only for a narrow energy span, making it necessary to have monochromatic X-rays for efficient collection and high-resolution imaging.

Compound refractive lenses

Main article: Compound refractive lens

Since refractive indices at X-ray wavelengths are so close to 1, the focal lengths of normal lenses get impractically long. To overcome this, lenses with very small radii of curvature are used, and they are stacked in long rows, so that the combined focusing power gets appreciable. Since the refractive index is less than 1 for X-rays, these lenses must be concave to achieve focusing, contrary to visible-light lenses, which are convex for a focusing effect. Radii of curvature are typically less than a millimeter, making the usable X-ray beam width at most about 1 mm. To reduce the absorption of X-rays in these stacks, materials with very low atomic number such as beryllium or lithium are typically used. Since the refractive index depends strongly on X-ray wavelength, these lenses are highly chromatic, and the variation of the focal length with wavelength must be taken into account for any application.

Reflection

Designs based on grazing-incidence reflection used in X-ray telescopes include that by Kirkpatrick–Baez, and several by Wolter (Wolter I–IV)

The basic idea is to reflect a beam of X-rays from a surface and to measure the intensity of X-rays reflected in the specular direction (reflected angle equal to incident angle). It has been shown that a reflection off a parabolic mirror followed by a reflection off a hyperbolic mirror leads to the focusing of X-rays. Since the incoming X-rays must strike the tilted surface of the mirror, the collecting area is small. It can, however, be increased by nesting arrangements of mirrors inside each other.

The ratio of reflected intensity to incident intensity is the X-ray reflectivity for the surface. If the interface is not perfectly sharp and smooth, the reflected intensity will deviate from that predicted by the Fresnel reflectivity law. The deviations can then be analyzed to obtain the density profile of the interface normal to the surface. For films with multiple layers, X-ray reflectivity may show oscillations with wavelength, analogous to the Fabry–Pérot effect. These oscillations can be used to infer layer thicknesses and other properties.

Diffraction

Symmetrically spaced atoms cause re-radiated X-rays to reinforce each other in the specific directions where their path-length difference 2d sin θ equals an integer multiple of the wavelength λ

In X-ray diffraction a beam strikes a crystal and diffracts into many specific directions. The angles and intensities of the diffracted beams indicate a three-dimensional density of electrons within the crystal. X-rays produce a diffraction pattern because their wavelength typically has the same order of magnitude (0.1–10.0 nm) as the spacing between the atomic planes in the crystal.

Each atom re-radiates a small portion of an incoming beam's intensity as a spherical wave. If the atoms are arranged symmetrically (as is found in a crystal) with a separation d, these spherical waves will be in phase (add constructively) only in directions where their path-length difference 2d sin θ is equal to an integer multiple of the wavelength λ. The incoming beam therefore appears to have been deflected by an angle 2θ, producing a reflection spot in the diffraction pattern.

X-ray diffraction is a form of elastic scattering in the forward direction; the outgoing X-rays have the same energy, and thus the same wavelength, as the incoming X-rays, only with altered direction. By contrast, inelastic scattering occurs when energy is transferred from the incoming X-ray to an inner-shell electron, exciting it to a higher energy level. Such inelastic scattering reduces the energy (or increases the wavelength) of the outgoing beam. Inelastic scattering is useful for probing such electron excitation, but not in determining the distribution of atoms within the crystal.

Longer-wavelength photons (such as ultraviolet radiation) would not have sufficient resolution to determine the atomic positions. At the other extreme, shorter-wavelength photons such as gamma rays are difficult to produce in large numbers, difficult to focus, and interact too strongly with matter, producing particle–antiparticle pairs.

Similar diffraction patterns can be produced by scattering electrons or neutrons. X-rays are usually not diffracted from atomic nuclei, but only from the electrons surrounding them.

Interference

X-ray interference is the addition (superposition) of two or more X-ray waves that results in a new wave pattern. X-ray interference usually refers to the interaction of waves that are correlated or coherent with each other, either because they come from the same source or because they have the same or nearly the same frequency.

Two non-monochromatic X-ray waves are only fully coherent with each other if they both have exactly the same range of wavelengths and the same phase differences at each of the constituent wavelengths.

The total phase difference is derived from the sum of both the path difference and the initial phase difference (if the X-ray waves are generated from two or more different sources). It can then be concluded whether the X-ray waves reaching a point are in phase (constructive interference) or out of phase (destructive interference).

Technologies

There are a variety of techniques used to funnel X-ray photons to the appropriate location on an X-ray detector:

• Grazing incidence mirrors in a Wolter telescope, or a Kirkpatrick–Baez X-ray reflection microscope.
• Zone plates.
• Bent crystals.
• Normal-incidence mirrors making use of multilayer coatings.
• A normal-incidence lens much like an optical lens, such as a compound refractive lens.
• Microstructured optical arrays, namely, capillary/polycapillary optical systems.
• Coded aperture imaging.
• Modulation collimators.
• X-ray waveguides.

Most X-ray optical elements (with the exception of grazing-incidence mirrors) are very small and must be designed for a particular incident angle and energy, thus limiting their applications in divergent radiation. Although the technology has advanced rapidly, its practical uses outside research are still limited. Efforts are ongoing, however, to introduce X-ray optics in medical X-ray imaging. For instance, one of the applications showing greater promise is in enhancing both the contrast and resolution of mammographic images, compared to conventional anti-scatter grids. Another application is to optimize the energy distribution of the X-ray beam to improve contrast-to-noise ratio compared to conventional energy filtering.

Mirrors for X-ray optics

The mirrors can be made of glass, ceramic, or metal foil, coated by a reflective layer. The most commonly used reflective materials for X-ray mirrors are gold and iridium. Even with these the critical reflection angle is energy dependent. For gold at 1 keV, the critical reflection angle is 2.4°.

The use of X-ray mirrors simultaneously requires:

• the ability to determine the location of the arrival of an X-ray photon in two dimensions,
• a reasonable detection efficiency.

Multilayers for X-Rays

No material has substantial reflection for X-rays, except at very small grazing angles. Multilayers enhance the small reflectivity from a single boundary by adding the small reflected amplitudes from many boundaries coherently in phase. For example, if a single boundary has a reflectivity of R = 10⁻⁴ (amplitude r = 10⁻²), then the addition of 100 amplitudes from 100 boundaries can give reflectivity R close to one. The period Λ of the multilayer that provides the in-phase addition is that of the standing wave produced by the input and output beam, Λ = λ/2 sin θ, where λ is the wavelength, and 2θ the half angle between the two beams. For θ = 90°, or reflection at normal incidence, the period of the multilayer is Λ = λ/2. The shortest period that can be used in a multilayer is limited by the size of the atoms to about 2 nm, corresponding to wavelengths above 4 nm. For shorter wavelength a reduction of the incidence angle θ toward more grazing has to be used.

The materials for multilayers are selected to give the highest possible reflection at each boundary and the smallest absorption or the propagation through the structure. This is usually achieved by light, low-density materials for the spacer layer and a heavier material that produces high contrast. The absorption in the heavier material can be reduced by positioning it close to the nodes of the standing-wave field inside the structure. Good low-absorption spacer materials are Be, C, B, B₄C and Si. Some examples of the heavier materials with good contrast are W, Rh, Ru and Mo.

Applications include:

• normal and grazing-incidence optics for telescopes from EUV to hard X-rays,
• microscopes, beam lines at synchrotron and FEL facilities,
• EUV lithography.

Mo/Si is the material selection used for the near-normal incidence reflectors for EUV lithography.

Hard X-ray mirrors

An X-ray mirror optic for NuStar space telescope working up 79 keV was made using multilayered coatings, computer-aided manufacturing, and other techniques. The mirrors use a tungsten/silicon (W/Si) or platinum/silicon-carbide (Pt/SiC) multicoating on slumped glass, allowing a Wolter telescope design.

Infrared window

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

 

As the main part of the 'window' spectrum, a clear electromagnetic spectral transmission 'window' can be seen between 8 and 14 μm. A fragmented part of the 'window' spectrum (one might say a louvred part of the 'window') can also be seen in the visible to mid-wavelength infrared between 0.2 and 5.5 μm.

The infrared atmospheric window refers to a region of the Infrared spectrum where there is relatively little absorption of terrestrial thermal radiation by atmospheric gases. The window plays an important role in the atmospheric greenhouse effect by maintaining the balance between incoming solar radiation and outgoing IR to space. In the Earth's atmosphere this window is roughly the region between 8 and 14 μm although it can be narrowed or closed at times and places of high humidity because of the strong absorption in the water vapor continuum or because of blocking by clouds. It covers a substantial part of the spectrum from surface thermal emission which starts at roughly 5 μm. Principally it is a large gap in the absorption spectrum of water vapor. Carbon dioxide plays an important role in setting the boundary at the long wavelength end. Ozone partly blocks transmission in the middle of the window.

The importance of the infrared atmospheric window in the atmospheric energy balance was discovered by George Simpson in 1928, based on G. Hettner's 1918 laboratory studies of the gap in the absorption spectrum of water vapor. In those days, computers were not available, and Simpson notes that he used approximations; he writes about the need for this in order to calculate outgoing IR radiation: "There is no hope of getting an exact solution; but by making suitable simplifying assumptions . . . ." Nowadays, accurate line-by-line computations are possible, and careful studies of the spectroscopy of infrared atmospheric gases have been published.

Mechanisms in the infrared atmospheric window

The principal natural greenhouse gases in order of their importance are water vapor H
₂O, carbon dioxide CO
₂, ozone O
₃, methane CH
₄ and nitrous oxide N
₂O. The concentration of the least common of these, N
₂O, is about 400 ppbV. Other gases which contribute to the greenhouse effect are present at pptV levels. These include the chlorofluorocarbons (CFCs) and hydrofluororcarbons (HFC and HCFCs). As discussed below, a major reason that they are so effective as greenhouse gases is that they have strong vibrational bands that fall in the infrared atmospheric window. IR absorption by CO
₂ at 14.7 μm sets the long wavelength limit of the infrared atmospheric window together with absorption by rotational transitions of H
₂O at slightly longer wavelengths. The short wavelength boundary of the atmospheric IR window is set by absorption in the lowest frequency vibrational bands of water vapor. There is a strong band of ozone at 9.6 μm in the middle of the window which is why it acts as such a strong greenhouse gas. Water vapor has a continuum absorption due to collisional broadening of absorption lines which extends through the window. Local very high humidity can completely block the infrared vibrational window.

Over the Atlas Mountains, interferometrically recorded spectra of outgoing longwave radiation show emission that has arisen from the land surface at a temperature of about 320 K and passed through the atmospheric window, and non-window emission that has arisen mainly from the troposphere at temperatures about 260 K.

Over Côte d'Ivoire, interferometrically recorded spectra of outgoing longwave radiation show emission that has arisen from the cloud tops at a temperature of about 265 K and passed through the atmospheric window, and non-window emission that has arisen mainly from the troposphere at temperatures about 240 K. This means that, at the scarcely absorbed continuum of wavelengths (8 to 14 μm), the radiation emitted, by the Earth's surface into a dry atmosphere, and by the cloud tops, mostly passes unabsorbed through the atmosphere, and is emitted directly to space; there is also partial window transmission in far infrared spectral lines between about 16 and 28 μm. Clouds are excellent emitters of infrared radiation. Window radiation from cloud tops arises at altitudes where the air temperature is low, but as seen from those altitudes, the water vapor content of the air above is much lower than that of the air at the land-sea surface. Moreover, the water vapour continuum absorptivity, molecule for molecule, decreases with pressure decrease. Thus water vapour above the clouds, besides being less concentrated, is also less absorptive than water vapour at lower altitudes. Consequently, the effective window as seen from the cloud-top altitudes is more open, with the result that the cloud tops are effectively strong sources of window radiation; that is to say, in effect the clouds obstruct the window only to a small degree (see another opinion about this, proposed by Ahrens (2009) on page 43).

Importance for life

Without the infrared atmospheric window, the Earth would become much too warm to support life, and possibly so warm that it would lose its water, as Venus did early in Solar System history. Thus, the existence of an atmospheric window is critical to Earth remaining a habitable planet.

As a proposed management strategy for global warming, passive daytime radiative cooling (PDRC) surfaces use the infrared window to send heat back into outer space with the aim of reversing rising temperature increases caused by climate change.

Threats

In recent decades, the existence of the infrared atmospheric window has become threatened by the development of highly unreactive gases containing bonds between fluorine and carbon, sulfur or nitrogen. The impact of these compounds was first discovered by Indian–American atmospheric scientist Veerabhadran Ramanathan in 1975, one year after Roland and Molina's much-more-celebrated paper on the ability of chlorofluorocarbons to destroy stratospheric ozone.

The "stretching frequencies" of bonds between fluorine and other light nonmetals are such that strong absorption in the atmospheric window will always be characteristic of compounds containing such bonds, although fluorides of nonmetals other than carbon, nitrogen or sulfur are short-lived due to hydrolysis. This absorption is strengthened because these bonds are highly polar due to the extreme electronegativity of the fluorine atom. Bonds to other halogens also absorb in the atmospheric window, though much less strongly.

Moreover, the unreactive nature of such compounds that makes them so valuable for many industrial purposes means that they are not removable in the natural circulation of the Earth's lower atmosphere. Extremely small natural sources created by means of radioactive oxidation of fluorite and subsequent reaction with sulfate or carbonate minerals produce via degassing atmospheric concentrations of about 40 ppt for all perfluorocarbons and 0.01 ppt for sulfur hexafluoride, but the only natural ceiling is via photolysis in the mesosphere and upper stratosphere. It is estimated that perfluorocarbons (CF
₄, C
₂F
₆, C
₃F
₈), originating from commercial production of anesthetics, refrigerants, and polymers can stay in the atmosphere for between two thousand six hundred and fifty thousand years.

This means that such compounds have an enormous global warming potential. One kilogram of sulfur hexafluoride will, for example, cause as much warming as 23 tonnes of carbon dioxide over 100 years. Perfluorocarbons are similar in this respect, and even carbon tetrachloride (CCl
₄) has a global warming potential of 1800 compared to carbon dioxide. These compounds still remain highly problematic with an ongoing effort to find substitutes for them.

Binding site

From Wikipedia, the free encyclopedia

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

 

Glucose binds to hexokinase in the active site at the beginning of glycolysis.

In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may include other proteins (resulting in a protein-protein interaction), enzyme substrates, second messengers, hormones, or allosteric modulators. The binding event is often, but not always, accompanied by a conformational change that alters the protein's function. Binding to protein binding sites is most often reversible (transient and non-covalent), but can also be covalent reversible or irreversible.

Function

Binding of a ligand to a binding site on protein often triggers a change in conformation in the protein and results in altered cellular function. Hence binding site on protein are critical parts of signal transduction pathways. Types of ligands include neurotransmitters, toxins, neuropeptides, and steroid hormones. Binding sites incur functional changes in a number of contexts, including enzyme catalysis, molecular pathway signaling, homeostatic regulation, and physiological function. Electric charge, steric shape and geometry of the site selectively allow for highly specific ligands to bind, activating a particular cascade of cellular interactions the protein is responsible for.

Catalysis

Activation energy is decreased in the presence of an enzyme to catalyze the reaction.

Enzymes incur catalysis by binding more strongly to transition states than substrates and products. At the catalytic binding site, several different interactions may act upon the substrate. These range from electric catalysis, acid and base catalysis, covalent catalysis, and metal ion catalysis. These interactions decrease the activation energy of a chemical reaction by providing favorable interactions to stabilize the high energy molecule. Enzyme binding allows for closer proximity and exclusion of substances irrelevant to the reaction. Side reactions are also discouraged by this specific binding.

Types of enzymes that can perform these actions include oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.

For instance, the transferase hexokinase catalyzes the phosphorylation of glucose to make glucose-6-phosphate. Active site residues of hexokinase allow for stabilization of the glucose molecule in the active site and spur the onset of an alternative pathway of favorable interactions, decreasing the activation energy.

Inhibition

Protein inhibition by inhibitor binding may induce obstruction in pathway regulation, homeostatic regulation and physiological function.

Competitive inhibitors compete with substrate to bind to free enzymes at active sites and thus impede the production of the enzyme-substrate complex upon binding. For example, carbon monoxide poisoning is caused by the competitive binding of carbon monoxide as opposed to oxygen in hemoglobin.

Uncompetitive inhibitors, alternatively, bind concurrently with substrate at active sites. Upon binding to an enzyme substrate (ES) complex, an enzyme substrate inhibitor (ESI) complex is formed. Similar to competitive inhibitors, the rate at product formation is decreased also.

Lastly, mixed inhibitors are able to bind to both the free enzyme and the enzyme-substrate complex. However, in contrast to competitive and uncompetitive inhibitors, mixed inhibitors bind to the allosteric site. Allosteric binding induces conformational changes that may increase the protein's affinity for substrate. This phenomenon is called positive modulation. Conversely, allosteric binding that decreases the protein's affinity for substrate is negative modulation.

Types

Active site

Main article: Active site

At the active site, a substrate binds to an enzyme to induce a chemical reaction. Substrates, transition states, and products can bind to the active site, as well as any competitive inhibitors. For example, in the context of protein function, the binding of calcium to troponin in muscle cells can induce a conformational change in troponin. This allows for tropomyosin to expose the actin-myosin binding site to which the myosin head binds to form a cross-bridge and induce a muscle contraction.

In the context of the blood, an example of competitive binding is carbon monoxide which competes with oxygen for the active site on heme. Carbon monoxide's high affinity may outcompete oxygen in the presence of low oxygen concentration. In these circumstances, the binding of carbon monoxide induces a conformation change that discourages heme from binding to oxygen, resulting in carbon monoxide poisoning.

Competitive and noncompetitive enzyme binding at active and regulatory (allosteric) site respectively.

Allosteric site

At the regulatory site, the binding of a ligand may elicit amplified or inhibited protein function. The binding of a ligand to an allosteric site of a multimeric enzyme often induces positive cooperativity, that is the binding of one substrate induces a favorable conformation change and increases the enzyme's likelihood to bind to a second substrate. Regulatory site ligands can involve homotropic and heterotropic ligands, in which single or multiple types of molecule affects enzyme activity respectively.

Enzymes that are highly regulated are often essential in metabolic pathways. For example, phosphofructokinase (PFK), which phosphorylates fructose in glycolysis, is largely regulated by ATP. Its regulation in glycolysis is imperative because it is the committing and rate limiting step of the pathway. PFK also controls the amount of glucose designated to form ATP through the catabolic pathway. Therefore, at sufficient levels of ATP, PFK is allosterically inhibited by ATP. This regulation efficiently conserves glucose reserves, which may be needed for other pathways. Citrate, an intermediate of the citric acid cycle, also works as an allosteric regulator of PFK.

Single- and multi-chain binding sites

Binding sites can be characterized also by their structural features. Single-chain sites (of “monodesmic” ligands, μόνος: single, δεσμός: binding) are formed by a single protein chain, while multi-chain sites (of "polydesmic” ligands, πολοί: many) are frequent in protein complexes, and are formed by ligands that bind more than one protein chain, typically in or near protein interfaces. Recent research shows that binding site structure has profound consequences for the biology of protein complexes (evolution of function, allostery).

Cryptic binding sites

Cryptic binding sites are the binding sites that are transiently formed in an apo form or that are induced by ligand binding. Considering the cryptic binding sites increases the size of the potentially “druggable” human proteome from ~40% to ~78% of disease-associated proteins. The binding sites have been investigated by: support vector machine applied to "CryptoSite" data set, Extension of "CryptoSite" data set, long timescale molecular dynamics simulation with Markov state model and with biophysical experiments, and cryptic-site index that is based on relative accessible surface area.

Binding curves

Sigmoidal versus hyperbolic binding patterns demonstrate cooperative and noncooperative character of enzymes.

Binding curves describe the binding behavior of ligand to a protein. Curves can be characterized by their shape, sigmoidal or hyperbolic, which reflect whether or not the protein exhibits cooperative or noncooperative binding behavior respectively. Typically, the x-axis describes the concentration of ligand and the y-axis describes the fractional saturation of ligands bound to all available binding sites. The Michaelis Menten equation is usually used when determining the shape of the curve. The Michaelis Menten equation is derived based on steady-state conditions and accounts for the enzyme reactions taking place in a solution. However, when the reaction takes place while the enzyme is bound to a substrate, the kinetics play out differently.

Modeling with binding curves are useful when evaluating the binding affinities of oxygen to hemoglobin and myoglobin in the blood. Hemoglobin, which has four heme groups, exhibits cooperative binding. This means that the binding of oxygen to a heme group on hemoglobin induces a favorable conformation change that allows for increased binding favorability of oxygen for the next heme groups. In these circumstances, the binding curve of hemoglobin will be sigmoidal due to its increased binding favorability for oxygen. Since myoglobin has only one heme group, it exhibits noncooperative binding which is hyperbolic on a binding curve.

Applications

Biochemical differences between different organisms and humans are useful for drug development. For instance, penicillin kills bacteria by inhibiting the bacterial enzyme DD-transpeptidase, destroying the development of the bacterial cell wall and inducing cell death. Thus, the study of binding sites is relevant to many fields of research, including cancer mechanisms, drug formulation, and physiological regulation. The formulation of an inhibitor to mute a protein's function is a common form of pharmaceutical therapy.

Methotrexate inhibits dihydrofolate reductase by outcompeting the substrate folic acid. Binding site in blue, inhibitor in green, and substrate in black.

In the scope of cancer, ligands that are edited to have a similar appearance to the natural ligand are used to inhibit tumor growth. For example, Methotrexate, a chemotherapeutic, acts as a competitive inhibitor at the dihydrofolate reductase active site. This interaction inhibits the synthesis of tetrahydrofolate, shutting off production of DNA, RNA and proteins. Inhibition of this function represses neoplastic growth and improves severe psoriasis and adult rheumatoid arthritis.

In cardiovascular illnesses, drugs such as beta blockers are used to treat patients with hypertension. Beta blockers (β-Blockers) are antihypertensive agents that block the binding of the hormones adrenaline and noradrenaline to β1 and β2 receptors in the heart and blood vessels. These receptors normally mediate the sympathetic "fight or flight" response, causing constriction of the blood vessels.

Competitive inhibitors are also largely found commercially. Botulinum toxin, known commercially as Botox, is a neurotoxin causes flaccid paralysis in the muscle due to binding to acetylcholine dependent nerves. This interaction inhibits muscle contractions, giving the appearance of smooth muscle.

Prediction

A number of computational tools have been developed for the prediction of the location of binding sites on proteins. These can be broadly classified into sequence based or structure based. Sequence based methods rely on the assumption that the sequences of functionally conserved portions of proteins such as binding site are conserved. Structure based methods require the 3D structure of the protein. These methods in turn can be subdivided into template and pocket based methods. Template based methods search for 3D similarities between the target protein and proteins with known binding sites. The pocket based methods search for concave surfaces or buried pockets in the target protein that possess features such as hydrophobicity and hydrogen bonding capacity that would allow them to bind ligands with high affinity. Even though the term pocket is used here, similar methods can be used to predict binding sites used in protein-protein interactions that are usually more planar, not in pockets.

Free people of color

From Wikipedia, the free encyclopedia

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

 

Free Women of Color with their Children and Servants, oil painting, by Agostino Brunias, Dominica, c. 1764–1796.

In the context of the history of slavery in the Americas, free people of color (French: gens de couleur libres; Spanish: gente de color libre) were primarily people of mixed African, European, and Native American descent who were not enslaved. However, the term also applied to people born free who were primarily of black African descent with little mixture. They were a distinct group of free people of color in the French colonies, including Louisiana and in settlements on Caribbean islands, such as Saint-Domingue (Haiti), St. Lucia, Dominica, Guadeloupe, and Martinique. In these territories and major cities, particularly New Orleans, and those cities held by the Spanish, a substantial third class of primarily mixed-race, free people developed. These colonial societies classified mixed-race people in a variety of ways, generally related to visible features and to the proportion of African ancestry.^{[citation needed]} Racial classifications were numerous in Latin America.

A freed African slave was known as affranchi (French: "freed"). The term was sometimes meant to include the free people of color, but they considered the term pejorative since they had been born free.

The term gens de couleur libres (French: [ʒɑ̃ də kulœʁ libʁ] ("free people of color") was commonly used in France's West Indian colonies prior to the abolition of slavery. It frequently referred to free people of mixed African and European ancestry.

In British North America, the term free Negro was often used to cover the same class of people—those who were legally free and visibly of African descent.

Saint-Domingue

By the late 18th century prior to the Haitian Revolution, Saint-Domingue was legally divided into three distinct groups: free whites (who were divided socially between the plantation-class grands blancs and the working-class petits blancs); freedmen (affranchis), and slaves. More than half of the affranchis were gens de couleur libres; others were considered freed black slaves. In addition, maroons (runaway slaves) were sometimes able to establish independent small communities and a kind of freedom in the mountains, along with remnants of Haiti's original Taino people. A large group of surviving Native Taino's also supported the Haitian Revolution, they were known as "indiens esclaves" which numbered about 5,000. In a 1780 census, there was also a group listed as “indiens sauvages”, which Haitian historians believe were the native Arawak and Taino that were known to live in tiny reclusive mountain communities at this point.

Dessalines talked about people whom he called “Rouges” (reds), or sometimes “Incas” in his letters. When they were spoken about in context of the war, he makes mention of cooperation between Africans and Natives in maroon communities that plotted against colonists on the southern peninsula. He’s also spoken about “Incas among his men” showing him secret burial quarters in the Artibonite valley that could be used by rebels as shelter and storage. There were 3,000 known Native peoples (both “esclaves” and “sauvages”) living in Haiti in the years before independence, according to a 1802 colonial census.

Dessalines did not forget these people and their sacrifices against Spain and now, France. He named the Haitian army “the Incas”, “the Army of the Sun” and eventually “the Indigenous Army” in honor of them. He also renamed the island “Haiti,” its pre-Columbian name.

When slavery was ended in the colony in 1793, by action of the French government following the French Revolution, there were approximately 28,000 anciens libres ("free before") in Saint-Domingue. The term was used to distinguish those who were already free, compared to those liberated by the general emancipation of 1793. About 16,000 of these anciens libres were gens de couleur libres. Another 12,000 were affranchis, black slaves who had either purchased their freedom or had been given it by their masters for various reasons.

Rights

Regardless of their ethnicity, in Saint-Domingue freedmen had been able to own land. Some acquired plantations and owned large numbers of slaves themselves. The slaves were generally not friendly with the freedmen, who sometimes portrayed themselves to whites as bulwarks against a slave uprising. As property owners, freedmen tended to support distinct lines set between their own class and that of slaves. Also often working as artisans, shopkeepers or landowners, the gens de couleur frequently became quite prosperous, and many prided themselves on their European culture and descent. They were often well-educated in the French language, and they tended to scorn the Haitian Creole language used by slaves. Most gens de couleur were reared as Roman Catholic, also part of French culture, and many denounced the Vodoun religion brought with slaves from Africa.

Under the ancien régime, despite the provisions of equality nominally established in the Code Noir, the gens de couleur were limited in their freedoms. They did not possess the same rights as Frenchmen, specifically the right to vote. Most supported slavery on the island, at least up to the time of the French Revolution. But they sought equal rights for free people of color, which became an early central issue of the unfolding Haitian Revolution.

The primary adversary of the gens de couleur before and into the Haitian Revolution were the working-class white people such as farmers and tradesmen of the colony, known as the petits blancs ("small whites"). Because of the freedmen's relative economic success in the region, sometimes related to blood ties to influential whites people, the petits blancs farmers often resented their social standing and worked to keep them shut out of government. Beyond financial incentives, the free coloreds caused the working-class whites further problems in finding women to start a family. The successful mulattos often won the hands of the small number of eligible women on the island. With growing resentment, the working-class whites monopolized assembly participation and caused the free people of color to look to France for legislative assistance.

French citizenship

The free people of color won a major political battle on May 15, 1791, when the Constituent Assembly in France voted to give full French citizenship to them, on the condition of having two free parents. The decree was revoked on September 24, 1791, and replaced by a new, more generous decree on April 4, 1792, that gave full French citizenship to all free people, regardless of the color of their skin and the statuses of their parents.

Struggle

In their competition for power, both the poor whites and free coloreds enlisted the help of slaves. By doing this, the feud helped to disintegrate class discipline and propel the slave population in the colony to seek further inclusion and liberties in society. As the widespread slave rebellion in the north of the island wore on, many free people of color abandoned their earlier distance from the slaves. A growing coalition between the free coloreds and the former slaves was essential for the eventual success of the Haitians to expel French influence.

The former slaves and the anciens libres still remained segregated in many respects. Their animosity and struggle for power erupted in 1799. The competition between the gens de couleur led by André Rigaud and the black Haitians led by Toussaint Louverture devolved into the War of the Knives.

After their loss in that conflict, many wealthy gens de couleur left as refugees to France, Cuba, Puerto Rico, the United States and elsewhere. Some took slaves with them. Others, however, remained to play an influential role in Haitian politics.

Caribbean

Free people of color were an important part generally in the history of the Caribbean during the period of slavery and afterward. Initially descendants of French men and African and Indian slaves (and later French men and free women of color), and often marrying within their own mixed-race community, some achieved wealth and power. By the late eighteenth century, most free people of color in Saint-Domingue were native born and part of colored families that had been free for generations.

Free people of color were leaders in the French colony of Saint-Domingue, which achieved independence in 1804 as the Republic of Haiti. In Saint-Domingue, Martinique, Guadeloupe, and other French Caribbean colonies before slavery was abolished, the free people of color were known as gens de couleur libres, and affranchis. Comparable mixed-race groups became an important part of the populations of the British colony of Jamaica, the Spanish colonies of Santo Domingo, Cuba, Puerto Rico, and the Portuguese colony of Brazil.

New Orleans and New France

Free woman of color with quadroon daughter. Late 18th-century collage painting, New Orleans.

Free people of color played an important role in the history of New Orleans and the southern area of New France, both when the area was controlled by the French and Spanish, and after its acquisition by the United States as part of the Louisiana Purchase.

When French settlers and traders first arrived in these colonies, the men frequently took Native American women as their concubines or common-law wives (see Marriage 'à la façon du pays'). When African slaves were imported to the colony, many colonists took African women as concubines or wives. In the colonial period of French and Spanish rule, men tended to marry later after becoming financially established. Later, when more white families had settled or developed here, some young French men or ethnic French Creoles still took mixed-race women as mistresses, often known as placées.

Popular stereotypes portray such unions as formal, financial transactions arranged between a white man and the mother of the mixed-race mistress. Supposedly, the young woman of mixed European and African ancestry would attend dances known as "quadroon balls" to meet white gentlemen willing to provide for her and any children she bears from their union. The relationship would end as soon as the man married properly. According to legend, free girls of color were raised by their mothers to become concubines for white men, as they themselves once were. 

However, evidence suggests that on account of the community's piety by the late 18th century, free women of color usually preferred the legitimacy of marriage with other free men of color. In cases where free women of color did enter extramarital relationships with white men, such unions were overwhelmingly lifelong and exclusive. Many of these white men remained legal bachelors for life. This form of interracial cohabitation was often viewed as no different than the modern conception of a common-law marriage.

As in Saint-Domingue, the free people of color developed as a separate class between the colonial French and Spanish and the mass of black slaves. They often achieved education, practiced artisan trades, and gained some measure of wealth; they spoke French and practiced Catholicism. Many also developed a syncretic Christianity. At one time the center of their residential community in New Orleans was the French Quarter. Many were artisans who owned property and their own businesses. They formed a social category distinct from both whites and slaves, and maintained their own society into the period after United States annexation.

Some historians suggest that free people of color made New Orleans the cradle of the civil rights movement in the United States. They achieved more rights than did free people of color or free blacks in the Thirteen Colonies, including serving in the armed militia. After the United States acquired the Louisiana Territory, Creoles in New Orleans and the region worked to integrate the military en masse. William C. C. Claiborne, appointed by Thomas Jefferson as governor of the Territory of Orleans, formally accepted delivery of the French colony on 20 December 1803.

Military service

Free men of color had been armed members of the militia for decades during both Spanish and French rule of the colony of Louisiana. They volunteered their services and pledged their loyalty to Claiborne and to their newly adopted country. In early 1804, the new U.S. administration in New Orleans under Governor Claiborne was faced with a dilemma previously unknown in the United States, the integration of the military by incorporating entire units of established "colored" militia. See, e.g., the 20 February 1804 letter from Secretary of War Henry Dearborn to Claiborne, stating that "it would be prudent not to increase the Corps, but to diminish, if it could be done without giving offense."

A decade later during the War of 1812, the militia which consisted of free men of color volunteered to join the force mustered by Andrew Jackson in preparation for the Battle of New Orleans, when the British began landing troops outside the city in December 1814 in preparation for an invasion of the city. The battle resulted in a decisive American victory, in which black soldiers played a crucial part. However, many black troops who had been promised freedom in exchange for service were forcibly returned to slavery after the battle's conclusion.

Definition

Free West Indian Dominicans, c. 1770

There was relatively little manumission of slaves until after the revolution. Throughout the slave societies of the Americas, some slave owners took advantage of the power relationships to use female slaves sexually; sometimes they had extended relationships of concubinage. However, in the Thirteen Colonies, the children of these relationships were not usually emancipated.

South Carolina diarist Mary Chesnut wrote in the mid-19th century that "like the patriarchs of old our men live all in one house with their wives and their concubines, and the mulattos one sees in every family exactly resemble the white children ..." In some places, especially in the French and Spanish Caribbean and South American slave societies, the ethnic European father might acknowledge the relationship and his children. Some were common-law marriages of affection. Slaveholders were more likely to free their mixed-race children of these relationships than they were to free other slaves. They also sometimes freed the enslaved women who were their concubines.

Many slave societies allowed masters to free their slaves. As the population of color became larger and the white ruling class felt more threatened by potential instability, they worked through their governments to increase restrictions on manumissions. These usually included taxes, requirements that some socially useful reason be cited for manumission, and a requirement that a newly freed person demonstrate a means of independent support. Masters might free their slaves for a variety of reasons, but the most common was a family relationship between master and slave.

Slaves sometimes gained a measure of freedom by purchasing themselves, when allowed to save some portion of earnings if leased out or selling produce. The master determined if one had to pay market or reduced value. In other cases, relatives who were already free and earning money purchased others. Sometimes masters, or the government, would free slaves without payment as a reward for some notable service; a slave who revealed slave conspiracies for uprisings was sometimes rewarded with freedom.

Many people who lived as free within the slave societies did not have formal liberty papers. In some cases these were refugees, who hid in the towns among free people of color and tried to maintain a low profile. In other cases they were "living as free" with the permission of their master, sometimes in return for payment of rent or a share of money they earned by trades. The master never made their freedom official, as in the case of Margaret Morgan, who had been living as a free person in Pennsylvania, but was captured in 1837 and sold together with her children under claims that they were still slaves according to the laws of Maryland.

Economic influence

Free people of color filled an important niche in the economy of slave societies. In most places they worked as artisans and small retail merchants in the towns. In many places, especially in the American South, there were restrictions on people of color owning slaves and agricultural land. But many free blacks lived in the countryside and some became major slaveholders. In the antebellum years, individual slaves who were freed often stayed on or near the plantations where they or their ancestors had been slaves, and where they had extended family. Masters often used free blacks as plantation managers or overseers, especially if the master had a family relationship with the mixed-race man.

In the early 19th century, societies required apprenticeships for free blacks to ensure they developed a means of support. For instance, in North Carolina, "By the late 1830s, then, county courts could apprentice orphans, fatherless or abandoned children, illegitimate children, and free black children whose parents were not employed.

However, the number of apprenticeships declined as the number of free blacks increased. In some Southern states after the Nat Turner slave rebellion of 1831, the legislatures passed laws that forbade the teaching of free blacks or slaves to read and write, which was a requirement for having an apprenticeship. There was fear if blacks could read and write, they might start slave revolts and rebellions. Blacks were not allowed to apprentice as an editor or work in a printing press. Despite the restrictions of some apprenticeships, many free blacks benefited from their time as an apprentice.

In Caribbean colonies, governments sometimes hired free people of color as rural police to hunt down runaway slaves and keep order among the slave population. From the view of the white master class in places such as Saint-Domingue or Jamaica, this was a critical function in a society in which the population of slaves on large plantations vastly outnumbered whites.

In places where law or social custom permitted it, some free people of color managed to acquire good agricultural land and slaves, and become planters themselves. Free blacks owned plantations in almost all the slave societies of the Americas. In the United States, free people of color may have owned the most property in Louisiana, as the French and Spanish colony had developed a distinct creole or mixed-race class before its acquisition by the United States. A man who had a relationship with a woman of color often also arranged for a transfer of wealth to her and their children, whether through deed of land and property to the mother and/or children under the system of plaçage, or by arranging for an apprenticeship to a trade for their mixed-race children, which provided them a better opportunity to make a skilled living, or by educating sons in France and easing their way into the military. In St. Domingue by the late colonial period, gens de couleur owned about one-third of the land and about one-quarter of the slaves, mostly in the southern part of the island.

Post-slavery

When the end of slavery came, the distinction between former free coloreds and former slaves persisted in some societies. Because of advantages in the social capital of education and experience, free people of color often became leaders for the newly freed people. In Saint-Domingue, Toussaint Louverture had gained freedom before he became a leader in the slave rebellion, but he is not believed to have been of mixed race.

In the United States, many of the African Americans elected as state and local officials during Reconstruction in the South had been free in the South before the Civil War. Other new leaders were educated men of color from the North whose families had long been free and who went to the South to work and help the freedmen. Some were elected to office.

Today

Main articles: Louisiana Creole people and Cajun

Many descendants of the gens de couleur, or free people of color, of the Louisiana area celebrate their culture and heritage through a New Orleans-based Louisiana Creole Research Association (LA Créole). The term "Créole" is not synonymous with "free people of color" or gens de couleur libre, but many members of LA Créole have traced their genealogies through those lines. Today, the multiracial descendants of the French and Spanish colonists, Africans, and other ethnicities are widely known as Louisiana Creoles. Louisiana's Governor Bobby Jindal signed Act 276 on 14 June 2013, creating the "prestige" license plate, "I'm Creole," honoring Louisiana Creoles' contributions and heritage.

The terms "Créole" and "Cajun" have sometimes been confused in Louisiana, as members of each group generally had ancestors who were French-speaking; but the terms are not synonymous. The Cajuns are descendants of French colonists from Acadia (in eastern Canada) who were resettled to Louisiana in the 18th century, generally outside the New Orleans area. Generations later, some of their culture relates to that of the Louisiana Creoles, but they are distinct. Members of each group may be multi-ethnic.