HYDROGEN BONDING

HYDROGEN BONDING

 

Hydrogen bonding is an attractive force which occurs in any compound whose molecule contains O-H or O-N bonds (as in water, alcohol, acids, amines, and amides).

The hydrogen is attached directly to one of the most electronegative elements, causing the hydrogen to acquire a significant amount of positive charge.

 Each of the elements to which the hydrogen is attached is not only significantly negative, but also has at least one "active" lone pair. e.g.

Adjacent molecule of the compound containing an O-H bond will be attracted to each other by virtue of these opposite charges. This force of attraction is known as the Hydrogen bonding. Usually hydrogen bond is represented by a dotted line, as shown below.

 

   

Hydrogen bonding has important effect on many physical properties (physical state, molecular mass, boiling points, solubility, acidity etc) of organic compounds.

1.   INCREASE IN THE SIZE AS WELL AS IN THE MOLECULAR MASS:

The weak electrostatic interactions of intermolecular hydrogen bonding, causes two or more molecules of a compound to exist as aggregates or associated molecules. This is seen in water molecules, which undergo molecular association. Alcohols and carboxylic acids (RCOOH) also exist as a group of molecules. Molecular association results in the increase in the size as well as in the molecular mass of the compound. These above examples are shown below:

 

                                                                 (Molecular association of carboxylic acid.)

2. HIGHER MELTING AND BOILING POINTS:

The compounds containing hydrogen bonds have high melting and boiling points. Due to hydrogen bonding, the intermolecular force of attraction in the compound becomes large. Consequently, larger energy is required in separating these molecules before they can melt or boil.

e.g. water molecule, molecular weight= 18 g/mole   B.Point= 100^oC,

while the methane with comparable weight is a gas.

It is important to realise that hydrogen bonding exists in addition to van der Waals attractions. For example, all the following molecules contain the same number of electrons, and the first two are much the same length. The higher boiling point of the butan-1-ol is due to the additional hydrogen bonding.

Comparing the two alcohols (containing -OH groups), both boiling points are high because of the additional hydrogen bonding due to the hydrogen attached directly to the oxygen - but they aren't the same.

The boiling point of the 2-methylpropan-1-ol isn't as high as the butan-1-ol because the branching in the molecule makes the van der Waals attractions less effective than in the longer butan-1-ol.

3. INFLUENCE ON THE PHYSICAL STATE:

Hydrogen bonding also influences the physical state of the substances (solid, liquid or gas).

Illustration:

Both oxygen and Sulphur belong to same group but H₂O is a liquid at ordinary temperature, while H₂S is a gas. This is explained on the basis of electronegativity values.

In water, oxygen is highly electronegative so that it forms hydrogen bonds. As a result the molecules of H₂O get associated with one another and this raises the boiling point of water. Consequently, water exists as liquid at room temperature. On the other hand, the difference in electronegativity of atoms in H₂S is less and hydrogen bonding in H₂S is almost negligible. As a result H₂S is not associated and exists as a gas at room temperature.

4. SOLUBILITY:

Hydrogen bonding also influences the solubility of one substance in another. Covalent compounds do not generally dissolve in water, but those that can form a hydrogen bond with water, readily dissolve in it. For example, alcohols like ethanol, ammonia, amines, lower aldehydes and ketones are soluble in water due to the formation of hydrogen bonds with water molecules.

                                             While

 

Hydrogen bonding also occurs in organic molecules containing N-H groups - in the same sort of way that it occurs in ammonia. Examples range from simple molecules like CH₃NH₂ (methylamine) to large molecules like proteins and DNA.

The two strands of the famous double helix in DNA are held together by hydrogen bonds between hydrogen atoms attached to nitrogen on one strand, and lone pairs on another nitrogen or an oxygen on the other one.

INTRODUCTION TO PHARMACY

INTRODUCTION TO PHARMACY

PHARMACY:

“Pharmacy is the art and science of preparing from natural and synthetic sources suitable and convenient materials for distribution and use in the treatment and prevention of disease; and the provision of drug-related information to the public. It involves the interpretation of prescription orders; the compounding, labeling and dispensing of drugs; drug product selection and drug utilization reviews; patient monitoring; and the provision of cognitive services related to use of medications.”

The word pharmacy is derived from Greek word “pharmakon”, meaning medicine or drug. Then, the pharmacist is ‘the person of drugs’ or ‘the expert on drugs’. He is the only expert on drugs, because expertise regarding drugs requires knowledge in depth in all the aspects of pharmacy as mentioned in the definition of the word pharmacy. It is expected from a pharmacist to have a sound knowledge of the identification, selection, pharmacological action, preservation, combination, analysis and standardization of drugs.

The physician may prescribe a drug and be primarily interested in the effect of those drugs on the patient. The nurse may administer a drug and be concerned with dosage forms and routes of administration. But the pharmacist is the only expert on drugs. It is his legally granted responsibility to handle drugs. It is his professional responsibility to know all about those drugs. The pharmacist alone is in that unique position of embracing complete drug expertise. Pharmacist is educated and licensed to dispense drugs and to provide drug information. They are the most accessible member of today’s health care team, and often are the first source of assistance and advice on many common ailments and health care matters.

EDUCATION:

There is one professional degree in Pharmacy: the doctorate (Pharm D). The Pharm D curriculum usually requires 5-6 years to complete the degree requirements.

Pharmacy curricula are courses in pharmacology, pharmacognosy, medicinal chemistry, physiology, anatomy, biochemistry, pharmacy law, clinical pharmacy and pharmaceutics.

Graduate Education:  Opportunities for students to specialize in certain professional areas have become more available and increasingly popular. Most prominent are hospital/institutional pharmacy, nuclear pharmacy, management, and various research facilities.

A master or PhD degree in pharmacy or a related field is required for research positions, and a Pharm D, MS, or PhD degree is necessary for administrative or faculty position.

PHARMACEUTICS:

“Pharmaceutics is the science of dosage form design.” The word ‘pharmaceutics’ is used in pharmacy to cover many stages in drug development that follow the discovery or synthesis of the drug, its isolation and purification, and testing for pharmacological effects and absence of serious toxicological problems.

Simply, pharmaceutics converts a drug into a medicine.

Drug & Medicine:

A medicine contains a drug. Drug is the pharmacologically active ingredient in a medicine. Other words used for drug are ‘medicinal agent’, ‘active ingredient’ or ‘active pharmaceutical ingredient (API)’.

For example, an aspirin tablet is a medicine which contains the drug aspirin. Paracetamol syrup is a medicine and contains paracetamol drug.

Pharmaceutics can be divided as follows:

1. Physical pharmacy: It involves the study of basic physical chemistry necessary for efficient dosage form design.

2. Biopharmaceutics: It includes the knowledge of how the drug arrives in body after administration.

3. Industrial pharmacy: Manufacturing of medicine.

4. Pharmaceutical microbiology: Involves the avoidance of microorganisms in medicines.

Chemical Properties of Carbohydrates

Chemical Properties of Carbohydrates with special reference to Glucose

1.      Formation of Glycosides

What are glycosides? Glycosides are molecules in which a sugar (carbohydrate) is bound to a non-sugar moiety (non-carbohydrate). In glycoside molecule, the sugar part is known as glycone and the non-sugar part is known as aglycone par. In the formation of glycosides, hydroxyl group (OH) of anomeric carbon of sugar part reacts with hydroxyl group of non sugars part through glycosidic linkage e.g. Amygdalin. This linkage is formed at anomeric carbon that can be of α or β configuration so the glycosides may α or β glycosides.

The aglycone may be attached through –OH or –NH₂ group forming O– or N– glycosides respectively. O-glycosides are more common in nature. Oligosaccharides and polysaccharides contain O-glycosidic bonds. N-glycosidic bonds occur in nucleotides and in glycoproteins.

2.      Formation of Osazone

What is Osazone? Osazone is yellowish, crystalline compound, produced as a result of heating sugars solutions with phenylhydrazine. Osazones are formed by those sugars which contain a free aldehyde or ketone group. For example one molecule of glucose reacts with three molecules of phenyl hydrazine to form glucosazone. On the other hand sucrose doesn’t possess free aldehyde or ketone group and thus cannot form Osazone until it is first hydrolyzed to monosaccharides.

Glucosazone (x 250)	Maltosazone (x 250)
Galactosazone (x 160)	Lactosazone (x 250)

Figure showing different types of Osazone crystals

3.      Formation of sugar alcohols

The aldehyde or ketone group of both aldoses and ketoses can be reduced to form the corresponding polyhydroxy alcohols. Glucose reduces to form sorbitol and fructose reduces to form sorbitol and mannitol.

Monosaccharides	Corresponding Alcohol
Glucose	Sorbitol
Mannose	Mannitol
Galactose	Dulcitol
Fructose	Sorbitol & Mannitol
Ribose	Ribitol
Glyceraldehyde	Glycerol
Dihydroxyacetone	Glycerol

Mannitol is frequently use in the patients of cerebral edema because it act as osmotic diuretic and decrease the water content of the body and thus decrease the brain swelling. Sorbitol is getting deposited in the lens of the eye especially in the patients of diabetes mellitus and contributes to the early cataract formation.

4.      Formation of sugar acid

Carbohydrates form the sugar acid on their oxidation. When glucose (aldoses) is oxidized under proper conditions, then it yields three types of sugar acids; namely gluconic acid, glucuronic acid, and glucaric acid.

  i.      Gluconic acid is formed under mild conditions and due to oxidation at C-1. Gluconic acid is used in the formation of salts of different drugs e.g. antimalarial drugs.

Glucuronic acid is formed by oxidation at C-6. Glucuronic acid is formed in the body. It is of great physiological importance because it is use in the body as detoxifying agent and inactivates the many substances like camphor, benzoic acid, steroid hormones and bilirubin etc.

iii.      Glucaric acid is formed via oxidation of glucose at C-1 & C-6.

5.      Reducing Properties of sugar in alkaline solutions.

Almost, all carbohydrates containing a free aldehyde or ketone group except sucrose. That is oxidized especially in alkaline pH. This means that they are good reducing agents in an alkaline medium. They readily reduce oxidizing ions such as Ag⁺, Hg²⁺, Bi³⁺, Cu²⁺, and ferricyanide³⁺. \

This reaction is the basis for the Benedict’s test and Fehling’s test.

6.      Action of acids on carbohydrates

Monosaccharides (such as glucose) are resistant to the action of hot diluted mineral acids. Strong acids dehydrate all carbohydrates leading to the formation of furfural (with pentoses) or 5-hydroxymethyl furfural (with hexoses). These products condense with phenols to yield characteristic colored products.

This reaction is the basis of the color test, known as Molisch’s test for sugars.

7.      Action of bases on carbohydrates

Dilute basic solutions at low temperature can bring about re-arrangement of groups at the anomeric carbon atoms and its adjacent carbon atom. For example glucose can be changed to fructose and mannose. Higher concentration of bases can cause the further changes i.e. more carbon atoms show the rearrangement of the groups. Fragmentation and polymerization can also result.

8.      Esters formation

Hydroxyl group of sugar can be esterifies with phosphates, acetates, propionates and stearates etc. Sugar phosphates are of great biological significance. Nucleoproteins of cells also contain the sugar phosphate in combination with various nitrogen bases.

9.      Amino sugars formation

A hydroxyl group of the monosaccharides can be replaced by an amino group (– NH₂) forming an amino sugar. For example D-glucosamine, D-galactosamine, D-fructosamine. In all these – NH₂ group is attached at C-2. These are present in nature. As they are derived by hexoses so they are also called hexosamine.

Glucosamine is constituent of hyaluronic acid. Galactosamine is present in chondroitin. Mannosamine is an important constituent of mucoproteins. Aminosugars also occur in many antibiotics e.g. erythromycin. In most cases amino sugar is N-acetylated.

10.  Fermentation

Fermentation is the process of converting a larger complex molecule into simple molecules by means of enzymes. Some of the hexoses sugars are converted to ethanol and CO₂ by a group of enzymes called as zymases.

C₆H₁₂O₆ → 2(C₂H₅OH) + 2CO₂

                                                    Glucose        Ethanol         Carbondioxide 

Glucose can be changed to fructose and mannose. Glucose, fructose and mannose can be readily fermented by common baker yeast. Galactose is fermented to negligible amount.

Importance of Carbohydrates

1.         Carbohydrates are widely distributed in plants and animals and have important structural and metabolic roles.

2.         In plants, glucose is synthesized from carbon dioxide and water by photosynthesis and stored as starch or used to synthesize cellulose.

3.         Animals can synthesize carbohydrate from lipid, glycerol and amino acids, but in most animal carbohydrate is derived from plants sources.

4.         Glucose is the most important carbohydrate.

5.         Most dietary carbohydrate is absorbed into the bloodstream as glucose, and other sugars are converted into glucose in the liver.

6.         Glucose is the major metabolic fuel of mammals (except ruminants) and a universal fuel of the fetus.

7.         It is the precursor for synthesis of all the other carbohydrates in the body, including glycogen for storage; ribose and deoxyribose in nucleic acids; and galactose in lactose of milk. Glucose is also present in glycolipids and in glycoproteins.

8.         Various diseases associated with carbohydrate metabolism include diabetes mellitus, galactosemia, glycogen storage diseases, and lactose intolerance.

9.         Oligosaccharides are present in combination with proteins at all cell membranes on the extracellular face.

10.     These are also present in secreted proteins such as antibodies and blood clotting factors.

11.     Complexes of carbohydrates with proteins (glycoproteins) have been shown to act as receptors on cell membranes which are thus involved in molecular recognition.

12.     Carbohydrate derivatives such as heparin sulphate (a glycoprotein) are involved in the adhesion of one neuron to the other during the development of nervous system. For example the aggregation of the retinal neurons.

13.     The glucosaminoglycans are the integral constituents of the gel like extracellular matrix.

Ribose is an integral part of high energy phosphate compounds i.e., ATP, GTP (guanosine triphosphate), UTP (uridine triphosphate) and CTP (cytidine triphosphate) and secondary messengers such as cAMP (cyclic adenosine monophosphate) and cGMP ((cyclic guanosine monophosphate).