Noncovalent Molecular Forces - Part 1
Lecture Supplement page 200
dd-
d+
d+
Fd+
d-
d+
d-
Chemistry 14C Part 3
Structure Controls Everything
Physical properties
Boiling point
Solubility
etc.
Chemical properties
Reactions
Reactivity
+

Biological properties
Drug effects
etc.
Example: Penicillin G (an antibiotic)
Ring strain allows irreversible
H
enzyme inhibition
N
O
S
Influence antibiotic behavior
N
O
O Na
O
Salt enhances
water solubility
Noncovalent Molecular Forces
•Definition: Attractive forces (other than covalent bonding) between atoms or molecules
•Why should I study this? Noncovalent forces control association of molecules
which causes
Physical properties: Melting point, boiling point, solubility, etc.
Molecular organization into larger structures: Membranes, etc.
Molecular recognition: Substrate/enzyme docking, etc.
How Do We Measure Noncovalent Forces?
Consider evaporation of water...
•Stronger attraction = more energy required to disrupt attraction
= more energy needed for evaporation
= higher boiling point (bp)
•Boiling point easily measured
•Therefore bp a useful approximation of attractive forces
Evaporation
add energy
Liquid water
•Attractive force keeps molecules close
Water vapor
•Attractive force disrupted
•Covalent bonds still intact
How Do We Measure Noncovalent Forces?
•Boiling point (bp): Temperature at which vapor pressure of substance = ambient pressure
•Melting point (mp): Influenced by...
Attractive forces
Crystal packing
} Therefore mp is ambiguous measure of attractive forces
What Kinds of Noncovalent Forces Occur?
Consider these substances:
NaCl bp 1413 oC
H2O bp 100 oC
BrF bp 22 oC
Ar bp -186 oC
Increasing boiling point indicates
increasing magnitude of attractive forces
NaCl
bp 1413 oC
•What attractive force is operating?
•What is the nature of association between Na and Cl?
Cl
EN 3.0
Na
0.9
• DEN = 3.0 - 0.9 = 2.1
•Attractive force = ionic bond = anion-cation
= electrostatic (opposite charges attract)
•Evaporation or melting = separating opposite charges
•NaCl evaporates as Na+ and Cl- not Na-Cl
•NaCl heat of vaporization = 188 kcal mol-1
•High bp and mp typical of ionic compounds
= Na+
= Cl-
Ionic versus Covalent Bonds
Chemical bond = sharing of electron pair
•Ionic bond: Highly unequal sharing of electron pair
•Covalent bond: Approximately equal sharing of electron pair
DEN
Bonding
0.0 - 0.4
Nonpolar covalent
0.5 - 0.9
Slightly polar covalent
1.0 - 1.3
Moderately polar covalent bond
1.4 - 1.7
Highly polar covalent bond
1.8 - 2.2
Slightly ionic bond
2.3 - 3.3
Highly ionic bond
Increasing DEN causes
Increasing ionic (polar) character
•Reducing bond length reduces polarity Example: C–H DEN = 0.4; short bond  polarity
BrF
bp 22 oC (liquid at room temperature)
•What attractive force is operating?
•What is the nature of association between Br and F?
F
EN 4.0
d-
DEN = 4.0 - 2.8
= 1.2
= not ionic
= polar covalent
Br
2.8
d+
d-
d+
•Attractive force = dipole-dipole
= electrostatic (d+/d-)
•Bp suggests dipole-dipole attraction weaker than cation-anion
H2O
bp 100 oC (liquid at room temperature)
•What attractive force is operating?
•What is the nature of association between H and O?
H
EN 2.1
O
3.5
DEN = 3.5 - 2.1
= 1.4
= not ionic
= polar covalent
d+
dd+
d+
dd+
Attractive force = electrostatic
= dipole-dipole
= hydrogen bonding
Hydrogen Bonding
d+
dd+
d+
dd+
In general... Hydrogen bonding requires a donor and an acceptor
Hydrogen bond donor
X
H
Must have large d+
X = high EN = F, O, N
(rarely anything else)
A
Hydrogen bond acceptor
Has high electron density to attract d+
•Must have lone pair
•Can be small, neutral atom: O or N
•Or can be any anion
•Examples: H2O, (CH3)3N, I-
http://en.wikipedia.org/wiki/File:Hex_ice.GIF
Hydrogen Bonding
•Common attractive force
•Not always dipole-dipole
•Example: F- in CH3CH2OH
•Important in biology
•Many O-H, N-H, H2O in organisms
•Example: DNA base pairs
O
N
ddd+
Fd+
d-
H
N
N
d+
d+
d-
N
N
d+
H
d-
N
N
O
CH3
H
d+
d-
Adenine
Thymine
•Also influences protein structure
•Hydrogen bond strongest when linear
Dynamic: H-O-H |||||| OH2 ~3 x 10-12 s lifetime
Adenine
Thymine
Guanine
Cytosine
Fig 26-11 Vollhardt
Ar
bp -186 oC (monoatomic gas at room temperature)
What attractive force is operating?
•Ionic? No electronegativity difference  no ions
•Dipole-dipole? No covalent bonds  no bond dipoles
•Hydrogen bonding? No hydrogens
•No attractive force? = no energy required for vaporization?
•Bp -186 oC > -273 oC (absolute zero)
•Therefore some attractive force must be present
•Bp is very low so attractive force must be weak
•Student homework: Figure out what attractive force exists between two Ar atoms
Noncovalent Molecular Forces - Part 2
Lecture Supplement page 206
Summary of Part 1
•Physical properties such (boiling point, solubility, etc.) controlled by noncovalent association
•Stronger attractive force = more energy required for vaporization = higher boiling point
•Noncovalent attractive forces caused by electrostatic attractions
Examples
NaCl
bp 1413 oC
Noncovalent attractive force = anion-cation
BrF
bp
Noncovalent attractive force = dipole-dipole
H2 O
bp 100 oC
22 oC
Noncovalent attractive force = hydrogen bonding
H-bond donor usually O-H or N-H bond
H-bond acceptor = neutral atom with lone pair and high d- = O or N
or any anion with lone pair
H-bonds of wide biological importance: Protein and DNA structure etc.
Ar
bp -186 oC
Noncovalent attractive force = ?
Ar
bp -186 oC (monoatomic gas at room temperature)
What attractive force is operating?
•Ionic? Dipole-dipole? Hydrogen bonding?
•No attractive force? = no energy required for vaporization?
•bp -186 oC > -273 oC (absolute zero) so some weak attractive force must be present
e- e-
d
-
+
d
e-e- Ar ee - e e
e- e-
d
-
e-e- Ar ee - e e
ball of electrons
•Induced charges
•Momentary electrostatic attraction Weak force
•Called London force
•All molecules have electrons so all molecules influenced by this force
}
d+
Strength of London Forces
What influences strength of London forces?
Boiling point
Atomic radius
-269 oC
0.32 Å
Polarizability: Ability to distort electron cloud
•Distortion easy = soft Example: Rn
-246 oC
-186 oC
-152
oC
-107 oC
-62 oC
Increasing attraction
•Distortion difficult = hard Example: He
0.69 Å
0.97 Å
1.10 Å
1.30 Å
1.45 Å
What controls polarizability?
•Larger atomic radius = softer
•Larger electronegativity = harder
•Surface area effect?
Strength of London Forces
Surface area effect?
•Compare molecules with same polarizability but different surface areas
•Hydrogens = small = hard
CH4
Boiling point: -162 oC
Surface area: 56.6 Å2
MW:
16
CH3CH3
CH3CH2CH3
-88 oC
80.1 Å2
30
-42 oC
102.7 Å2
44
Conclusion
•Increasing surface area = increasing London force
•Maybe just a molecular weight effect?
CH3CH2CH2CH3
-0.5 oC
125.2 Å2
58
Strength of London Forces
Molecular weight effect?
•Compare molecules with same polarizability and different surface areas, but same
molecular weight, such as isomers of C5H12
Pentane
2-Methylbutane
2,2-Dimethylpropane
CH3
CH3
H
CH3
C
CH2CH2CH3
H
Boiling point:
Shape:
36 oC
Most elongated
Highest surface area
CH3
C
CH2CH3
CH3
C
CH3
H
CH3
30 oC
9.5 oC
Most spherical
Lowest surface area
Conclusion
stronger
stronger
Higher surface area = _______________
attraction = ________________
London forces
Other Noncovalent Interactions
Ion-dipole
•Bond dipole attracted to anion or cation
•Example: Na+ and Cl- in water
Cation-pi
•Cation attracted to pi electron cloud
K+
Cl-
d+
H
dO
d+
Na+
H
•Explains water solubility of NaCl
Aromatic ring pi cloud
•Important in some enzyme-substrate binding
Other Noncovalent Interactions
Pi stacking
•Also called aromatic stacking
Important in DNA
Aromatic rings
Relative Strength of Noncovalent Forces
•Approximate ranking of noncovalent force strengths useful
Cation-anion (ionic bonds)
Covalent bonds
>
Dipole-dipole
Hydrogen bonding
Ion-dipole
Cation-pi
Pi stacking
>
Strongest force
London forces
Weakest force
•When more than one force operates, strongest force dominates
Example: In CH3OH evaporation, H-bonding harder to overcome than London forces
Application of Noncovalent Interactions: Solubility
Water
O
H
H
+
O
Acetic acid
H
H3C
Oil layer
O
+
O
CH3(CH2)16
Vinegar layer
(water + acetic acid)
O
O
O
O
Oil (glycerol tristearate)
(CH2)16CH3
(CH2)16CH3
O
Questions
•Why acetic acid dissolves in water?
•Why oil does not dissolve in water?
Application of Noncovalent Interactions: Solubility
What causes one substance to dissolve in another?
•Solubility is an equilibrium issue...
BBBBBBBBBBBBBBBBBB
ABABABA
ABABABA
BABABAB
ABABABA
Two layers
A and B immiscible
Homogeneous
A and B dissolve
AAAAAAAAAAAAAAAAAA
•Dissolving: A interrupts attractive forces in B
•Soluble: A/B attractions better than A/A and B/B attractions
•Insoluble: A/B attractions not better than A/A and B/B attractions
•“Better” = stronger attractions and/or more attractions
Application of Noncovalent Interactions: Solubility
Water + acetic acid:
Polar bonds
O
Hydrogen bond donor
H
H3C
Hydrogen bond acceptor
O
•Many attractive interactions
•Water + CH3COOH soluble
Water + oil:
O
CH3(CH2)16
•Poor attraction between oil and water
O
O
O
O
(CH2)16CH3
(CH2)16CH3
O
•Strong attraction between water and water
•Water + oil insoluble
Like dissolves like
Melamine-
Melamine
Solubility in water: 3.2 g/L
Cyanuric Acid
Solubility in water: 2.7 g/L
Melamine cyanurate
Insoluble in water…