Hemoglobin and Myoglobin

CHEM10006

Chemistry for
Biomedicine

A/Prof. Megan Maher

Bio21 Room 437
megan.maher@unimelb.edu.au
1
Inorganic chemistry for
biomedicine

Week 12 – Module #3

2
 Topics and ILOs
Topic/Concept ILOs References
Hemoglobin and myoglobin 1. Understand the roles of Mahaffy chapters 27 and 29
hemoglobin and
myoglobin in oxygen
binding and carriage in
the blood.
2. Understand principles of
iron coordination by
heme
3. Recall how oxygen binds
to iron in hemoglobin
and myoglobin
4. Recall how CO and CO2
bind to hemoglobin
5. Understand the
cooperativity in binding
of O2 to hemoglobin
3
 O2-binding proteins
Respiration: energy from oxidation of food
(1/n)(CH2O)n + H2O ® CO2 + 4 H+ + 4 e-
O2 is the oxidant:
O2 + 4 H+ + 4 e- ® 2 H2O
BUT, [O2]max ~ 10-3 M ONLY in water: animals require
large
Large animals need more O2. amounts of Or which
is achieved by
Carrier, storage proteins concentrate O2.hemoglobin
andmyoglobin
haemoglobin myoglobin 4
(blood) (muscle)
 bin
have a
homegroups
qwill
Myoglobin and hemoglobin
Mogo

in the
core of
Mb - a monomer homeHb - an a2 b2 tetramer
the is an
group
O2 storage iron O2 transport
5
in tissues from lungs
 myoglobin contains
which
q
Myoglobin binds
I havegroup
are oxygen

• Dioxygen binding protein of

muscle
• 17,500 Da
• 153 amino acids
• 1 haem group (FeII complex)
• Binds O2 in muscle

The haem unit is responsible for

binding O2

6
 Porphyrin ligand
The haem group consists of an Fe(II) centre at the centre of a
porphyrin ligand. a detonated iron
smoke
nitrogen fig'd
the

N
of • The porphyrin ligand is a flat
N H H N
unsaturated, conjugated molecule
which upon deprotonation is able
N to bind a metal ion at its centre.

• It is aromatic and has many

resonance forms. 7
 Porphyrin ligand
the nitrogen will become
deprotonated
• The porphyrin molecule
is a tetradentate ligand.

to
N
• Porphyrin and closely
related molecules are
N M o
N
found in many biological
systems containing
N metals.

• Commonly ligands bind

to vacant coordination
sites on the metal centre.
MIIL complex
8
 The porphyrin ligand

The haem group has two propanato groups attached to the

porphyrin ring.
O

O
The substituents are: O-
bulky O-
negatively charged
N N
hydrophilic.
M
There are also methyl N N
and vinyl substituents (not
shown).
9
The heme
group
f's

10
The heme group in myoglobin
histodere
the binds to • Imidazole group from
the central histidine side chain
bindthe coordinates the Fe in the
iron to
iron to the axial position
protier • Crowding of coordination
site allows only very small
molecules to have access to
Fe(II).
•
O
Note that although O is an
2
oxidant the Fe(II) centre is
1
in the +2 oxidation state
when coordinated by O2.
the iron
in the heme is Felt 11
 hemoglobin
bidtighterthan
will • Hemoglobin transfers oxygen from
lungs to the site of use - muscle cells.
myoglobin
• O2 then transferred to myoglobin for
use by muscles.

peeing • Myoglobin has a greater affinity for O2

than haemoglobin.

• Myoglobin converted to
oxymyoglobin even at low O2
concentrations such as those that
exist in cells.

Hamas • K = [MbO ]/[Mb][O ]

M 2 2

as is
landto
that Oz
12

hemegroup
the
 Hemoglobin independent
of
• Four heme groups and hemegroups
are
red
four distinct protein

o
chains. 0

• Hemoglobin may be
considered as a É
tetramer of myoglobin.
• Hemoglobin has a I

molecular weight of ~
64,500.

There
is communication
a-chain 141 amino acids between the
0 0
b-chain 146 amino acids
a 2b 2 tetramer 13

different heme
 diff
megrp

Cooperativity in hemoglobin
• KM = [MbO2]/[Mb][O2]
because
the
independent
gthegyPower
• For hemoglobin not
KH = [HbO2]/[Hb][O2]O
2.8 corgis

The 2.8 exponent

Percent saturation
results from the fact
that the binding of
four O2 molecules is
not independent.
14
pO2, mmHg
 Cooperativity in hemoglobin
• Once one O2 is bound, conformational change occurs resulting
in easier uptake of a second O2. means that looding and
fully
• The uptake of the second O2
A fully releasing Or makes
leads to further conformational
change which makes the uptake of the third O2 easier.hemoglobin's
function
of
transporting Or
• The uptake of the third O2 assists in the uptake of a fourth O2.

• Cooperativity is lost if haemoglobin is broken down into

monomers.

15
 Cooperativity in hemoglobin

• Cooperativity is important in oxygen transport.

• It is important that in the oxygen-rich environment of the

lungs that the haemoglobin is fully loaded.

• The cooperativity effect also means that when O2 starts to

be lost, successive O2 molecules are lost more easily

i.e. it fully unloads in oxygen-poor environments.

16
 Cooperativity in hemoglobin

• Hemoglobin is saturated in lungs and deoxygenated in

capillaries.

• The cooperativity means that both the loading and

unloading of O2 are efficient processes.
that Or
means goes
• Hemoglobin takes O2 where it is needed.g 10 Cells that are
locking Oz
• Without the cooperativity of haemoglobin we would suffer
asphyxiation in pure O2.

17
 Mechanism of cooperativity in
plexgenated
hemoglobin
hates fit sit below the porphyrin rig
In the deoxgenated heme the Fe(II) ion is too big to sit in the N4
plane of the porphyrin.
lands to
deoxygenated hemoglobin
a water

Of
water The Fe(II) ion sits below
the plane of the four
porphyrin nitrogen atoms.

Fe-N (porphyrin) bond

distances ~ 2.18 Å.

Deoxy 18
form
 Mechanism of cooperativity in
hemoglobin
When O2 binds to the Fe(II) centre the d electrons Fe(II) are
redistributed in a manner that makes the Fe(II) centre smaller.
heme will the
oxygenated
Feit moveinto
The Fe(II) ion sits within
phorphin ring the plane of the
g porphyrin nitrogen
Ine atoms.

Fe-N (porphyrin) bond

distances ~ 2.0 Å
this movement
Oxy form willcausethe phorphi
Wshide
move a
19

ringto slightly 32nd

 ng I heme l o
allow
groups to
Mechanism of cooperativity in uptake easier
hemoglobin of Oz
The movement of the Fe(II) causes the histidine group to move by
~ 0.08 Å. which
is moving the whole submit
subsequently moving the
other
p and leads to a significant subunit
This small movement is amplified
conformational change in the whole protein.

The conformational change

results in a protein that has an
improved affinity for O2 at the
other haem units.

Oxy form
20
Hemoglobin – deoxy form

21
Hemoglobin – oxy form

22

bind
 monoxide bad bn
carbon
means
g
that will
Or
then O which
9 more strongly not be transported
Carbon monoxide poisoning around
thecell
• Carbon monoxide will bind much more strongly than O2 to
the Fe(II) centre in haemoglobin.
• Thus exposure to low concentrations of carbon monoxide is
very dangerous because CO competes much more effectively
than O2 for the vacant site on the Fe centre.
• Carbon monoxide will bind in an end-on manner i.e. Fe-
• The angle at C is 180 .
• This end-on arrangement leads to a steric clash between the
CO and the surrounding protein chain.
• In O2 there is a significant bend at the coordinated oxygen
atom which means that there is no steric clash with the
surrounding protein chain.
• The steric clash with CO diminishes its binding ability but it
still competes for the haem site more effectively than O2. 23
 dropcauses Or to leave the heme group
A pit which means that Coz levels that are
The Bohr effect highwill cause
Oz to be
High concentrations of CO2 causes the pH to drop. deposited

CO2 + H2O H+ + HCO3-

Under these conditions O2 is released from haemoglobin.

Thus oxygen is released wherever CO2 concentration is high – Bohr

effect.

Bohr effect – First described by Danish physiologist Christian Bohr

(father of Niels)
24
 THE UNIVERSITY OF MELBOURNE

SCHOOL OF CHEMISTRY

SEMESTER 1 EXAMINATION, 2018

SUBJECT: CHEMISTRY FOR BIOMEDICINE, CHEM10006

Student Number: ___________________________

Exam Duration: 3 hours Reading Time: 15 minutes

This paper has 29 pages.

Authorized materials:
Unassembled molecular model kits.
Casio FX82(any suffix) calculator ONLY.
Note: Calculators are permitted in accordance with the rules of the Faculty of Science.
They may be used for the processing of numerical information only. They must not
have been programmed nor should they store additional information.
Calculators will be randomly checked during the course of the examination.

Instructions to Invigilators:
Students will attempt Section A on the examination paper itself. For Section A, students must
also enter their answers on the computer scan sheet provided. Please remind students to leave
the exam paper and the scan sheet on their desk for collection at the end of the examination.
A 14-page script book is required for Section B of the paper.

Instructions to Students:
This assessment consists of two sections, Section A and Section B. Section A carries one half of the
total marks available while Section B carries the remaining half. It is suggested that you spend
equal time on each section. The marks available for each question are proportional to the
suggested completion times given at the end of each question. You must answer Section A
on the paper itself and also enter your answers on the computer scan sheet provided.
Answer Section B in the examination script book provided.
A table of selected physical constants, useful quantities and conversion factors is given in
Appendix 1, structures of nucleobases in Appendix 2, structures of the 20 common amino acids
in Appendix 3 and the D-aldohexose "family tree" in Appendix 4.
Please ensure that the exam paper, the scan sheet and the script book used to answer Section B
are all left on your desk at the end of the examination.

Paper to be held by Baillieu Library - NO

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CHEM10006 Semester 1, 2018

THIS PAGE HAS BEEN INTENTIONALLY LEFT BLANK

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SECTION A

The suggested time for this section is 1.5 hours

Your answers to this section of the examination must be circled on this examination script, which
must be handed in at the end of the examination period. You must also show your answers to this
section, together with your student number, on the computer scan sheet provided.

Please enter your student enrolment number in the spaces provided. In addition, ensure that
your student enrolment number is recorded on each page of Section A.

A table of selected physical constants, useful quantities and conversion factors is provided at the end
of the exam paper in Appendix 1, structures of nucleobases in Appendix 2, structures of the 20
common amino acids in Appendix 3 and the D-aldohexose "family tree" in Appendix 4.

Question A1.
What is the overall change in internal energy, DU, for a system that undergoes the following
two steps?

Step 1: The system gives off 30.0 J of heat while performing 70.0 J of work.

Step 2: The system absorbs 70.0 J of heat while 30.0 J of work is done on it.

A. 0.0 J B. +200 J C. +600 J D. –60.0 J E. +140.0 J

(2 minutes)

Question A2.
The heat capacity of liquid water is 75.4 J mol–1 K–1 while the enthalpy of fusion of ice is
6.020 kJ mol–1. What is the smallest number of ice cubes at 0°C, each containing 18 g of
water, needed to cool 500.0 g of liquid water from 20°C to 0°C?

A. 1 B. 7 C. 14 D. 15 E. 126
(3 minutes)

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CHEM10006 Semester 1, 2018

Question A3.
When a 0.105 g sample of ethylene (C2H4) is burned in a calorimeter, the temperature increases
by 2.14°C. Calculate the heat of combustion for one mole of ethylene if the heat capacity of the
calorimeter is 2.47 kJ K–1.

A. –5.29 kJ B. –50.3 kJ C. –572 kJ D. 661 kJ E. –1.41 ´ 103 kJ

(3 minutes)

Question A4.

Under which conditions must a reaction be spontaneous at all temperatures?

A. DH is positive and DS is positive

B. DH = 0 and DS is negative

C. DS = 0 and DH is positive

D. DH is negative and DS is positive

E. DH is negative and DS is negative

(2 minutes)

Question A5.
For the reaction 2A + B ® 2C, the following data are collected:

[A]0 [B]0 Initial Rate

Expt. 1 0.10 M 0.20 M 300 M s-1

Expt. 2 0.30 M 0.40 M 3,600 M s-1

Expt. 3 0.30 M 0.80 M 14,400 M s-1

What is the rate law for the above reaction?

A. Rate = k [A]2 [B]

B. Rate = k [A] [B]

C. Rate = k [A] [B]2

D. Rate = k [A]2 [B]2

E. Rate = k [A]2 [B] / [C]2

(2 minutes)

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Question A6.
The rate constant for a reaction increases from 10.0 s-1 to 100.0 s-1 when the temperature is
increased from 27°C to 127°C. What is the approximate activation energy, assuming Arrhenius
kinetics, for the reaction in kJ mol-1 ?

A. 23.0 B. 12.7 C. 5.00 D. 18.3 E. 45.6

(3 minutes)

Question A7.
For the reaction 2A + B ® C, the following mechanism is proposed:
Step 1: A+B ⇌ D (fast equilibrium)

Step 2: D+B®E (slow)

Step 3: E + A ® C + B (fast)

What is the rate law for the formation of C?

A. Rate = k [A]

B. Rate = k [A]2 [B]

C. Rate = k [A] 2 [B]2

D. Rate = k [A] [B]

E. Rate = k [A] [B]2

(3 minutes)

Question A8.
Which one of the following statements is NOT correct?
A. The reaction order can always be determined from the stoichiometry of the balanced
chemical reaction.

B. Catalysts are substances that change the reaction rate but are not consumed in the
reaction.

C. According to collision theory, the rate of a reaction depends on the number of effective
collisions per second between reactant molecules.

D. The Arrhenius equation shows the relationship between temperature and the rate
constant.

E. The units of the second order rate constant are mol-1 L s-1.

(3 minutes)
© 2018, The University of Melbourne Page 5 of 29
CHEM10006 Semester 1, 2018

Question A9.
Consider the following statements about species present in the biogeochemical oxygen cycle
and the chemistry of oxygen.

I. Water, hydrogen peroxide, H2O2, and ozone, O3, are polar molecules.

II. Water is capable of acting as an oxidizing agent.

III. Both the protonated superoxide ion, HO2, and the hydroxonium ion, H3O+, are
radical species.

IV. The solubility of oxygen in water increases with temperature.

V. The removal of dissolved atmospheric gases from pure water will be associated
with an increase in pH.

Which of the above statements are CORRECT?

A. I, II, III B. I, II, V C. I, II D. III, IV E. All are correct.

(2 minutes)

Question A10.
Consider the following statements about species present in the biogeochemical nitrogen cycle
and the chemistry of nitrogen.

I. The conversion of NH3 to HNO2 to is a redox process.

II. The nitronium ion, NO2+ is linear.

III. In an acidic solution the amino acid lysine will carry a 1+ charge.

IV. The hybridization at the N atoms in hydrogen cyanide, HCN is sp.

V. The pH of a 1x 10-9 M solution of nitric acid, HNO3 will be 9.

Which of the above statements are CORRECT?

A. I, II B. III, V C. III, IV, V D. V E. I, II, IV

(2 minutes)

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Question A11.
Consider the following statements about species present in the biogeochemical phosphorus
cycle and the chemistry of phosphorus.
I. In a basic solution the monomethyl ester of phosphoric acid will carry
a -1 charge.

II. At 37 °C the free energy change for the hydrolysis of ATP4- to ATP3-is positive in
sign.

III. The conversion of P4O10 to phosphoric acid is a redox process.

IV. The electron pair geometry at the P atom in phosphine, PH3, is tetrahedral.

V. A solution of sodium phosphate, Na3PO4, in water will be basic.

Which of the above statements are CORRECT?

A. I, II B. I, IV, V C. I, V D. III, IV, V E. IV, V

(2 minutes)

Question A12.
Consider the following statements about the molecules carbon monoxide, CO, nitrogen
monoxide, NO, dinitrogen, N2 and carbon dioxide, CO2

I. Both NO and CO are radical species.

II. The boiling point of CO is higher than that of N2.

III. Both CO and CO2 react with water to form acidic solutions.
IV. At the same temperature the reaction between the hydroxide ion, OH-, and CO2
proceeds at a greater rate than the reaction between CO2 and water.
V. Both CO and NO are capable of forming complexes with transition metal ions.

Which of the above statements are CORRECT?

A. I, II B. IV, V C. I, II, III D. II, IV, V E. II

(2 minutes)

© 2018, The University of Melbourne Page 7 of 29

CHEM10006 Semester 1, 2018

Question A13.
Consider the following statements about water, H2O.

I. Water molecules will solvate cations but not anions.

II. Pure water contains no ionic species.

III. The pH of pure water is dependent on temperature.

IV. Methane, CH4, is more soluble in water than ammonia, NH3.

V. In ice, each water molecule forms 2 hydrogen bonds with adjacent water
molecules.
Which of the above statements are CORRECT?

A. I, II, III B. I C. III D. II, IV, V E. I, II, III, IV

(2 minutes)

Question A14.
The pH of a 0.200 M solution of sodium methanoate, NaHCO2, in water is 8.5. Based on this
information it may be concluded that the Ka of methanoic acid, HCO2H, is closest to?

A. 3.3 x 10–6

B. 2.0 x 10–4

C. 5.0 x 10–11

D. 3.0 x 10–9
E. 2.0 x 10–2
(2 minutes)

Question A15.
Consider the carbanion (CH3–), the carbocation (CH3+) and the molecules H2CO and
(CH3)3CCl.
The hybridization at the carbon atoms in these species is:

CH3– CH3+ H2CO (CH3)3CCl

A. sp2 sp3 sp2 sp3

B. sp3 sp3 sp2 sp3

C. sp3 sp2 sp3 sp3

D. sp3 sp2 sp2 sp3

E. sp3 sp3 sp3 sp3

(2 minutes)
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Question A16.
Which one of the following Newman projections represents the LEAST stable conformation
about the C2–C3 bond in 3-pentanol?
H CH3 CH3 OH CH2CH3
HO H H OH H 3CH2C H H CH2CH3 H CH3

H 3C CH2CH3 H H H H H CH3 H OH
H CH2CH3 OH H H

A. B. C. D. E.

(3 minutes)

Question A17.
Which one of the chair structures below represents the MOST stable conformation of
cis-1-amino-3-methylcyclohexane?
NH 2 NH 2

NH 2
NH 2

NH 2

A. B. C. D. E.

(3 minutes)

Question A18.
Levofloxacin (below) is an antibiotic used to treat a number of bacterial infections. What is the
configuration of the chiral (stereogenic) carbon (labelled with an *) within Levofloxacin?

A. (R)- B. (S)- C. (E)- D. (Z)- E. trans-

(3 minutes)

© 2018, The University of Melbourne Page 9 of 29

CHEM10006 Semester 1, 2018

The following structures are required to answer questions A19 – A20:

The (S, S)-enantiomer of Ethambutol is a drug used in the treatment of tuberculosis, while the
(R, R)-enantiomer causes blindness.
OH
H
N OH H
N N
H N
H
HO
HO

I. II.

OH
H
N OH H
N N
H N
H
HO
HO

III. IV.

Question A19.

Which of the structure above (I – IV) represents the (R, R)–enantiomer?

A. I. B. II. C. III. D. IV. E. None of the

structures.
(3 minutes)

Question A20.

Of the structures above, structures I and II are related as:

A. enantiomers

B. cis/trans isomers

C. diastereomers

D. structural isomers

E. identical molecules

(3 minutes)

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Question A21.
Alitretinoin (molecule shown below) is a form of Retinoic acid, derived from vitamin A. What
is the stereochemistry of this molecule?

A. (7E, 9E, 11E, 13Z)-retinoic acid

B. (7Z, 9E, 11E, 13Z)-retinoic acid

C. (7E, 9Z, 11E, 13Z)-retinoic acid

D. (7E, 9E, 11E, 13E)-retinoic acid

E. (7E, 9Z, 11E, 13E)-retinoic acid

(3 minutes)

Question A22.

The major product of the reaction depicted below is:

OH OH
HO HO
HO
An approximately
equal mixture of
OH OH OH
compounds A and C
OH

A. B. C. D. E.

(3 minutes)

© 2018, The University of Melbourne Page 11 of 29

CHEM10006 Semester 1, 2018

Consider the reaction below to answer questions A23 to A24:

Br + KCN CN + CH3 + +
CH3 CN

1 2 3 4

formed in 1:1 ratio

Question A23.

Compounds 1 and 2 are the products of an

A. SN1 reaction

B. SN2 reaction

C. E1 reaction
D. E2 reaction

E. None of the above

(2 minutes)

Question A24.

Compounds 3 and 4 are the products of an

A. SN1 reaction

B. SN2 reaction

C. E1 reaction

D. E2 reaction

E. None of the above

(2 minutes)

© 2018, The University of Melbourne Page 12 of 27

CHEM10006 Semester 1, 2018 Student enrolment number....................................

Consider the reaction scheme below to answer questions A25 to A28:

Question A25.
The transformation of compound 1 to compound 2 in step 1 is an example of what sort of
transformation?

A. an addition

B. an elimination

C. a substitution

D. a reduction

E. an oxidation
(2 minutes)

Question A26.
A suitable reagent for the transformation of compound 2 to compound 3 in step 2 is:

A. sodium borohydride (NaBH4)

B. hydrochloric acid (HCl)

C. potassium permanganate (KMnO4)

D. potassium hydroxide (KOH)

E. thionyl chloride (SOCl2)
(2 minutes)

© 2018, The University of Melbourne Page 13 of 29

CHEM10006 Semester 1, 2018

Question A27.
A suitable reagent for the transformation of compound 3 to compound 4 in step 3 is:

A. dichloromethane (CH2Cl2)

B. aqueous hydrochloric acid (HCl(aq))

C. sodium chloride (NaCl)

D. ammonium chloride (NH4Cl)

E. thionyl chloride (SOCl2)

(2 minutes)

Question A28.
The conversion of compound 4 to compound 5 in step 4 is an example of what sort of
reaction?

A. an E1 reaction

B. an E2 reaction

C. an addition/elimination reaction

D. an SN1 reaction

E. an SN2 reaction
(2 minutes)

Question A29.
Which of the following statements about DNA is CORRECT?

A. The five-carbon monosaccharide found in DNA is 2-deoxy-D-ribose.

B. The classes of heterocyclic base found in DNA are purines and pyrimidines.

C. Bases pairing occurs between: guanine and cytosine; adenine and thymine.
D. In a nucleotide unit the components are sequentially linked by:

phosphate—monosaccharide—heterocyclic base
E. All of the above.

(2 minutes)

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Question A30.
The Ksp of Zn(OH)2 is 3.0 x 10–16. What is the [Zn2+]sat if the water pH is 8.0?

A. 3.0 x 10-4 mol L-1

B. 3.0 mol L-1

C. 3.0 x 10-10 mol L-1

D. 3.0 x 10-3 mol L-1

E. 30 mol L-1
(2 minutes)

Question A31.

Which one of the following complexes may exist in cis/trans forms? (en = ethylenediamine)

A. Co(NH3)4Cl2+
B. Ni(NH3)(H2O)32+

C. Cr(H2O)3Cl3

D. Mn(en)(H2O)42+
E. Co(en)33+
(2 minutes)

Question A32.

Consider the following statements concerning carbonic anhydrase.

I. the zinc(II) is redox active in carbonic anhydrase

II. carbon dioxide binds directly to the zinc centre in carbonic anhydrase

III. the zinc(II) is in a tetrahedral environment

IV. the Lewis acidity of the zinc (II) at the centre of carbonic anhydrase is important
to its function
V. Carbonic anhydrase promotes both the forward and reverse reactions.

Which of the above statements are TRUE?

A. I, IV and V

B. I, II, and IV
C. III, IV and V

D. I and IV
E. IV and V
(2 minutes)

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CHEM10006 Semester 1, 2018

Question A33.
Consider the following statements relating to the primitive earth, i.e. a stage in the history of
the earth where life had begun to evolve but before photosynthesis led to a significant quantity
of O2 in the atmosphere.

I. Iron existed mainly in the +2 oxidation state.

II. The H+ / H2 redox couple was important in controlling the available oxidation
states of metal species
III. In natural waters, zinc was readily available to biological systems in the +2
oxidation state.
IV. Copper was available to biological systems in the +2 oxidation state.

V. Iron (III) was incorporated into many enzymes.

Which of the above statements are TRUE?

A. I and IV

B. I, II and III

C. II, III, IV and IV

D. II, III and IV

E. I, IV and V

(2 minutes)

Question A34.
Consider the following concentration cell at STP:

Cu(s) | Cu2+ (aq, 0.01 M) || Cu2+ (aq, 0.10 M) | Cu(s)

What is the cell potential?

A. 0.0 V B. 0.34 V C. -0.34 V D. 0.0592 V E. 0.0296 V

(2 minutes)

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Question A35.
Which term below best defines the 'quaternary structure' of a protein?

A. The arrangement of two or more polypeptide subunits into a single functional complex

B. The folding of the polypeptide backbone in three-dimensional space.

C. The interaction of amino acid side chains.

D. The sequence of amino acids in a polypeptide chain.

(2 minutes)

Question A36.
Consider the following amino acids; lysine (Lys), aspartic acid (Asp), phenylalanine (Phe),
histadine (His), tyrosine (Tyr), and glycine (Gly). Which amino acids are likely to bind to a
metal centre through their sidechains as univalent monodentate ligands?
A. Gly and His

B. Lys and Phe

C. Phe and Gly

D. Asp and Tyr

E. Lys and His

(2 minutes)

Question A37.

Glucose has the molecular formula of C6H12O6. What is the % by mass of carbon in glucose?
A. 20.7%

B. 59.9%
C. 40.0%

D. 79.3%
E. 33.0%

(2 minutes)

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CHEM10006 Semester 1, 2018

Question A38.
The diameter of an atom was determined and a value of 2.35 × 10–8 cm was obtained. How
many nanometres is this?

A. 2.35 × 101 nm

B. 2.35 × 10–19 nm

C. 2.35 × 10–15 nm

D. 2.35 × 10–1 nm
E. 2.35 ´ 107 nm

(2 minutes)

Question A39.
Calculate the freezing point depression of an aqueous aqueous of 0.106 m MgCl2 (assume
complete dissociation.). Note: Kf for water is 1.86 K mol–1 kg.
A. 0.197 °C B. 0.319 °C C. 0.066 °C D. 0.394 °C E. 0.591 °C

(2 minutes)

****END OF SECTION A****

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CHEM10006 Semester 1, 2018

Chemistry for Biomedicine: Semester 1 Examination

SECTION B

The suggested time for this section is 1.5 hour

ANSWER THIS SECTION IN THE EXAMINATION SCRIPT BOOKLET PROVIDED

A table of selected physical constants, useful quantities and conversion factors is provided in
Appendix 1, structures of nucleobases in Appendix 2, structures of the 20 common amino
acids in Appendix 3 and the D-aldohexose "family tree" in Appendix 4.

Students are advised to answer ALL Questions, B1 to B11:

Question B1.

(a) For the oxidation of ethanol, C2H5OH(l):

C2H5OH (l) + 3O2 (g) ® 3H2O (l) + 2CO2 (g)
Calculate the DH° at 25°C, given the following data:
DH°

C2H4(g) + 3O2(g) ® 2CO2(g) + 2H2O(l) -1411 kJ

2C(graphite) + 3H2(g) + 1/2 O2(g) ® C2H5OH(l) -278 kJ

C2H4(g) + H2O(l) ® C2H5OH(l) -44 kJ

(b) The combustion of methanol takes place according to the reaction:

2CH3OH(l) + 3O2(g) ® 4H2O(l) + 2CO2(g)
Calculate DH for the combustion of one mole of methanol under standard
conditions. Use the following standard enthalpies of formation:
DfH° for CH3OH (l) = –238.5 kJ mol-1

DfH° for CO2 (g) = –393.5 kJ mol-1

DfH° for H2O (l) = –285.6 kJ mol-1

(c) Diatomic nitrogen and oxygen make up ~ 99% of unpolluted dry air. Calculate
DrG° for the following reaction if DfG° for NO is 86.57 kJ mol-1. Is the reaction
spontaneous? Give reasons for your answer.
N2(g) + O2(g) ® 2NO(g)
(4 + 4 + 2 = 10 minutes)

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CHEM10006 Semester 1, 2018

Question B2.
In the presence of acid, sucrose is converted to a mixture of glucose and fructose. At
298 K, the first order rate constant is 5.9 x 10-5 s-1.

(a) What is the half-life of this reaction?

(b) How long does it take for the concentration of sucrose to drop to one quarter of its
initial value?

(c) Given a 0.5 M concentration of sucrose at 298 K, calculate the length of time
needed for the concentration of sucrose to drop to 0.005 M?

90
(d) Sr has a half-life of 28.1 years and is one of the more dangerous long-term
by-products of nuclear explosions. Calculate how long it would take for the
radioactivity of a sample of 90Sr to drop to one-thousandth of its initial value, if
the decay follows first order kinetics.

(2 + 3 + 4 + 4 = 13 minutes)

Question B3.
(a) Draw structures for the following species. In your structures clearly indicate the
electron pair geometry and shape and show all lone pairs. Where required, show
formal charges on your structures.
i. the nitrate ion, NO3–

ii. the polyphosphate ion, P3O105–

iii. dimethyl sulfoxide, (CH3)2SO

(6 marks)

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CHEM10006 Semester 1, 2018

Question B4.
(a) 0.25 mole of gaseous HCl is added to 0.50 mole of ammonia, NH3, in 0.50 L of
water. The Ka for NH4+ = 5.5 x 10–10.

i. calculate the pH of this solution.

ii. calculate the pH of the solution after the addition of a further 0.10
mole of gaseous HCl to the solution.

Ignore volume changes in your calculation.

(b) Individual amino acids have isoelectric points and because they contain acidic
and basic amino acids the same is the case for proteins. Haemoglobin (Hb) has
pI = 6.8. What is the sign of the net charge on Hb at pH=5.6? Under these
circumstances to what electrode (+ve or -ve) would Hb migrate in an
electrophoretic separation?

(e) 1,4-diaminobutane (also known as putrescene) contains two basic amino groups.
The two equilibria involved in the protonation of 1,4-diaminobutane are:
C4H12N2 + H2O ⇌ C4H12N2H+ + OH- Kb1 = ?

C4H12N2H+ + H2O ⇌ C4H12N2H2+ + OH- Kb2 = ?

Would Kb2 be larger or smaller than Kb1 ? Explain your reasoning.

(9 marks)

Question B5.

Consider the stereoisomers of 1-bromo-2,4-dimethylcyclohexane shown below:

(a) Draw the most stable chair conformation for compound A.

(b) Label the bromine and the methyl groups as being either axial or equatorial.

(c) Are stereoisomers A and B chiral? Explain.

(8 minutes)

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CHEM10006 Semester 1, 2018

Question B6.

Consider the structure of the anaesthetic drug, Levobupivacaine

Levobupivacaine

(a) Assign the configuration (R or S) of the asymmetric centre in Levobupivacaine.

(b) List the four requirements of aromaticity that allows the 6-membered ring
possessing the two –CH3 substituents to be called ‘aromatic’, whereas the
nitrogen-containing 6-membered ring is not.

(6 minutes)

Question B7.
(a) Draw a Newman projection about the C2–C3 bond for the (2R, 3R) isomer of
2-chloro-3-methoxypentane.

(b) Draw the structure of (Z)-3-methyl-2-pentene, and the major product that is
formed by its reaction with HBr.
(8 minutes)

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CHEM10006 Semester 1, 2018

Question B8.
When fungi attack agricultural crops they can leave behind poisonous compounds
known as mycotoxins. Plants can modify these mycotoxins by adding a sugar group,
which can be unmasked by hydrolysis in the human digestive tract. One such modified
mycotoxin is alternariol, A, for which the glycoside B has been recently isolated from
tomatoes (Agric. Food. Chem., 2016, 64, 8892).

OH O OH O

O O

HO HO
OH
OH O O
HO OH
OH
A B

(a) Consider the structure of B:

i. Which anomer is it?

ii. What is the name of the sugar that the tomato plant has used to produce B?

(b) Show a mechanism for the acid induced hydrolysis of B to A.

(7 minutes)

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CHEM10006 Semester 1, 2018

Question B9.
Etelcalcetide, C (shown below), is a peptide based drug used for the treatment of
secondary hyperparathyroidism in people with chronic kidney disease (CKD) on
hemodialysis. In the structure below, the N-terminus and C-terminus have been
identified and the individual amino acid residues have been numbered:
N-terminus C-terminus
H2N NH
#6 #4 #2
HN residue #1
#5 #3
O
O O O O
H H H
HN N N N
N N N NH2
H H H
O O O
#8 S
S
#7 NH NH NH
HO
NH2 HN NH2 HN NH2 HN NH2
O

Using the numbering scheme, consider the structure of C:

(a) For each residue (#1 to #8), identify the name of the amino acid it is derived
from and whether it is a D or L amino acid.

(b) The N-terminus (residue #7) is not a free amine. Identify what class of
functional group it has been modified to.

(c) The C-terminus (residue #1) is not a free carboxylic acid. Identify what class
of functional group it has been modified to.

(d) The final unusual modification of the peptide concerns the linkage between
residues #7 and #8. What type of bond links the two amino acid residues
together?

(8 minutes)

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CHEM10006 Semester 1, 2018

Question B10.
Siderophores are chelating molecules secreted by microorganisms that are able to bind
iron ions very strongly.

(a) Draw the simplified structure of enterobactin bound to iron?

In your drawing please indicate,

i. Oxidation state of the iron,

ii. Coordination geometry of the central metal, including donor atoms and
overall charge.
(b) Comment of the relative stabilities of the iron complexes formed by iron binding
to three catechol ligands or enterobactin. Why is there a difference in the stability
constants of the two complexes?

(7 minutes)

Question B11.

Myoglobin (Mb) and Haemoglobin (Hb) are two important biological molecules.

(a) Briefly describe the biological function of myoglobin and haemoglobin

(b) Describe the structure of haemoglobin. In your answer please include;

i. the tertiary structure Hb,

ii. the coordination geometry of the central metal in the oxygenated form
including donor atoms and ligand charges,
iii. the metal oxidation state,

(c) Describe further the function of haemoglobin. In your answer please include:
i. The nature of structural changes in haemoglobin on coordination of
oxygen,
ii. The meaning of cooperativity on coordination of oxygen to haemoglobin.

(8 minutes)

****END OF PAPER****

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APPENDIX 1.
Selected physical constants, useful quantities and conversion factors.

Avogadro constant (NA) 6.0221 ´ 1023 mol-1

1 Atomic mass unit (u) 1.6605 ´ 10-27 kg
8.314 J K-1 mol-1
Gas constant (R)
or 0.08206 L atm K-1 mol-1

Speed of light (c) 2.9979 ´ 108 m s-1

Planck constant (h) 6.6261 ´ 10-34 J s photon-1
Rydberg constant (Â ) 3.29 ´ 1015 Hz
Mass of an electron (me) 9.109 ´ 10-31 kg
Bohr radius (ao) 53 pm
1 Atmosphere (atm) 101 325 Pa = 760 mm Hg
1 Bar 100 kPa = 0.987 atm
Faraday constant (F) 9.6485 ´ 104 C mol-1
RT/F (at 298 K) 0.0257 V
2.303 RT/F (at 298 K) 0.0592 V
Absolute zero, 0 K -273.15 °C
Specific heat of water 4.18 J g-1 ºC-1

Molar Masses Selected Standard Reduction Potentials

Element M/g mol-1
H 1.008 Half Reaction E° / V
He 4.00 O2 + 4H+ + 4e- ® 2H2O 1.23 V
C 12.01 I2 + 2e- ® 2I- 0.54 V
N 14.01 Cu2+ + 2e- ® Cu 0.34 V
O 16.00
2H+ + 2e- ® H2 0.00 V
Na 22.99
Cd2+ + 2e- ® Cd -0.40 V
Mg 24.31
S 32.07 Zn2+ + 2e- ® Zn -0.76 V
Cl 35.45 2H2O + 2e- ® H2 + OH- -0.83 V
Ca 40.08 Mg2+ + 2e- ® Mg -2.37 V
Cu 63.55
I 126.90
Pu 244.00

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CHEM10006 Semester 1, 2018

APPENDIX 2: STRUCTURES OF THE NUCLEOBASES

NH2 O NH2 O O
N N N NH N NH NH

N N N N NH2 N O N O N O
H H H H H
adenine guanine cytosine thymine uracil

APPENDIX 3: STRUCTURES OF THE 20 COMMON AMINO ACIDS

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CHEM10006 Semester 1, 2018

APPENDIX 4: THE D-ALDOHEXOSE “FAMILY TREE”

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