Chemistry: Heterocyclic compounds

Normal values for hemoglobin

Women: 12.1 to 15.1 g/dL Men: 13.8 to 17.2 g/dL Children: 11 to 16 g/dL pregnant women: 11 to 12 g/dL

bilirubin

bilirubin is a yellow breakdown product of normal heme catabolism. Its levels are elevated in certain diseases and it is responsible for the yellow colour of bruises and the brown colour of faeces. Bilirubin consists of an open chain of 4 pyrrole-like rings (tetrapyrrole). In heme by contrast, these 4 rings are connected into a larger ring called protoporphyrin. Bilirubin is a very similar to the pigment phycobilin, used by certain algae to capture light energy and to the pigment phytochrome used by plants to sense light. All of these contain an open chain of 4 pyrrolic rings

derivates of thiophene

biotin (vitamin H)

role of biotin

biotin is necessary for cell growth, the production of fatty acids and the metabolism of fats and amino acids. Biotin assists in various metabolic reactions involving the transfer of CO2 carboxytransferase). Helpful in maintaining a steady blood sugar level. Recommended as a dietary supplement for strengthening hair and skin. Biotin deficiency is rare because in general, intestinal bacteria produce biotin in excess of the body's daily requirements.

cytochrome

cytochromes are generally membrane bound hemoproteins that contain heme groups and carry out electron transport. The main difference from the hemoglobin structure is that the heme is covalently bounded by the SH group of cysteine and the 2 coordinative bonds are by histidine and by methionine side chains. They are either found as monomeric proteins (cytochrome c) or as subunits of bigger enzymatic complexes that catalyse redox reactions. They are found in the mitochondrial inner membrane and endoplasmic reticulum of eukaryotes in the chloroplasts of plants in photosynthetic microorganisms and in bacteria

hemeglobin

haemoglobin abbreviated Hb, is the iron containing oxygen transport metalloprotein in the red blood cells of the blood in vertebrates and other animals. In mammals, the protein makes up about 97% of the red cells dry content and around 35% of the total content (including water). Hb transports oxygen from the lungs or gills to the rest of the body, such as to the muscles where it releases its load of oxygen. Hemoglobin also has a variety of other gas transport and effect modulation duties which varies from species to species and may be quite diverse in vertebrates

haemoglobin levels

haemoglobin levels are amongst the most commonly performed blood tests usually as part of a full blood count or complete blood count. Results are reported in g/L, g/dL or mol/L. 1g/dL= 0.621mmol/L If the total Hb concentration in the blood falls below a set point is called anemia.

symptoms of biotin deficiency

hair loss (alopecia) conjunctivitis dermatitis (in the form of a scaly, red rash around the eyes, nose, mouth and genital area). Neurological symptoms in adults such as depression, lethargy, hallucination and numbness and tingling of the extremities

ampholite

has both positive and negative charges

heme iron

heme iron serves as a source or sink of electrons during electron transfer or redox chemistry (cytochrome c)

2 classes of heterocyclic compounds

non- aromatic and aromatic

Huckel's Rule can be extended to what?

Huckel's rule can be extended to heterocyclic aromatic compounds. A single heteroatom can contribute 0 or 2 of its lone-pair electrons as needed to the p system so as to satisfy so as to satisfy (4n+2) p electron requirement. In pyrrole, the unshared pair belonging to nitrogen must be added to the 4p electrons of the 2 double bonds in order to meet the 6 p electron requirement. The oxygen in furan has 2 electron pairs. One pair is like the pair of pyrrole and contributing 2 electrons to complete the 6 p electron requirement for aromatic satisfaction. The other electron pair of furan is an extra pair not needed to satisfy (4n+2) rule for aromaticity. The bonding in thiophene is similar to that of furan

proline

proline is an alpha amino acid, one of the 20 DNA encoded amino acids. It is not an essential amino acid, which means humans can synthesise it. It is the unique proteogenic amino acid where the alpha amino group is secondary.

pyracetam

pyracetam is a nootropic drug (improves one or more aspects of mental function such as working memory, motivation and attention.

antipyretics

pyramidone (4-dimethylamino-1,5-dimethyl-2-phenyl-pyrazol-3-one). Analgin (metamizole sodium) is a non-steroidal anti-inflammatory drug (NSAID), commonly used in the past as a powerful painkiller and fever reducer. It was discovered that the drug carries a small risk of causing agranuloctosis- a very dangerous and potentially fatal condition. Several national medical authorities have banned metamizole either totally or have restricted it to be available only on prescription

5 membered heterocyclic compound with 2 heteroatoms

pyrazole imidazole thiazole

Polyvinyl pyrrolidone (PVP)

PVP was used as a plasma volume expander for trauma victims after the 1950s. It is used as a binder in many pharmaceuticals tablets. PVP added to iodine forms a complex called povidone-iodine that possesses disinfectant properties. This complex is used in various products like solutions, ontments, pessaries, liquid soaps and surgical scrubs.

reaction of nucleophilic substitution

Pyrrole, furan and thiophene take place in the reaction of nucleophilic substitution due to their aromatic character. The order of their reactivity is furan>thiophene>pyrrole

reaction of electrophilic substitution

Pyrrole, furan and thiophene take place in the reaction with electrophilic reagants and they can be nitrated, sulfonated, alkylated and acylated. They are much more reactive than benzene

pyrazole and pyrazoles

pyrazole refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterised by a 5 membered ring structure composed of 3 carbon atoms, 2 nitrogen atoms in adjacent positions and to the unsubstituted parent compounds. Structurally related compound are pyrazoline and pyrazolidine. In medicine, pyrazoles are used for their analgesic, anti-inflammatory, antipyretic, antiarrhymtic, tranquilising, muscle relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities

6 membered heterocyclic compounds with one and two heteroatoms

pyridine pyrimidine

5 membered heterocyclic compounds with one and two heteroatoms (aromatic heterocycles)

pyrrole furan thiophene pyrazole imidazole thiazole

non-aromatic heterocyclic compounds

saturated monocyclic ring are named according to ring size as: 3- iran 4-etan 5-olan 6- ane (Even this system doesn't apply to nitrogen-containing rings and finds only limited use in common practice)

structure and function of cytochromes

the heme group is a highly conjugated ring system (which means its electrons are very mobile) surrounding a metal ion which readily interconverts between the oxidation states. For many cytochromes, the metal ion present is that of iron which interconverts between Fe2+ (reduced) and Fe3+ (oxidised). Cytochromes are thus capable performing oxidation and reduction. Because the cytochromes are held within membranes in an organised way, the redox reactions are carried out in the proper sequence for maximum efficiency.

5 membered rings with one heteroatom vs benzene

the main difference of the electronic state in these heteroatoms and benzene is that electronic density is non-regularly distributed in heterocyclic compounds while the electronic density in the benzene is distributed absolutely regular

5 membered rings with one heteroatom

these heterocycles have characteristics associated with aromaticity. From an orbital point of view, pyrrole has a planar pentagonal structure in which the 4 carbons and the nitrogen have sp^2 hybridisation. Each ring atom forms 2 sp^2-sp^2 sigma bonds to its neighbouring ring atoms, and each forms one sp^2-sp^2 sigma bond to a hydrogen. With non- hybrid p-orbital C atoms form 2 pi bonds. N atom accounts for aromaticity with its non-shared electron paired

thiophene

thiophene is a heterocyclic organic compound and is a 5 membered aromatic ring. At room temperature, thiophene is a colourless liquid with a mildly pleasant odour reminiscent of benzene with which thiophene shares some similarities. Like benzene, thiophene forms an azeotrope with water

Vitamin B12 (cobalamin)

vitamin B12 is an especially common vitamin of the vitamin B12 family. It is usually prescribed for the following reasons: after surgical removal of part or all of the stomach or intestine to ensure there are adequate levels of vitamin B12 in the bloodstream to treat pernicious anemia, vitamin B12 deficiency due to low intake from food, thyrotoxicosis, hemorrhage, malignancy, liver or kidney disease. Vitamin is also used to perform the Schilling test to check your ability to absorb vitamin B12

degradation of haemoglobin in vertebrate animals

When red blood cells reach the end of their life due to aging or defects, they are broken down, the Hb molecule is broken up and the iron gets recycled. When the porphyrin ring is broken up, the fragments are normally secreted in the bile by the liver. This process also produced one molecule of carbon monoxide for every molecule of heme degraded; this is one of the few natural sources of CO production in the human body and is responsible for the normal blood levels of CO even in people breathing pure air. The other major final product of heme degradation is bilirubin

pyrrole

pyrrole is a heterocyclic organic compound, that is a 5 membered aromatic ring. Substituted derivatives are also called pyrroles. Pyrroles are very weak bases compared to amines and other aromatic compounds like pyridine where the ring nitrogen isn't bonded to a hydrogen atom. pKb of 10. Protonation results in loss of aromaticity and is therefore unfavourable. Pyrrole undergoes electrophilic aromatic substitution predominantly at the 2 and 5 positions, though the substitution product at position 3 and 4 is obtained in low yields.

Thiamine (Vitamin B1)

thiamine takes part in decarbxylation of pyruvic acid as coenzyme in pyruvatedecarboxylase.

5 membered ring with one heteroatom- criteria for aromaticity

1) Molecule must be cyclic 2) Every atom in the ring must have a p orbital, which overlaps with p orbitals on either side (completely conjugated). 3) Molecule must be planar. 4) It must contain an odd number of pairs of pi electrons; must satisfy Huckel's rule (4n+2) pi electrons, where n is an integer starting at zero.

chemical properties of 5 membered rings with one heteroatom

1. Acid base properties-ampholites 2. Reactions of electrophilic substitution 3. Reaction of nucleophilic substitution

heterocyclic compounds based on size of ring

3 membered 4 membered 5 membered 6 membered

4-hydroxyproline

4-hydroxyproline is an uncommon amino acid abbreviated HYP. Hydroxyproline is a major component of the protein collagen. Hydroxyproline and proline play key roles for collagen stability.

heme

A heme is a prosthetic group that consists of and iron (Fe) ion contained in the centre of a large heterocyclic organic ring called a protoporphyrin

the important derivatives of pyrrole, furan and thiophene

A= pyrrole B= porphyrin C= Protoporphyrin

Huckel's Rule

Among planar, monocyclic, fully conjugated polyenes, only those possessing (4n+2) pi electrons, where n is an integer, will have special aromatic stability. E.g: Benzene with 6 pi electrons satisfies Huckel's rule for n=1

vitamin H

Biotin

Biotin

Biotin is a water soluble B complex vitamin which is composed of an uredo tetrahydroimidizalone ring fused with a tetrahydrothiophene. Prosthetic group of pyruvatecarboxylase

furan

Furan (furane and furfuran) is a heterocyclic organic compound that is a 5 membered aromatic ring. It is typically derived by the thermal decomposition of pentose-containing materials, cellulosic solids especially pine-wood. Furan is a colourless, flammable, highly volatile liquid with a boiling point close to room temperature. It is toxic and may be carcinogenic

acid-base properties-ampholites

Furan and pyrrole manifest more basic properties, while the thiophene is a very weak organic base. On the other hand, furan and thiophene are CH acids, while pyrrole is a very weak organic acid capable of making salts with sodium and potassium

binding of ligands

Haemoglobins oxygen binding capacity is decreased in the presence of carbon monoxide (CO) because both gases compete for the same binding sites on Hb. Carbon monoxide is binding preferentially in place of oxygen. Carbon dioxide occupies difference binding site on the Hb. CO2 is more readily dissolved in deoxygenated blood, facilitating its removal from the body after the oxygen has been released to tissues undergoing metabolsi,

Hemoproteins

Hemoproteins have diverse biological functions including: 1)transportation of diatomic gases 2) chemical catalysis 3) diatomic gas detection 4) electron transfer

Imidazole

Imidazole is a heterocyclic aromatic organic compound soluble in water and polar solvents. Imidazolea are a class of heterocycles with similar ring structure but varying substituents. The ring system present in important biologically active molecules such as amino acid histidine and the related histamine. They can act as a base and as a weak acid. It exists in 2 tautomeric forms with the hydrogen atom moving between the 2 nitrogens, Many drugs contain an imidazole ring such as antifungal drugs and nitroimidazole. The compound has an aromatic sextet which consists of 1 pi electron from the N atom and one from each carbon atom and 2 from the NH nitrogen. Imidazole is a base an an excellent nucleophile. It reacts with the NH nitrogen attacking alkylating and acylating compounds. It is not particularly susceptible to electophilic attacks at the carbon atoms and most of these reactions are substitutions that keep the aromaticity intact. The carbon 2 is the carbon most likely to have a nucleophile attack, but in general nucleophilic substitutions are difficult with imidazole

Hemoglobin structure

hemoglobin consists of a protein part globin and a non-protein part-heme group. The heme group is a chelate formed from protoporphyrin and iron ion (Fe2+). The globin consists of 4 protein units: 2 alpha and 2 beta protein chains. They differ on the number of amino acids. Each protein unit is attached to one heme group with coordination bond between Fe2+ and imidazole ring of amino acid histidine. Each heme group is able to bind one oxygen molecule, thus one Hb molecule can bind 4 oxygen molecules. The binding affinity of Hb for oxygen is increased by the oxygen saturation of the molecule with the first oxygen bound influencing the shape of the binding sites for the next oxygen molecules in a way favourable for binding. This positive cooperative binding is achieved through steric conformational changes of the Hb protein complex i.e when one subunit is Hb becomes oxygenated this induces a conformational or structural change in the whole complex causing the other subunits to gain an increased affinity for oxygen.

proteins linked to a heme are called what?

hemoproteins

heterocyclic compounds

heterocyclic compounds are cyclic compounds that contain at least one atom other than carbon within their ring. As hetero atom can be N, O, S, B, Al, Si, P, Sn, As, Cu, but common atoms are N, O, S They may be either aromatic or non-aromatic compounds

Imidazole importance

imidazole has become an important part of many pharmaceuticals. Synthetic imidazoles are present in many fungicides and antifungal, antiprotozoal and antihypertensive medications. Imidazole is a part of the theophylline molecule, found in tea leaves and coffee beans which stimulates the central nervous system.

biological significance and applications of imidazole

imidazole is incorporated into many important biological molecules. The most obvious is the amino acid histidine which has an imidazole side chain. Histidine is a building block of many proteins and enzymes and plays a vital part in the structure and binding functions of hemoglobin. Histidine can be decarboxylated to histamine which is also a common biological compound. It is a component of the toxin that causes urticaria, which is basically an allergic reaction.

heterocyclic compounds with fused rings

indole quinoline purine isoquinoline