Title: Welcome to CHEM BIO 3OA3! Bio-organic Chemistry [OLD CHEM 3FF3]
1Welcome to CHEM BIO 3OA3!Bio-organic
ChemistryOLD CHEM 3FF3
2- Instructor Paul Harrison
- ABB 418, ext. 27290
- Email pharriso_at_mcmaster.ca
- Course website http//www.elm.mcmaster.ca/
- Lectures MW 0830, F 1030 (ABB/106)
- Office Hours M 1230-230 or by appointment
- Labs
- 230-530 R or F (ABB 217)
- Every week
- Labs start next Fri. Sept. 17, 2009
3Web site update
- ELM page
- Lectures 1 includes everything for today, and
approx. 1 week of material intro and bases - Course outline
- Detailed course description lecture-by-lecture
- Calendar
4- For Thursday 11th Friday 12th
- Check-in, meet TA, safety and Lab 1 (Isolation of
Caffeine from Tea) - Lab manuals Available on web MUST bring printed
copy - BEFORE the lab, read lab manual intro, safety and
exp. 1 - Also need
- Duplicate lab book (20B3 book is ok)
- Goggles (mandatory)
- Lab coats (recommended)
- No shorts or sandals
- Obey safety rules marks will be deducted for
poor safety - Work at own pacesome labs are 2 or 3 wk labs.
In some cases more than 1 exp. can be worked in a
lab periodyour TA will provide instruction
5- Evaluation
- Assignments 2 x 5 10
- Labs -write up 15
- - practical mark 5
- Midterm 20
- Final 50
- Midterm test
- Fri. Oct. 30, 2009 at 700 pm
- Assignments Oct. 9 Oct. 19
- Nov. 13 Nov. 23
- Note academic dishonesty statement on outline-NO
copying on assignments or labs (exception when
sharing results)
6- Texts
- Dobson Foundations of Chemical Biology,
(Optional- bookstore) - Background Refreshers
- An organic chemistry textbook (e.g. Solomons)
- A biochemistry textbook (e.g. Garrett)
- 2OA3/2OB3 old exam on web
- This course has selected examples from a variety
of sources, including Dobson - Buckberry Essentials of Biological Chemistry
- Dugas, H. "Bio-organic Chemistry"
- Waldman, H. Janning, P. Chemical Biology
- Also see my slides on the website
7- What is bio-organic chemistry? Biological chem?
Chemical bio? - Chemical Biology
- Development use of chemistry techniques for
the study of biological phenomena (Stuart
Schreiber) - Biological Chemistry
- Understanding how biological processes are
controlled by underlying chemical principles
(Buckberry Teasdale) - Bio-organic Chemistry
- Application of the tools of chemistry to the
understanding of biochemical processes (Dugas) - Whats the difference between these???
- Deal with interface of biology chemistry
8Simple organics eg HCN, H2CO (mono-functional) C
f 20A3/B3
BIOLOGY
CHEMISTRY
Life large macromolecules cellscontain 100,
000 different compounds interacting
Biologically relevant organics polyfunctional
1 Metabolism present in all cells (focus of
3OA3) 2 Metabolism specific species, eg.
Caffeine (focus of 4DD3)
How different are they?
CHEMISTRY Round-bottom flask
BIOLOGY cell
9- Exchange of ideas
- Biology Chemistry
- Chemistry
- Explains events of biology mechanisms,
rationalization - Biology
- Provides challenges to chemistry synthesis,
structure determination - Inspires chemists biomimetics ? improved
chemistry by understanding of biology (e.g.
enzymes)
10Key Processes of 1 Metabolism
- Bases sugars ? nucleosides
nucleic acids - Sugars (monosaccharides)
polysaccharides - Amino acids
proteins - Polymerization reactions cell also needs the
reverse process - We will look at each of these processes, forwards
and backwards, in 4 parts, comparing and
contrasting the reactions - How do chemists synthesize these structures?
- How might these structures have formed in the
pre-biotic world, and have led to life on earth? - How are they made in vivo?
- Can we design improved chemistry by understanding
the biology biomimetic synthesis?
11Properties of Biological Molecules that Inspire
Chemists
- Large ? challenges for synthesis
- for structural prediction (e.g. protein
folding) - 2) Size ? multiple FGs (active site) ALIGNED to
achieve a goal - (e.g. enzyme active site, bases in NAs)
- 3) Multiple non-covalent weak interactions ? sum
to strong, stable binding non-covalent complexes - (e.g. substrate, inhibitor, DNA)
- 4) Specificity ? specific interactions between 2
molecules in an ensemble within the cell -
12- 5) Regulated ? switchable, allows control of cell
? activation/inhibition - 6) Catalysis ? groups work in concert
- 7) Replication ? turnover
- e.g. an enzyme has many turnovers, nucleic
acids replicate
13Evolution of Life
- Life did not suddenly crop up in its current form
of complex structures (DNA, proteins) in one
sudden reaction from mono-functional simple
molecules - In this course, we
- will follow some of the
- ideas of how life may
- have evolved
14RNA World
- Catalysis by ribozymes occurred before protein
catalysis - Explains current central dogma
- Which came first nucleic acids or protein?
- RNA world hypothesis suggests RNA was first
molecule to act as both template catalyst - catalysis replication
15- How did these reactions occur in the pre-RNA
world? In the RNA world? in modern organisms? - CATALYSIS SPECIFICITY
- How are these achieved? (Role of NON-COVALENT
forces BINDING) - a) in chemical synthesis
- b) in the pre-biotic world
- c) in vivo how is the cell CONTROLLED?
- d) in chemical models can we design better
chemistry through understanding biochemical
mechanisms?
16Relevance of Labs to the Course
- Labs illustrate
- Biologically relevant small molecules (e.g.
caffeine Exp 1, related to bases) - Cofactor chemistry pyridinium ions (e.g. NADH,
Exp 2 4) - Biomimetic chemistry (e.g. simplified model of
NADH, Exp 2) - Chemical mechanisms relevant to catalysis (e.g.
NADH, Exp 2) - Structural principles characterization (e.g.
sugars anomers of glucose, anomeric effect,
diastereomers, NMR, Exp 3)
17- Application of biology to stereoselective
chemical synthesis (e.g. yeast, Exp 4) - Synthesis of small molecules (e.g. peptides,
drugs, dilantin, esters, Exp 5,6,7) - Chemical catalysis (e.g. protection activation
strategies relevant to peptide synthesis in vivo
and in vitro, Exp 5) - Comparison of organic and biological reactions
(Exp. 6) - Enzyme mechanisms and active sites (Exp. 7)
- All of these demonstrate inter-disciplinary area
between chemistry biology
18- Two Views of DNA
- Biochemists view shows overall shape,
ignores atoms bonds - Chemists view atom-by-atom structure,
functional groups illustrates concepts from
2OA3/2OB3 - GOAL to think as both a chemist and a
biochemist i.e. a chemical biologist!
19Biochemists View of the DNA Double Helix
Minor groove
Major groove
20Chemists View
21BASES
- Aromatic structures
- all sp2 hybridized atoms (6 p orbitals, 6 p e-)
- planar (like benzene)
- N has lone pair in both pyridine pyrrole ?
basic (H acceptor or e- donor)
226 p electrons, stable cation ? weaker acid,
higher pKa ( 5) strong conj. base
sp3 hybridized N, NOT aromatic ? strong acid, low
pKa ( -4) weak conj. base
- Pyrrole uses lone pair in aromatic sextet ?
protonation means loss of aromaticity
(BAD!) - Pyridines N has free lone pair to accept H
- ? pyridine is often used as a base in organic
chemistry, since it is soluble in many common
organic solvents
23- The lone pair also makes pyridine a H-bond
acceptor e.g. benzene is insoluble in H2O but
pyridine is soluble - This is a NON-specific interaction, i.e., any
H-bond donor will work
24What about pyrrole?
25Other groups form H-bonds
- Electronegative atoms, e.g. carbonyl group
- Acetone is soluble in water, but propane is not
- Again, non-specific interactions
26Bifunctional compounds
27Bifunctional compounds
28Contrast with Nucleic Acid Bases (A, T, C, G, U)
Specific!
- Evidence for specificity?
- Why are these interactions specific? e.g. G-C
A-T
29- Evidence?
- If mix G C together ? exothermic reaction
occurs change in 1H chemical shift in NMR other
changes ? reaction occurring - Also occurs with A T
- Other combinations ? no change!
e.g. Guanine-Cytosine
- Why?
- In G-C duplex, 3 complementary H-bonds can form
donors acceptors molecular recognition
30- Can use NMR to do a titration curve
- Favorable reaction because ?H for complex
formation -3 x H-bond energy - ?S is unfavorable ? complex is organized ?
3 H-bonds overcome the entropy of complex
formation - Note In synthetic DNAs other interactions can
occur
31- Molecular recognition not limited to natural
bases
Forms supramolecular structure 6 molecules in a
ring
? Create new architecture by thinking about
biology i.e., biologically inspired chemistry!
32Synthesis of the Bases in Nucleic Acids
- Thousands of methods in heterocyclic chemistry
well do 1 example - Juan Or (1961)
- May be the first step in the origin of life
- Interesting because H-CN/CN- is probably the
simplest molecule that can be both a nucleophile
electrophile, and also form C-C bonds
32
33Mechanism?
33
34Other Bases?
All these species are found in interstellar
space observed by e.g. absorption of IR
radiation a natural example of IR
spectroscopy! Try these mechanisms!
34
35Properties of Pyridine
- Weve seen it as an acid an H-bond acceptor
- Lone pair can act as a nucleophile
35
36- Balance between aromaticity charged vs
non-aromatic neutral! - ? can undergo REDOX reaction reversibly
-
36
37- Interestingly, nicotinamide may have been present
in the pre-biotic world - NAD or related structure may have controlled
redox chemistry long before enzymes involved!
37
38Another example of N-Alkylation of Pyridines
This is an SN2 reaction stereospecific with
INVERSION
38
39References
- Solomons
- Amines basicity ch.20
- Pyridine pyrrole pp 644-5
- NAD/NADH pp 645-6, 537-8, 544-6
- Bases in nucleic acids ch. 25
- Also see Dobson, ch.9
- Topics in Current Chemistry, v 259, p 29-68
39