natural polymer. protein a protein is a complex, high-molecular- weight, organic compound that...

Natural Polymer

Protein• A protein is a complex, high-molecular-

weight, organic compound that consists of amino acids joined by peptide bonds.

• Proteins are essential to the structure and function of all living cells and viruses.

Examples of Amino acids

• L-alanine L-Asparagine

Peptide bond

• 1. amino acid

• 2. amino acid – ionic form

• 3. formation of peptide linkage

Polysaccharides

• Polysaccharides are relatively complex carbohydrates.

• They are polymers made up of many monosaccharides joined together by glycosidic linkages

• They are very large, often branched, molecules. They tend to be insoluble in water, and have no sweet taste.

Example of polysaccharides

• starch

• glycogen

• cellulose

• Polysaccharides have a general formula of Cn(H2O)n-1 where n is usually a large number between 200 and 500.

e.g. Starch

• Starches are insoluble in water.

• They can be digested by hydrolysis catalyzed by enzymes called amylases, which can break the alpha-linkages. Humans and other animals have amylases, so they can digest starches.

• Potato, rice, wheat, and maize are major sources of starch in the human diet.

Structure of Starch

e.g. Cellulose

• The structural components of plants are formed primarily from cellulose. Wood is largely cellulose and lignin, while paper and cotton are nearly pure cellulose.

• Cellulose is a polymer made with repeated glucose units bonded together by beta-linkages.

Structure of Cellulose

Glycogen

• Glycogen is a polysaccharide that is the principal storage form of glucose in animal cells.

• Most of glucose units are linked by a α-1,4 glyco

sidic linkage, a few of them also makes a α-1,6 glycosidic bond with a second glucose which results in creating of a branch. Glycogen has a large number of non-reducing ends with a free hydroxy group at carbon 4.

Glycogen (with glycosidic linkage)

• Glycogen

• Reducing sugar must have this structure:

DNA• Deoxyribonucleic acid (DNA) is a

nucleic acid —usually in the form of a double helix— that contains the genetic instructions specifying the biological development of all cellular forms of life, and most viruses.

• DNA is a long polymer of nucleotides and encodes the sequence of the amino acid residues in proteins using the genetic code.

Nucleotide

• Each spiral strand, composed of a sugar phosphate backbone and attached bases, is connected to a complementary strand by hydrogen bonding (non- covalent) between paired bases, adenine (A) with thymine (T) and guanine (G) with cytosine (C).

• Adenine and thymine are connected by two hydrogen bonds (non-covalent) while guanine and cytosine are connected by three.

Development of Aspirin

Stage 1

• Lead compound?

Salicylic acid

Stage 2

• One of the hydroxy functional groups in salicylic acid was modified with an acetyl group(forming an ester), which greatly reduced the negative side effects of salicylic acid.

Stage 3

• Aspirin was at first available as a powder in sachets, but due to its low solubility. Bayer then decided to pellet the powder and solid as tablets.

Stage 4

• No, it was not properly performed, as we can see that there was no short-term and long term testings conducted on animals. Besides, the Phase 1 and Phase 2 of clinical research also had not been conducted as Bayer distributes aspirin powder to physicians to give to the patients directly.

Stage 5

• FDA modifies the aspirin’s labeling information

Development of cis-platin

Compound Discovery

• Square planar Pt(II) complex

• Discovered by Barnett Rosenberg (Michigan) in mid 1960’s

• discovered that electrolysis products from a platinum electrode inhibited mitosis in Escherichia coli (E. coli) bacteria. The bacteria grow to 300 times their normal length but cell division fails.

• In the 1970s, a series of experiments were conducted at Michigan State University to test the effects the cis-diamminedichloroplatinum(II), along with other platinum coordination complexes, on tumors artificially implanted in rats. This study found that cis-diamminedichloroplatinum(II) was the most effective out of this group, which started the medicinal career of cis-platin.

• Approved for clinical use by the American Food and Drug Administration (FDA) in 1978, it revolutionized the treatment of certain cancers. Detailed studies on its molecular mechanism of action, using a variety of spectrocopic methods including X-ray, NMR and other physico-chemical methods, revealed its ability to form irreversible crosslinks with bases in DNA.

• Uses of Cis-platin:

• widely used anticancer drug for testicular cancer, ovarian cancer and nasopharyngeal cancer

Mode of Action• Cis-platin is given to patients by injection.• It retains its neutral form in the serum due to high [Cl-].• It passes through the cell membrane.• Hydration of cis-platin in cytoplasm due to low [Cl- ].• Cationic Pt(II) complexes reacts with DNA to form Pt-

DNA adduct.

Mode of action• inside the cell:

Pt (NH3)2Cl2 + H2O [ Pt (NH3)2Cl(H2O)]+ + Cl-

[Pt(NH3)2Cl(H2O)]+ + H2O [Pt(NH3)2(H2O)2]2+

DNA: Deoxyribonucleic acid • Polymers of nucleotides• A Nucleotide = a ribose + phosphate +nitrogen

base

Nitrogen Bases are linked by hydrogen bonding

Double helical structure

Pt - DNA Adduct

• Cis-platin reacts preferably at the GG sequence via coordinating to the N7 of guanine

• A [Pt(NH3)2(dGdG)] complex was prepared and characterized by X-ray crystallography

Pt-DNA Adduct• Platination of DNA

caused deformation of the helix because the destacking of guanine bases, which would normally be parallel to one another.

no more cell division and stop cancer.

Side Effect of taking cis-platin

• Problem of toxic side effects: kidney damage, nerve damage, nausea and vomiting, hearing loss, hair loss, etc.

• Hydrolytic products of cis-platin, [Pt(NH3)2(H2O)2]2+

, [ Pt (NH3)2Cl(H2O)]+ are

highly electrophilic and reactive to other intracellular components.

Development -carboplatin

• Same curing effect but with lower required doses and reduced side effects

• less toxic to the peripheral nervous system and the kidneys

• due to the presence of the bidentate dicarboxylate ligand in carboplatin slows down the degradation of carboplatin into potentially damaging derivatives.

2nd generation :carboplatin

Development

• 3rd generation

Part 1:Over-the Counter Drugs

1) Aspirin

2) Acetaminophen

3) Vitamin C

Aspirin

• used as an analgesic (against minor pains and aches)

• antipyretic (against fever)• anti-inflammatory• an anticoagulant ("blood-thinning") effect

and is used in long-term low-doses to prevent heart attacks.

Paracetamol or acetaminophen

• a common analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains.

• a major ingredient in numerous cold and flu medications and many prescription analgesics.

• safe in standard doses, but, accidental overdoses are fairly common.

Vitamin C

• prevents scurvy.

• It is a strong antioxidant.

Part 2:Perscription Drugs

4) Albuterol

5) Amlodipine

6) Loratadine

7) Amoxicillin

8) Omeprazole

Albuterol

• Relieve the symptoms of asthma

• protection against exercise-induced asthma

Loratadine

• a drug used to treat allergies

• relieve nasal congestion.

Amoxicillin

• an antibiotic used to treat bacterial infections caused by susceptible microorganisms.

• acts by inhibiting the synthesis of bacterial cell walls.

Omeprazole

• used in the treatment of dyspepsia-a constant pain in the stomach.

• Constant pains include indigestion, heartburn and nausea.

• Most oral omeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach

Green Chemistry

12 principles

• Atom Economy

• = (Molecular Weight of desired product) / (Molecular Weight of all reactants) * 100%

% Yield = (Actual yield) / (Theoretical yield) * 100%

Atom Economy

FM: 74.0 102.9 98.1 136.9

CH3(CH2)2CH2OH + NaBr + H2SO4 CH3(CH2)2CH2Br + NaHSO4 + H2O

mol: 0.0219 0.0258 0.0460 0.0175

% yield =???? =80%

% atom economy = 136.9/(74.0+102.9+98.1) = 50%

it produces too much side products during the reaction, therefore it is

much better to reduce the amount of waste generated in the first place.

Supercritical CO2

Advantages for extraction:• High penetration power (like a gas) but high

extraction power as a liquid• Can dissolve most organic cpds of small

molecular masses• Leaves no residual trace of liquid o material• Friendly to the environment• Low toxicity• Stable, no rxn with most organic cpds• Relative low critical temp.

Extraction of caffeine

• Green beans are soaked in water• Supercritical CO2 is forced through the

green coffee beans many times.• Caffeine, being a small molecule, can

easily dissolve in supercritical CO2.• After extraction, the supercritical CO2 fluid

is then vaporized for reuse and the caffeine can then be isolated for resale to e.g. cola manufacturers.