Some uses of Lemon Juice

Lemon is one of those super foods with a myriad health and cosmetic benefits. There are a few persons for whom it is an allergen, so make sure you are not allergic to this natural product, before you start enjoying the many benefits.

1. Lemon being a citrus fruit , fights against infection. It helps in production of WBC's and antibodies in blood which attacks the invading microorganism and prevents infection.

2. Lemon is an antioxidant which deactivates the free radicals preventing many dangerous diseases like stroke, cardiovascular diseases and cancers.

3. Lemon lowers blood pressure and increases the levels of HDL (good cholesterol) .

4. Lemon is found to be anti-carcinogenic which lower the rates of colon, prostate, and breast cancer . They prevent faulty metabolism in the cell, which can predispose a cell to becoming carcinogenic. Also blocks the formation of nitrosamines in the gut.

5. Lemon juice is said to give a glow to the skin.

6. A few drops of lemon juice in hot water are believed to clear the digestive system and purify liver as well.

7. The skin of lemon dried under the sun and then ground to make powder can be applied to the hair for a few minutes before bath which relieves head ache and cools the body.

8. Applying lemon juice to acne dries the existing ones and prevents from getting more.

9. Lemon juice acts as a natural hair lightner and skin bleach which reduces the pigment melanin and prevents the risk of chemical allergic reactions which is common with hair dyes and bleaches.

10. Lemon juice is given to relieve gingivitis, stomatitis, and inflammation of the tongue.

11. Lemon juice is given to prevent common cold.

12. Lemon juice is given to prevent or treat urinary tract infection and gonorrhea.

13. Lemon juice is applied to the sites of bites and stings of certain insects to relieve its poison and pain.

14. Lemon juice relieves colic pain and gastric problems .

15. Lemon juice soothes the dry skin when applied with little glycerin .

16. Lemon juice used for marinating seafood or meat kills bacteria and other organisms present in them, thereby prevents many gastro-intestinal tract infections.

17. Lemon juice with a pinch of salt (warm) every morning lowers cholesterol levels and brings down your weight.

18. Lemon juice is the best drink to prevent dehydration and shock in case of diarrhea.

19. Lemon juice can also be used as a mouthwash. It removes plaque, whitens the teeth and strengthens the enamel.

20. A table spoon on thick lemon syrup everyday relieves asthma.

21. Lemon juice relieves chilblains and itchy skin.

22. Gargling lemon juice relieves throat infection and also used as a treatment for diphtheria .

23. Lemon juice is an excellent treatment for dandruff and greasy hair .

24. Lemon applied over the face removes wrinkles and keeps you young.

25. Lemon juice helps to prevent and cure osteoarthritis .

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History of Aromacity | Heterocyclics | Polycyclics

History of Aromacity

The first known use of the word "aromatic" as a chemical term -- namely, to apply to compounds that contain the phenyl radical -- occurs in an article by August Wilhelm Hofmann in 1855.If this is indeed the earliest introduction of the term, it is curious that Hofmann says nothing about why he introduced an adjective indicating olfactory character to apply to a group of chemical substances, only some of which have notable aromas. It is the case, however, that many of the most odoriferous organic substances known are terpenes, which are not aromatic in the chemical sense. But terpenes and benzenoid substances do have a chemical characteristic in common, namely higher unsaturation indexes than many aliphatic compounds, and Hofmann may not have been making a distinction between the two categories.

The cyclohexatriene structure for benzene was first proposed by August Kekulé in 1865. Over the next few decades, most chemists readily accepted this structure, since it accounted for most of the known isomeric relationships of aromatic chemistry. However, it was always puzzling that this purportedly highly-unsaturated molecule was so unreactive toward addition reactions.
The discoverer of the electron J. J. Thomson, in 1921 placed three equivalent electrons between each carbon atom in benzene.

An explanation for the exceptional stability of benzene is conventionally attributed to Sir Robert Robinson, who was apparently the first (in 1925 ) to coin the term aromatic sextet as a group of six electrons that resists disruption.
In fact, this concept can be traced further back, via Ernest Crocker in 1922,to Henry Edward Armstrong, who in 1890, in an article entitled The structure of cycloid hydrocarbons, wrote the (six) centric affinities act within a cycle...benzene may be represented by a double ring (sic) ... and when an additive compound is formed, the inner cycle of affinity suffers disruption, the contiguous carbon-atoms to which nothing has been attached of necessity acquire the ethylenic condition.
Here, Armstrong is describing at least four modern concepts. First, his "affinity" is better known nowadays as the electron, which was only to be discovered seven years later by J. J. Thomson. Second, he is describing electrophilic aromatic substitution, proceeding (third) through a Wheland intermediate, in which (fourth) the conjugation of the ring is broken. He introduced the symbol C centered on the ring as a shorthand for the inner cycle, thus anticipating Eric Clar's notation. It is argued that he also anticipated the nature of wave mechanics, since he recognized that his affinities had direction, not merely being point particles, and collectively having a distribution that could be altered by introducing substituents onto the benzene ring (much as the distribution of the electric charge in a body is altered by bringing it near to another body).
The quantum mechanical origins of this stability, or aromaticity, were first modelled by Hückel in 1931. He was the first to separate the bonding electrons in sigma and pi electrons.
Characteristics of aromatic (Aryl) compounds
An aromatic compound contains a set of covalently-bound atoms with specific characteristics:
A delocalized conjugated π system, most commonly an arrangement of alternating single and double bonds
Coplanar structure, with all the contributing atoms in the same plane
Contributing atoms arranged in one or more rings
A number of π delocalized electrons that is even, but not a multiple of 4. This is known as Hückel's rule. Permissible numbers of π electrons include 2, 6, 10, 14, and so on
Special reactivity in organic reactions such as electrophilic aromatic substitution and nucleophilic aromatic substitution
Whereas benzene is aromatic (6 electrons, from 3 double bonds), cyclobutadiene is not, since the number of π delocalized electrons is 4, which of course is a multiple of 4. The cyclobutadienide (2−) ion, however, is aromatic (6 electrons). An atom in an aromatic system can have other electrons that are not part of the system, and are therefore ignored for the 4n + 2 rule. In furan, the oxygen atom is sp² hybridized. One lone pair is in the π system and the other in the plane of the ring (analogous to C-H bond on the other positions). There are 6 π electrons, so furan is aromatic.
Aromatic molecules typically display enhanced chemical stability, compared to similar non-aromatic molecules. The circulating π electrons in an aromatic molecule produce ring currents that oppose the applied magnetic field in NMR. The NMR signal of protons in the plane of an aromatic ring are shifted substantially further down-field than those on non-aromatic sp² carbons. This is an important way of detecting aromaticity. By the same mechanism, the signals of protons located near the ring axis are shifted up-field. Planar monocyclic molecules containing 4n π electrons are called antiaromatic and are, in general, destabilized. Molecules that could be antiaromatic will tend to alter their electronic or conformational structure to avoid this situation, thereby becoming non-aromatic. For example, cyclooctatetraene (COT) distorts itself out of planarity, breaking π overlap between adjacent double bonds. Aromatic molecules are able to interact with each other in so-called π-π stacking: the π systems form two parallel rings overlap in a "face-to-face" orientation. Aromatic molecules are also able to interact with each other in an "edge-to-face" orientation: the slight positive charge of the substituents on the ring atoms of one molecule are attracted to the slight negative charge of the aromatic system on another molecule.
Many of the earliest-known examples of aromatic compounds, such as benzene and toluene, have distinctive pleasant smells. This property led to the term "aromatic" for this class of compounds, and hence to "aromaticity" being the eventually-discovered electronic property of them.

Aromatic compound classifications

The key aromatic hydrocarbons of commercial interest are benzene, toluene, ortho-xylene and para-xylene. About 35 million tonnes are produced worldwide every year. They are extracted from complex mixtures obtained by the refining of oil or by distillation of coal tar, and are used to produce a range of important chemicals and polymers, including styrene, phenol, aniline, polyester and nylon.

Heterocyclics

In heterocyclic aromatics, one or more of the atoms in the aromatic ring is of an element other than carbon. This can lessen the ring's aromaticity, and thus (as in the case of furan) increase its reactivity. Other examples include pyridine, imidazole, pyrazole, oxazole, thiophene, and their benzannulated analogs (benzimidazole, for example).

Polycyclics

Polycyclic aromatic hydrocarbons (PAH) are molecules containing two or more simple aromatic rings fused together by sharing two neighboring carbon atoms (see also simple aromatic rings). Examples are naphthalene, anthracene and phenanthrene.
Substituted aromatics
Many chemical compounds contain simple aromatic rings in their structure. Examples include trinitrotoluene (TNT), acetylsalicylic acid (aspirin), paracetamol, and DNA, which contains both purine and pyrimidine.
Aromaticity in other systems
Aromaticity is found in ions as well: the cyclopropenyl cation (2e system), the cyclopentadienyl anion (6e system), the tropylium ion (6e) and the cyclooctatetraene dianion (10e). Aromatic properties have been attributed to non-benzenoid compounds such as tropone. Aromatic properties are tested to the limit in a class of compounds called cyclophanes.
A special case of aromaticity is found in homoaromaticity where conjugation is interrupted by a single sp³ hybridized carbon atom. When carbon in benzene is replaced by other elements in borabenzene, silabenzene, germanabenzene, stannabenzene, phosphorine or pyrylium salts the aromaticity is still retained. Aromaticity is also not limited to compounds of carbon, oxygen and nitrogen.
Metal aromaticity is believed to exist in certain metal clusters of aluminium. Möbius aromaticity occurs when a cyclic system of molecular orbitals formed from pπ atomic orbitals and populated in a closed shell by 4n (n is an integer) electrons is given a single half-twist to correspond to a Möbius topology. Because the twist can be left-handed or right-handed, the resulting Möbius aromatics are dissymmetric or chiral. Up to now there is no doubtless proof, that a Möbius aromatic molecule was synthesized.Aromatics with two half-twists corresponding to the paradromic topologies first suggested by Johann Listing have been proposed by Rzepa in 2005.In carbo-benzene the ring bonds are extended with alkyne and allene groups.

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Synthesised Hydrocarbons |Metal-Organic Frameworks | Polymer

Synthesised Hydrocarbons

An alternative to hydrides is to use regular hydrocarbon fuels as the hydrogen carrier. Then a small hydrogen reformer would extract the hydrogen as needed by the fuel cell. However, these reformers are slow to react to changes in demand and add a large incremental cost to the vehicle powertrain.
Direct methanol fuel cells do not require a reformer, but provide a lower energy density compared to conventional fuel cells, although this could be counter balanced with the much better energy densities of ethanol and methanol over hydrogen. Alcohol fuel is a renewable resource.
Solid-oxide fuel cells can run on light hydrocarbons such as propane and methane without a reformer, or can run on higher hydrocarbons with only partial reforming, but the high temperature and slow startup time of these fuel cells makes them prohibitive for automobiles.

Carbon nanotubes



Hydrogen carriers based on nanostructured carbon (such as carbon buckyballs and nanotubes) have been proposed. Despite occasional claims of greater than 50 wt% hydrogen storage, it has generally come to be accepted that less than 1 wt% is practical.

Metal-Organic Frameworks

Another class of synthetic porous materials that could store hydrogen efficiently are Metal-Organic Frameworks. In 2006, chemists at UCLA and the University of Michigan have achieved hydrogen storage concentrations of up to 7.5% weight in a Metal Organic Framework material. However, the storage was achieved at the low temperature of 77 Kelvin.

Polymer

Aug 4 2006 - A team of Korean researchers led by Professor Lim Ji-sun of Seoul National University’s School of Physics found a new material with the hydrogen storage efficiency of 7.6 percent based on first-principles electronic structure calculations for hydrogen binding to metal-decorated polymers of many different kinds, the hydrogen can be stored in solid matter in normal temperatures and pressures by attaching a titanium atom to a polyacetylene.

Glass microspheres

Hollow glass microspheres can be utilized for controlled storage and release of hydrogen.
Hydrogen-Storage Materials Based on Imidazolium Ionic Liquids
In 2007 Dupont and others reported Hydrogen-Storage Materials Based on Imidazolium Ionic Liquids. Simple alkyl(aryl)-3-methylimidazolium N-bis(trifluoromethanesulfonyl)imidate salts that possess very low vapour pressure, high density, and thermal stability and are not inflammable can add reversibly 6-12 hydrogen atoms in the presence of classical Pd/C or Ir0 nanoparticle catalysts and can be used as alternative materials for on-board hydrogen-storage devices. These salts can hold up to 30 g L-1 of hydrogen at atmospheric pressure, which is twice that compressed hydrogen gas can attain at 350

Phosphonium borate

In 2006 researchers of University of Windsor reported on reversible hydrogen storage in a non-metal phosphonium borate .The phosphino-borane on the left accepts one equivalent of hydrogen at one atmosphere and 25°C and expels it again by heating to 100°C. The storage capacity is 0.25 wt% still rather below the 6 to 9 wt% required for practical use.

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Triaryl Phosphate | Phosphorus Flame Retardant

Triaryl Phosphate (T.A.P.)

Phosphorus Flame Retardant

TAP ( Triaryl Phosphate ) is a low viscosity synthetic Triaryl phosphate ester, Triaryl Phosphate finds uses in wide variety of application as Flame retardant plasticizer

Uses of riaryl Phosphate (T.A.P.)

Leather cloth (PVC) : Upholstery, Book binding, Seat covers
Utility articles: Footwear, Raincoats, Handbags, Fiber glass cellulose acetate
Extruded articles : Cables (PVC & rubber), hoses, flexible pipe, coal mining, conveyor belts
Coatings: Nitrocellulose lacquers, phenolic resins, lube oils

Typical properties
Physical appearance :Clear Liquid
Phosphorus content:wt % 9.0
Specific gravity @ 25° C:1.21±0.005
Boiling Point (decomposes )°C :415° C
Flash Point °C :220°C
Solubility (G/100 g Solvent): Water Insoluble , Completely soluble in Methylene chloride ,Methanol ,Toluene ,Methyl Ethyl Ketone

TAP is recommended for use in plastisols for fabrics coating in formulation of fire resistant fluid and other applications where its low, stable viscosity offers improved processing.
TAP can give a driver finish to coated fabrics than other Triaryl phosphate EASTER. TAP has high plastcizers efficiency that enables formulator to achieve better flame retardance at lower cost. It can also be used as flame retardant in phenolic laminates The use of proper equipment is recommended. Excess exposure to the product should be avioded.
Wash thoroughly after handling. Product should be stored in cool, dry and well ventilated area away from incompatible materials. Unless stated, shelf life of the product will be 12 months from the date of packing. For additional handling & toxicological information, consult PAC Material safety Data sheet.

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Isotopes | High Resolution Mass Spectrometry

Isotopes

Since a mass spectrometer separates and detects ions of slightly different masses, it easily distinguishes different isotopes of a given element. This is manifested most dramatically for compounds containing bromine and chlorine, as illustrated by the following examples. Since molecules of bromine have only two atoms, the spectrum on the left will come as a surprise if a single atomic mass of 80 amu is assumed for Br. The five peaks in this spectrum demonstrate clearly that natural bromine consists of a nearly 50:50 mixture of isotopes having atomic masses of 79 and 81 amu respectively. Thus, the bromine molecule may be composed of two 79Br atoms (mass 158 amu), two 81Br atoms (mass 162 amu) or the more probable combina3. tion of 79Br-81Br (mass 160 amu). Fragmentation of Br2 to a bromine cation then gives rise to equal sized ion peaks at 79 and 81 amu.

The presence of chlorine or bromine in a molecule or ion is easily detected by noticing the intensity ratios of ions differing by 2 amu. In the case of methylene chloride, the molecular ion consists of three peaks at m/z=84, 86 & 88 amu, and their diminishing intensities may be calculated from the natural abundances given above. Loss of a chlorine atom gives two isotopic fragment ions at m/z=49 & 51amu, clearly incorporating a single chlorine atom. Fluorine and iodine, by contrast, are monoisotopic, having masses of 19 amu and 127 amu respectively. It should be noted that the presence of halogen atoms in a molecule or fragment ion does not change the odd-even mass rules given above.

Two other common elements having useful isotope signatures are carbon, 13C is 1.1% natural abundance, and sulfur, 33S and 34S are 0.76% and 4.22% natural abundance respectively. For example, the small m/z=99 amu peak in the spectrum of 4-methyl-3-pentene-2-one (above) is due to the presence of a single 13C atom in the molecular ion. Although less important in this respect, 15N and 18O also make small contributions to higher mass satellites of molecular ions incorporating these elements.

Fragmentation Patterns

The fragmentation of molecular ions into an assortment of fragment ions is a mixed blessing. The nature of the fragments often provides a clue to the molecular structure, but if the molecular ion has a lifetime of less than a few microseconds it will not survive long enough to be observed. Without a molecular ion peak as a reference, the difficulty of interpreting a mass spectrum increases markedly. Fortunately, most organic compounds give mass spectra that include a molecular ion, and those that do not often respond successfully to the use of milder ionization conditions. Among simple organic compounds, the most stable molecular ions are those from aromatic rings, other conjugated pi-electron systems and cycloalkanes. Alcohols, ethers and highly branched alkanes generally show the greatest tendency toward fragmentation.
The mass spectrum of dodecane illustrates the behavior of an unbranched alkane. Since there are no heteroatoms in this molecule, there are no non-bonding valence shell electrons. Consequently, the radical cation character of the molecular ion (m/z = 170) is delocalized over all the covalent bonds. Fragmentation of C-C bonds occurs because they are usually weaker than C-H bonds, and this produces a mixture of alkyl radicals and alkyl carbocations. The positive charge commonly resides on the smaller fragment, so we see a homologous series of hexyl (m/z = 85), pentyl (m/z = 71), butyl (m/z = 57), propyl (m/z = 43), ethyl (m/z = 29) and methyl (m/z = 15) cations. These are accompanied by a set of corresponding alkenyl carbocations (e.g. m/z = 55, 41 &27) formed by loss of 2 H. All of the significant fragment ions in this spectrum are even-electron ions. In most alkane spectra the propyl and butyl ions are the most abundant.

The presence of a functional group, particularly one having a heteroatom Y with non-bonding valence electrons (Y = N, O, S, X etc.), can dramatically alter the fragmentation pattern of a compound. This influence is thought to occur because of a "localization" of the radical cation component of the molecular ion on the heteroatom. After all, it is easier to remove (ionize) a non-bonding electron than one that is part of a covalent bond. By localizing the reactive moiety, certain fragmentation processes will be favored. These are summarized in the following diagram, where the green shaded box at the top displays examples of such "localized" molecular ions. The first two fragmentation paths lead to even-electron ions, and the elimination (path #3) gives an odd-electron ion. Note the use of different curved arrows to show single electron shifts compared with electron pair shifts.

The charge distributions shown above are common, but for each cleavage process the charge may sometimes be carried by the other (neutral) species, and both fragment ions are observed. Of the three cleavage reactions described here, the alpha-cleavage is generally favored for nitrogen, oxygen and sulfur compounds. Indeed, in the previously displayed spectra of 4-methyl-3-pentene-2-one and N,N-diethylmethylamine the major fragment ions come from alpha-cleavages

The complexity of fragmentation patterns has led to mass spectra being used as "fingerprints" for identifying compounds. Environmental pollutants, pesticide residues on food, and controlled substance identification are but a few examples of this application. Extremely small samples of an unknown substance (a microgram or less) are sufficient for such analysis.
The following mass spectrum of cocaine demonstrates how a forensic laboratory might determine the nature of an unknown street drug.
Even though extensive fragmentation has occurred, many of the more abundant ions (identified by magenta numbers) can be rationalized by the three mechanisms shown above. The m/z = 42 ion might be any or all of the following: C3H6, C2H2O or C2H4N. A precise assignment could be made from a high-resolution m/z value (next section).Odd-electron fragment ions are often formed by characteristic rearrangements in which stable neutral fragments are lost. Mechanisms for some of these rearrangements have been identified by following the course of isotopically labeled molecular ions.

5. High Resolution Mass Spectrometry

Formula C6H12 C5H8O C4H8N2

Mass 84.0939 84.0575 84.0688

In assigning mass values to atoms and molecules, we have assumed integral values for isotopic masses. However, accurate measurements show that this is not strictly true. Because the strong nuclear forces that bind the components of an atomic nucleus together vary, the actual mass of a given isotope deviates from its nominal integer by a small but characteristic amount (remember E = mc2). Thus, relative to 12C at 12.0000, the isotopic mass of 16O is 15.9949 amu (not 16) and 14N is 14.0031 amu (not 14). By designing mass spectrometers that can determine m/z values accurately to four decimal places, it is possible to distinguish different formulas having the same nominal mass. The table on the right illustrates this important feature, and a double-focusing high-resolution mass spectrometer easily distinguishes ions having these compositions. Mass spectrometry therefore not only provides a specific molecular mass value, but it may also establish the molecular formula of an unknown compound.

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HOW TO CLEAN pH ELECTRODES | HOW TO REJUVENATE pH ELECTRODES

HOW TO CLEAN pH ELECTRODES

Cleaning of the electrode (note that in case of gel electrodes replacing of the reference solution is usually impossible):

General
Soak in 0.1M HCl for half an hour.
Drain and refill the reference solution.
Soak the electrode in filling solution for one hour.

Inorganic:
Soak in 0.1M tetrasodium EDTA solution for 15 minutes.
Drain and refill the reference solution.
Soak the electrode in filling solution for one hour.

Protein:
Soak in 1% pepsin / 0.1M HCl for 15 minutes.
Drain and refill the reference solution.
Soak the electrode in filling solution for one hour.

Grease and Oil:
Rinse with detergent or ethanol solution.
Drain and refill the reference solution.
Soak the electrode in filling solution for one hour. Electrode response may be enhanced by substituting a mixture of 1:1 pH 4 buffer and filling solution for the soaking solution.

Cleaning of the clogged junction:
Pollution by sulfides:
Use a solution of 8% thiocarbamide in 1 mol/L HCl.
Keep the electrode in the above solution till junction's color turns pale.
Pollution by silver chloride:
Use concentrated ammonia solution.
Keep the electrode in the above solution for about 12 hours.
Rinse and put into pH 4 buffer for at least 1 hour.
Other contamination have to be removed by cleaning with distilled water, alcohol or mixtures of acids. If nothing else helps you may consider use of ultrasonic cleaner as last resort.



HOW TO REJUVENATE pH ELECTRODES

Note: following procedures are a last resort. They may work, they may won't. You may try them before throwing electrode away.

First of all - clean the electrode as described in electrode cleaning section, then:

Soak the electrode for 4-8 hours in 1M HCl solution.

Rinse it and move to pH 7 buffer for an hour.

Give it a try.

If the electrode is still not working:
Fill the electrode with filling solution.
Move to the fume hood!
Place the electrode in the 10% nitric acid solution on a hotplate. Heat to boiling, and keep it in the solution for 10 minutes.
Place 50 mL of filling solution in a second clean beaker. Heat, although boiling is not necessary.
While the electrode is still hot, transfer it to the beaker of heated filling solution. Set aside to cool. When the electrode has cooled, test the electrode as described in the testing electrode parameters section. This rejuvenating procedure is particularly effective with gel filled combination electrodes. Do not be concerned if a small amount of the gel protrudes through the reference frit during the boiling in nitric acid step. This is both acceptable and useful.

If this procedure does not result in a pH electrode that responds quickly and has a slope of 55 - 61 mV/pH unit, the electrode is unrecoverable and should be thrown away. Remember, the procedure was proposed for the electrode that was to be thrown away anyway.
Some manufacturers suggest the electrode may be reactivated by treating with a diluted solution of hydrofluoric acid followed by subsequent conditioning in electrolyte. Before considering the procedure, take into account that hydrofluoric acid is extremally dangerous! Safer (but still dangerous) approach can be to use some slightly acidic solution containing fluorides, like 20 wt% ammonium bifluoride, NH4HF2 - put glass bulb part of the electrode in the solution for a minute followed by 15 seconds bath in 6 M hydrochloric acid. Rinse the electrode well and soak for 24 hours in a pH buffer with pH .

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Bond Stretching

Energy due to Bond Stretching Whenever a bond is compressed or stretched the the energy goes up.

The energy potential for bond stretching and compressing is described by an equation similar to Hooke's law for a spring, except a cubic term is added.

This cubic term helps to keep the energy from rising too sharply as the bond is stretched.

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Kurkure Facts | plastic manufacturer

Related tags: plastic food, plastic wholesale, plastic product, plastic manufacturer .
What parameters/protocols are followed for the safe manufacturing of Kurkure?
A very stringent process and a strict quality control are observed while manufacturing each and every pack of Kurkure. Each and every raw material that is received in the Kurkure factory like Rice Meal, Corn Meal and Gram meal is thoroughly checked for all quality parameters. Incase of any ingredient that does not meet its stringent internal quality parameters or those prescribed in the regulations, are rejected.

What is Kurkure made up of?
Kurkure is made of Rice meal, Corn meal, Gram Meal, Edible oil, Seasonings, Salt, Spices and Condiments, Spices and Flavors. All these ingredients are such that they are used daily in all households today for preparation of various edible items.

Is Kurkure a safe snacking option?
Kurkure is not only a safe product but also a healthier snack. It is not harmful to health. The product is made with Rice bran oil which is one of the healthier oils as it is naturally high in the good fats and low in saturated fats. By cooking in RICE BRAN oil, the saturated fat has been reduced by 40%. Saturated fats are the ones to watch out for, because excess of saturated fat can increase blood cholesterol levels.

Is the recent allegations regarding Kurkure containing plastics true or false?
The discussions which say “Kurkure contains plastic” are completely false and there is no evidence in any of the contentions you have seen in the “chain mail”. Kurkure is a new age fried food and contains Rice meal, Corn meal, Gram Meal, Edible oil, Seasonings, Salt, Spices and Condiments and Flavours . All the raw materials used in Kurkure are compliant with the Prevention of Food Adulteration Act and Rules that govern the manufacture, distribution and sale of all foods. All ingredients are such that are used daily in all households today for preparation of various edible items.

Is it true that Kurkure burns due to the high percentage of corn starch in it?
No, there is no truth in the statement that if you burn Kurkure then Kurkure burns due to the high percentage of corn starch in it. The process of making Kurkure involves blending of the raw materials to deliver homogenous mix, addition of water for further processing, extrusion of the mix, frying to develop taste and texture and then application of consumer loveable flavour. The product is then packed into the best packaging laminate to ensure delivery of acceptable quality Kurkure to consumers. The extrusion process used in the manufacture of Kurkure is also one of the safest processes which are now being used for making baby foods.

How to identify if Kurkure contains Plastic?
If you want to find whether Kurkure contains Plastic , hold 2 pieces of Kurkure in your each hand. Light a candle. Burn the tip of both the pieces in the candle. Try to stick both the burnt ends of each piece. If they stick, then sure there’s something suspicious.
And if Kurkure contains plastic is a false thing that is to say we use only the above mentioned flours, we have achieved the milestone of preparing edible plastics.

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Platinum extraction | rhodium | tin white metal

Related tags: precious metals , gold scrap .

Platinum is considered one of the most precious metals. It is rare, scarce, and very costly. Currently platinum deposits are concentrated primarily in South Africa and Russia.
The cost of platinum has traditionally ranged from $350-$450 per ounce with a few exceptions and in recent times the cost has increased to $1100 to $1300 per ounce.

Pure platinum is a tin white metal, it is malleable, ductile and harder than silver.
It does not discolor in air, dissolve in acid, and it has a melting point of 3224 degree F. it is generally found as part of the Platinum Group Metals (PGM’s); Platinum, Palladium, Rhodium, Ruthenium, Iridium and Osmium.

When platinum was first discovered in Columbia back in the early 1700’s the inhabitants called it “platina,” which meant silver of less value. But, as refining processes were developed, this metal was applied for many purposes. Nowadays global demand exceeds 5.5 million ounces. Approximately 20% of the goods produced in the world contain platinum or are produced using platinum.

Applications and benefits of Platinum plating
Platinum electroplating is used to coat electrodes that are used in the refining of oil, and in the manufacturing of fertilizers, acids, and explosives. The automotive industry uses platinum plated catalytic converters to treat automobile exhaust emission. In the medical industry, platinum plate is used on instruments such as catheters and connectors for surgical equipment. The electrical and electronics industries use platinum plating for low voltage and low energy contacts. In electroplating, platinum is often used to coat titanium, niobium, or stainless steel anodes. It is also used in the jewels industry. Platinum’s shine is purer than silver or gold, enhancing the brilliancy of gemstones and diamonds. Platinum plating does not tarnish or oxidize and it is hypoallergenic – very few people ever experience an allergic reaction.

Platinum electroplate coatings typically range from 0.5 to 5 microns depending on the application. It is applied utilizing a rack fixture that is submerged in a chloroplatinic acid or a sulfate based platinum solution. The finished product will range in color from tin white to a matte gray finish depending on the base metal finish, activation process, and the thickness of the platinum coating.

Silver has the capability to platinum plate on brass, castings, copper, invar, kovar, steel, stainless steel, and titanium on items up to 24 inches in length.

Benefits of Platinum plating
Hard deposits
Smooth deposits
Pore-free deposits
Excellent wear resistance
Low electrical resistance
Excellent corrosion resistance

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chemical Synthesis of S-Propanolol | Drug synthesis

Related tags: chemical synthesis, propanolol, pharmacokinetics, drug synthesis

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chemical Synthesis of Atorvastatin | atorvastatin calcium

Related tags: atorvastatin calcium, chemical synthesis, atorvastatin side effects.

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Synthesis of Allethrolone

Synthesis of Allethrolone

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Chemical Synthesis of Esopremazole

Synthesis of Esopremazole

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Chemical Science of CSIR Syllabus

Related tags: chemical analysis, syllabus questions, Mass spectroscopy
PAPER 1– SECTION A
1. General information on science and its interface with society to test the candidate’s awareness of science, aptitude of scientific and quantitative reasonsing.
2. COMMON ELEMENTRY COMPUTER SCIENCE ( Applicable to all candidates offering subject areas ).
3. History of development of computers, Mainframe, Mini, Micro’s and Super Computer Systems.
4. General awareness of computer Hardware i..e. CPU and other peripheral devices ( input / output and auxiliary storage devices ).
5. Basic knowledge of computer systems, software and programming languages i.e. Machine language, Assembly language and higher level language.
6. General awareness of popular commercial software packages like LOTUS, DBASE, WORDSTAR, other Scientific application packages.

PAPER 1 – SECTION B
1. Structure and Bonding : Atomic orbitals, electronic configuration of atoms ( L – S coupling ) and the periodic properties of elements ; ionic radii, ionization potential, electron affinity, electronegativity; concept of hybridization. Molecular orbitals and electronic configuration of homonuclear and heteronucelar diatomic molecules. Shapes of polyatomic molecules; VSEPR, theory. Symmetry elements and point groups for simple molecules. Bond lengths, bond angles, bond order and bond energies. Types of Chemical Bond ( weak and strong ) intermolecular forces, structure of simple ionic and covalent solids, lattice energy.
2. Acids and Bases : Bronsted and Lewis acids and bases, pH and pKa, acid-based concept in non-acqueous media ; HSAB concept. Buffer solution.
3. Redox Reactions : Oxidation numbers, Redox potential, Electrochemical series, Redox indicators.
4. Energetics and Dynamics of Chemical Reactions : Law of conservation of energy, Energy and entheipy of reactions. Entropy, free-energy, relationship between free energy change and equilibrium. Rates of chemical reactions (first-and second-order reactions). Arrhenius equation and concept of transition state. Mechanisms, including SN 1 and SN 2 reactions, electron transfer reactions, catalysis. Coiligative properties of solutions.
5. Aspects of s, p, d, f, Block Elements : General characteristics of each block. Chemical principles involved in extractions and purification of iron, copper, lead, zinc and aluminium. Coordination chemistry; structural aspects, isomerism, octahedral and tetrahedral crystal – field splitting of dorbitals. CFSE, magnetism end colour of transition metal ions. Sandwich compounds, metal carbonyls and metal clusters. Rare gas compounds, non-stoichiometric oxides. Radio activity and transmutation of elements, isotopes and their applications.
6. IUPAC Nomenciature of Simple Organic and Inorganic Compounds.
7. Concept of Chirality : Recognition of symmetry elements and chiral structures; R – S nomenciature, diastereoisomerism in acyclic and cyclic systers; E – Z isomerisms. Conformational analysis of simple cyclic ( chair and boat cyclo hexanes ) and acyclic systems. Interconversion of Fischer, Newman and Sawhorse projections.
8. Common Organic Reactions and Mechanisms : Reactive intermediates, Formation and stability of carbonium ions, carbanians, carbenes, nitrenes, radicals and arynes. Nucleophilic, electrophilic, radical substitution, addition and elimination reactions. Familiar name reactions : Aldol, Perkin, Stobbe, Dieckmann condensations; Holmann, Schmidt, Lossen, Curtius, Backmann and Fries rearrangements; Reimer – Tiemann, Reformatsky and Grignard reactions. Diels – Aider reactions; Clasien rearrangements; Friedeal – Crafts reaftions; Witting reactions; and robinson annulation. Routine functional group transformations and interconversions of simple functionalities. Hydroboration, Oppenaur oxidations; Clemmensen, Wolff-Kishner, Meerwein – Ponndorf – Verley and Birch reductions.
9. Elementary principles and applications of electronic, vibrational, NMR, EPR and Mass Spectral techniques to simple structural problems.
10. Data Analysis : Types of errors, propagation of errors, accuracy and precision, least-squares analysis, average standard deviation.

11. Statistical Tharomodynamics : Thermodynamic probability and entropy; Maxwell – Boltzmann, Bose – Einstein and Fermi – Dirac statistics. Partition function; rotational translational, vibratioanl and electronic partition functions for diatomic molecules; calculations of thermodynamic functions and equilibrium constants. Theories of specific heat for solids.
12. Non-equilibrium Thermodynamics : Postulates and methodologies, linear laws, Gibbs equation, Onsager reciprocal theory.
13. Reaction Kinetics : Methods of determining rate laws. Mechanisms of photochemical, chain and oscillatory reactions. Collision theory of reaction rates; steric factor, treatment of unimolecular reactions. Theory of absolute reaction rates, comparison of results with Eyring and Arrhenius equations, ionic reactions; salt effect. Homogeneous catalysis and Michaelis – Menten kinetics; heterogeneous catalysis.
14. Fast Reaction : Luminescence and Energy transfer processes. Study of kinetics by stopped flow technique, relazation method, flash photolysis and magnetic resonance method.
15. Macromolecules : Number – average and weight average molecular weights ; determination of molecular weights. Kinetics of polymerization. Stereochemistry and mechanism of polymerization.
16. Solids : Dislocation in solids, Schottky and Frenkel defects, Electrical properties; insulators and semiconductors; superconductors, band theory of solids, Solid-state reactions.
17. Nuclear Chemistry : Radioactive decay and equilibrium. Nuclear reactions ; Q value, cross sections, types of reactions, Chemical effects of nuclear transformations; fission and fusion, fission products and fission yields. Radioactive technique; tracer technique, neutron activation analysis, counting techniques such as G. M. ionization and proportional counter.
18. Chemistry of Non-transition Elements : General discussion on the properties of the non-transition elements; special features of individual elements; synthesis, properties and structure of their halides and oxides, polymorphyism of carbon, phosphorus and sulphur. Synthesis, properties and structure of boranes, carboranes, borazines, silicates carbides, silicones, phosphazenes, sulphur-nitrogen compounds; peroxo compounds of boron, carbon and sulphur; oxy acids of nitrogen, phosphours, sulphur and halogens, interhalogens pseudohalides and noble gas compounds.
19. Chemistry of Transition Elements : Coordination chemistry of transition metal ions ; Stability constants of complexes and their determination; stabilization of unusual oxidation states. Stereochemistry of coordination compounds. Ligandfield theory, splitting of d-orbitals in low-symmetry environments. Jahn – Teller effect; interpretation of electronic spectra including charge transfer spectra ; spectrochemical series, nephelauxetic series ,Magnetism; Dia-, para-, ferro- and antiferromagnetism, quenching of orbital angular moment, spinorbit copling, inorganic reaction mechanisms; substitution reactions, trans effect and electron transfer reactions, photochemical reaction of chromium and ruthenium complexes. Fluxional molecules iso-and heteropolyacids ; metal clusters. Spin crossover in coordination compounds.
20.Chemistry of Lanthanides and Actinides : Spectral and magnetic properties; Use of lanthanide compounds as shift reagents.
21. Organometallic Chemistry of Transition Elements : Synthesis, structure and bonding, organometallic reagents in organic synthesis and in homogeneous catalytic reactions ( hydrogenation, hydroformayalation, isomerisation and polymerization ); pl-acid metal complexes, activation of small molecules by coordination.
22. Topics in Analytical Chemistry : Adsorption partition, exclusion electrochromatography, Solvent extraction and ion exchange, methods. Application of atomic and molecular absorption and emission spectroscopy in quantitative analysis Light scattering techniques including nephelometry and Raman spectroscopy. Electroalytical techniques: voltammetry, cyclit, voltammetry, polarography, amperometry, coulometry and comductometry ion-elective electrodes. Annodic stripping voltammetry; TGA, DTA, DSC and online analysors.
23. Bioinorganic Chemistry : Metal ions in Biology, Molecular mechanism of ion transport across membranes; ionophores. Photosynthesis, PSL, PSH; nitrogen fixation, oxygen uptake proteins, cytochromes and ferrodoxins.
24. Aromaticity : Huckel’s rule and concept of aromaticty (n) annulences and heteroannulenes, fulterenes (C60).
25. Stereochemistry and conformational Analysis : Nwere method of asymmetric synthesis ( including enzymatic and catalytic nexus ), enantio and diastereo selective synthesis. Effects of conformation on reactivity in acyclic compounds and cyclohexanes.
26. Selective Organic Name Reactions : Favorskli reaction; Stork enamine reaction; Michael addition, Mannich Reaction; Sharpless asymmetric epoxidation; Ene reaction, Barton reaction, Holmann-Loffer-Freytag reaction, Shapiro reaction, Baeyer-Villiger reaction, Chichibabin reaction.
27. Mechanisms of Organic Reactions : Labelling and Kinetic isotope effects, Hamett equation, ( sigma-rho ) relationship, non-classical carbonium ions, neighbouring group participation.
28. Pericyclic Reactions : Selection rules and stereochemistry of electrocyclic reactions, cycloaddition and sigmatropic shifts, Sommelet, Hauser, Cope and Claisen rearrangements.
29. Heterocyclic Chemistry : Synthesis and reactivity of furan, thiophene, pyrrole, pyridine, quinoline, isoquinoline and indole; Skraup synthesis, Fisher indole synthesis.30. Reagents in Organic Synthesis : Use of the following reagents in organic synthesis and functional group transformations ; Complex metal hybrids, Gilman’s reagent, lithium dimethycuprate, lithium disopropylamide (LDA) dicyclohexylcarbodimide. 1,3 – Dithiane (reactivity umpolung), trimethysilyl iodide, tri-n-butyltin hybride, Woodward and provost hydroxylation, osmium tetroxide, DDQ, selenium dioxide, phase transfer catalysts, crown ethers and Merrified resin, Peterson’s synthesis, Wilkinson’s catalyst, Baker yeast.
31. Chemistry of Natural Products : Familiarity with methods of structure elucidation and biosynthesis of alkaloids, terponoids, steroids, carbohydrates and proteins.
32. Bio-organic Chemistry : Elementry structure and function of biopolymers such as proteins and nucleric acids.
33. Photochemistry : Cis – trans isomeriation, Paterno – Buchi reaction, Norrish Type I and II reactions, photoreduction of ketones, di-pimethane rearrangement, photochemistry of areanes.
34. Spectroscopy : Applications of mass, UV – VIS, IR and NMR spectroscopy for structural elucidation of compound.

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Mechanism of Diels-Alder reaction

Diels-Alder reaction

This reaction was discovered by two German chemists named Otto Diels and Kurt Alder. Conjugated dienes undergo a cycloaddition reaction with multiple bonds to form unsaturated six-membered rings. This reaction involves the 1,4-addition of a diene and a dienophile. This reaction proved to be of great importance as yield was 100% and hence they received the Nobel Prize in 1950.






Reaction mechanism
The Diels-Alder reaction is a thermal cycloaddition whose mechanism involves the sigma-overlap of the pi-orbitals of the two unsaturated systems. There is not a single mechanism for all Diels-Alder reaction. At first approximation, we can divide them into two classes:

1.Synchronous and symmetrical (concerted) mechanisms when the two new bonds are formed simultaneously. In the transition state, the two forming bonds have the same lengths. The combination of ethylene and butadiene is one example.
2.Multistage (non-concerted) and asynchronous mechanisms. The transition state is a di-radical, one bond being formed, the other not.

Real mechanisms are a mixture of these two extremes, one bond being more properly formed and thus shorter than the other.
















To have an idea of the mechanism and to calculate the activation energy of a reaction, we have to find its transition state, using a gradient minimization. The transition state of the Diels-Alder addition of butadiene and ethylene shows that it looks like the reactants. It is called an early transition state.
Typically, the Diels-Alder reaction works best when either the diene is substituted with electron donating groups (like -OR, -NR2, etc) or when the dienophile is substituted with electron-withdrawing groups (like -NO2, -CN, -COR, etc).

Conformational requirements of the diene
One quirk of the Diels-Alder reaction is that the diene is required to be in the s-cis conformation in order for the Diels-Alder reaction to work. The s-cis conformation has both of the double bonds pointing on the same side of the carbon-carbon single bond that connects them. In solution, the carbon-carbon single bond in the diene that connects the two alkenes is constantly rotating, so at equilibrium there is usually some mixture of dienes in the s-trans conformation and some in the s-cis conformation. The ones that are at that moment in the s-trans conformation do not react, while the ones in the s-cis conformation can go on to react.






Because of the Diels-Alder's requirement for having the diene in a s-cis conformation, dienes in rings react particularly rapidly because they are "locked" in the s-cis conformation. Unlike dienes in open chains in which there is usually some proportion of the diene in the unreactive s-trans conformation, dienes in rings are held in the reactive conformation at all times by the constraints of the ring, making them react faster.







Stereochemistry of Diels-Alder reaction
If the dienophile is disubstituted (substituted twice), there is the possibility for stereochemistry in the product. In the Diels-Alder reaction, you end up with the stereochemistry that you started with. In other words, if the substituents started cis (on the same side) on the dienophile, they end up cis in the product. If they started trans (opposite sides) on the dienophile, they end up trans in the product.

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Photochromic materials

Photochromic materials


Photochromic molecules can belong to various classes: triarylmethanes, stilbenes, azastilbenes, nitrones, fulgides, spiropyrans, naphthopyrans, spiro-oxazines, quinones.




Spiropyrans and Spriooxazines

Spiro-mero photochromism.
One of the oldest, and perhaps the most studied, families of photochromes are the spiropyrans.

Very closely related to these are the spirooxazines.

For example, the spiro form of an oxazine is a colorless leuco dye; the conjugated system of the oxazine and another aromatic part of the molecule is separated by a sp³-hybridized "spiro" carbon. After irradiation with UV light, the bond between the spiro-carbon and the oxazine breaks, the ring opens, the spiro carbon achieves sp² hybridization and becomes planar, the aromatic group rotates, aligns its π-orbitals with the rest of the molecule, and a conjugated system forms with ability to absorb photons of visible light, and therefore appear colorful. When the UV source is removed, the molecules gradually relax to their ground state, the carbon-oxygen bond reforms, the spiro-carbon becomes sp³ hybridized again, and the molecule returns to its colorless state.

This class of photochromes in particular are thermodynamically unstable in one form and revert to the stable form in the dark unless cooled to low temperatures. Their lifetime can also be affected by exposure to UV light. Like most organic dyes they are susceptible to degradation by oxygen and free radicals. Incorporation of the dyes into a polymer matrix, adding a stabilizer, or providing a barrier to oxygen and chemicals by other means prolongs their lifetime.

Diarylethenes

Dithienylethene photochemistry

The "diarylethenes" were first introduced by Irie and have since gained widespread interest, largely on account of their high thermodynamic stability. They operate by means of a 6-pi electrocyclic reaction, the thermal analog of which is impossible due to steric hindrance. Pure photochromic dyes usually have the appearance of a crystalline powder, and in order to achieve the color change, they usually have to be dissolved in a solvent or dispersed in a suitable matrix. However, some diarylethenes have so little shape change upon isomerization that they can be converted while remaining in crystalline form.

Photochromic quinones

Some quinones, and phenoxynaphthacene quinone in particular, have photochromicity resulting from the ability of the phenyl group to migrate from one oxygen atome to another. Quinones with good thermal stability have been prepared, and they also have the additional feature of redox activity, leading to the construction of many-state molecular switches that operate by a mixture of photonic and electronic stimuli.

Inorganic photochromics

Many inorganic substances also exhibit photochromic properties, often with much better resistance to fatigue than organic photochromics. In particular, silver chloride is extensively used in the manufacture of photochromic lenses. Other silver and zinc halides are also photochromic.

Fulgides

Triarylmethanes

Triphenylmethane, or triphenyl methane, is the hydrocarbon with the formula (C6H5)3CH. This colorless solid is soluble in nonpolar organic solvents, but not water. Triphenylmethane has the basic skeleton of many synthetic dyes called triarylmethane dyes, many of them are pH indicators, and some display fluorescence. A trityl group in organic chemistry is a triphenylmethyl group Ph3C, e.g. triphenylmethyl chloride — trityl chloride

Examples of triarylmethane dyes are bromocresol green or malachite green

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Photochromism

Photochromism

Photochromism is the reversible transformation of a chemical species between two forms by the absorption of electromagnetic radiation, where the two forms have different absorption spectra. Trivially, this can be described as a reversible change of color upon exposure to light. The phenomenon was discovered in the late 1880s, including work by Markwald, who studied the reversible change of color of 2,3,4,4-tetrachloronaphthalen-1(4H)-one in the solid state. He labeled this phenomenon "phototropy", and this name was used until the 1950s when Yehuda Hirshberg, of the Weizmann Institute of Science in Israel proposed the term "photochromism".Photochromism can take place in both organic and inorganic compounds, and also has its place in biological systems (for example retinal in the vision process).


Photochromism does not have a rigorous definition, but is usually used to describe compounds that undergo a reversible photochemical reaction where an absorption band in the visible part of the electromagnetic spectrum changes dramatically in strength or wavelength. In many cases, an absorbance band is present in only one form. The degree of change required for a photochemical reaction to be dubbed "photochromic" is that which appears dramatic by eye, but in essence there is no dividing line between photochromic reactions and other photochemistry. Therefore, while the trans-cis isomerization of azobenzene is considered a photochromic reaction, the analogous reaction of stilbene is not. Since photochromism is just a special case of a photochemical reaction, almost any photochemical reaction type may be used to produce photochromism with appropriate molecular design. Some of the most common processes involved in photochromism are pericyclic reactions, cis-trans isomerizations, intramolecular hydrogen transfer, intramolecular group transfers, dissociation processes and electron transfers (oxidation-reduction).
Another somewhat arbitrary requirement of photochromism is that it requires the two states of the molecule to be thermally stable under ambient conditions for a reasonable time. All the same, nitrospiropyran (which back-isomerizes in the dark over ~10 minutes at room termperature) is considered photochromic. All photochromic molecules back-isomerize to their more stable form at some rate, and this back-isomerization is accelerated by heating. There is therefore a close relationship between photochromic and thermochromic compounds. The timescale of thermal back-isomerization is important for applications, and may be molecularly engineered. Photochromic compounds considered to be "thermally stable" include some diarylethenes, which do not back isomerize even after heating at 80 C for 3 months.

Since photochromic chromophores are dyes, and operate according to well-known reactions, their molecular engineering to fine-tune their properties can be achieved relatively easily using known design models, quantum mechanics calculations, and experimentation. In particular, the tuning of absorbance bands to particular parts of the spectrum and the engineering of thermal stability have received much attention.

Sometimes, and particularly in the dye industry, the term "irreversible photochromic" is used to describe materials that undergo a permanent color change upon exposure to ultraviolet or visible light radiation. Because by definition photochromics are reversible, there is technically no such thing as an "irreversible photochromic"—this is loose usage, and these compounds are better referred to as "photochangable" or "photoreactive" dyes.

Apart from the qualities already mentioned, several other properties of photochromics are important for their use. These include
Quantum yield of the photochemical reaction. This determined the efficiency of the photochromic change with respect to the amount of light absorbed. The quantum yield of isomerization can be strongly dependent on conditions (see below).

Fatigue resistance. In photochromic materials, fatigue refers to the loss of reversibility by processes such as photodegradation, photobleaching, photooxidation, and other side reactions. All photochromics suffer fatigue to some extent, and its rate is strongly dependent on the activating light and the conditions of the sample.

Photostationary state. Photochromic materials have two states, and their interconversion can be controlled using different wavelengths of light. Excitation with any given wavelength of light will result in a mixture of the two states at a particular ratio, called the "photostationary state". In a perfect system, there would exist wavelengths that can be used to provide 1:0 and 0:1 ratios of the isomers, but in real systems this is not possible, since the active absorbance bands always overlap to some extent.

Polarity and solubility. In order to incorporate photochromics in working systems, they suffer the same issues as other dyes. They are often charged in one or more state, leading to very high polarity and possible large changes in polarity. They also often contain large conjugated systems that limit their solubility.

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Fischer Indole Synthesis

Fischer Indole Synthesis

Overall Reaction

This oldest indole synthesis method transforms aryl hydrazones to indoles and requires elevated temperatures and the addition of Brønsted or Lewis acids.

This reaction is good for preparing 2-, 3-, 5-and 7-substituted indoles but is poorer for the preparation of 4- and 6-substituted indoles, due to lack of regioselectivity.

Mechanism of Fischer Indole Synthesis

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Drug Screening

Screening and Design

The process of finding a new drug against a chosen target for a particular disease usually involves high-throughput screening (HTS), wherein large libraries of chemicals are tested for their ability to modify the target.
For example, if the target is a novel GPCR, compounds will be screened for their ability to inhibit or stimulate that receptor (see antagonist and agonist): if the target is a protein kinase, the chemicals will be tested for their ability to inhibit that kinase.

Another important function of HTS is to show how selective the compounds are for the chosen target. The ideal is to find a molecule which will interfere with only the chosen target, but not other, related targets. To this end, other screening runs will be made to see whether the "hits" against the chosen target will interfere with other related targets - this is the process of cross-screening. Cross-screening is important, because the more unrelated targets a compound hits, the more likely that off-target toxicity will occur with that compound once it reaches the clinic.

It is very unlikely that a perfect drug candidate will emerge from these early screening runs. It is more often observed that several compounds are found to have some degree of activity, and if these compounds share common chemical features, one or more pharmacophores can then be developed. At this point, medicinal chemists will attempt to use structure-activity relationships (SAR) to improve certain features of the lead compound:
increase activity against the chosen target
reduce activity against unrelated targets
improve the "drug-like" or ADME properties of the molecule.

This process will require several iterative screening runs, during which, it is hoped, the properties of the new molecular entities will improve, and allow the favoured compounds to go forward to in vitro and in vivo testing for activity in
the disease model of choice.

While HTS is a commonly used method for novel drug discovery, it is not the only method. It is often possible to start from a molecule which already has some of the desired properties. Such a molecule might be extracted from a natural product or even be a drug on the market which could be improved upon (so-called "me too" drugs). Other methods, such as virtual high throughput
screening, where screening is done using computer-generated models and attempting to "dock" virtual libraries to a target, are also often used.

Another important method for drug discovery is drug design, whereby the biological and physical properties of the target are studied, and a prediction is made of the sorts of chemicals that might (eg.) fit into an active site. Novel pharmacophores can emerge very rapidly from these exercises.

Once a lead compound series has been established with sufficient target potency and selectivity and favourable drug-like properties, one or two compounds will then be proposed for drug development. The best of these is generally called the lead compound, while the other will be designated as the "backup".

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Drug design | construction of drug molecule

Drug design

Drug design is the approach of finding drugs by design, based on their biological targets. Typically a drug target is a key molecule involved in a particular metabolic or signalling pathway that is specific to a disease condition or pathology, or to the infectivity or survival of a microbial pathogen.
Some approaches attempt to stop the functioning of the pathway in the diseased state by causing a key molecule to stop functioning.
Drugs may be designed that bind to the active region and inhibit this key molecule.
However these drugs would also have to be designed in such a way as not to affect any other important molecules that may be similar in appearance to the key molecules. Sequence homologies are often used to identify such risks.
Other approaches may be to enhance the normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state.
The structure of the drug molecule that can specifically interact with the biomolecules can be modeled using computational tools.
These tools can allow a drug molecule to be constructed within the biomolecule using knowledge of its structure and the nature of its active site.
Construction of the drug molecule can be made inside out or outside in depending on whether the core or the R-groups are chosen first. However many of these approaches are plagued by the practical problems of chemical synthesis.Newer approaches have also suggested the use of drug molecules that are large and proteinaceous in nature rather than as small molecules.
There have also been suggestions to make these using mRNA. Gene silencing may also have therapeutical applications.

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Rational drug design | method of drug design

Rational drug designing

Unlike the historical method of drug discovery, by trial-and-error testing of chemical substances on animals, and matching the apparent effects to treatments, rational drug design begins with a knowledge of specific chemical responses in the body or target organism, and tailoring combinations of these to fit a treatment profile.
Due to the complexity of the drug design process two terms of interest are still serendipity and bounded rationality.
Those challenges are caused by the large chemical space describing potential new drugs without side-effects.
A particular example of rational drug design involves the use of three-dimensional information about biomolecules obtained from such techniques as x-ray crystallography and NMR spectroscopy.
This approach to drug discovery is sometimes referred to as structure-based drug design. The first unequivocal example of the application of structure-based drug design leading to an approved drug is the carbonic anhydrase inhibitor dorzolamide which was approved in 1995.
Another important case study in rational drug design is imatinib, a tyrosine kinase inhibitor designed specifically for the bcr-abl fusion protein that is characteristic for Philadelphia chromosome-positive leukemias (chronic myelogenous leukemia and occasionally acute lymphocytic leukemia). Imatinib is substantially different from previous drugs for cancer, as most agents of chemotherapy simply target rapidly dividing cells, not differentiating between cancer cells and other tissues.

The activity of a drug at its binding site is one part of the design. Another to take into account is the molecule's druglikeness, which summarizes the necessary physical properties for effective absorption. One way of estimating druglikeness is Lipinski's Rule of Five.

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Beta blocker | Clinical use

Beta blocker

Beta blockers (sometimes written as β-blockers) are a class of drugs used for various indications, but particularly for the management of cardiac arrhythmias and cardioprotection after myocardial infarction.
Whilst once first-line treatment for hypertension, their role was downgraded in June 2006 in the United Kingdom to fourth-line as they do not perform as well as other drugs, particularly in the elderly, and there is increasing evidence that the most frequently used beta-blockers especially in combination with thiazide-type diuretics carry an unacceptable risk of provoking type 2 diabetes.

Propranolol was the first clinically useful beta adrenergic receptor antagonist. Invented by Sir James W. Black it revolutionized the medical management of angina pectoris and is considered to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.


Pharmacology

Beta blockers block the action of endogenous catecholamines (epinephrine (adrenaline) and norepinephrine (noradrenaline) in particular), on β-adrenergic receptors, part of the sympathetic nervous system which mediates the "fight or flight" response.

There are three known types of beta receptor, designated β1, β2 and β3. β1-Adrenergic receptors are located mainly in the heart and in the kidneys. β2-Adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-receptors are located in fat cells.


β-Receptor antagonism
Stimulation of β1 receptors by epinephrine induces a positive chronotropic and inotropic effect on the heart and increases cardiac conduction velocity and automaticity. Stimulation of β1 receptors on the kidney causes renin release. Stimulation of β2 receptors induces smooth muscle relaxation (resulting in vasodilation and bronchodilation amongst other actions), induces tremor in skeletal muscle, and increases glycogenolysis in the liver and skeletal muscle. Stimulation of β3 receptors induces lipolysis.

Beta blockers inhibit these normal epinephrine-mediated sympathetic actions, but have minimal effect on resting subjects. That is, they reduce the effect of excitement/physical exertion on heart rate and force of contraction, dilation of blood vessels and opening of bronchi, and also reduce tremor and breakdown of glycogen.

It is therefore expected that non-selective beta blockers have an antihypertensive effect. The
antihypertensive mechanism appears to involve: reduction in cardiac output (due to negative chronotropic and inotropic effects), reduction in renin release from the kidneys, and a central nervous system effect to reduce sympathetic activity.

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand.

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade – resulting in depression of sinus node function and atrioventricular node conduction, and prolonged atrial refractory periods. Sotalol, in particular, has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin angiotensin aldosterone system with a resultant decrease in blood pressure due to decreased sodium and water retention.


Intrinsic sympathomimetic activity
Some beta blockers (e.g. oxprenolol and pindolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low level agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta blocker therapy.

Agents with ISA are not used post-myocardial infarction as they have not been demonstrated to be beneficial. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia.

α1-Receptor antagonism
Some beta blockers (e.g. labetalol and carvedilol) exhibit mixed antagonism of both β- and α1-adrenergic receptors, which provides additional arteriolar vasodilating action.


Other effects
Beta blockers decrease nocturnal melatonin release, perhaps partly accounting for sleep disturbance caused by some agents.Beta blockers protect against social anxiety: "Improvement of physical symptoms has been demonstrated with beta-blockers such as propranolol; however, these effects are limited to the social anxiety experienced in performance situations."Beta blockers can impair the relaxation of bronchial muscle (mediated by beta-2) and so should be avoided by asthmatics.


Clinical use
Large differences exist in the pharmacology of agents within the class, thus not all beta blockers are used for all indications listed below.

Indications for beta blockers include:
Hypertension
Angina
Mitral valve prolapse
Cardiac arrhythmia
Congestive heart failure
Myocardial infarction
Glaucoma
Migraine prophylaxis
Symptomatic control (tachycardia, tremor) in anxiety and hyperthyroidism
Essential tremor
Phaeochromocytoma, in conjunction with α-blocker


Beta blockers have also been used in the following conditions:
Hypertrophic obstructive cardiomyopathy
Acute dissecting aortic aneurysm
Marfan syndrome (chronic treatment with propranolol slows progression of aortic dilation and its complications)
Prevention of variceal bleeding in portal hypertension
Possible mitigation of hyperhidrosis
Congestive heart failure
Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition, studies in the late 1990s showed their positive effects on morbidity and mortality in congestive heart failure. Bisoprolol, carvedilol and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure.
The beta blockers are a benefit due to the reduction of the heart rate which will lower the myocardial energy expenditure. This is turns prolongs the diastolic filling and lengthens coronary perfusion.Beta blockers have also been a benefit to improving the ejection fraction of the heart despite an initial reduction in it.
Trials have shown that Beta blockers reduce the absolute risk of death by 4.5% over a 13 month period. As well as reducing the risk of mortality, the number of hospital visits and hospitalizations were also reduced in the trials.

Anxiety and performance enhancement
Some people, particularly musicians, use beta blockers to avoid stage fright and tremor during public performance and auditions. The physiological symptoms of the fight/flight response associated with performance anxiety and panic (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Officially, beta blockers are not approved for anxiolytic use by the U.S. Food and Drug Administration.

Since they lower heart rate and reduce tremor, beta blockers have been used by some Olympic marksmen to enhance performance, though beta blockers are banned by the International Olympic Committee (IOC). Although they have no recognisable benefit to most sports, it is acknowledged that they are beneficial to sports such as archery and shooting.


Adverse effects
Adverse drug reactions (ADRs) associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, abnormal vision, decreased concentration, hallucinations, insomnia, nightmares, clinical depression, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism. Mixed α1/β-antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly associated with edema.
Central nervous system (CNS) adverse effects (hallucinations, insomnia, nightmares, depression) are more common in agents with greater lipid solubility, which are able to cross the blood-brain barrier into the CNS. Similarly, CNS adverse effects are less common in agents with greater aqueous solubility (listed below).
Adverse effects associated with β2-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction, alteration of glucose and lipid metabolism) are less common with β1-selective (often termed "cardioselective") agents, however receptor selectivity diminishes at higher doses.
A 2007 study revealed that diuretics and beta-blockers used for hypertension increase a patient's risk of developing diabetes whilst ACE inhibitors and Angiotensin II receptor antagonists (Angiotensin Receptor Blockers) actually decrease the risk of diabetes.[12] Clinical guidelines in Great Britain, but not in the United States, call for avoiding diuretics and beta-blockers as first-line treatment of hypertension due to the risk of diabetes.
Beta blockers must not be used in the treatment of cocaine, amphetamine, or other alpha adrenergic stimulant overdose. The blockade of only beta receptors increases hypertension, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha adrenergic system stimulation unopposed.The appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant abuse are vasodilators like nitroglycerin, diuretics like furosemide and alpha blockers like phentolamine.


Examples of beta blockers

Dichloroisoprenaline, the first beta blocker.

Non-selective agents
Alprenolol
Carteolol
Levobunolol
Mepindolol
Metipranolol
Nadolol
Oxprenolol
Penbutolol
Pindolol
Propranolol
Sotalol
Timolol

β1-Selective agents
Acebutolol
Atenolol
Betaxolol
Bisoprolol[16]
Esmolol
Metoprolol
Nebivolol

Mixed α1/β-adrenergic antagonists
Carvedilol
Celiprolol
Labetalol

β2-Selective agents
Butaxamine (weak α-adrenergic agonist activity)


Side Effects / Health Consequences
Low Blood Pressure
Slow Heart Rate
Impaired Circulation
Loss of Sleep
Heart Failure
Asthma
Depression
Sexual Dysfunction
Nausea
Headaches
Dizziness
Muscle Cramps

Comparative information


Pharmacological differences

Agents with intrinsic sympathomimetic action (ISA)
Acebutolol, carteolol, celiprolol, mepindolol, oxprenolol, pindolol

Agents with greater aqueous solubility
Atenolol, celiprolol, nadolol, sotalol

Agents with membrane stabilising activity
Acebutolol, betaxolol, pindolol, propranolol

Agents with antioxidant effect
Carvedilol
Nebivolol

Indication differences

Agents specifically indicated for cardiac arrhythmia
Esmolol, sotalol

Agents specifically indicated for congestive heart failure
Bisoprolol, carvedilol, sustained-release metoprolol, nebivolol

Agents specifically indicated for glaucoma
Betaxolol, carteolol, levobunolol, metipranolol, timolol

Agents specifically indicated for myocardial infarction
Atenolol, metoprolol, propranolol

Agents specifically indicated for migraine prophylaxis
Timolol, propranolol

Propranolol is the only agent indicated for control of tremor, portal hypertension and esophageal variceal bleeding, and used in conjunction with α-blocker therapy in phaeochromocytoma.

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