Nanyang Technological University

Division of Chemistry and Biological Chemistry

Academic Year 2020/21 Semester 2

Course Coordinator Richard D. WEBSTER and ZHANG Zhengyang
Course Code CM4011
Course Title Advanced Analytical Chemistry
Pre-requisites {CM2011 and CM2062 and CM3062} or by permission
No of AUs 3
Contact Hours On-line or face to face lectures - 35 hours
Mid-term assessments - 4 hours
Proposal Date 15 January 2020

Course Aims
The lectures provide an advanced account of modern analytical methods and instruments that are
used to quantify chemical and biological samples and to monitor the progress of reactions. Students
will understand the principles of advanced electrochemical, spectroscopic and chromatographic
techniques applied to chemical analysis. The students will be able to use their in-depth knowledge of
analytical chemistry to devise experiments that can quantify a range of diverse chemical components.
The students will learn problem solving skills where they apply their theoretical knowledge to real life
problems in the environment.

Intended Learning Outcomes (ILO)

By the end of this course, you (as a student) would be able to:

1. Quality Assurance and Calibration Methods

a. Explain the steps in Quality Assurance (Use objectives, Specifications and
Assessment).
b. Describe how method validation is performed.
c. Calculate the limit of detection (LOD) and limit of quantification (LOQ) and
understand how they differ.
d. Explain how and why standard additions are performed and how to calculate the
concentration.
e. Describe the principles of internal standards.

2. Automated Measurements of Priority Pollutants

a. Explain how PM2.5/10 levels are determined, first by separation into their respective
sizes (by impactors or cyclones), and then their quantification by (direct weighing,
beta attenuation monitoring, or with a tapered element oscillating microbalance).
b. Describe how the gases SO2 (fluorescence), O3 (absorbance or chemiluminescence)
and CO (infrared) are measured.
c. Explain the equilibria between the major nitrogen/oxygen containing gaseous
pollutants.
d. Explain how NO, NOX (fluorescence) and NO2 (chemiluminescence) are measured.

3. Electrolytic Methods
a. Describe why flowing current affects the cell potentials.
b. Explain IR drop and polarisation (concentration and kinetic).
c. Calculate “charge” and describe how it relates to electron count and mols of
compounds (Faraday’s law).

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 d. Explain how electrochemical electrolysis cells are constructed.
e. Describe how the Karl Fischer (KF) titration works and how to calculate the water
content from the measurements.
f. Explain the principles of ion chromatography.
g. Describe the pros and cons of ion chromatography (IC) and ion-selective electrodes
(ISE) measurements and when you would use the techniques.

4. Voltammetric Analysis
a. Describe the concepts of voltammetry.
b. Explain the different ways that voltammetric excitation signals can be applied and
the advantages and disadvantages of the different voltammetric techniques.
c. Explain how a potentiostat functions and what is the purpose of having 3
electrodes.
d. Explain the difference between hydrodynamic and stationary electrode
voltammetry.
e. Describe why current-voltage curves have a specific shape in hydrodynamic
voltammetry.
f. Explain how pH effects voltammograms for reactions that involve protons.
g. Explain the differences and similarities in pulsed voltammetric methods.
h. Describe how the oxygen and glucose voltammetric sensors function.

5. Cyclic voltammetry
a. Explain how cyclic voltammetry is performed.
b. Explain why comproportionation reactions occur.
c. Explain the use of cyclic voltammetry to determine electrochemical mechanisms.

6. EPR spectroscopy
a. Describe the Zeeman effect.
b. Explain what hyperfine interactions are and why they occur in a magnetic field.
c. Describe how the nuclear spin quantum number affects the hyperfine pattern.
d. Explain the important rules for predicting hyperfine coupling patterns for all nuclei
(2nI + 1) and the binomial expansion (Pascal's triangle) for I = 1/2 nuclei.
e. Describe why isotopes affect the line intensities.
f. Explain the methods of preparing radicals.
g. Describe the difference between spin traps and spin labels.

7. Optical Sensors
a. Describe the scientific concepts of absorbance and fluorescence.
b. Explain how optical fibres transmit light and the importance of the “cone of
acceptance” and “critical angle”.
c. Explain the different ways that optodes can function in sensing, including through
absorbance (transmission and reflectance) and fluorescence and be able to draw
simple schematic diagrams.

8. Capillary Electrophoresis
a. Explain how ions are separated in capillary zone electrophoresis.
b. Describe how charge is related to electrophoretic mobility.
c. Explain how the solution is transported from anode to cathode.
d. Describe the arrival of species in the detector.
e. Describe what is apparent mobility.
f. Explain how zone dispersion arises in capillary zone electrophoresis.
g. Describe how stacking of solute ions in the capillary occurs.

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 h. Describe electroosmotic flow under low pH.
i. Explain how covalent coatings reduces electroosmosis and wall adsorption.
j. Describe hydrodynamic and electrokinetic sample injection.
k. Describe common detection methods in capillary electrophoresis.
l. Explain how micellar electrophoretic chromatography separates neutral molecules
and ions.
m. Explain how capillary gel electrophoresis separates macromolecules and discuss the
speed of separation with molecular exclusion chromatography.
n. Discuss how microfluidic devices function.

9. Mass spectrometry
a. Explain how ions are created in mass spectrometer.
b. Describe how magnetic sector mass spectrometer separates gaseous ions.
c. Describe how ions are detected.
d. Explain the high resolution obtained by double-focusing mass spectrometer.
e. Explain the operations of transmission quadrupole and time-of-flight mass
spectrometer.
f. Describe how resolving power is defined.
g. Describe how to determine molecular ion from the mass spectrum.
h. Explain how to predict the relative intensities of isotopic peaks for a given
composition.
i. Interpret the fragment ions arising from bond cleavage to determine the molecular
structure.
j. Calculate the molecular composition from the rings + double bonds equation.
k. Explain how electrospray ionization creates ions in liquid chromatography.
l. Describe how atmospheric pressure chemical ionization crate gaseous ions.
m. Explain how collisionally activated dissociation produce fragmented ions.
n. Describe the working principle of matrix-assisted laser desorption/ionization.
o. Describe the peaks obtained in reconstructed total ion chromatogram and extracted
ion chromatogram.
p. Describe the working principle in selected ion monitoring.
q. Explain how molecules can be ionized from the surface of an object in ambient
atmosphere.
r. Explain how ion mobility spectrometer separates gas-phase ions.

Course Content

S/N Topic Approx.

Lecture
Hours
1 Quality Assurance and Calibration Methods: Method blanks, standard 3
operating procedures, method validation, limits of detection and
quantification, calibration curves, standard additions and internal
standards.
2 Automated Measurements of Priority Pollutants: Air quality index and 2
pollutant standards index, PM2.5 and PM10 and methods of separation and
quantification, inorganic gases including SO2, NOX, O3, CO and their
methods of detection and quantification though absorbance,
luminescence and infrared measurements.
3 Electrolytic Methods: The effect of current on cell potentials,
concentration and kinetic polarisation, controlled potential electrolysis,
coulometry, Karl Fischer (KF) titrations and ion chromatography. 3

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 4A Voltammetric Analysis: Linear sweep voltammetry, electrode materials,
microelectrodes, hydrodynamic effects, differential pulse voltammetry,
square-wave voltammetry, stripping methods and voltammetric sensors. 3
4B Cyclic voltammetry: Diagnostic features, scan rate dependence,
electrochemical mechanisms, comproportionation, reduction of aromatic
halides, hydroquinones, quinones, phenols, disproprtionation, reversible
dimerization and the square scheme mechanism. 3
5 EPR spectroscopy: Basic theory, rules for interpreting spectra of organic
radicals, examples of spectra, methods or preparing paramagnetic
compounds and spin traps. 3
6 Optical Sensors: Beer-Lambert law, optodes, total internal reflection,
absorbance (transmission, reflectance) and fluorescence 2
6 Capillary Electrophoresis: Principles of capillary electrophoresis,
electrophoresis, electroosmosis, mobility, theoretical plates and
resolution, conducting capillary electrophoresis, controlling the
environment inside the capillary, sample injection and composition,
conductivity effects (stacking and skewed peaks), detectors, micellar
electrokinetic chromatography, capillary gel electrophoresis, method
development, lab-on-a-chip. 8
7 Mass spectrometry: Molecular mass and nominal mass, separation of
masses by magnetic field, electron ionization, resolving power, molecular
ion and isotope patterns, high-resolution mass spectrometry, rings and
double bonds, identifying molecular ion peak, interpreting fragmentation
patterns, types of mass spectrometers, transmission quadrupole mass
spectrometer, time-of-flight mass spectrometer, orbitrap mass
spectrometer, chromatography-mass spectrometry interfaces,
electrospray ionization, atmospheric pressure chemical ionization, direct
electron ionization, photoionization, chromatography-mass spectrometry
techniques, selected ion monitoring and extracted ion monitoring,
selected reaction monitoring, electrospray of proteins, electron-transfer
dissociation for protein sequencing, open-air sampling for mass
spectrometry, direct analysis in real time, desorption electrospray
ionization, ion mobility spectrometry. 8

Assessment (includes both continuous and summative assessment)

Component Course Related Weighting Team/Individual Assessment

LO Programme Rubrics
Tested LO or
Graduate
Attributes
Mid-term 1-5b Competence 20% Individual See
Test 1
Mid-term 6-7 and 20% Individual Appendix
Test 2
Final All Creativity 60% Individual 1
Examination
Total 100%

Formative feedback
You will be given feedback in four ways:
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1. By response to postings on the course discussion board.
2. Through the marking of the mid-terms.
3. Through one-on-one discussions via appointment with the course instructor
4. General feedback will be provided to the students following the final exam.

Learning and Teaching approach

Approach How does this approach support students in achieving the learning
outcomes?

Blend of online The bulk of the content will be delivered online. This allows (a) extensive
and face-to- face use of animations and laboratory videos and (b) use of interactive
lectures. questions so that students may immediately test their learning. Face to
face lectures and experimental demonstrations will be employed for
selected topics.

Reading and References

D. A. Skoog, D. M. West, F. J. Holler and S. R. Crouch "Fundamentals of Analytical Chemistry (9th
Edition)", Brooks/Cole, Cengage Learning, 2014. ISBN: 9780495558286

Reference textbook: D. C. Harris and C. A. Lucy “Quantitative Chemical Analysis (9th Edition)", W. H.
Freeman and Company, 2016. ISBN: 9781319154141

Course Policies and Student Responsibilities

(1) General
You are expected to complete all online activities in good time.

(2) Absenteeism
If you miss a lecture, you are expected to make up for the lost learning activities. If you miss one of
the mid-term tests with a valid reason and approval (such as a medical certificate), then the total CA
will come from the other mid-term test. If you miss both mid-term tests with a valid reason then an
additional make-up test will be set to obtain the total CA mark.

Academic Integrity
Good academic work depends on honesty and ethical behaviour. The quality of your work as a
student relies on adhering to the principles of academic integrity and to the NTU Honour Code, a set
of values shared by the whole university community. Truth, Trust and Justice are at the core of NTU’s
shared values.

As a student, it is important that you recognize your responsibilities in understanding and applying
the principles of academic integrity in all the work you do at NTU. Not knowing what is involved in
maintaining academic integrity does not excuse academic dishonesty. You need to actively equip
yourself with strategies to avoid all forms of academic dishonesty, including plagiarism, academic
fraud, collusion and cheating. If you are uncertain of the definitions of any of these terms, you should
go to the academic integrity website for more information. Consult your instructor(s) if you need any
clarification about the requirements of academic integrity in the course.

Course Instructors

Instructor Office Location Phone E-mail

Richard WEBSTER SPMS-CBC-04-06 6316 8793 webster@ntu.edu.sg
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 ZHANG Zhengyang SPMS-CBC-03-02 6513 6059 zhang.zy@ntu.edu.sg

Planned Weekly Schedule

Week Topic Course LO Readings/ Activities

1 Quality Assurance / Air Quality 1 Lecture and online
Measurements
2 Air Quality Measurements / 2 Online content
Electrolysis
3 Electrolysis 3 Online content
4 Voltammetry 4 Online content
5 Voltammetry 5 Online content
6 Mid-term Test 1 / EPR Spectroscopy 6a to 6d Lecture and online content
7 EPR Spectroscopy / Optical Sensors 6e to 6g, 7 Online content
8 Capillary Electrophoresis 8a to 8f Lecture and online
9 Capillary Electrophoresis 8g to 8l Lecture and online
10 Capillary Electrophoresis / Mass 8n to 8n, Lecture and online
spectrometry 9a to 9d
11 Mass spectrometry 9e to 9h Lecture and online
12 Mid-term Test 2 / Mass 9i to 9l Lecture and online
spectrometry
13 Mass spectrometry 9m to 9r Lecture and online

The above schedule is for illustrative purposes and is subject to the exigencies of the calendar

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Appendix 1: Assessment Criteria for all components

Mid-term Test 1 and 2 – MCQ questions (two tests worth 20 marks each).

Standards
Fail standard Pass standard High standard
(0-7 marks) (8-15 marks) (16-20 marks)
Answers to the Answers to the questions Answers to the questions
questions are mostly are mostly correct. are almost always correct.
incorrect.

Final Examination – short answer questions and calculations (exam worth 60 marks).

Standards
Fail standard Pass standard High standard
(0-24 marks) (25-48 marks) (49 -60 marks)
Answers demonstrate Answers to the standard Answers to all questions
the ability to repeat level question are correct show a high and consistent
factual knowledge but and show the ability to level of critical analysis of
not to apply it outside apply concepts from the the information presented
of the lecture context. course, but a high level of and creative solutions to
Answers do not have critical thinking is absent. the problems.
a strong logical Answers are reasonably Answers are highly logical
underpinning or logical, but with gaps. and demonstrate strong
maybe attempts to reasoning. Answers are
answer both ways at concise and to the point.
the same time.

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 CBC Programme Learning Outcome

The Division of Chemistry and Biological Chemistry (CBC) offers an undergraduate degree major in
Chemistry that satisfies the American Chemical Society (ACS) curricular guidelines and equips students
with knowledge relevant to the industry. Graduates of the Division of Chemistry and Biological
Chemistry should have the following key attributes:

1. Competence
Graduates should be well-versed in the foundational and advanced concepts of chemical science, be
able to evaluate chemistry-related information critically and independently, and be able to use
complex reasoning to solve emergent chemical problems.

2. Creativity
Graduates should be able to synthesize and integrate multiple ideas across the curriculum, and
propose innovative solutions to emergent chemistry-related problems based on their training in
chemistry.

3. Communication
Graduates should be able to demonstrate clarity of thought, independent thinking, and sound scientific
analysis and reasoning through written and oral reports to audiences with varying technical
backgrounds. They should also be able to effectively engage other professional chemists in
collaborative endeavours.

4. Character
Graduates should be able to act in responsible ways and uphold the high ethical standards that the
society expects of professional chemists.

5. Civic-mindedness
Graduates should be aware of the impact of chemistry on society, and how chemistry can be applied to
benefit mankind. They should also be aware of and uphold the best chemical safety practices.