BOND MAKING AND BREAKING
The DH for Reactions in terms of Bond Energies (Bond Dissociation
Enthalpies).
This segment of EXBAN presents a brief review of the DH for reactions in
terms of bond breaking and making events. This is done to emphasize the large
energies required to break bonds in comparison with overall DH values for
reactions that can be negative or positive depending on the energy balance of
the bonds ruptured and formed. Two factors that must be kept in mind:
(a) In the present depiction bonds are “pulled apart” and the fragments “snap”
together to form new bonds in “tinker-toy” fashion. The overall DH for
reactions can always be represented in this way, or in terms of the balance
of bond breaking and making events employing appropriate bond
dissociation enthalpies. The path the reaction actually takes for the
transition between reactants and products will, of course, be quite different,
and depend on the mechanism, e.g. whether the reaction is uncatalyzed, or
catalyzed, etc.
(b) The misconception considered in this website is connected with the energy
associated with bond breaking. The reactions here, including the coupled
reaction, are examined, therefore, in terms of the DH’s of the processes
involved. Entropic contributions often contribute to the spontaneity of
reactions, and can become the principal driving force for reactions or phase
changes. It is, indeed, entropy that is responsible for the concentration
dependence of reactions. However, bond breaking and making, as with the
examples given here, is often the main factor in determining the spontaneity
of reactions.
The DH of hydrolysis of ATP in terms of a balance of bond
breaking and making processes.
Due to the relatively weak phosphoanhydride linkage (high energy
phosphate bond) the magnitude of the energy required to break the
bonds in the reactants is seen to be more than offset by the
corresponding decrease from bond formation in the products
Rupture of an O-H bond in water requires a very significant (~ 490
kJ/mole) input of energy. (The arrow depicting bond rupture appears
with a break inserted in that the energy involved (bond dissociation
enthalpy), is more than an order of magnitude larger than the DH for
the overall reaction.)
Breaking a phosphoanhydride bond requires considerably less but still
cost energy. At this point the bond breaking is complete with an input
of > 750 kJ of energy.
Energy begins to decrease with bond making. The magnitude of the
decrease (blue) due to formation of the P-O bond here is much greater
than the input (red) involved in breaking P~O anhydride bond.
The reaction is complete with the formation of an O-H bond.
The overall decrease of ~24 kJ/mole occurs, is the DH of hydrolysis. The
value of this exothermic process is at least an order of magnitude smaller
than the input needed to break even the weakest bond, i.e. the
phosphoanhydride, or “high energy phosphate” bond..
In this second example formation of the phosphodiester link in DNA
shown here is the reverse of a hydrolysis reaction. The endothermic
nature of this condensation is again examined in terms of bond
breaking and making.
The reaction again begins with bond rupture in the reactants.
Almost as much energy is required to break the alcoholic O-H bond
as an O-H bond in water.
Rupture of the P-O bond in the phosphate group also requires a
significant energy input It is considerably greater than that required to
break the phosphoanhydride bond in ATP.
The P-O bond in the phosphodiester link, is also significantly weaker
(blue) than the phosphate P-O bond (red).
As a result, even with formation of a strong O-H that results in the
production of water, the reaction remains endothermic.
The reaction requires a larger input of energy to break the bonds in the
reactants than the decrease due to the weaker bonds, in particular the
phosphodiester link, that are formed in the products.
The hydrolysis of a phosphoanhydride linkage in ATP that was
considered in the first example is more exothermic and spontaneous,
than hydrolysis of a phosphodiester linkage in DNA.
The more negative DG for ATP hydrolysis derives primarily from its more
exothermic nature (neg. DH). The greater exothermicity associated with ATP
hydrolysis is a consequence of the smaller input of energy (enthalpy) required to
rupture the weaker phosphoanhydride linkage in comparison with the
phosphodiester link in DNA:
DH(hydrolysis) (kJ/mole)
ATP + H2O → ADP + Pi
-24.2
DNA + H2O → 5’DNA + 3’DNA
-12.0
so that reversing the 2nd reaction in the direction of DNA formation:
ATP + H2O → ADP + Pi
-24.2
5’DNA + 3’DNA → DNA + H2O
12.0
results in an overall exothermic process if the condensation of the 2 DNA
fragments can be coupled to the ATP hydrolysis reaction:
5’DNA + 3’DNA + ATP → DNA + ADP + Pi
-11.8
In this coupled process the reactants are the 2 DNA fragments and a
molecule of ATP. Note that water does not become involved as a
reactant or product here.
The bond dissociation enthalpy for the 3’O-H is large…
followed by the rupture of the P-O bond on the phosphate of the 5’
terminal DNA stand.
The enthalpy increase ends with breaking a weak P-O phosphoanhydride
(high energy phosphate bond) in ATP.
The enthalpy decrease depicted here starts with formation of the
phosphodiester linkage. Note that the decrease (blue) is larger in
magnitude than the input required to rupture the phosphoanhydride
bond (red).
A much larger decrease in enthalpy occurs with formation of the P-O
bond at the exterior of the pyrophosphate group. (There is still an
anhydride P-O bond in the interior of the pyrophosphate.)
Coupling produces an exothermic (and exergonic) process resulting in the
spontaneous formation of the phosphodiester linkage. This relatively weak
bond was formed by breaking one that was even weaker (phosphoanhydride).
Coupling produces an exothermic (and exergonic) process resulting in the
spontaneous formation of the phosphodiester linkage. This relatively weak
bond was formed by breaking one that was even weaker (phosphoanhydride).
DNA synthesis or the joining, or splicing, of 2 single strands occurs in coupled
overall exothermic (and exergonic) processes. In the splicing reaction,
catalyzed by DNA ligase, ATP (NAD+ in the E.coli enzyme) as a cofactor
(cosubstrate) is required to drive the reaction.
The anhydride linkage in the cofactor does not combine with a solvent
molecule in its conversion to products. It can be thought of as drawing the H
and OH groups, instead, from the ends of the DNA strands allowing them to
collapse into a phosphodiester bond.
The mechanism again does not involve, as depicted here, complete rupture of bonds
prior to bond formation with the huge energy barrier that would imply. New bonds
form as old bonds are broken.
Not only do common intermediates involving e.g.,. formation of a
phosphoanhydride linkage at the end of the 3’ DNA strand, appear to
be implicated, but so does weak bonding of the cosubstrate to the
enzyme (Lehman, I.R. (1974) Science, 186, 790-797).
For a proposed mechanism for DNA ligation involving the E coli enzyme
with NAD+ as cosubstrate see: Horton, H.R., Moran, L.S., Ochs, R.S.,
Rawn.J.D. and Scrimgeour, K.G.; Principles of Biochemistry, 3rd Ed., p.643,
Prentice Hall, Saddle River, N.J., 2002.
The End