Noncovalent Interactions and Molecular Recognition

1
Noncovalent Interactions and Molecular Recognition

• Chapter 19
• Chemistry 224
• Bunde Spring 2009

2
Intermolecular Forces

• Forces that hold proteins, nucleic acids, and
  proteins in their active 3-d shapes are all weak,
  non-covalent interactions.
• Molecular recognition is defined as weak,
  reversible, selective binding between two
  chemical species. Selectivity is the key to
  molecular recognition
• Example enzyme substrate interactions

3
Non-Polar (Hydrophobic) Interactions

• Van der Waals interactions between hydrocarbons
• Hydrogen atoms interact with the electron density
  surrounding other atoms in the same molecule or
  in other molecules by means of weak, but
  significant, electrostatic attractive
  interactions
• When this attraction is to another sigma bond it
  is called a van der Waals interaction

4
Influence of van der Waals Interactions on
Physical Properties

• Boiling points of alkanes increase with
  increasing chain length, decrease with increasing
  branching
• Boiling points of fluoromethanes the maximum
  boiling point is achieved with difluoromethane
  when the number of C-H bonds equals the number of
  C-F bonds.
• Hydrogen atoms interact with the electron clouds
  of the fluorine atoms

5
Boiling Point and van der Waals Interactions

• Compound MP BP
• Methane -164 C -182 C
• Ethane -89 C -183 C
• Propane -42 C -190 C
• Butane -0.5 C -138 C
• Hexane 69 C -95 C
• Cyclohexane 81 C 6 C

6
Molecular Interactions
http//www.science.uwaterloo.ca/cchieh/cact/fig/i
nteraction.gif
7
Effect of Dipole-Dipole Interactions on Boiling
Points

• Compound Boiling Point (C)
• Butane -0.5 C
• Propyl Amine 48 C
• n-propanol 97 C
• Ethyl methyl ether 11 C
• Ethyl methyl amine 37 C
• Trimethyl amine 3 C

8
Hydrogen Bonds
The strength is determined by the atoms involved
and the directionality and distance
9
Hydrogen Bonding and Structure in Nucleic Acids
academic.brooklyn.cuny.edu/
10
Hydrogen Bonding and Structure in Proteins
11
Hydrogen Bonding and Solubility
12
Hydrogen Bonding and Melting and Boiling Points

• Compound BP (C) MP (C)
• 1-butanol 117 -90
• 2-methyl-1-propanol 108 -108
• 2-butanol 99 -115
• 2-methyl-2-propanol 82 26
• WHY? Interference with H-bonds and the degree of
  symmetry in crystal

13
Metal-Heteroatom Bonds

• Ligands
• Bidentate, Tridentate, Polydentate
• Ionophores
• Host-Guest Compounds (Cram, Pederson, and Lehn
  Nobel 1987)
• Crown ethers

14
Cyclic Antibiotics
Amphotericin B mode of action is to penetrate
cell membranes and disrupt the normal ion balance
in the cytoplasm
15
EDTA Metal Complex
EDTA
16
Crown Ether
M
Dibenzo-18-crown-6 ether
17
Cyclodextrin Molecules
18
Entropy Effects on Binding

• Compare the entropy of cyclic systems
  (cyclohexane) and non-cyclic systems (n-hexane)
• Cyclic system has limited conformations
• Linear chain has many, many conformations, some
  of which have low entropy than the chair or boat
  conformations of cyclohexane
• Disadvantages of cyclic systems in entropy are
  big advantages in molecular recognition

19
Hydrogen Bonding in Biopolymers

• Hydrogen Bonding in Proteins
• Hydrogen Bonding in Nucleic Acids
• Complementary Base Pairing
• Three Base Codon

20
Non-covalent Interactions in Proteins
21
Molecular Recognition of Chiral Molecules with
Chiral Enzymes

• Necessity of 3-point contact

22
Molecular Recognition

• Reading the genetic code (DNA? RNA)
• Translating RNA to amino acid sequence (RNA ?
  protein)
• Binding of substrates to enzymes binding of
  inhibitors to enzymes binding of regulatory
  molecules to enzymes
• Binding of drugs to drug receptors (inside cell
  and on cell membrane)
• Neurotransmitter action