z-Ch. 3 Importance of Weak Chemical Interactions

Weak bonds very important to shape of macromolecules & hence biological function
Can form and break under physiological conditions
Mediate interactions between enzymes & substrates and between macromolecules.
Especially between proteins & DNA or RNA
Also, between different parts of same macromolecule
Ex. Protein is linear chain covalently linked amino acids, but its shape and function are determined by the stable 3-D structure.
Weak include: van der Waals, hydrophobic, hydrogen, & ionic
Chemical Bonds
Covalent bonds hold atoms together in molecules.
Weaker attractive forces are important in holding together many macromolecules
Now customary to call weak positive interactions chemical bonds even though individually they are not strong enough to bind together two atoms
Bond strength
Strong bonds almost never fall apart at physiological temperatures
Weak bonds easily broken (fleeting) unless present in ordered groups (large numbers stabilize)
The stronger the bond, the shorter the bond length. Covalent: shorter that weak.
H:H (H2) = .74 A0 H H van der Waals: 1.2 A0
van der Waals
Limiting factor is steric: number of bonds only limited by the number of atoms that can touch each other simultaneously
Hydrogen bonds
Hydrogen bonds subject to more restrictions
H one hydrogen bond; oxygen typically 2 or less.
Chemical Bond Formation Involves a Change in the Form of Energy
A + B ? AB + energy
Spontaneous formation of a bond between two atoms involves the release of some of the internal energy & its conversion to another form.
The stronger the bond, the greater the amount of energy released upon its formation. (expressed as kcal/mole)
Rate of reaction directly proportional to the frequency of collision between A & B.
AB + energy ? A + B
Forces exist to break chemical bonds
Most important arises from heat energy
As temperature of a collection of molecules increases (move faster), the stability of their bonds decreases.
Amount of Energy added to break a bond is exactly equal to the amount released upon its formation. First law of thermodynamics: energy (except as it is interconvertible with mass) can neither be created or destroyed.
Equilibrium Constant
Keq = [AB] / [A][B]
When equilibrium is reached the # of bonds forming per unit of time = the number of bonds breaking.
Does not matter whether we begin with only free A & B or only molecule AB or any other combination of concentrations of A,B, and AB, the proportions will reach the concentrations given by Keq.
Equilibrium eq.s
At Equilibrium, the rate of forward reaction equals the rate of reverse reaction (also, G = 0) vf = vr
kf[A][B]=kr[AB]
kf/kr = [AB]/[A][B]
Keq = kf/kr = [AB]/[A][B]
Free Energy and Keq
2nd Law of Thermodynamics: in any chemical/physical process, it goes spontaneously in direction of disorder [an increase in entropy].
Decrease in free energy always occurs in spontaneous reactions as they go to equilibrium.
The free energy lost as equilibrium is approached is either transformed into heat or used to increase the entropy (release in another form or entropy).
Gibb’s Free Energy Concept
Important: Always a change in form of energy as the proportion of atoms (bonded and unbonded) move toward equilibrium concentrations (if displaced from equilibrium concentrations).
Energy change is expressed as change in G, in honor of Josiah Gibbs, 19th century physicist.
Simplest explanation of free energy is the energy available to do work.
Keq related to G
G = -RTln Keq
R [1.98] is universal gas constant; T is absolute temperature [0K]. Keq = e-^G/RT e= 2.718
G values as low as -2 kcal/mole can drive bond forming reactions to virtual completion if all reactants are at molar concentrations.
Covalent bonds Are Very Strong (water example)
H2 + ? O2 ? H2O
Formation of covalent bonds from free atoms, such as hydrogen or oxygen, are very large and negative in sign (-50 -110)
Therefore, equation shows that Keq of the bonding reaction will be very large, so [H2] & [O2] unbound is very small.
Kinetic Energy of Motion
At 250 C, the average kinetic energy of motion (heat) is 0.6 kcal/mole.
Weak bonds even at their weakest have energies only slightly higher than the kinetic energy of motion.
Van der Waals: 1-2kcal (strongest 3-7 like H bond)
Since average kinetic energy has a significant spread, there always exists some with sufficient energy to break the strongest of weak bonds.
van der Waals Forces
Arise from nonspecific attractive forces that occur when two atoms come close to each other. (induced fluctuating charges caused by nearness of molecules, both polar and nonpolar.
Depends on distance between interacting groups.
Also, exists a more powerful van der Waals repulsive force at shorter distances
Variation of van der Waals Forces with Distance
Repulsive force derived from overlapping of outer electron shells of the atoms involved.
Attractive and repulsive forces balance at a certain distance specific for each type of atom.
Distance is the so called van der Waals radius.
strongest type of van der Waals
The strongest type of van der Waals contact arises when a molecule contains a cavity exactly complementary in shape to a protruding group of another molecule. Example: Antigen-Antibody
H Bonds
In absence of surrounding H2O molecules
Bond energies range between 3 to 7 kcal
The stronger bonds involving greater charge differences between donar and acceptor
Thus, H bonds weaker than covalent but considerably stronger than van der Waals
Hydrogen bond will hold two atoms together closer than sum of van der Waals radii, but not as close as covalent would hold them.
Hydrogen Bonds, Unlike van der Waals are Highly Directional
In strongest H bonds, the H atom points directly at acceptor atoms (a)
If it points > 300 away, bond energy is much less.
Some Ionic Bonds Are H Bonds
Organic molecules often contain ionic groups that contain 1 or more units of net charge: positive or negative.
Examples: nucleotides (phosphate negative charge; amino acids (NH3+ & COO-)
These are neutralized by nearby oppositely charged groups
Electrostatic forces acting between oppositely charged groups are called ionic bonds. (in aqueous soln: 5 kcal
Weak ionic interactions
Weak binding effective only when interacting surfaces are close
This proximity possible only when molecular surfaces have complementary surfaces.
Ex: protruding group (positive chg) on one surface is matched by a cavity (neg chg) on another.
I.e. interacting molecules have “lock and key”
Some molecules rarely ever bind to other molecules of the same kind (no symmetry for internal self-interaction).
Ex some polar molecules contain an H atom but no suitable acceptor atoms.
Others can accept H bonds but have no H atoms to donate.
Weak Bonds Between Molecules in Aqueous Solutions
Molecule will tend to move until it is next to a molecule with which it can interact and form the strongest possible bond.
Uniqueness of molecular Shapes and Selective Stickiness
Recall: Energy of H bonds per atomic group is much greater than that of van der Waals contacts.
Thus, molecules will form H bonds in preference to van der Waals contact.
But, look at benzene: cannot form H bonds; thus, benzene molecules rapidly separate from water attaching to themselves by van der Waals. Impossible to insert a non H bonding organic molecule into water.
Polar Molecules & Water
Polar like glucose & pyruvate: OH or C=O form excellent H bonds & are soluble in H2O. [hydrophillic]
Insertion into water lattice breaks H2O-H2O H bonds, but simultaneously forms H bonds between polar organic and water.
Since alternative arrangements may not be as energetically satisfactory as H2O-H2O arrangements, even the most polar have limited solubility.
Hydrophobic “Bonds” Stabilize Macromolecules
Strong tendency of water to exclude nonpolar groups referred to as hydrophobic bonding.
Often call all the bonds between nonpolar gps in H2O hydrophobic bonds.
Misnomer, phenomenon it seeks to explain is absence, not presence of bonds: not in H2O contact.
van der Waals (hydrophobic) [Read: ala/gly to 3rd molecule]
Non-polar groups and H2O
Nonpolar Gps Arrange Themselves to Minimize Contact with H2O
Weak Bonds Attach Enzyme (E) to Substrate (S)
Weak bonds are basis for E binding S.
E catalyze both directions of a chemical reaction; thus, must have affinities for both sets of molecules.
Change in free energy of binding is never very large; thus, E-S complexes can be both made and broken apart rapidly as a result of thermal movement. Function quickly: 106/sec
If E bound to S or more importantly P by more powerful bonds, they would act slowly
Weak Bonds Mediate Most Protein-DNA & Protein-Protein Interactions.
These interactions lie at the heart of how cells detect and respond to signals, express genes, replicate, repair and recombine their DNA, …… and how those processes are regulated.
Although molecules bound together by only 1 or 2 secondary bonds frequently fall apart, a collection can result in a stable aggregate.
Double-helical DNA never falls apart spontaneously
Also, despite low energy of individual weak bond, the combined effects of many such bonds can produce affinity and specificity.

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