Pharmaceutical and Biological Chemistry

Code

PHAR1026

School

Pharmacy

Level

1

Credits

20

Semesters

Autumn Malaysia

Summary

This course provides some of the basic groundwork in the chemistry of organic compounds to allow further study of medicinally important biologically active materials as the course progresses. Major areas covered in the course are: fundamental description of atomic structure and bonding, principles of stereochemistry, selected functional group chemistry, reaction mechanisms, and the involvement of these concepts in biochemistry. The course follows on from A-level Chemistry studies, but the approach used may be rather different from that used in the teaching of A-level. Pharmaceutical scientists need to understand the properties of drug molecules, and how drug molecules interact with biological systems. In this course, a strong emphasis is placed on appreciating why organic molecules have particular properties, and why reactions occur, thus developing an ability to predict outcomes, rather than relying on remembering a vast amount of factual material. These general principles will be exploited throughout the Pharmaceutical and Health Sciences programme.

The course also introduces students to working in a scientific laboratory and to the safety precautions required, including safe handling of chemicals and equipment. The course will provide students with experience in pharmaceutical analysis and synthetic medicinal chemistry. Generic laboratory skills will be developed including following experimental protocols, execution of accurate and precise work, and making of quantitative measurements. These generic practical skills will be extensively utilized and are essential for the safe execution of further practical sessions in subsequent courses in Year-2 through to Year-3 of the programme.

INTRODUCTORY LECTURE (1 lecture)
1. Nomenclature, functional groups. Atom, electron, valence electron

INTRODUCTORY CONCEPTS IN STRUCTURE, BONDING AND MECHANISM (4 lectures)
1-2. Drawing molecules. Structure representation (Lewis and formal charge). Introduction to atomic structure and covalent bonding. Electron movement and the use of curly arrows. 
3-4. Introduction to orbital hybridization. Properties of covalent bonds, inductive and mesomeric effects. Nucleophiles and electrophiles.  

WORKSHOP ON FUNDAMENTALS (2 hours)

CHEMDRAW WORKSHOP 1 (2 hours)

STEREOCHEMISTRY (4 lectures)
1. Conformations of acyclic compounds – ethane and butane, Newman projections.  Conformations of cyclic compounds - cyclopropane, cyclobutane, cyclopentane.
2. Conformations of cyclohexane – boat and chair, axial/equatorial groups, drawing conformations. Conformations of substituted cyclohexanes. Conformations of heterocycles. 
3. Optical isomers – chiral and achiral centres. Enantiomers – optical activity, racemic mixtures, properties. Assigning configuration at chiral centres – Cahn-Infold-Prelog rules, R/S configurations. Geometric isomers – E/Z nomenclature.
4. Configuration, nomenclature. Geometrical isomers. Diastereoisomers - acyclic, cyclic, epimers. Meso compounds. Conformation versus configuration.

WORKSHOP ON STEREOCHEMISTRY (2 hours)

CHEMDRAW WORKSHOP 2 (2 hours)

PRACTICAL ON POLARIMETER (3 hours)

RESONANCE & CONJUGATION (2 lectures)
1-2. Resonance & pi-system, conjugated & aromatic system, and Hückel rule.

ACIDS AND BASES (6 lectures)
1-2. Definitions of pH and pK, acids and bases, polyprotic acids and bases. Calculation of pH for solutions of weak acids, weak bases, mixtures of weak acids/bases and their salts. Calculation of pH during course of titrations.
3. Actions, preparation, properties and uses of buffers. Calculation of pH change associated with addition of an acid or base.
4-6. Effect of chemical structure on acidity and basicity. Electron-withdrawing, electron-donating, mesomeric effects.

PRACTICAL ON ACID-BASE TITRATION (3 x 3 hours)
1. Calibration of glassware - check the calibration of apparatus needed to measure volumes.
2. Standardisation of HCl - use the calibrated apparatus to determine the strength of HCl.
3. Assay of aspirin tablets - hydrolyse sample of powdered aspirin tablets using NaOH and use the standardized HCl to determine how much NaOH was used in the hydrolysis, and therefore how much aspirin was present.

WORKSHOP ON RESONANCE & ACIDS AND BASES (2 hours)

NUCLEOPHILIC REACTIONS 1 (5 lectures)    
1. Reaction mechanism - nucleophiles, electrophiles.  Reaction kinetics as related to mechanism.  Intermediates and transition states.  
2-3. Nucleophilic substitution at saturated carbon - SN2 reactions, stereochemistry, substituent effects, nucleophilicity and basicity.  Leaving groups.  SN1 reactions, stereochemistry, carbocations.  
4. Scope of nucleophilic substitution - halide, oxygen, sulfur, nitrogen, cyanide, acetylide ion as nucleophiles.  Intramolecular substitution.
5. Elimination reactions - E2 and E1 reactions in acyclic and cyclic systems.  Direction of elimination - Saytzeff and Hofmann. Elimination versus substitution.

PRACTICAL ON ASPIRIN SYNTHESIS AND PURITY DETERMINATION (2 x 3 hours) NSY
1. Synthesis of aspirin – synthesize aspirin from salicylic acid and acetic anhydride. Purify the aspirin product via recrystallization.
2. Purity determination of aspirin - the purity of the re-crystallised product will be assessed using three different methods: melting point (qualitative), thin layer chromatography (TLC) (qualitative), and spectroscopic assay (quantitatively).

NUCLEOPHILIC REACTIONS 2 (6 lectures)
1. Organometallic compounds as nucleophiles.
2-3. Nucleophilic addition to carbonyl groups - aldehydes and ketones.  Oxygen and sulfur as nucleophiles - acetals, ketals.  Hydride as nucleophile - complex metal hydride reductions. Carbon as nucleophile - cyanide, organometallics.    
4-5. Nucleophilic substitution on carbonyl group - carboxylic acid derivatives.  Leaving groups and reactivity.  Oxygen and sulfur as nucleophiles - esters, lactones, thioesters.  Nitrogen as nucleophile - amides, lactams.  Hydride as nucleophile - reduction with complex metal hydrides.  
6. Nucleophilic substitution on derivatives of sulfuric and phosphoric acids – sulfonic acids, sulfonamides. Phosphates, pyrophosphates, ATP.

WORKSHOP ON NUCLEOPHILIC REACTIONS (2 hours)

Target Students

BSc Pharmaceutical and Health Sciences students

Classes

• One 2-hour workshop each week for 6 weeks
• One 1-hour lecture each week for 10 weeks
• Two 1-hour lectures each week for 11 weeks
• One 3-hour laboratory each week for 6 weeks

Assessment

• 20% Coursework: In module
• 20% Practical write-up: In module
• 60% Written exam (2-hour): 2 hours - end of semester

Assessed by end of autumn semester

Educational Aims

Learning Outcomes

After successful completion of this module, you should be able to:
A. Knowledge and understanding
A4 Molecular basis of drug structure, design and activity, including the application of fundamental concepts in chemistry, chemical biology and molecular biology

B. Intellectual skills
B1 Critically appraise, analyse and summarise information
B3 Understand principles of experimental and research methodology
B5 Analyse and critically evaluate scientific data

C. Professional/practical skills
C2 Undertake practical experimental work using appropriate materials, operating procedures and instruments

D. Transferable/key skills
D1 Effective communication in a variety of forms, including written, verbal and visual
D2 Critically use information resources, including library and electronic sources
D3 Work effectively as an individual or as part of a team

Conveners

• Dr New Siu Yee
• Prof Kuan Hon Lim