SEMMELWEIS
PETER PAZMANY
UNIVERSITY
CATHOLIC UNIVERSITY
Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework**
Consortium leader
PETER PAZMANY CATHOLIC UNIVERSITY
Consortium members
SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER
The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund ***
**Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben
***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg.
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Semmelweis University
semmelweis-egyetem.hu
ORGANIC AND BIOCHEMISTRY
(Szerves és Biokémia )
Chemical reactions vs. non-covalent interactions:
where is the borderline?
(Kémiai reakciók vs. nem kovalens kölcsönhatások: hol a határ? )
Compiled by dr. Péter Mátyus
with contribution by dr. Gábor Krajsovszky
Formatted by dr. Balázs Balogh
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
semmelweis-egyetem.hu
Table of Contents
1. Non-covalent interactions
4 –
4
2. A comparison of the typical energies of interactions
5 –
5
3. Coulomb potential
6 –
6
4. Non-polar covalent bond
9 – 10
5. Polar molecule
11 – 11
6. Dispersion interactions
12 – 15
7. Hydrophobic and biological interactions in biological
systems
16 – 21
8. Hydrogen bond
22 – 29
9. van der Waals forces
30 – 33
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Non-covalent interactions
Intermolecular vs.
Intramolecular (covalent)
Where do they play a role:
Physical properties e.g. boiling point, solubility.
Biology: shape of macromolecules; drug-receptor interaction, etc
Types:
i) dispersion
ii) dipolar
iii) hydrogen-bridge
iv) ionic
v) hydrofobic
i-iv: electrostatic
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
A comparison of the typical energies of interactions
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Interaction type
Typical energy (kJ mol-1)
Covalent bond
150-1000
Ionic bond
250
Dispersion force
2
Dipole-dipole interaction
2
Hydrogen bond
20
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Energy (force of attraction)
electrostatic:
Coulomb potential
Charges close together:
large force attraction
Charges further apart:
smaller force of attraction
Distance between charges
The force of attraction that exists between two opposite charges varies as the
distance between the charges increases. The force of attraction decreases rapidly as
the distance between the charges increases.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Bond polarization: polar bond, permanent dipole
Partial negative
charge
Partial positive
charge
Cl
H
3.1
2.1
Dipole moment
The relative distribution of electrons in a molecule of hydrogen chloride, HCl. The
distribution of electrons is skewed towards the highly electronegative chlorine
atom.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Non-polar covalent bond
Polar bond in non-polar molecule
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Non-polar covalent bond
Electrons
Both atoms pull electrons towards
themselves with
equal strength
the electrons are
evenly distributed
the molecule is neural
When two atoms of the same element are joined by covalent bond, electrons are shared
equally between the two atoms. The resulting molecule is non-polar.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Non-polar molecule
O
C
O
Equal pulls
cancel each
other out
A molecule of carbon dioxide features two polarized bonds. However, the two bonds
exert equal ‘pulls’ in opposite directions and cancel each other out. So carbon
dioxide is a non-polar molecule.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Polar molecule
H
O
H
A water molecule features two polarized bonds. Water is a non-symmetrical
molecule: the dipole moments do not ‘pull’ in equal and opposite
directions, so they do not cancel each other out. Therefore, water is a polar
molecule.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Dispersion interaction
i) short in time (10-16 s)
ii) very weak interaction
iii) very short in distance
- influenced by molecule shape and size
- important in biological systems
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
The mechanism by which a dipole is induced.
So this area has a greater
density of electrons...
The high density of electrons
in an area of negative charge
repel other electrons …
… than this area.
Attraction
As a results, this area is
relatively negative...
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A force of attraction exists
between the areas of
opposite charge.
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… while this area is
relatively positive.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Planar
Many points of close association
→ stronger dispersion forces
Irregular
Few points of close association
→ weaker dispersion forces
Planar molecules are able to associate closely with one another, allowing
extensive dispersion forces to occur. By contrast, irregularly shaped
molecules cannot associate so closely, so less extensive dispersion forces
can occur.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Small molecules
→ few electrons
→ limited opportunities
for induced dipoles
Larger molecules
→ more electrons
→ more opportunities
for induced dipoles
Large molecules, with a large number of electrons and more opportunities for
induced dipoles to arise, experience greater dispersion forces than smaller molecules,
which possess fewer electrons and experience fewer induced dipoles.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Hydrophobic and dispersion interactions in biology
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Hydrophilic
region
Hydrophobic
region
This molecule is
relative un stable
Water
molecule
Only the hydrophilic portion
of the molecule is exposed to
the aqueous surroundings
Hydrophobic regions
fold away from aqueous
surroundings
This molecule is
more stable
The packing of the hydrophobic
regions is stabilized by dispersion
forces
The folding of a polypeptide possessing hydrophobic and hydrophilic portions. The darker
hydrophobic portions fold away from the aqueous surroundings; this arrangement is stabilized
by dispersion forces which operate between the tightly packed hydrophobic portions.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
The origin of hydrophobicity in non-polar molecules
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Chloromethane: polar
H
H
H
C
O
Cl
H
H
Dipolar interaction
Ethanol: polar
O
H
CH3CH2
O
H
Hydrogen
bond
H
C
C
H
Dipolar interaction
H
H
O
or
CH 3CH 2
H H
Can only participate in
dispersion forces;
inadequate for interaction
with water
H
O
H
Ethane: non-polar
H
O
H
H H
No interaction
For a molecule to be water-soluble it must be able to participate in dipolar interactions or
hydrogen bonds with water. Polar molecules can participate in dipolar interactions (and, in
some cases, hydrogen bonds) and so are water-soluble: they are hydrophilic. By contrast, nonpolar molecules cannot participate in dipolar interactions or hydrogen bonds, and so are not
water-soluble; they are hydrophobic.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Add hydrophobic
molecules
When hydrophobic molecules are
added, the network of hydrogen
bonds in the water is partially
disrupted, lowering the water’s
stability.
Hydrogen-bonded
water molecules
Add hydrophilic
molecules
Stability is recaptured by the
hydrophobic molecules forming a
separate layer from the water molecules,
so the network of hydrogen bonds in the
water is not disturbed.
When
hydrophilic
molecules are added, the
hydrogen bond network is
not disrupted; the mixture
of molecules is stable one.
Hydrophobic molecules disrupt the network of hydrogen bonds that exist in water. Consequently hydrophobic
molecules partition to form a separate layer (just like oil forms a separate layer which floats on water).
Hydrophilic molecules can integrate into a network of hydrogen bonds, and so can mix fully with water.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Dipolar interaction between permanent dipoles has long life!
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Hydrogen Bond
acceptor: oxygen, fluorine, nitrogen
donor: H-fluorine, H-oxygen, H-nitrogen
Role:
biological systems(e.g. proteins, nucleic acids)
solubility
etc.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Induced partial positive charge
Electron distribution
X
H
X
Attraction between δ- on X and δ+ on H
X must be O, N, or F
The formation of a hydrogen bond. A hydrogen bond forms between an
electronegative atom (O, N, or F), and a hydrogen atom which is itself
bonded to an atom of O, N, or F.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
H
N H
N
N
N
H
H3C
O
CH3
H N
N
O
N H
N
N
Cannot form
adequate hydrogen
bonds for stable
interaction
H
N H
N
N
N
N
H3C
O
H N
X
N
N
O
Cytosine
Thymine
H
N
O
N H
N
N
N
H N
N
O
O
H N
H
Adenine
Two purines
together are too
bulky to enable
complementary
strands to form a
double helix
Thymine
H
N H
N
N
N
Cytosine
Thymine
Two pyrimidines
together are too
small to enable
complementary
strands to form a
double helix
Cannot form
hydrogen
X adequate
bonds for stable
interaction
Guanine
H
O
N
O
N
N
H N
N
N
X
N
N H
N
N H
O
N
H
H
Guanine
H N
N
H N
Adenine
X
N
O
O
Adenine
H N
Guanine
Cytosine
Hydrogen bonds only exist between two specific pairs of nucleotide bases: A and T, and C and
G. Other base pairings are not possible.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
O
R
H
O
Requirement 2:
O, N, or F
N
N
H
N
O
R
H
Requirement 1:
H joined to O, N, or F
Folding
H
R
Hydrogen bond joins
carbonyl oxygen and amino
hydrogen from different
points along the peptide
backbone
H
R
N
N
O
O
O
H
N
A polypeptide contains both the components necessary for hydrogen bond
formation. Consequently, hydrogen bonds can form between different
regions of a polypeptide chain, or between different polypeptide chains.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
H
O - HN
CH2
O
H
H
N
C
Serine
CH2
CH2
O
Glutamine
CH2
O
H
OH - O
O
C
CH2
CH2
NH2
Two possible ways in which hydrogen bonds form between the side chains
of the amino acids serine and glutamine.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Solute molecules dissolve in
(mix completely with) the solvent.
Hydrogen bonds exist between
solvent molecules …
… and between solvent
and solute molecules.
Molecules of a water-soluble compound and molecules of water mingle
freely with each other: the two types of molecule are able to mix
completely.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Insoluble molecules aggregate
and form a separate layer …
No hydrogen bonds form between the
solvent and insoluble molecule.
… while the solvent molecules
also aggregate.
If a compound is insoluble in water, its molecules cannot mix freely with
molecules of water. Instead, the two types of molecule remain completely
separate. Occasionally, a small amount of the solute dissolves, while the
majority floats on top of the solution.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Dipolar interaction attracts
δ- on the water’s oxygen
atom to the positive cation
+
+
+
+
+
+
Dipolar interaction attracts
δ+ on the water’s hydrogen
atoms to the negative anion
The hydration of ions by water molecules. The interaction of ions and water molecules is
stabilized by dipolar interactions, which exist between the charge on the ion and the partial
charge on the polar water molecule. The partial negative charge on a water molecule’s oxygen
atom is attracted to a cation’s positive charge, while the partial positive charge on a water
molecule’s hydrogen atom is attracted to an anion’s negative charge.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
van der Waals forces:
attractive (e.g. hydrogen bond, hydrophobic)
repulsive (between filled orbitals of interacting molecules)
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
van der Waals repulsion
+
+
Full atomic orbital
Repulsion between
positively charged nuclei
Overlap violates Pauli
exclusion principle
Two full atomic orbitals cannot overlap, as this would violate the Pauli exclusion principle
(which states that an atomic orbital can contain a maximum of just two electrons). This limits
how closely two atoms can interact. The nuclei of neighbouring atoms repel each other
because they both carry like positive charges. This repulsion also limits how closely two
atoms can interact.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
Solid, liquid, gas
Solid
Many non-covalent
interactions
Liquid
Fewer non-covalent
interactions
Gas
Virtually no non-covalent
interactions
Molecular solids, liquids, and gases are characterized by the number of noncovalent forces that exist between their composite molecules.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
In biological systems:
All types of non-covalent forces in action….
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
NH2
in water
+ H+
+
NH3
- H+
N
N
in water
- H+
CO2H
N
H
Lysine gains a proton when
dissolved in water, to form a
positively charged side chain
O
O
Lysine
COO
-
N
+ H+
O
H
Aspartic acid loses a proton
when dissolved in water, to a
negatively charged side chain
O
O
Aspartic acid
N
N
C
N
O
O
- OOC
+
H3N
N
O
O
O
N
N
O
Ionic forces operate between the
positively charged side chain of
lysine and the negatively charged
side chain of aspartic acid
Polypeptide chain
Ionic forces can operate between a positively charged side chain of one amino acid and a
negatively charged side chain of a different amino acid located elsewhere in a polypeptide chain.
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Organic and Biochemistry: Chemical reactions vs. non-covalent
interactions
O
Hydrophilic interactions:
polar amino acids with
water on exterior
H
H
H
H
O
O
H
H
O
O
CH2
Hydrophobic interactions:
non-polar amino acid side
chains interior
C
N
CH2
CH3
H
CH3
O
CH3
R
CH2
CH2
C
N
CH2
H
Hydrogen bond:
polar amino acid
side chains
O
O
N
O
C
Hydrogen bond:
peptide backbone
R
H
H
O
CH2
- OOC
+
NH3
Ionic salt bridge:
charged side chains
The various non-covalent forces that can operate in a biological molecule,
such as a polypeptide.
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